40 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; international journal of retina (ijretina) 2020, volume 3, number 3. p-issn. 2614-8684, e-issn.2614-8536 improvement of leukemic retinopathy after leukapheresis in chronic myelogenous leukemia with leukostasis: a case report ruchyta ranti1, sauli ari widjaja1,2, wimbo sasono1,2, muhammad firmansjah1,2, ima yustiarini1,2, ady dwi prakosa1,2, moestidjab1,2, gatut suhendro1,2 1 department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia 2 vitreoretinal division, department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia abstract introduction: to report a case of bilateral leukemic retinopathy due to leukostasis that was successfully managed by leukapheresis. case presentation: 31-year-old male with mild visual disturbance was referred to ophthalmology department. he suffered from chronic myelogenous leukemia (cml) with white blood cell (wbc) count 533.900/microl. he was started on hydroxyurea, allopurinol, and once leukapheresis. ophthalmologic evaluation revealed visual acuity of 4/4 in the right eye and 4/6,3 in the left eye. funduscopy examination showed the presence of bilateral papilledema, venous engorgement, tortuosity, and retinal hemorrhages. then this patient continued with second leukapheresis. result: visual acuity, laboratory examination, and funduscopic finding was evaluated. his visual acuity was improved, papilledema and retinal blood vessels abnormality had markedly reduced concurring with the patient’s hematological remission. decreasing wbc count after leukapheresis has improved blood flow that reflected from the retinal findings and visual acuity improvement. conclusion: leukapheresis treatment is sufficient to improved clinical condition for leukemic retinopathy caused by cml with leukostasis. keywords: chronic myelogenous leukemia (cml), hyperleukocytosis, leukostasis, leukemic retinopathy cite this article: ranti, ruchyta et al. improvement of leukemic retinopathy after leukapheresis in chronic myelogenous leukemia with leukostasis. international journal of retina, [s.l.], v. 3, n. 1, feb. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/87 date accessed: 19 feb. 2020. doi: https://doi.org/10.35479/ijretina.2020.vol003.iss001.87 introduction *correspondence to: ruchyta ranti, department of ophthalmology, faculty of medicine universitas airlangga,, surabaya, indonesia ruchyta@gmail.com chronic myelogenous leukemia (cml) which is also known as chronic myeloid leukemia is a myeloproliferative disorder characterized by increased proliferation of granulocyte cells. cml occupies 20% of all leukemia in adults.1 the white blood cell counts of patients diagnosed with chronic myeloid leukemia (cml) vary greatly. study by koshy et al., revealed that leukemic ophthalmic lesions were found in 43.8% patients with acute and chronic leukemias. ocular involvement is more often seen in adults, acute and myeloid leukemias.2 https://www.ijretina.com/index.php/ijretina/article/view/87 https://doi.org/10.35479/ijretina.2020.vol003.iss001.87 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 41 leukostasis is characterized by the occlusion of the microvasculature by white blood cells.3 we report the case of a previously healthy man with mild visual loss, striking fundus changes, and an extremely high white blood cell count who had significant recovery of vision after leukapheresis. case presentation a 31-year-old man was diagnosed blast phase of cml from internal medicine department and referred to ophthalmology department after reporting mild visual loss in both eyes for 3 months. additional history revealed epistaxis, back pain, night sweats, and weight loss. a complete blood count revealed white blood cell (wbc) count of 533.900/mm3 (reference range: 3.500 to 11.000/mm3), platelet count of 139.000 (reference range: 150.000 to 400.000/mm3), and hemoglobin concentration of 8.7 g/dl (reference range: 14-18 g/dl). the patient was treated with hydroxyurea, allopurinol, and two sessions of leukapheresis. at his first visit, after the first leukapheresis, examination showed best-corrected visual acuity (bcva) of 4/4 in the right eye and 4/6,3 in the left eye. anterior segment examination by slit lamp biomicroscope showed no abnormality. posterior segment examination revealed papilledema, dilated retinal veins, diffuse retinal hemorrhages, and white-centered hemorrhages on both eyes (figure 1). figure 1. fundus photographs of the right and left eyes illustrate the present of papilledema, dilated retinal veins and tortuosity, diffuse retinal hemorrhages, and whitecentered hemorrhages (roth’s spot). the patient was diagnosed with leukemic retinopathy in both eyes. there was no specific therapy from ophthalmology department. second examination was done 3 weeks after the second leukapheresis. a complete blood count revealed wbc count of 112.770/mm3, platelet count of 522.000, and hemoglobin concentration of 10,3 g/dl. his visual acuity was improved (4/5 on left eye), papilledema and retinal blood vessels abnormality had markedly reduced concurring with the patient’s hematological remission (figure 2). discussion the manifestation of leukemia in the eye can be in the form of direct infiltration of leukemia cells or is the impact of leukocytosis, anemia, and thrombocytopenia.4 it can involve in various ocular tissue. conjunctival involvement, is not a common presentation of leukemias. cellular involvement is found at all levels of the substantia propria and can be diffuse or patchy, tending to concentrate along blood vessels. figure 2. fundus photographs of the right and left eyes showed reduced papilledema and retinal blood vessels abnormality 3 weeks after the second leukapheresis. the involvement of choroid and ciliary body may occur in anterior segment. clinically, it is characterised by a change in iris colour, and a pseudohypopyon. the intra-ocular pressure (iop) can be high enough to cause signs and symptoms of acute glaucoma with normal depth anterior chamber. orbital infiltration in leukaemia presents with exophthalmos, lid oedema, chemosis and pain. all types of leukaemia may involve the orbit; however, anterior segment and 42 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; orbital involvement is more common in acute and lymphoid leukaemias.5 leukemic retinopathy is a common complication in both acute and chronic forms.6 fundus examination can illustrate the effects of cml in the body. its pathophysiology is still unclear but other mechanisms that may play a role in cml include: anemia; leukostasis; hyperviscosity syndrome; leukoembolization; endothelial lesions and local thrombosis secondary to toxic products released by leukemia cells; angiogenic factors released by the ischemic retina; and elevated serum levels of angiogenic growth factors.7 treatment of the underlying causes of the ocular findings could actually result in their improvement or even resolution. this patient has received cytoreduction treatment with hydroxyurea. this medication has rapid onset and short duration so that it can manage hyperviscosity syndrome with shorter period of myelum suppression. to anticipate hyperuricemia caused by hydroxyurea therapy, this patient was given oral allopurinol to altered uric acid production. leukapheresis is the best option for patient with hyperleukocytosis and not pregnant, combined with hydroxyurea to give the best result in decreasing leukocyte.8 three weeks after second leukapheresis, visual acuity left eye become 4/5. fundus examination showed improvement along with decreasing leukocyte. the results obtained in this case report are inversely proportional to the results of the study by soman et al. where statistically there was no correlation between the number of leukocytes and ophthalmic menifestations.9 the ocular abnormality found in leukemic retinopathy can also mimic some other disease such as retinal vein occlusion, congenital or hereditary vein turtoisity, papilloedema, or even infection. it is recommended that ophthalmologist have to run other supportive diagnostic test (color vision test, contrast sensitivity test, optical coherence tomography, visual field examination, brain imaging) if the underlying systemic disease is unknown. conclusion this case report underlined the importance of routine eye examinations in patients with leukemia and vice versa in healthy patients with signs of leukemic retinopathy to complete blood tests and referral to hematologist for further management, because the key is to treat the underlying malignancy. references 1. besa, e. c. (2015). chronic myelogenous leukemia. diakses 1 maret 2016, available from: http://emedicine.medscape.com/article/19942 5-overview 2. koshy j, john mj, thomas s, kaur g, batra n, xavier wj, 2015. ophthalmic manifestations of acute and chronic leukemias presenting to a tertiary care center in india. indian journal of ophthalmology. pp 659–664. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/p mc4687193/ 3. schiffer ca, 2015. hyperleukocytosis and leukostasis in hematologic malignancies. uptodate. available from: http://www.uptodate.com/contents/hyperleuk ocytosis-and-leukostasis-in-hematologicmalignancies 4. rosenthal ar, 1983. ocular manifestations of leukemia: a review. elsevier. available from: https://www.sciencedirect.com/science/article /pii/s016164208380013x 5. sharma t, grewal j, gupta s, murray pi, 2004. ophthalmic manifestations of acute leukaemias: the ophthalmologist’s role. eye. pp 663-672. available from: https://www.nature.com/articles/6701308 http://emedicine.medscape.com/article/199425-overview http://emedicine.medscape.com/article/199425-overview https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4687193/ https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4687193/ http://www.uptodate.com/contents/hyperleukocytosis-and-leukostasis-in-hematologic-malignancies http://www.uptodate.com/contents/hyperleukocytosis-and-leukostasis-in-hematologic-malignancies http://www.uptodate.com/contents/hyperleukocytosis-and-leukostasis-in-hematologic-malignancies https://www.sciencedirect.com/science/article/pii/s016164208380013x https://www.sciencedirect.com/science/article/pii/s016164208380013x https://www.nature.com/articles/6701308 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 43 6. dobberstein h, solbach u, weinberger a, wolf s, 1999. correlation between retinal microcirculation and blood viscosity in patients with hyperviscosity syndrome. clinical hemorheology and microcirculation. pp 31-35. available from: https://www.ncbi.nlm.nih.gov/pubmed/11185 681 7. jackson n, reddy sc, hishamuddin m, & low hc, 1996. retinal findings in adult leukaemia: correlation with leukocytosis. clinical laboratory haematology. pp 105-109.
 available from: http://onlinelibrary.wiley.com/doi/10.1046/j.1 365-2257.1996.d01-217.x/full 8. aqui n & o’doherty u, 2014. leukocytapheresis for the treatment of hyperleukocytosis secondary to acute leukemia. hematology, pp 457-460. 9. soman s, kasturi n, srinivasan r, vinod kv, 2017. ocular manifestations in leukemias and their correlation with hematologic parameters at a tertiary care setting in south india. american academy of ophthalmology. pp 1723. available from: https://www.ophthalmologyretina.org/article/ s2468-6530(17)30132-x/pdf this work licensed under creative commons attribution https://www.ncbi.nlm.nih.gov/pubmed/11185681 https://www.ncbi.nlm.nih.gov/pubmed/11185681 http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2257.1996.d01-217.x/full http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2257.1996.d01-217.x/full https://www.ophthalmologyretina.org/article/s2468-6530(17)30132-x/pdf https://www.ophthalmologyretina.org/article/s2468-6530(17)30132-x/pdf published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 1 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 future eye related disease due to myopia referano agustiawan president of indonesian vitreo retinal society *correspondence to: referano agustiawan, referanoagustiawan@gmail.com, jec eye hospitals, jakarta, indonesia in 2010, myopia has been one of the leading causes of refractive error, with a prevalence of 27% worldwide.1-2 this figure is predicted to increase every year especially after covid-19 pandemic. who predicted that in 2050, there will be an explosion of myopia cases worldwide due to pandemic. this figure is predicted to reach 9.8% of the world's population or around 938 million people. since the pandemic, the insufficient time spent outdoors, and the increasing amount of time on cellphones and computers have been the major cause of myopia cases.1,3,4 the cause of myopia can occur multifactorial, a mixture of genetics and the environment.5,6 environmental causes that have been mentioned are the amount of time using gadgets, lack of time spent outdoors, low levels of vitamin d, and poor diet. 7-14 a rapid increase in myopia cases has been found in many countries. in china, there are around 80% of students aged 12 years who are now myopia and 10-20% of them have high myopia exceeding -6 d. this incident can also be found in indonesia. based on research by gajah mada university, studies done in 312 children, 41% of them had myopia and 21% of them had severe refractive errors. this number has grown rapidly, especially since the pandemic.3 this phenomenon needs to be watched out for by parents because eye health plays an important role in children's health and scholar achievement. 1,3 recent research now can predict the occurrence of myopia as early as possible. studies about the axial length growth is being developed to determine whether a child's axial length is normal for his or her age to predict the likelihood of future myopia. an article discusses how we can predict myopia based on current axial length, changes in axial length, prediction using axial length growth charts, and using the al/cr ratio.15 prediction using the current axial length is done by a study in singapore. they found that myopia can occur at an axial length of 23.69±0.69mm in girls and 24.08±0.67mm in boys, regardless of age. this figure is the cut-off for predicting myopia onset.16-17 another way of predicting myopia is using the changes in the axial length. the collaborative longitudinal evaluation of ethnicity and refractive error (cleere) study, collects data on children over 11 years of age, found that children who are still emmetropic have an annual axial length growth of about 0.1 mm per year. they also found that axial length grows the fastest 1 year before the onset of myopia where it grew by 0.33 mm on average. this rate will decrease by 0.20.27mm/year after the initial myopia onset.18 the use of axial length growth charts can also be used to predict future 4 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; myopia. by comparing the current child's axial length to match their age-normal result. if the child is above the 50% percentile, there is a high risk of developing myopia in the future.19-20 another way is to use the al/cl ratio. a longer axial length in comparison to the corneal radius generally indicates a greater risk of becoming myopic. a study in china and europe showed that children who have an al/cr ratio of more than 3 have a higher chance of myopic error. measurement of the al/cr ratio requires measurements using keratometry or corneal topography. therefore, it is very important to have routine eye examinations once every 6-12 months to prevent eye diseases that can endanger our vision.21-22 one of the ways to prevent myopia is to reduce screen time, spending more time on outdoor activities, and consume a good diet.1 however, when myopia has occurred, it must be treated properly. myopia that is not corrected properly can cause dangerous complications that can lead to blindness. one of the conditions that can arise in children with refractive disorders is lazy eye. this happens because there is severe myopia in one eye so that the child's brain will rely on a healthy eye. this lazy eye cannot be cured with ordinary glasses or contact lenses and if left untreated can be a big risk factor visual impairment related disease.3 even if appropriate correction is given, myopia is still a risk for sightthreatening diseases such as glaucoma, cataracts, retinal tears which will lead to retinal detachment, and myopic maculopathy or myopic macular degeneration. this condition can especially be found in conditions that have high myopia.23-24 in a systematic review about glaucoma, the risk of developing glaucoma was 50% higher in people with moderate to severe myopia (odds ratios 2.5 and 1.7) compared to low myopia.25 in cataracts it was also found to be higher (17% more likely) in patients with high myopia to perform cataract surgery (or 3.4 and 2.9) compared to low myopia.26 in cases of retinal detachment, the increase in cases reaches 5-6x higher in people with high myopia. this is because someone with high myopia has longer eyes so that the retina is more stretched and causes vulnerability to cause retinal tears. high myopia is also a cause of central retinal degenerative changes such as chorioretinal atrophy, posterior staphyloma, and lacquer cracks. another risk in cases of high myopia is myopic muscular degeneration where the incidence rate increases with age and increasing myopia. this condition may develop in the form of atrophic changes or be complicated by choroidal neovascular membrane formation. in more advanced conditions, myopic maculopathy can cause loss of central vision for which there is currently no treatment.27-28 with the rising numbers of myopia, the visual impairment caused by myopia will rise in the future. as ophthalmologists especially in the vitreoretinal field, we must be aware of the potential social dangers in indonesia due to an increase cases in myopia. the steps we can take to reduce the number of myopia cases are by working with related parties (government, society, media, etc.) to increase their awareness of this case. increasing education related to myopia will make it easier for all of us to overcome this problem. inavrs encourages eye specialists in indonesia to conduct research related to myopia. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 5 references 1. holden, b., et al. "myopia: a growing global problem with sight-threatening complications." community eye health journal. 2015;28: 35. 2. holden ba, fricke tr, wilson da, jong m, naidoo ks, sankaridurg p, et al. global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. ophthalmology. 2016;123(5):1036– 42. 3. humaniora. "fenomena myopia booming kurang disadari oleh masyarakat indonesia." 2023, from https://mediaindonesia.com/humaniora/531810/fenomena-myopia-booming-kurang-disadari-olehmasyarakat-indonesia. 4. wang j, li y, musch dc, et al. progression of myopia in school-aged children after covid-19 home confinement. jama ophthalmol. 2021;139(3):293–300. doi:10.1001/jamaophthalmol.2020.6239 5. farbrother je et al. linkage analysis of the genetic loci for high myopia on 18p, 12q, and 17q in 51 uk families. investigative ophthalmology & visual science 2014;45: 2879–2885. 6. kiefer, a. k. et al. genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia. plos genet 9, 2013. 7. lim lt et al. impact of parental history of myopia on the development of myopia in mainland china school-aged children. ophthalmology and eye diseases 2014;6: 31–35. 8. fledelius hc, goldschmidt e, haargaard b and jensen h. human parallels to experimental myopia? a literature review on visual deprivation. acta ophthalmol 2014. 9. flitcroft di. emmetropisation and the aetiology of refractive errors. eye 2014;28: 169–179. 10. morgan ig, ohno-matsui k and saw sm. myopia. lancet 2012;379: 1739–1748 11. french an, ashby, rs, morgan ig and rose ka. time outdoors and the prevention of myopia. exp eye res 2013;114: 58–68. 12. yazar, s. et al. myopia is associated with lower vitamin d status in young adults. invest ophthalmol vis sci 2014; doi:10.1167/iovs.14-14589. 13. read sa, collins mj and vincent sj. light exposure and physical activity in myopic and emmetropic children. optom vis sci 2014;91: 330–341. 14. lim ls et al. dietary factors, myopia, and axial dimensions in children. ophthalmol 2010;117: 993– 997. 15. haines, c. "predicting future myopia from axial length.2022." from https://www.myopiaprofile.com/predict-future-myopia-axial-length/. 16. rozema j, dankert s, iribarren r, lanca c, saw s-m. axial growth and lens power loss at myopia onset in singaporean children. investigative ophthalmology & visual science. 2019;60(8):3091-3099. 17. zadnik k, sinnott lt, cotter sa, et al. prediction of juvenile-onset myopia. jama ophthalmology.2015;133(6):683-689. 18. mutti do, hayes jr, mitchell gl, et al. refractive error, axial length, and relative peripheral refractive error before and after the onset of myopia. invest ophthalmol vis sci. 2007;48(6):2510-2519. 19. tideman jwl, polling jr, vingerling jr, et al. axial length growth and the risk of developing myopia in european children. acta ophthalmol. 2018;96(3):301-309. 20. sanz diez p, yang l-h, lu m-x, wahl s, ohlendorf a. growth curves of myopia-related parameters to clinically monitor the refractive development in chinese schoolchildren. graefes arch clin exp ophthalmol. 2019;257(5):1045-1053. 6 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 21. he x, zou h, lu l, zhao r, zhao h, li q, zhu j. axial length/corneal radius ratio: association with refractive state and role on myopia detection combined with visual acuity in chinese schoolchildren. plos one. 2015 feb 18;10(2):e0111766. 22. tideman jwl, polling jr, jaddoe vwv, vingerling jr, klaver ccw. environmental risk factors can reduce axial length elongation and myopia incidence in 6to 9-year-old children. ophthalmology. 2019 jan;126(1):127-136. 23. saw sm, gazzard g, shih-yen ec, chua wh. myopia and associated pathological complications.ophthalmic physiology and optics. 2005;25(5):381–91. 24. mitchell p, hourihan f, sandbach j, wang jj. the relationship between glaucoma and myopia: the blue mountains eye study. ophthalmology 1999;106(10):2010–5. 25. marcus mw, de vries mm, junoy montolio fg, jansonius nm. myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. ophthalmology 2011;118(10):1989–94 e2. 26. younan c, mitchell p, cumming rg, rochtchina e, wang jj. myopia and incident cataract and cataract surgery: the blue mountains eye study. invest ophthalmol vis sci 2002;43(12):3625–32. 27. flitcroft di. the complex interactions of retinal, optical and environmental factors in myopia aetiology. prog retin eye res 2012;31(6):622–60. 28. ohno-matsui k, kawasaki r, jonas jb, cheung cm, saw sm, verhoeven vj, et al. international photographic classification and grading system for myopic maculopathy. am j ophthalmol2015;159(5):877–83 e7. future eye related disease due to myopia referano agustiawan president of indonesian vitreo retinal society published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 33 international journal of retina (ijretina) 2018, volume 1, number 1. p-issn. 2614-8684, e-issn.2614-8536 bilateral exudative retinal detachment due to hypertensive retinopathy and choroidopathy in young patient with chronic kidney disease indha dwi kartikasari, nadia artha dewi, mirza metita, safaruddin refa department of ophthalmology, universitas brawijaya, saiful anwar hospital malang abstract introduction: severe systemic hypertension in chronic kidney disease can cause significant damage to the eye. although hypertensive retinopathy is a well-known complication, hypertensive optic neuropathy and choroidopathy are much less common. the aim of this study is to report retinal manifestation in young patient with chronic kidney disease. method: a 26-year-old man with underlying disease chronic kidney disease (ckd) gr-v underwent bilateral bullous exudative retinal detachments. retinal arteriolar narrowing, vascular tortuosity, arteriovenous nicking, optic disc swelling, retinal haemorrhage, elschnig spot, siegrist streak were identified in both eyes. blood pressure was 200/140mmhg with visual acuity 0,5/60 ou. the patient was diagnosed with bilateral hypertensive retinopathy and choroidopathy with bulous exudative retinal detachments. results: after antihypertensive treatment, visual acuity improved, but the exudative retinal detachments and retinal hemorrhages reduced. a patient with those findings should be considered as having hypertensive retinopathy and choroidopathy and treated as soon as possible because of the poor prognostic. conclusion: hypertensive choroidopathy is a rare finding associated with acute increases in blood pressure. when the choroid is associated, the hypertensive event is often more acute and associated with increased morbidity. it is necessary to obtain fundus exam in any patient with elevated blood pressure and concomitant vision complaints. therefore, screening hypertensive patients involves close collaboration between internist and ophthalmologist. keywords: hypertensive choroidopathy, hypertensive retinopathy, exudative retinal detachment, elschnig’s spot, siegrist streak, chronic kidney disease cite this article: kartikasari, indha dwi; dewi, nadia artha. bilateral exudative retinal detachment due to hypertensive retinopathy and choroidopathy in young patient with chronic kidney disease. international journal of retina, [s.l.], v. 1, n. 1, july 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/20> introduction *correspondence to: indha dwi kartikasari, department of ophthalmology, universitas brawijaya, indhadk@gmail.com severe systemic hypertension in chronic kidney disease can cause significant damage to the eye. although hypertensive retinopathy is a well-known complication, hypertensive neuropathy and choroidopathy are much less common. elevation of systemic blood pressure as in renovascular disease causes both focal and generalized retinal arteriolar constriction, presumably mediated by autoregulation. a prolonged duration of particularly high blood pressure can be associated with a breakdown of the inner blood-retinal barrier, with extravasation of plasma and red blood cells. retinal hemorrhages, cottonwool spots, intraretinal lipid, and, in severe cases, the development of a macular star configuration of intraretinal lipid can be seen1–3. when the choroidal vessels are severely affected by elevated blood pressure, as in acute hypertension, fibrinoid necrosis of choroidal arterioles can cause occlusion of areas of choriocapillaris, with a subsequent breakdown of the outer blood-retinal barrier. although the retinal vascular changes and optic neuropathy are well known, hypertensive choroidopathy usually does not receive as much attention. hypertensive choroidopathy has been reported in toxemia of pregnancy, renal disease, pheochromocytoma, and malignant hypertension4. 34 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; hypertension retinopathy occur almost half in ckd population, while hypertension choroidopathy only on 0,1%5. we report a case of hypertensive retinopathy and hypertensive choroidopathy with bilateral exudative retinal detachments in young patient with chronic kidney disease. case illustration a 26-year-old man presented with a painless loss of vision in his both eyes. he had a history of chronic kidney disease (ckd) gr-v on hemodyalisis since 2 months ago. ophthalmic examination revealed visual acuity of 0.5/60 ou. pupils reacted normally without an afferent pupillary defect. he had normal extraocular motility, and ocular alignment in both eyes. slit lamp examination revealed subconjunctival haemorrhage in both eyes. retinal examination revealed retinal arteriolar narrowing, vascular tortuosity, arteriovenous nicking, optic disc swelling, retinal hemorrhage, intraretinal exudation and macular star formation, exudative retinal detachment, elsching spot, and siegrist streak. the blood pressure was 200/140 mmhg. hemoglobin 8,0 g/dl, rbc 2,96 x 106/µl, wbc 13.130/µl, hematocrit 24,10%, plt 114.000/µl, rbs 150 mg/dl, ureum 249,70 mg/dl, creatinin 20,61mg/dl. urinalysis ph 8,5; density 1,015; glucose1+; protein 3+; keton, bilirubin, urobilinogen, nitrit negative; wbc 2+, blood 3+; epithel 1,1 lpk, cylinder negative; rbc 41,9 lpb; wbc 46,5 lpb, crystal negative, bacteria 2750,8 x 103 /ml, shown in the laboratory result. the patient was diagnosed with bilateral hypertensive retinopathy and choroidopathy with bullous exudative retinal detachment and treated with antihypertensive treatment glyceryl trinitrate (gtn) drip 20-200 µ /mnt and furosemide drip 10 mg/hour, amlodipine 1x10 mg tab, valsartan 1x80 mg tab, lansoprazole 1x30 mg intravena (iv), and metoclopramide 3x10 mg iv. figure 1. subkonjungtival haemorrhage on both eyes figure 2. fundus photograhy show bilateral disc edema, retinal bleeding, exudative retinal detachment, elschnig spot, siegrist streak , and macular star (courtesy by vitreo-retina division) patient came at outpatient clinic after 2 weeks with improvement in visual acuity to 1/60 with better retinal findings, but decreasing in general condition. according to systemic condition, 2 weeks later the patient passed away. figure 3. there were reducing of subconjunctival haemorrhage on both eyes after 3 weeks published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 35 figure 4. fundus photography after 3 weeks show reducing of bilateral disc edema, retinal bleeding, and exudative retinal detachment(courtesy by vitreo-retina division) figure 5. ocular usg right eye (above) left eye (below) when sitting postion (left photo) and supine position (right photo) showed shifting fluid as gravitation. (courtesy by vitreo-retina division) discussion severe systemic hypertension is associated with significant damage of end organs, such as eyes, heart, central nervous system, and kidneys. choroidal lesions are less commonly recognized than retinal and optic nerve lesions6. subconjunctival haemorrhage associated with valsava maneuver and drastically increased blood pressure7. accelerated hypertension and/or ophthalmic/ciliary artery occlusion may result in choroidal ischemia. with complete ophthalmic artery occlusion, both the retinal and choroidal circulations are compromised. compromise of ciliary arteries may occur without retinal artery involvement, leading to choroidal ischemia, which causes hypertensive choroidopathy. some of these are attributed to a breakdown of the inner blood-retinal barrier with retinal endothelial cell decompensation. furthermore, there are large fenestrations in the walls of the choriocapillaris, so the choroidal vascular bed has no blood ocular barrier. this causes leakage of plasma into the choroidal fluid. angiotensin ii and other vasoconstrictors in the choroidal fluid result in vasoconstriction and ischemia of the choroidal vasculature. this cascade is followed by rpe ischemia and the subsequent breakdown of the blood retinal barrier in the rpe and result as elcshnig spot and 36 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; siegrist streak. the rpe becomes necrotic, this may result in exudative retinal detachment8. the narrowed arterioles, vascular tortuosity, and arteriolovenous nicking in the retinal vessels were also observed. these findings are relatively common in longstanding hypertension. it seems that the patient had a history of longstanding chronic hypertension, and a sudden bp elevation triggered it off and formed this condition. after antihypertension treatment, the exudative retinal detachment and others condition remain still. in most cases with hypertensive choroidopathy, visual acuity returns to normal by controlling their bp. however, there is a case reporting that the visual acuity was not recovered in spite of being controlled the bp9. a patient with these findings should be considered as hypertensive retinopathy and choroidopathy and treated with antihypertension therapy as soon as possible. in exudative retinal detachment, when the fluid is not resolving and retinal detachment is chronic and bullous, permanent damage to retinal pigment epithelium as well as outer retinal structures occurs and persistence of subretinal fibrin may lead to subretinal fibrotic scar formation. to avoid these complications, surgical intervention either external drainage or pars plana vitrectomy is planned after failure of conventional treatment. however, surgical treatment is never the first line of management in these conditions10. this disease has poor prognosis caused by continuous process during the damage of blood vessel, even if the bp is in a good state, the complication still occurs in 50% patient9. hypertensive choroidopathy is a less-common complication of systemic hypertension but can be the harbinger of a potentially life-threatening hypertensive emergency with end-organ damage. choroidal involvement in the setting of hypertensive emergency is usually the sign of an acute, dramatic increase in systemic blood pressure in a young person and associated with poor visual and systemic prognosis. conclusion hypertensive choroidopathy is a rare finding associated with acute increases in blood pressure. when the choroid is involved, the hypertensive event is often more acute and associated with increased morbidity. it is necessary to obtain a fundus exam in any patient with elevated blood pressure and concomitant vision complaints. therefore, screening hypertensive patients involves close collaboration between internist and ophthalmologist. antihypertensive is the first line treatment, but if the exudative retinal detachment not resolve and retinal detachment is chronic and bullous, surgical intervention to drain the fluid can be planned. references 1. a. g. lee and h. a. beaver, “acute bilateral optic disk edema with a macular star figure in a 12year-old girl,” survey of ophthalmology, vol. 47, no. 1, pp. 42–49, 2002. 2. a. grosso, f. veglio, m. porta, f. m. grignolo, and t. y. wong, “hypertensive retinopathy revisited: some answers, more questions,” british journal of ophthalmology, vol. 89, no. 12, pp. 1646–1654, 2005. 3. t. y. wong and p. mitchell, “hypertensive retinopathy,” the new england journal of medicine, vol. 351, no. 22, pp. 2310–2317, 2004. 4. m. o. m. tso and l. m. jampol, “pathophysiology of hypertensive retinopathy,” ophthalmology, vol. 89, no. 10, pp. 1132–1145, 1982. 5. bajracharya l, shah d, rait k, koirala s. ocular evaluation in patients with chronic renal failurea hospital based study. nepal med coll j, 2008;10(4)209-214 6. b. p. luo and g. c. brown, “update on the ocular manifestations of systemic arterial hypertension,” current opinion in ophthalmology, vol. 15, no. 3, pp. 203–210, 2004. 7. shoji kishi, mark o. m. tso dan hayreh, sohan singh. fundus lesions in malignant hypertension: a pathologic study of experimental hypertensive optic neuropathy. arch ophthalmol. 1985;103(8):1198-1206 8. hayreh, sohan singh. ocular vascular occlusive disorders. new york : springer, 2015 9. m. ugarte, s. horgan, s. rassam, t. leong, and c. h. kon, “hypertensive choroidopathy: recognizing clinically significant end-organ damage,” acta ophthalmologica, vol. 86, no. 2, pp. 227–228, 2008. 10. ganesan s. and rishi e. surgical implications in exudative retinal detachment, sci j med & vis res foun 2017;xxxv:29–36. this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 35 international journal of retina (ijretina) 20xx, volume xx, number xx. (filled by editor) p-issn. 2614-8684, e-issn.2614-8536 surgical management on posterior uveitis with vitreous opacity suspected retinal detachment firda ayu muthie1, sauli ari widjaja1,2, wimbo sasono1,2, muhammad firmansjah1,2, ima yustiarini1,2, ady dwi prakosa1,2, moestidjab1,2, gatut suhendro1,2 1 department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia 2 vitreoretinal division, department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia abstract introduction: posterior uveitis entities are varying between infective or non-infective in aetiology. it can affect the adjacent structures such as retina, vitreous, optic nerve head and retinal blood vessels. vitreous opacity is the most common features of posterior uveitis and posterior segment evaluation is critical to determine the aetiology and management. case presentation: 32-year-old male with gradual visual loss on right eye since 2 years ago and getting worse 1.5 months before admission. visual acuity (va) was hand movement. posterior segment evaluation revealed vitreous opacity and ultrasound examination showed membrane shaped lesion attached to the optic nerve suggested retinal detachment. discussion: vitrectomy was done for diagnostic and therapeutic purpose. va was remarkably improved by 6/6 and persist until 6 months post vitrectomy, and progressive improvement on posterior segment. conclusion: surgical in the management of posterior uveitis can be divided based on indication, either for therapeutic or diagnostic purposes or to manage its complications. vitrectomy is one of the modality to manage vitreoretinal complications associated with uveitis. keywords: posterior uveitis, retinal detachment, vitreous opacity, vitrectomy cite this article: muthie, firda ayu. surgical management on posterior uveitis with vitreous opacity suspected retinal detachment. international journal of retina, [s.l.], v. 3, n. 1, feb. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/83 date accessed: 17 feb. 2020. doi: https://doi.org/10.35479/ijretina.2020.vol003.iss001.83 introduction *correspondence to: firda ayu muthie, department of ophthalmology, faculty of medicine universitas airlangga,, surabaya, indonesia firda.muthie@gmail.com posterior uveitis may be focal, multifocal, or diffuse with involvement of posterior segment structures such as choroid, retina, retinal blood vessels and optic nerve head.1 the entities are varying between infective or non-infective in etiology. a thorough diagnostic work-up directed by the history of presenting complaints, patient’s symptoms and signs, and clinical examination is mandatory.2 pars plana vitrectomy has long been used for the management of various forms of uveitis and allows detailed fundus observation during surgery.3, 4 https://www.ijretina.com/index.php/ijretina/article/view/83 https://doi.org/10.35479/ijretina.2020.vol003.iss001.83 36 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; case presentation a case report of 32-year-old male with chief complain of gradually blurred vision on his right eye since 2 years ago and getting worse 1.5 months before admission. visual acuity was 1/300 and 6/6 on his right and left eye respectively. intraocular pressure was perfectly normal on both eyes. he has unremarkable medical history and no history of drug usage. the anterior segment was completely between normal limit on both eyes. no flare or cell were found on both eyes. posterior segment on his right eye was difficult to be evaluated because of the vitreous opacity. ultrasound examination was performed to determine the haziness. b-scan ultrasonography on the right eye showed membrane shaped lesion attached to optic nerve, less mobile with reflectivity around 20-30% retina choroid sclera (rcs) complex on vitreous cavity. figure 1. ultrasound examination on the right eye showed membrane shaped lesion attached to the optic nerve. laboratory result was between normal limit but we didn’t perform any immunology examination due to resources limitation. steroid was given orally and topically only after the surgery because there were no sign of inflammation preoperatively. methylprednisolone 8 mg tapering off was given three times daily orally for about 2 weeks and fluorometholone eye drop was given for about a month on right eye results vitrectomy was performed on right eye. there was dense vitreous and membranes in vitreous cavity due to inflammation. retina was attached. there were diffuse vascular involvement and some retinal bleeding around the optic nerve, but there were no active bleeding nor blood in vitreous was found. vasculitis was found by the presence of perivascular sheathing and some exudation around the affected vessels. venous dilatation were found with focal arterial sclerotic. unfortunately we could not performed vitreous biopsy to this patient due to insurance issues and the patient refused to do this procedure. visual acuity on right eye was 1/300 preoperatively and still remain the same in one day post-operatively. on the next day there were significant improvement on right eye by 5/12 and continue to progress by 5/8.5 in a week postoperative followed by a remarkable improvement of posterior segment condition. two weeks postoperative his visual acuity became 5/5. 6 months follow up post-operatively, the visual acuity remains 5/5. intra ocular pressure were also monitored for each follow up and it vary between 12.2 mmhg to 17.2 mmhg. fundus photography had been performed each time the patient came to follow up. figure 2. fundus photography on both eyes 2 days post operative published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 37 figure 3. fundus photography on both eyes a month post-operative optical coherence tomography angiography (oct-a) and spectral domain oct (sd-oct) was performed 30 days post-operative, and both showed normal configuration. the image showed by angiography was superficial inner retina that contains a vascular projection of retinal nerve fiber layer (rnfl) and ganglion cell layer (gcl). there were no avascular zone nor neovascularization. figure 4. oct angiography of the right eye showed normal superficial retina vasculature the sd-oct showed normal configuration of each retinal layer and there were no membrane was found. figure 5. sd-oct of the right eye 30 days post operative treatment. it shows normal retinal layer and no membrane was found. discussion the clinical symptoms of the patient was not fully developed as uveitis. but the visual loss happened gradually and became worst and this patient had a good respond to steroid treatment. the ultrasound examination supported the diagnosis of uveitis because of the membrane shape like was found. posterior uveitis has a broad differential diagnosis. once the diagnosis of posterior uveitis is confirmed, next important step is to determine the extent of involvement of the inflammation.1 although epiretinal membrane (erm) is common in uveitis,5 the membrane that seen on ultrasound was only found in vitreous cavity due to the dense opacity of the vitreous and not involving the retina. because of the dense vitreous opacity in this case, we could not performed oct. oct is helpful in confirming the presence of epiretinal membranes and in distinguishing inflammatory macular edema from that due to vitreomacular traction, thereby identifying cases that are more likely to respond to surgical intervention. epiretinal membranes that are associated specifically with uveitis seem to differ from idiopathic erm in cellular composition, suggesting that they may emerge through a different pathogenic mechanism. in this case, sdoct showed normal retinal layer on right eye.6,7 the indications for surgery in the management of uveitis can be divided as: 5 1. visual rehabilitation: surgery for removal of cataract, band keratopathy, corneal scars, pupillary membranes, removal of dense vitreous membranes. 2. management of complications: anti-glaucoma surgery, vitreous haemorrhage, retinal detachment and chronic hypotony. 3. diagnostic: aqueous tap, vitreous biopsy, tissue biopsy (iris, choroid). 38 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; vitrectomy is an option for atypical clinical presentations of uveitis. it also done for uveitis that not responds to empirical treatment with corticosteroids/ immunosuppressants and for rapidly progressive disease with inconclusive noninvasive work-up or if there is strong suspicion of malignancy.8 the vitrectomy technique is using standard threeport vitrectomy because it is preferable while performing combined diagnostic and therapeutic vitrectomy to get the best visualization of the fundus. this method is also allowing better diffusion of intraocular medications and yielding more vitreous sample for analyzation.7 in uveitis, the dictum is to operate in a quiet eye, especially, if it is for an elective surgery as for visual rehabilitation. it is mandatory to wait for at least 3 months after the last episode of active disease.8 preoperative ancillary assessment might include bscan ultrasonography or ultrasonic biomicroscopy in the presence of media opacity or hypotony to detect underlying chorioretinal pathology, such as exudative retinal or choroidal detachment, and cyclitic membranes, which might influence the surgical plan.7 conclusion surgery in the management of uveitis can be divided based on indication, either for therapeutic or can be for diagnostic purposes or to manage complications.7 vitrectomy is a good modality to manage vitreoretinal complications associated with uveitis, in this case vitrectomy was useful for diagnostic procedure and for visual rehabilitation. pre-operative factors include proper patient selection and counseling and pre-operative control of inflammation. it is now well-recognized that chronic inflammation, even low grade, can irreversibly damage the retina and optic nerve and therefore inflammatory control both preand postoperatively is vital.6 references 1. sharma, preeti, & majumder, parthopratim. (2015). diagnosis and management of posterior uveitis. current indian eye research. 2017, 1-10. 2. biswas, j., sudharshan, s., & ganesh, s. (2010). current approach in the diagnosis and management of posterior uveitis. indian journal of ophthalmology, 58(1), 29. 3. kaza, h., modi, r., rana, r., panda, k. g., barik, m. r., ali, m. h., & basu, s. (2018). effect of adjunctive pars plana vitrectomy on focal posterior segment inflammation: a case-control study in tuberculosis-associated uveitis. american academy of ophthalmology 2018:1-7. 4. sato, t., kinoshita, r., taguchi, m., sugita, s., kaburaki, t., sakurai, y., & takeuchi, m. (2018). assessment of diagnostic and therapeutic vitrectomy for vitreous opacity associated with uveitis with various etiologies. medicine, 97(2), e9491.3. 15. 5. kempen jh, altaweel mm, holbrook jt, et al. the multicentre uveitis steroid treatment trial: rationale, design, and baseline characteristics. am j ophthalmol 2010;149:550–561. 6. nicholson, b. p., zhou, m., rostamizadeh, m., mehta, p., agrón, e., wong, w., sen, h. n. (2014). epidemiology of epiretinal membrane in a large cohort of patients with uveitis. ophthalmology, 121(12), 2393–2398. 7. vitale, albert. (2006). vitrectomy in patients with uveitis. review of opthlamology. accessed on 22nd may 2019: https://www.reviewofophthalmology.com/articl e/vitrectomy-in-patients-with-uveitis https://www.reviewofophthalmology.com/article/vitrectomy-in-patients-with-uveitis https://www.reviewofophthalmology.com/article/vitrectomy-in-patients-with-uveitis published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 39 8. murthy, s., pappuru, r., sangwan, v., kamat, s., & latha, km. (2013). surgical management in patient with uveitis. indian journal of ophthalmology, 61(6), 284. this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 69 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 clinical outcomes of surgery for advanced stage retinopathy of prematurity: a case report dian estu yulia, marissa jayawinata, mario marbungaran hutapea department of ophthalmology, faculty of medicine, universitas indonesia, cipto mangunkusumo national central hospital jakarta, indonesia abstract introduction: advanced stages of retinopathy of prematurity (rop) could lead to childhood blindness and retinal surgery is needed as the main treatment. this case aims to report the clinical outcomes after surgery for advanced-stage rop case report: a female infant was admitted to the pediatric ophthalmology clinic in cipto mangunkusumo national central hospital jakarta with a lack of visual contact in both eyes at 53 weeks of post menstrual age (pma). the infant was delivered at 28 weeks of gestational age with a birth weight of 1100 g. the baby was treated in nicu for 24 days and received oxygen therapy in the previous hospital. retinal examination revealed that the patient had stage 5 rop in the right eye and stage 4b rop in the left eye. furthermore, blinking reflect was absent in both eyes. vitrectomy and endolaser were performed for the baby’s left eye. surgery was not conducted for the infant’s right eye due to poor prognosis. six weeks after surgery, the infant underwent examination under anesthesia (eua) which showed that the retina was reattached with no vitreous hemorrhage, and intraocular pressure measurement was 7 mmhg. the result of the visual acuity test by cardiff acuity cards was 6/60 on both eyes. followed up eua reported that the refraction test result on the left eye was s-3.75 c-5.75 x 85o and an undetermined result on the right eye due to opacity in the visual axis. discussion: several surgeries have been described as the treatment of choice for advanced-stage rop, including scleral buckling and vitrectomy with or without the addition of endolaser. previous studies illustrated that stage 5 rop has a low success rate on lens-sparing vitrectomy compared to stage 4a and 4b. the outcome success rate was the best in stage 4a rop. moreover, stage 4b rop had a moderate success rate with sufficient visual outcomes. conclusion: the functional outcome of vitrectomy surgery may not equate to anatomic success. retinal reattachment and moderate visual outcome were achieved by performing vitrectomy and endolaser in this case. followed-up periodically is necessary for advanced stage rop postoperatively. keywords: stage 4 rop, stage 5 rop, vitrectomy, visual acuity cite this article: yulia, dian estu; jayawinata, marissa; hutapea, mario marbungaran. clinical outcomes of surgery for advanced stage retinopathy of prematurity: a case report. international journal of retina, [s.l.], v. 6, n. 1, p. 67, mar. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/210>. doi: https://doi.org/10.35479/ijretina.2023.vol006.iss001.210. 70 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; introduction retinopathy of prematurity (rop) is a vasoproliferative disease affecting preterm infants.1 estimation of rop cases globally in 2010 was 184.700 babies, and 20.000 of them suffered from childhood blindness or severe visual impairment.2 probable higher risk for rop was found in premature babies with live sustaining treatment in the neonatal intensive care unit (nicu).2 more than 40% of preterm birth worldwide were collected from developing countries, including india, china, bangladesh, pakistan, and indonesia.1 therefore, the risk of rop cases scaled up in those countries.1 multicentre study of 34 hospitals in 17 major provinces in indonesia showed that the incidence of all-stage rop was 18% and severe rop was 4%.3 the early treatment for retinopathy of prematurity (etrop) study reported that type 1 rop was indicated early management, such as laser ablation within 48 – 72 hours of the first diagnosis. however, some eyes treated progressed to stage 4 and 5 rop.4 surgical interventions, including scleral buckling and vitrectomy, were considered to treat advanced-stage rop.5 prior to the current standard treatment of lens-sparing vitrectomy, scleral buckling was the treatment of choice.6 despite the controversy, scleral buckling still had beneficial effects on the anterior traction of stage 4 rop.7 lens-sparing vitrectomy was best performed in rop stage 4a due to the high rate of anatomical and vision outcome success.6 meanwhile, in jin choi et al. study showed that the success rate of stage 4b and 5 rop was 62% and 13%, respectively.8 moreover, poor visual outcomes were found in stage 4b rop despite successful retinal reattachment, and unfavorable outcomes were found in stage 5 rop.8 this case aims to report the clinical outcomes after surgery for advanced-stage rop. case report a 53 weeks of pma female infant presented to the pediatric ophthalmology clinic in cipto mangunkusumo national central hospital jakarta with a lack of visual contact in both eyes. the baby had a history of spontaneous delivery at 28 weeks of gestational age with a birth weight of 1100 g. the infant had been managed in the neonatal intensive care unit (nicu) for 24 days in the previous hospital, during which the baby received oxygen therapy due to poor respiratory status. history of sepsis, blood transfusion, and heart disorder was denied. ophthalmic examination demonstrated an absence of blink reflex on both eyes in response to light flash. retcam® examination revealed stage 4b rop in the left eye and stage 5 rop in the right eye. correspondence to: dian estu yulia, cipto mangunkusumo hospital, jakarta, indonesia. dianestu.dianestu@gmail.com a b figure 1. right eye a) anterior segment photo in stage 5 rop b) fundus photo showing total retinal detachment published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 71 the infant underwent vitrectomy and endolaser in the left eye under general anesthesia using laryngeal mask. this procedure commenced with traction released from the core to the peripheral area by vitrectomy followed by ablating the retinal with endolaser therapy. the vitreous cavity was filled with air at the end of the procedure. vitrectomy was not performed on the infant’s right eye due to poor prognosis. upon examination under anesthesia (eua) after surgery, the retina was found reattached with no vitreous hemorrhage, and intraocular pressure (iop) measurement was 7 mm hg. postoperatively, a visual acuity test was performed using cardiff acuity cards and revealed 6/60 on both eyes. a follow-up eua was conducted, describing an iop of 16 mmhg on both eyes, an axial length of 15.49 mm on the right, and 20.48 mm on the left. moreover, it revealed that recurrent detachment did not occur on the left eye with the refraction test result on the left eye was s-3.75 c-5.75 x 85o and an undetermined result on the right eye due to opacity in the visual axis. discussion surgical management is required for advanced stage rop.9 the choice of surgical technique depends on the rop stage, with the best visual outcome achieved when it is done at stage 4a rop.9 several procedures, including vitrectomy and scleral buckling, have been used to treat advanced-stage rop.7 however, the anatomical and functional outcome of vitrectomy are more favorable than scleral buckling in stage 4 rop.7 since in the scleral buckle technique, there is a secondary procedure to remove the encircling element and leads to compression of anterior segment structure, which induces severe myopia. therefore, vitrectomy is preferred as a treatment of choice for stage 4 rop.7 surgical outcomes for stage 5 rop are mainly poor, with an anatomic success rate was 13%.8,10 in our case, vitrectomy with endolaser was performed to treat stage 4b rop on the left eye. the endolaser procedure was intended to manage vascular activity. the same procedure was not implemented for the right eye with stage 5 rop due to poor prognosis. a b figure 2. preoperative findings of the left eye. a) anterior segment photo in stage 4b rop patient. b) fundus photo showing retinal detachment figure 3. fundus photo of the 72 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; kusuka, s. study reported that mean visual acuity postoperatively in stage 4a rop ranges from 20/500 to 20/58 and for stage 4b rop ranges from 20/1600 to 20/200.10 in this case, visual acuity was improved from the absence of blinking reflect in the first visit to 6/60 in both eyes after surgery. furthermore, the refraction test was conducted using autorefraction with s-3.75 c-5.75 x 85o as the left eye result and undetermined result in the right eye due to opacity in the visual axis. in choi et al. study, the mean follow-up period of 5.6 years was conducted in the advanced stage of rop with the vitrectomy procedure.8 it described that visual acuity measurement was required in followed up due to the possibility of unfavorable outcomes despite achieving retinal reattachment.8 myopic outcomes after vitrectomy, as described in our case, commonly occur. apart from myopia, other intraand post-operative risks associated with rop surgery include iatrogenic retinal breakage, vitreous hemorrhage, glaucoma, and cataracts10 which was observed to occur in a study with an average followup of 2.2 years.6 notably, none of these risks were found on follow-up time in our study. a study by xu et al. that described surgical outcomes in stage 4 rop patients who underwent vitrectomy also described no observed complications such as uveitis, ocular hypertension, endophthalmitis, or any ocular or systemic adverse events in any of the patients with a follow-up of 12-36 months.11 therefore, we recommend that periodical follow-up for the next 5 years after surgery is required to detect refraction error, retinal reattachment, and further complications that may occur. conclusion the functional outcome of vitrectomy surgery may not equate to anatomical success. retinal reattachment and moderate visual outcome were achieved by performing vitrectomy and endolaser in this case. followed-up periodically is necessary for advanced stage rop postoperatively. references 1. azad r, gilbert c, gangwe a, zhao p, wu w, sarbajna p et al. retinopathy of prematurity: how to prevent the third epidemics in developing countries. asia-pacific journal of ophthalmology. 2020;9(5):440-448. 2. blencowe h, lawn j, vazquez t, fielder a, gilbert c. preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. pediatric research. 2013;74(s1):35-49. 3. siswanto j, bos a, dijk p, rohsiswatmo r, irawan g, sulistijono e et al. multicentre survey of retinopathy of prematurity in indonesia. bmj paediatrics open. 2021;5(1):e000761. 4. tasman w. revised indications for the treatment of retinopathy of prematurity results of the early treatment for retinopathy of prematurity randomized trial. evidence-based eye care. 2004;5(3):156-157. 5. bhende p, gopal l, sharma t, verma a, biswas r. functional and anatomical outcomes after primary lens-sparing pars plana vitrectomy for stage 4 retinopathy of prematurity. indian journal of ophthalmology. 2009;57(4):267. 6. yu y, kim s, kim s, choung h, park g, heo j. lens-sparing vitrectomy for stage 4 and stage 5 retinopathy of prematurity. korean journal of ophthalmology. 2006;20(2):113. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 73 7. ramak r, reza k, mohammad r, fariba g, mehdi n. surgical management in advanced stages of retinopathy of prematurity; our experience. journal of ophthalmic and vision research. 2009;4(3):185-190. 8. choi j, kim j, kim s, yu y. long-term results of lens-sparing vitrectomy for stages 4b and 5 retinopathy of prematurity. korean journal of ophthalmology. 2011;25(5):305. 9. shah p. retinopathy of prematurity: past, present and future. world journal of clinical pediatrics. 2016;5(1):35. 10. kusaka s. current concepts and techniques of vitrectomy for retinopathy of prematurity. taiwan journal of ophthalmology. 2018;8(4):216. 11. xu y, zhang q, kang x, zhu y, li j, chen y, et al. early vitreoretinal surgery on vascularly active stage 4 retinopathy of prematurity through the preoperative intravitreal bevacizumab injection. acta ophthalmologica. 2013;91(4):e304-e10. this work licensed under creative commons attribution abstract case report discussion conclusion published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 87 international journal of retina (ijretina) 2020, volume 03, number 02. p-issn. 2614-8684, e-issn.2614-8536 optical coherence tomography angiography to detect non-exudative neovascular age-related macular degeneration mimicking chronic central serous chorioretinopathy 1manuel a p vilela, 1federal university of health sciences of porto alegre, rs, brazil. abstract chronic central serous chorioretinopathy (ccsc) can produce an overlap of signs that can be difficult to distinguish from cases with non-exudative neovascular age-related macular degeneration (nneamd). around 2-10% of the patients with ccsc will develop neovascularization. sometimes both diseases could be present at the same individual. the purpose of this narrative review is to discuss the current information concerning the signs in oct angiography (octa) that eventually could help to differentiate these situations and analyze the best diagnostic evidence. keywords: central serous chorioretinopathy, optical coherence tomography angiography, age-related macular degeneration, macula, retina cite this article: vilela, manuel a p. optical coherence tomography angiography to detect non-exudative neovascular age-related macular degeneration mimicking chronic central serous chorioretinopathy.. international journal of retina, [s.l.], v. 3, n. 2, sep. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/104 introduction *correspondence to: manuel a p vilela, federal university of health sciences of porto alegre, rs, brazil, mapvilela@gmail.com most of the time it is not hard to differentiate chronic central serous chorioretinopathy (ccsc) from non-exudative neovascular agerelated macular degeneration (nneamd). but in older patients (60-70 years old) with chronic subretinal/intraretinal fluid (srf/irf) and retinal pigment epithelium (rpe)/bruch's membrane (bm) changes might produce an area of overlap that can be difficult to distinguish. and eventually, both diseases could be present at the same individual. these are situations with some similarities even for the commonest diagnostic technologies used in real-life practice like optical coherence tomography (oct), intravenous fluorescein angiography (ivfa), or indocyanine green angiography (icga). the correct recognition is of pivotal importance cause it could be related to the potential presence of choroidal neovascularization (cnv) especially type 1 and severe functional visual loss. for the csc the prognosis is much better (all in all 80% will retain 20/40 or more). however, 12% of these patients can have a bad prognosis, with legally blind in both eyes after 10 years. cnv has been reported in 2-10% of the csc cases. oct b scan shows specific signals like drusen in amd, but srf/irf, pigment epithelium detachment (ped) and modifications at the outer retina and rpe occurs in both situation. in chronic cases, some of these signals should be valorized.1-3 88 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; the purpose is to review the current information concerning the signs in oct angiography (octa) that eventually could help to differentiate these situations and analyze the best diagnostic evidence. clinical detection aspects dye-based angiographies can localize on csc but not in all cases the leakage site at the rpe plane. it could be uni or multifocal, uni or bilateral. the leakage and the height of the subretinal fluid (srf) or another sign reduces the conditions to find out active or chronic choroidal neovascularization.4-6 table summarizes how to make a precise diagnosis with the use of dye-based angiographies and b-scan oct. double sign and time for development are strongly related to cnv in both diseases, and especially the time for developing cnv is longer in both situations (more than 10 years in csc).1,7 it is in the ccsc where some aspects are shared, sometimes inconclusive (basically in the absence of the descend traits) with nneamd including (a) irregular and detached rpe; (b) thicker, opaque or hyperdense srf or irf (cme pattern), (c) mle/ez modifications, (d) foveal thinning and (e) increased choroidal thickness. sometimes the pachychoroid spectrum is seen in both cases8. the recent use of octa has shown identical efficiency than the gold standard diagnostic resources, with high sensitivity and specificity. sometimes it appears better than the gold standard but other times a little bit worst. considering the facilities it tends to be more used.1-8 in different studies, the prevalence range of cnv diagnosis using octa in ccsc is 8.3-44.8%. this heterogeneity is too high. there are significant differences between these populations (sample size, different inclusion/exclusion criteria, cross-sectional or longitudinal study). such variability was assumed to be not only due to sampling errors but also to the different effects on the population. in real-life, these results are much better than isolated ivfa, and more specific than the combination of ivfa/oct.8-14 table 1. diagnostic aspects of csc and amd csc amd ped more likely to be smaller, circular, regular, and with clear content (81%). if irregular, or flat, dense (chronic) => cnv higher, irregular, thicker, multiple and with more discontinuities srf higher and if irf present (cystoid edema) => cnv srf plane, irf more prevalent external retina hypertrophic outer retinal changes are more common (but less expressive) hyper-reflective band (outer retina/rpe) with posterior shadowing (42.9%); mle/ez discontinuities more expressive and prevalent ct increased (not all cases) pachy (42%) published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 89 in octa during acute csc we can identify high flow signals. hyper/mixed choroidal perfusion pattern is present in almost 100% at this stage. in ccsc hyperperfusion is seen only in 50% and this pattern is definitively different from normal subjects.15,16 chan et al5 showed that octa in ccsc with irregular ped have demonstrated dilated capillaries inside (21/26 patients 81% ) and not a suspect pattern in fa (78% 14/18 eyes). the presence of an irregular, flat, and dense ped in ccsc is a strong indication of the cnv existence. this specific situation shows more sensitivity of the octa (35.6%) versus the combination of dye-based angiographies and structural b san oct (25%).4,12 when used for this specific differentiation the icga and octa seem to be quite similar and their diagnostic capability ranges from 68%100%.17 this evidence supports the use of the new method considering all the facilities involved. (figure) other relevant signs in octa are the flow void zones and darker areas. probably they are related to the choroidal perfusion state. first of all, they are frequent in both cases (amd ou csc). these patterns indicate a potential long-term contribution to pathogenesis. for csc they are described in areas (75%) and spots (52.9%). the age and ccsc have shown an increased total area of flow voids. the presence of higher srf (> 485 nm) blocks the choriocapillaris (cc) analysis. and the state of the deeper choroidal vessels can be related to changes in rpe and retina.14-16,18,19 these flow void areas mean microcirculatory deficiencies are detected in the fellow eyes of both situations and this pattern is also different from normal subjects. this could explain (observing the unaffected eyes) how the long-standing dilated choroidal vessels can affect the cc/rpe. recurrent episodes in ccsc have demonstrated abnormal flow even after resolution.20,21 figure 1. ccsc in 81years old male. superficial (a) and deeper (b) plexus preserved but a cnv is evident (c ). manual segmentation (d) helps the diagnosis (e). in conclusion, nneamd and ccsc sometimes have some similar aspects in older age, and because of that, the detection of a cnv is essential. octa can help in this differentiation with very good sensitivity in a rapid and noninvasive way. 90 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; references 1. daruich a, matet a, dirani a, et al. central serous chorioretinopathy: recent findings and new physiopathology hypothesis. prog retin eye res 2015; 48:82-118. 2. daruich a, matet a, behar-cohen f. central serous chorioretinopathy. in: vilela map, putz c, dantas am (eds). retina clínica. rio de janeiro, cultura médica, 2016. 3. mrejen m, balaratnasingam c, kaden tr, et al. longterm visual outcomes and causes of vision loss in chronic central serous chorioretinopathy. ophthalmology 2019; 126(4):576-588. 4. hage r, mrejen s, krivosic v, et al. flat irregular retinal pigment epithelium detachments in chronic central serous chorioretinopathy and choroidal neovascularization. am j ophthalmol 2015;159(5):890–903. 5. chan sy, wang q, wei wb, jonas jb. optical coherence tomographic angiography in central serous chorioretinopathy. retina 2016;36:20512058. 6. cheung cmg , lee wk, koizumi h, et al. pachychoroid disease. eye 2019; 33(1):14-33. 7. fung at, yannuzzi la, freund kb. type 1(sub-retinal pigment epithelial) neovascularization in central serous chorioretinopathy masquerading as neovascular age-related macular degeneration. retina 2012;32:1829-1837. 8. moussa m, leila m, khalid h, lolah m. detection of silent type i choroidal neovascular membrane in chronic central serous chorioretinopathy using en face swept-source optical coherence tomography angiography j ophthalmol 2017, article id 6913980, https://doi.org/10.1155/2017/6913980. 9. bonini filho ma, de carlo te, ferrara d, et al. association of choroidal neovascularization and central serous chorioretinopathy with optical coherence tomography angiography. jama ophthalmol 2015; 133(8):899-906. 10. quaranta-el maftouhi m, el maftouhi a, eandi cm. chronic central serous chorioretinopathy imaged by optical coherence tomographic angiography. am j ophthalmol 2015;160(3):581-587. 11. gołębiewska, j, brydak-godowska j, moneta-wielgos j, et al. correlation between choroidal neovascularization shown by oct angiography and choroidal thickness in patients with chronic central serous chorioretinopathy j ophthalmol 2017;article id 3048013, https://doi.org/10.1155/2017/3048013. 12. bosquet e, bonnin s, mrejen s, et al. optical coherence tomography angiography of flat irregular pigment epithelium detachment in chronic central serous chorioretinopathy.. retina 2018;38(3):629-638 13. sahoo nk, mishra sb, iovino c, et al. optical coherence tomography angiography findings in cystoid macular degeneration associated with central serous chorioretinopathy.. br j ophthalmol 2019; doi: 10.1136/bjophthalmol-2018-313048. 14. tang p, shields r, silva ra. optical coherence tomography angiography findings in chronic central serous chorioretinopathy after photodynamic therapy. ophthalmic surg lasers imaging retina 2019;50(1):25-32. 15. seo ej, um t, yoon yh. abnormal choroidal flow on optical coherence tomography angiography in central serous chorioretinopathy. clin exp ophthalmol 2019;47(4):505-512. 16. de bats f, cornut p-l, wolff b et al. dark and white lesions observed in central serous chorioretinopathy on optical coherence tomography angiography. eur j ophthalmol 2018;28(4):446-453. 17. min jy, lv y, yu s, gong yy. findings of octangiography compared to fluorescein and indocyanine green angiography in central serous chorioretinopathy. lasers surg med 2018;50(10):987– 993. 18. savastano mc, dansingani kk, rispoli m, et al. classification of haller vessel arrangements in acute and chronic central serous chorioretinopathy imaged with en face optical coherence tomography. retina 2018;38(6):1211-1215. 19. matet a, daruich a, hardy s, behar-cohen f. patterns of choriocapillaris flow signal voids in central serous chorioretinopathy: an optical coherence tomography angiography study. retina 2019; doi: 10.1097/iae.0000000000002271 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 91 20. rochepeau c, kodjikian l, garcia ma, et al. optical coherence tomography angiography quantitative assessment of choriocapillaris blood flow in central serous chorioretinopathy. am j ophthalmol 2018;194:26-34. 21. yun c, huh j, ahn sm, et al. choriocapillaris flow features and choroidal vasculature in the fellow eyes of patients with acute central serous chorioretinopathy. graefes arch clin exp ophthalmol 2019;257(1):57–70. this work licensed under creative commons attribution iv published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; international journal of retina (ijretina) 2019, volume 2, number 1. p-issn. 2614-8684, e-issn.2614-8536 management of rhegmatogenous retinal detachment: tips and tricks for the beginners lingam gopal* *national university health system, singapore *correspondence to: lingam gopal, national university health system, singapore, gopal_lingam@nuhs.edu.sg introduction in the portfolio of a vitreo retinal surgical practice, management of retinal detachments occupies the premium position. the following serves as an introduction with a philosophical slant rather than as a detailed listing of the dos and don’ts. it is primarily addressed to the vitreo retinal trainee. hence, i would like to offer an advance apology to the trained and experienced retinal surgeons who may browse through this article. is it retinal detachment? the first step is to determine if the lesion seen in the fundus is elevated retina or other mimicking condition. while most often the diagnosis of retinal detachment is straightforward there could be confusion on occasions. conditions that can be confused with retinal detachment are retinal edema (as in berlin’s edema); retinoschisis; choroidal detachment; thick vitreous membranes (as in uveitis), altered blood etc1. evaluation should include careful slit lamp biomicroscopy, indirect ophthalmoscopy and where needed ultrasonography (even when there is view of some fundus details). in eyes with hazy media, it is the combination of information from ophthalmoscopic evaluation, iop, and ultra sound features that guide the clinician as to the true nature of the condition. is it rhegmatogenous retinal detachment? once the presence of retinal elevation is confirmed, the next is to know whether it is caused by a break or not. in most cases the rhegmatogenous nature of retinal detachment is obvious from the appearance of the retinal detachment as well as the presence of visible retinal break. there are however situations when it may not be that obvious. 1. chronic retinal detachments can on occasion have some tendency towards shifting fluid, lack the characteristic undulations and can be confused with secondary retinal detachments. 2. retinal detachments in the milieu of uveitis can sometimes cause confusion since a retinal break can occur due to the traction caused by the vitreous membranes (due to uveitis) and can actually lead to rhegmatogenous retinal detachment. if the break is not obvious, it may be wrongly identified as exacerbated inflammation and treated with enhanced steroids and immunosuppression. indicators as to the true nature of the problem arerelatively quiet eye; undulations on retinal surface; the extent of retinal detachment following lincoff’s rules; pigment in vitreous cavity etc. once again, no one sign can be sine qua non. a high index of suspicion and a thorough evaluation are needed to confirm the rhegmatogenous nature of the problem. 3. there are several instances of retinal detachments secondary to tumors such as melanoma having been subjected to scleral buckling. this error in judgment can occur especially, when the surgeon did not evaluate the eye in detail before surgery and relied upon the input from less experienced personnel. this is one instance where ultra sonography is valuable even in the presence of clear media. a tumor underlying the retinal detachment is missed mostly when the examination is very casual. discussion with patient/relatives: in the discussion with the patient, it is important if one is able to indicate broadly the approach to surgery; the expected success in terms of reattachment of retina; the expected recovery of vision (if surgery is successful); any limitations in travel; risks of surgery including risk of loss of existing vision (especially relevant when operating on eyes with attached macula); need for multiple surgeries (if anticipated) etc. the patients often misinterpret expression of published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; v percentage of success as the expected visual improvement. this can become very important while operating on eyes with chronic retinal detachments where anatomical success does not translate into visual success. planning the approach: there is no confusion in case of obviously complicated cases where in vitreo retinal surgery would be the only approach possible such as in cases of gross proliferative vitreo retinopathy(pvr), giant retinal tears, posterior retinal tears, macular holes with retinal detachment, choroidal colobomas with retinal detachment, vitreous hemorrhage with retinal detachment etc. in case of simple retinal detachments, the options one has are between pneumatic retinopexy, scleral buckling and pars plana surgical approach. a lot would depend on one’s training and individual discretion. the following guidelines may be helpful if one has an open mind to choose between the options: a) if choosing pneumatic retinopexy, please make sure that the entire retina can be evaluated well with binocular indirect ophthalmoscope and scleral indentation to exclude additional retinal breaks – especially inferiorly. even minimal vitreous hemorrhage or peripheral cortical cataract can interfere with proper visualization all round. just because there is an obvious horseshoe tear superiorly, does not mean there are no other less obvious breaks elsewhere. failure to identify the additional breaks is the most common cause for failure of pneumatic retinopexy unfairly blamed on new breaks/ pvr etc. b) avoid pneumatic retinopexy in relatively large breaks. chances of sub retinal migration of the bubbles are high. c) retinal detachments due to retinal dialysis are mostly managed with scleral buckling. there are several advantages to managing them with scleral buckling instead of performing vitreo retinal surgery. most of these are young individuals with no posterior vitreous detachment, and clear lenses. d) retinal detachments clearly related to lattice degeneration with atrophic holes are again best managed with scleral buckling. even eyes with some amount of intra retinal and sub retinal gliosis can do well with scleral buckle in these circumstances. e) pseudophakic eyes with retinal detachment: most pseudophakic detachments are managed by pars plana route. since iatrogenic cataract is not an issue, pars plana route permits a more through vitrectomy and gas tamponade. the role of encirclage is also grossly reduced when the vitreous is more diligently excised. f) addition of encirclage to pars plana surgery would be occasionally needed in eyes where vitreous cannot be closely shaved (as in phakic eyes) along with presence of inferior retinal breaks that could potentially lift up because of contracture of residual vitreous. in the presence of a broad vitreous base and significantly condensed and partly fibrotic peripheral vitreous, adding an encirclage will reduce the risk of recurrent retinal detachment. g) addition of encirclage to scleral buckling: segmental buckles need more closely spaced sutures compared to buckles with encirclage. in the absence of an encirclage, the two extreme ends of the buckle tend to lift up beyond the mattress suture and are effectively not indenting the eye wall. however, most cases of retinal detachments due to lattice related atrophic holes can be managed by segmental buckling without encirclage. where the lesions are in several quadrants, it is preferable to place an encircling band in addition to produce a more uniform and sustained indentation. in the condition of a retinal dialysis, the edges of the dialysis may remain uncovered due to similar reasons and hence it is recommended to add an encircling element. h) choice of gas tamponade after vitrectomy: simple rhegmatogenous retinal detachments with superior breaks distributed in not more than one quadrant can be managed with short acting gases such as sf6. eyes with wider distribution of breaks or relatively inferior breaks are best managed with longer acting gases such as c2f6 or c3f8. importance of preoperative detailed evaluation one cannot over emphasize the need for detailed preoperative evaluation. a detailed retinal drawing is optional but valuableespecially when scleral buckling is performed. the conditions during the surgery may not be as good as in the clinic from the perspective of indirect ophthalmoscopic visualization. in addition to the physical impediments caused by the operation theatre set up, trolleys and sterile draping, the cornea can become edematous and the pupil may constrict causing sub optimal visualization. the presence of a detailed drawing can function as an excellent road map to help localize the lesions under these circumstances. in addition, the act of performing a detailed retinal drawing forces the novice surgeon to become familiar with the retinal condition so well that surgical time can actually be shortened. vi published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; issues that could potentially compromise the final outcome 1. decision to do scleral buckling when the visualization is inadequate. 2. attracted by one obvious large tear and missing the other tiny tears along the vitreous base. 3. dace technique (drainair injectioncryoexoplant) that has gone awry: too many bubbles of air that interfere with proper localization of break as well as appropriateness of the buckle location. 4. not evaluating the location of the break vs buckle relationship at conclusion (after drainage). in some cases the break may fall just at the edge of buckle and may not be adequately supported. if identified during surgery, what is needed is a small additional step of shifting the buckle posteriorly to avoid recurrences. 5. not placing an adequately wide buckle: there is a general tendency to choose the buckles with narrow width (#276/277) since it makes it easier to place the mattress sutures. however this choice should not be at the expense of inadequate coverage of the break. one should not hesitate to place a broader buckle such as #279 if needed. 6. sub retinal bleed at conclusion of srf drainage: this is not an often-predictable problem. contrary to intuitive thinking, significant bleeds can occur at conclusion of drainage even in younger age groups and in non-myopic eyes. cauterization of the knuckle of choroid does not always prevent the bleed. most significant bleeds occur at conclusion of drainage when the pressure is released suddenlyeven before the sutures can be tightened. one way out can be to do controlled drainage. drain some amountinject bssdrain more and then tighten the buckle sutures. if despite the precautions bleed occurs and has migrated into sub retinal space, one can inject a bubble of c3f8 and place patient prone to permit the blood to shift away from macula. 7. inadequate cryo induced chorio retinal adhesion around the retinal break: this situation can arise when the retina in the area of break is highly elevated and the ice ball formed by the cryo probe is not reaching the retina. theoretically freezing the choroidrpe complex should be enough to cause adequate chorio retinal adhesion once the retina falls on the treated rpe. however due to the high degree of parallax the freezing of the choroid/rpe may not be at the right place– as desired. in such cases, one can supplement with post-operative laser as long as there is no recollection of fluid around the break. 8. fish mouthing: this is not an uncommon complication after placing circumferential buckles for large horseshoe tears. injecting a bubble of gas and positioning the patient can easily remedy this complication. the use and misuse of silicone oil: in addition to more common indications such as severe pvr, coloboma related retinal detachments, large giant retinal tears (180 degrees and more) etc, one may have to use silicone oil in patients who cannot posture themselves, patients who need to fly immediately after surgery, and one eyed patients (for early visual rehabilitation). one should not take usage of silicone oil lightly. once injected, we have committed the patient for at least one more surgery. the worry of facing a recurrent total retinal detachment after gas tamponade should not push novice surgeons to over use of silicone oil. with use of silicone oil, we post pone the issues but do not get rid of them. long-term complications are well known.2 shallow inferior recurrent retinal detachments may go unnoticed. there is a tendency to postpone removal of silicone oil even when retina is well attached – for fear of facing possible recurrence after removal of silicone oil. some surgeons keep convincing themselves that it is ok to leave the oil in till it causes complications. some surgeons place silicone oil for inferior breaks, where gas tamponade with additional encirclage would have sufficedjust to avoid converting so called ‘suture less vitrectomy’ to a sutured one. adopting new techniques: change is a constant phenomenon and this applies to the field of vitreo retinal surgery as well. adopting a new technique does not mean one should forget an old techniqueespecially one as robust as scleral buckling. it is accepted that scleral buckling is less forgiving but the tendency to manage all cases of retinal detachment with pars plana approach should be abhorred. the new technique of using a 25g chandelier light along with the wide-angle visualization system (biom etc) and performing scleral buckling has certain advantages.3 unlike with indirect ophthalmoscopy, the image of the retina can be magnified making it easier to localize smaller lesions. use of this hybrid technique may be the best way of bringing some of the young surgeons back to fold of scleral buckling. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; vii references: 1. bhomaj s khare c. retinal detachment – in post graduate ophthalmology. editorszia chaudhari, murugesan vanathi. jaypee highlights, new delhi. chapter-12.11; page1255 2. federman jl, schubert hd. complications associated with the use of silicone oil in 150 eyes after retina-vitreous surgery. ophthalmology. 1988;95(7):870-876. 3. temkar s. takkar b, azad sv, venkatesh p. endoillumination (chandelier) assisted scleral buckling for a complex case of retinal detachment. ind j ophthalmol 2016;64:845-6. 82 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; international journal of retina (ijretina) 2018, volume 1, number 2. p-issn. 2614-8684, e-issn.2614-8536 management of rhegmatogenous retinal detachment with buckle sclera and cryoretinopexcy ria mutiara , ramzi amin department of ophthalmology, universitas sriwijaya abstract introduction: retinal detachment is divided into three categories. the most common type is the regmatogen retinal detachment (rhegmatogenous retinal detachment), which is the result of the tearing of the retinal lining. actions can be buckle sclera, vitrectomy pars plana and pneumatic retinopexy. the purpose of this case report to reported management of rhegmatogenous retinal detachment with buckle sclera and cryoretinopexcy. method: a 58 years old man with chief complaint the left eye blurred like a curtain covered since 5 days,floaters (+), photopsia (+),headache (+), patients never complain of lost vision suddenly before, eyeball pain is not there.history of trauma (+),on examination, the visual acuity 6/9 re and 1/60 le, anterior segment lens cloudy (+)nuclaer gr iii, fundus photograph we found retinal contours of the blood vessels well, tear (+) is directed at 2-3 hours of superior-temporal and fovea reflex (-), b-scan ultrasound of the posterior segment the retina is not intact, membran like lession detachment which attach to optic nerve. results: the sclera buckles and cryoretinopexy were performed under general antesthesia. visual acuity post-operative on left eye 2/60. subconjunctival bleeding (+), the fundus photographs retinal attach but the macular reflex is still negative. post-operative theraphy with topical steroid and antibiotic eye drops, oral antibiotic, and oral analgetic. follow up 1-month post-operative visual acuity 5/60 with fundus photograph obtained retina attach. conclusion: a diagnosis of retinal detachment can be found, with the discovery of fullthickness breaks or defects occurring from the retinal neurosensory, this break will allow the vitreous to enter the defect gap between the retinal neurosensory and rpe. based on the clinical features of the posterior segment, the detachment area was found with the location of the linchoff rule 2 break based on the american academy of ophthalmology. the objective of operative therapy was to reattach the retinal portion of which one of them was buckle sclera and cryoretinopexcy. keywords: retinal detachments, buckle sklera, cryoretinopexy cite this article: mutiara, ria mutiara. management of rhegmatogenous retinal detachment with buckle sclera and cryoretinopexcy. international journal of retina, [s.l.], v. 2, n. 1, aug. 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/33>. introduction *correspondence to: ria mutiara, department of ophthalmology, universitas sriwijaya, ria.mutiara26@gmail.com retinal detachment is divided into three categories. the most common type is the regmatogen retinal detachment (rhegmatogenous retinal detachment), which is the result of the tearing of the retinal lining. the second category is the tractional retinal detachment based on the occurrence of vitreous attachment with the retina which results in the pull of neurosensory from rpe. in certain circumstances there may be a combination of regmatogen and tractional. the third category is the exudative retinal detachment associated with the inflammatory process, malignancy. in this type of exudation occurs the accumulation of subretinal fluid which ends in the release of the retinal layer.1-3 epidemiological data in the united states the incidence of retinal detachment was 12.5 cases per 10,000 per year. approximately 4050% of cases occur with myopia risk factor, 3040% with history of cataract surgery and 1020% is ocular injury. cases of trauma occur most at the age of the child and cases with myopia often occur at the age of 25-40 years.3,4 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 83 the operative management principle of the retinal detachment is to glue back the loose retinal layer by previously identifying and closing when there is a retinal tear and release of traction from vitreoretina. actions can be buckle sclera, vitrectomy pars plana and pneumatic retinopexy. the consideration of the choice of operative therapy depends on the underlying pathogenesis of each case of retinal detachment.4,5 method patient a 58 years old man, with medical record 105776 come to the eye polyclinic on 25 january 2018, with chief complaint the left eye blurred like a partially covered curtain since 5 days, since 5 days ago the patient complained of sudden blurred vision on the left eye. complaints in without red eyes. vision is felt like a closed curtain. complaints are felt after the patient fell in the field while working 8 days ago, since ± 6 days ago complained to the left eye floters (+), photopsia (+). headache (+), patients never complain of sudden loss of vision before, pain in the eyeball (-). history of trauma (+), visual acuity 6/9 re, 1/60 le, intraocular pressure in normal limit, claudy lens nuclear gr iii,posterior segment retinal contours of the blood vessels well, tear (+) is directed at 2-3 hours of superior-temporal and fovea reflex (-), b-scan ultrasound of the posterior segment the retinal is not intact, membran like lession detachment which attach to optic nerve figure 1: fundus photograph right eye tear (+) is directed at 2-3 hours of superior-temporal and left eye in normal limit figure 2 : b-scan ultrasound of the posterior segment pre operative retinal is not intact, membran like lession detachment which attach to optic nerve result buckle sclera with cryoretinopexcy were perfomed in rhegmatogenous retinal detachment. the installation of the encircling band surrounds the eyeball under the rectus muscle and the tyre band from 1 to 5 hours through the bottom of the inferior, and lateral, with visual acuity post operative 2/60, subconjunctival bleeding (+), the fundus photograph retinal attach but the macular reflex is still negative. at 1 month follow up examination fundus photograph and b-scan ultrasound obtained retinal attach, but reflex fovea still negative. 84 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; figure 3 : pre and post operative retinal fundus photograph, post operatif retinal attach but the macular reflex is still negative figure 4 : b-scan ultrasound of the posterior segment post operative retinal attach discussion in anamnesa obtained right eye complaints blurred suddenly since 5 days ago, blurred vision felt like closed the complaint curtain felt after the patient fell. found complaint view like seeing flash of light. in the literature it is mentioned that the typical signs and symptoms of the retina detachment are usually preceded by floaters, flash / photopsia due to mechanical stimuli that occur from vitreoretinal traction that is detached from the retina, narrowed viewing field and blurred vision. according to johannes arnoldus, groningen university, said the risk factor of rhegmatogen retinal detachment highest incidence more in men, the average age with the highest incidence of 55-65 years. 5.15-18 an ophthalmologic examination was performed to determine the diagnosis in the viscous patient 1/60 ph (). then in the posterior segment of the funduscopic examination obtained normal papillary area, no fovea reflex in the macula and obtained a break in the superotemporal retina at the area of 2 and 3 hours. diagnostic leads to ablatio retina rhegmatogen due to a break that causes partial accumulation of fluid subretinally, ablation of tracional abnormalities may be excluded in patients with diabetes mellitus, ablation of exudative retina due to malignancy or inflammatory disease whereas in these patients no systemic abnormalities, malignancies and ocular inflammatory disease. based on the clinical picture of the posterior segment found detachment area. these fundus photo shots are also adjusted for break locations with linchoff rules 2 based on the american academy of ophthalmology, diagnostic and advanced management. 5,6,9,10,15-23 scleral buckling technique can be chosen because of the break position found and the retinal loss of 1-2 quadrants. according to martinez et al, added pars plana vitrectomy, this operative combination is performed to reduce the risk of failure or recurrent retinal ablatio and a better prognosis than buckle sclera alone. according to garcia's article, arumia et al, reporting the results of this combined surgery provides a successful retinal attached operation of 96%, the risk of recurrent retinal ablation is lower and cryoretinopexcy is needed in the area around the retinal break, to prevent the vitreous from entering the retina and attaching the retina to choroid. use of general anesthesia is done to prevent the occurrence of complications that may occur intraoperatif.6, -8,15,20,23 follow-up assessed is visus progress, intraocular pressure, silicon oil condition (this condition can be seen 6-12 months postoperatively), retina attached or not and also need to assess the optical condition of the patient to assess the optic nerve.1,15,16,21, 22 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 85 the prognosis in this patient is quo ad vitam dubia ad bonam. if the patient presents with ablatio retina rhegmatogen with initial visus 1/60 to 5/60. this is adjusted to the prognosis of patients with post-traumatic retinal post ablatio from 8 days to surgery. improvement of the visus we expect according to study from martinez, et al if involving macula then can reach the final visus 6 /30.8,20,21,23 conclusion the rhegmatogen-type retina ablatio is the most common form that can lead to a fullthickness retinal break. in retinal ablatio therapy given depends on the risk factors that accompany buckle sclera with cryoretinopexy is one of the treatment options in the retina ablatio. combination operative therapy is selected to minimize the complications that can occur. patients are encouraged to follow-up regularly every month to evaluate postoperative long-term success. references 1. liesegang t j. basic and clinical science course. section 12. retina and vitreous. the foundation of the american academy of ophthalmology; 2014-2015 2. iwase t, jo yj, oveson bc. effect of prophylactic 360° laser treatment for prevention of retinal detachment after phacovitrectomy: prophylactic 360° laser treatment for prevention of retinal detachment. bmc ophthal-mol. 2013;10(13):77. 3. yang hs, kim yj, kim jg. new prophylactic intraoperative septated circumferential barrier laser in macular surgery. can j ophthalmol. 2016;51(2):102–7 4. bouheraoua nacim, hrarat linda, parsa cameron f, et al. decreased corneal sensation and subbasal nerve density, and thinned corneal epithelium as a result of 360-degree laser retinopexy. ophthalmology. 2015;122(10):2095–102 5. martínez-castillo vj, garcía-arumí j, boixadera a. pars plana vitrectomy alone for the management of pseudophakic rhegmatogenous retinal detachment with only inferior breaks. ophthalmology. 2016;123(7):1563–9. 6. ryan sj. retinal reattachment: surgical principles and technique. surgical retina. retina. fourth edition. vol.3. 2005 7. regillo cd, brown gc, flynn hw. vitreoretinal disease; the essentials. new york-stuttgart 1999 8. peyman ga, meffert sa, conway md. surgical techniques for the treatment of retinal tears and complicated retinal detachment. vitreoretinal surgical techniques. second edition. new orleans, la, usa.2007 9. kanski jj. clinical ophthalmology. seventh edition. chapter 16. retinal detachment; 2011 10. williamson th. rhegmatogenous retinal detachment. vitreoretinal surgery. springer. london 2007 11. chou t, siegel m. the mechanics of retinal detachment. new jersey institute of technology, newark, nj, 07102-1982 12. lai tyy. retinal complications of high myopia. the hongkong medical diary.2007 13. lewkonia,m.s, davies, j.d.salmon. british journal ophthalmology. lattice degeneration in a family with retinal detachment and cataract. sept 1973 14. lattice degeneration. conditions and diseases. (http://www.retinalmd.com/en/resources/conditi ons-and-disease). download at 4th december 2016 15. gout i, mellington f, tah v et al. retinal detachment-an updat of the disease and its epidemilogy-a discussion on research and clinical experience at the prince charles eye unit, windsor, england. oxford university, england.2011 16. jain p, nagpal m, videkar r, patil a. evaluation of possible risk factors for retinal re-detachment after silicone oil removal.aioc 2010 17. mehdizadeh m, afarid m, haghighi ms. retinal redetachment after cataract surgery in eyes with previous skleral buckling. journal of ophthalmic and vision research 2011;vol. 6 18. schwartz sg, flynn hw. primary retinal detachment: scleral buckle or pars plana vitrectomy? curr opinion ophthalmol. 20011;17:245–50. 19. burton tc. the influence of refractive error and lattice degeneration on the incidence of retinal detachment. trans am ophthalmol soc. 1989;87:143–157. 20. connolly bp, regillo cd. rhegmatogenous retinal detachment. in: tansman w, jaeger ea, eds. duane's ophthalmology. 2013 ed. philadelphia, pa: lippincott williams & wilkins; 2013:vol 3, chap 27. 21. shunmugam m, shah an, hysi pg, williamson th. the pattern and distribution of retinal breaks in eyes with rhegmatogenous retinal detachment. am j ophthalmol 2014;157:221-226. http://www.retinalmd.com/en/resources/conditions-and-disease/ http://www.retinalmd.com/en/resources/conditions-and-disease/ 86 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 22. schepens cl, okamura id, brockhurst rj. the scleral buckling procedures. surgical techniques and management. ama arch ophthalmol 1957;58(6):797-811. 23. custodis e. treatment of retinal detachment by circumscribed diathermal coagulation and by scleral depression in the area of tear caused by imbedding of a plastic implant. klin monbl augenheilkd augenarztl fortbild 1956;129(4):476-495. this work licensed under creative commons attribution published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 87 international journal of retina (ijretina) 2018, volume 1, number 2. p-issn. 2614-8684, e-issn.2614-8536 polypoidal choroidal vasculopathy: successful combined therapeutic approach a case report mirza metita1, yorihisa kitagawa2, hiroyuki shimada2, hiroyuki nakashizuka2 1department of ophthalmology, faculty of medicine universitas brawijaya, saiful anwar hospital indonesia 2department of ophthalmology, nihon university hospital japan abstract introduction: to report a case of pcv that has been successfully treated with intravitreal injection of t-pa, ranibizumab, and pneumatic displacement. method: a 65 years old man presented with blurred vision of his right eye. no systemic abnormalities were found. initial visual acuity re was 6/18. funduscopy examination showed submacular hemorrhage in posterior pole. octa, fa and icg confirmed the diagnosis of pcv. we performed anterior chamber paracentesis and intravitreal injection of 0,05 ml t-pa, 0,05 ml ranibizumab, and 0,3 ml 100% c3f8 at a time in retrobulbar anesthesia. the patient was instructed to maintain face down positioning for 2 days. results: we evaluated the visual acuity, central retinal thickness (crt), and central pigment epithelial detachment (ped) thickness for 2 years. the visual acuity was increasing gradually from 6/18 to 6/6 in the first year. the hemorrhage was displaced completely, the crt and central ped thickness were decreased. in the second year the patient had recurrence of pcv with serous retinal detachment and treated with intravitreal aflibercept. conclusion: combined treatment of intravitreal t-pa, ranibizumab, and c3f8 can be used as a beneficial therapy for pcv. keywords: polypoidal choroidal vasculopathy, tissue plasminogen activator, anti-vegf, pneumatic displacement. cite this article: metita, mirza et al. polypoidal choroidal vasculopathy. international journal of retina, [s.l.], v. 2, n. 1, aug. 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/46>. introduction *correspondence to: mirza metita, department of ophthalmology, universitas brawijaya, metitamirza@yahoo.com polypoidal choroidal vasculopathy (pcv) is a retinal disease characterized by multiple, serosanguineous detachment of the retinal pigment epithelium and neurosensory retina associated with secondary bleeding or leakage from the polypoidal lesions. it was originally described as an inner choroidal vascular abnormality with 2 distinct components of a network of branching vessels external to the choriocapillaris and terminal aneurysmal dilations sometimes seen clinically as reddish orange, spheroidal, polyplike structures or polypoidal vascular lesions.1,2 pcv likely comes in 2 varieties: a subset of choroidal neovascularization from a variety of causes, but most commonly attributable to neovascular age-related macular degeneration (amd), or a distinct disease from amd that is typically found in mostly darkly pigmented younger individuals, and without other fundus findings typical of amd.3 subretinal hemorhage and hemorrhagic ped occur more often in patients with pcv than in patients with typical neovascular amd. moreover, submacular hemorrhage also is a more common complication of pcv than of typical neovascular amd.4 several studies report that pcv have shown a prevalence of 22.3%–61.6% among asians and 8%–13% in caucasians who present with presumed neovascular amd. there is a marked male preponderance of 63%–78.5% and only 5.9%–24.1% have bilateral disease.5 indocyanine green angiography traditionally has been the gold standard investigation tool used to diagnose pcv. single or multiple polyps can be seen in the early phase of icga. 88 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; as noted, both flash digital fundus photography icga or the confocal scanning laser ophthalmoscope systems can detect at least 80% of the typical nodular lesions of the pcv, although the bvn and other features may be visualized better with confocal scanning laser ophthalmoscopy. in the absence of icga, differentiating pcv from typical amd remains challenging. other controversies remain as to whether pcv belongs to the amd spectrum, because several hallmarks of amd, including drusen, pigmentary changes, and atrophy, are relatively uncommon in pcv.6 the treatment modalities for pcv are photodynamic therapy, intravitreal anti-vegf, laser photocoagulation, pneumatic displacement, tissue plasminogen activator (tpa), and vitrectomy. we report a case of pcv that has been treated with intravitreal ranibizumab, pneumatic displacement and t-pa. case report a 65 years old man presented with blurred vision of his right eye. no systemic abnormalities were found. initial visual acuity re was 6/18. fundoscopy examination showed submacular hemorrhage in posterior pole. oct showed ped and serous retinal detachment (srd), fa and icg showed leakage and polypoidal lesion that confirmed the diagnosis of pcv. figure 1. a 65 years old man presented with blurred vision a. color fundus photography showed submacular hemorrhage b. leakage in fluorescein angiography c. icg showed polyp, pulsation (+) d. oct showed ped and srd we performed anterior chamber paracentesis (0,3 ml) and intravitreal injection of t-pa (25 μg/0,05 ml, 40,000 iu), ranibizumab (0,5 mg/0,05 ml), and 0,3 ml 100% c3f8 at a time in retrobulbar anesthesia. the patient was instructed to maintain face down positioning for 2 days. we evaluated the visual acuity, central retinal thickness (crt), and central pigment epithelial detachment (ped) thickness in 1 week, 1 month, 3 months and 1 year after treatment. the visual acuity was increasing gradually from 6/18 to 6/6 in the first year. the hemorrhage was displaced completely, the crt and central ped thickness were decreased. there are no adverse events occured due to the treatment. figure 2. colour fundus photography showed improvement and hemorrhage displacement after treatment a. 1 week b. 1 month c. 3 months d. 1 year published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 89 figure 3. oct showed decreased central retinal thickness and central ped thickness after treatment a. 1 week b. 1 month c. 3 months d. 1 year in the second year the patient had recurrence of pcv with serous retinal detachment and treated with intravitreal aflibercept. figure 4. recurrence of pcv after 2 years treatment a. srd and increasing central retinal thickness b. 3 months after intravitreal aflibercept discussion the incidence of pcv in japanese appears to be remarkably high. clinical studies from japan indicate that 54.7% of patients have pcv in neovascular age-related macular degeneration. this figure, however, could be an underestimation of pcv in this population, which could contain a significant number of asymptomatic subjects with pcv in a regressed or quiescent stage. the age of diagnosis can range from the 20s to the 80s, but pcv is most commonly diagnosed between the ages of 60 and 70 years. initially pcv had been thought to be a condition exclusively found in women. however asian pcv studies suggest that pcv is more common in males than females. reported male : female ratios include 3,7:1 in korean, 2,2:1 in chinese, and 3,5:1 in japanese. the reason for these epidemiologic differences in sex, unilaterality, and location in the different ethnic groups is not known.7,8,9,10 in our case we report a male, in 60s with unilateral blurred vision because of pcv. the clinical presentation that we found is mild decreased visual acuity and submacular hemorrhage in posterior pole. the principal clinical manifestations secondary to pcv are seen in the posterior segment. variably sized serous and serosanguineous detachments of the neurosensory retina and pigment epithelium around the optic nerve or in the central macula are the most frequent presentation. the typical presentations for a patient who is symptomatic for less than three months is extensive subretinal exudation and bleeding with minimal cystic change in the retina and a surprisingly good visual acuity. this difference between the severity of the serosanguineous detachments and good vision is explained by the minimal intraretinal changes.2,6 in the early phase of icga, pulsation of polypoidal vessels may sometimes be observed. seven of 74 patients (9.5%) with pcv had pulsatile polypoidal vessels in the macula. pulsations is a characteristic feature of pcv that is best appreciated by a dynamic video angiography system and missed in a flash imaging system. this could present as an important distinction from neovascular amd and indicates arterial involvement and increased intravascular pressure transmitted from the inner choroidal vasculature. 11 kokame et al report that continuous monthly intravitreal ranibizumab in eyes with active pcv shows stabilisation of vision, resolution of subretinal haemorrhage and a decrease in macular oedema. monthly intravitreal injection of ranibizumab for 3 months has a short-term beneficial anatomic effect by dissapeared polyp, decreased retinal thickness, reduction of subretinal fluid and ped. 12,13 treatments for submacular hemorrhage with intravitreal rtpa and expansive gas injection have shown promising results. however, in case of submacular hemorrhage positioned primarily superior to or close to the foveola, this therapeutic method may not be performed because additional central visual loss may occur by shifting more 90 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; blood into the central macular area. moreover, complication of pneumatic displacement with or without vitrectomy include vitreous hemorrhage, endophthalmitis, retinal detachment, and recurrence of submacular hemorrhage. guthoff et al report that there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rtpa and gas. after 7 months post treatment, best-corrected visual acuity was significantly higher in the bevacizumab/rtpa/gas group than rtpa/gas group. 14 in this case we treated the patient with combination of intravitreal ranibizumab, t-pa and gas injection. subretinal hemorrhage treatment by non-vitrectomized technique with intravitreal injection of rt-pa, ranibizumab, and gas is useful to achieve hemorrhage displacement, lesion and visual improvement in 6 months. 15 in this case, two years post treatment we found serous retinal detachment in oct indicating that the patient had recurrence of pcv. we treated with intravitreal aflibercept injection pro re nata and after 3 months the srd was resolved. gomi et al reported that 5,6% patients had recurrence of pcv after photodynamic therapy.16 kitagawa et al reported that recurrence was observed in 10 eyes (50%) within 6 months after treatment intravitreal t-pa, ranibizumab and gas injection.15 among giving treatment pro re nata and fixed interval dosing every 2 months injection, intravitreal aflibercept was well tolerated and improved the visual outcomes in patients with polypoidal choroidal vasculopathy as evaluated at 1 year follow up examinations. 17 conclusion combined treatment of intravitreal t-pa, ranibizumab, and c3f8 can be used as a beneficial therapy for pcv. reference 1. tomiyasu t, nozaki m, yoshida m, ogura y. characteristics of polypoidal choroidal vasculopathy evaluated by optical coherence tomography angiography. investigative ophthalmology & visual science. 2016 ; 57: 324-330 2. yannuzzi la, sorenson j, spaide rf, lipson b. idiopathic polypoidal choroidal vasculopathy (ipcv). retina. 1990 ; 10: 1–8. 3. alasil et al. en face imaging of the choroid in polypoidal choroidal vasculopathy using sweptsource optical coherence tomography. american journal of ophthalmology. 2015;159: 634–643. 4. cho et al. anti–vascular endothelial growth factor monotherapy in the treatment of submacular hemorrhage secondary to polypoidal choroidal vasculopathy. american journal of ophthalmology. 2013;156:524–531 5. wong cw, wong ty, cheung cmg. polypoidal choroidal vasculopathy in asians. journal of clinical medicine. 2015 ; 4(5) : 782-821 6. cheung et al. polypoidal choroidal vasculopathy : definition, pathogenesis, diagnosis, and management. ophthalmology. 2018 may;125(5):708724. 7. imamura y, engelbert m, iida t, freund kb, yanuzzi la. polypoidal choroidal vasculopathy : a review. survey of ophthalmology. 2010 ; 55 (6) : 501-515 8. byeon sh, lee sc, oh hs, kim ss, koh hj, kwon ow. incidence and clinical patterns of polypoidal choroidal vasculopathy in korean patients. japanese journal of ophthalmology. 2008 ; 52(1): 57-62. 9. maruko i, iida t, saito m, nagayama d, saito k. clinical characteristics of exudative age-related macular degeneration in japanese patients. american journal of ophthalmology. 2007 ; 144 (1) : 15-22.e2 10. sho et al. polypoidal choroidal vasculopathyincidence, demographic features, and clinical characteristics. arch ophthalmol. 2003; 121(10):1392-1396 11. yuzawa m, mori r, kawamura a. the origins of polypoidal choroidal vasculopathy. british journal of ophthalmology. 2005 ; 89 : 602–607. 12. kokame gt, yeung l, lai jc. continuous anti-vegf treatment with ranibizumab for polypoidal choroidal vasculopathy: 6-month results. british journal of ophthalmology. 2010 ; 94 : 297e301. 13. frutos et al. short-term anatomic effect of ranibizumab for polypoidal choroidal vasculopathy. european journal of ophthalmology. 2008 ; 18 (4) ; 645-648 14. guthoff r, guthoff t, meigen t, goebel w. intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration. retina. 2011 ; 31 : 36–40. 15. kitagawa et al. intravitreal tissue plasminogen activator, ranibizumab, and gas injection for submacular hemorrhage in polypoidal choroidal vasculopathy. ophthalmology. 2016 ; 1e9 16. gomi et al. the efficacy of intravitreal bevacizumab for polypoidal choroidal vasculopathy. british journal of ophthalmology. 2008;92:70–73 17. maiko et al aflibercept for polypoidal choroidal vasculopathy: as needed versus fixed interval dosing. retina. 2016 :36 (8) ; 1527–1534 this work licensed under creative commons attribution https://www.ncbi.nlm.nih.gov/pubmed/29331556 https://www.ncbi.nlm.nih.gov/pubmed/?term=byeon%20sh%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/?term=lee%20sc%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/?term=oh%20hs%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/?term=kim%20ss%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/?term=koh%20hj%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/?term=kwon%20ow%5bauthor%5d&cauthor=true&cauthor_uid=18369702 https://www.ncbi.nlm.nih.gov/pubmed/18369702 https://www.ncbi.nlm.nih.gov/pubmed/18369702 https://www.sciencedirect.com/science/article/pii/s0002939407003303#! https://www.sciencedirect.com/science/article/pii/s0002939407003303#! https://www.sciencedirect.com/science/article/pii/s0002939407003303#! https://www.sciencedirect.com/science/article/pii/s0002939407003303#! https://www.sciencedirect.com/science/article/pii/s0002939407003303#! https://journals.lww.com/retinajournal/toc/2016/08000 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 51 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 a rare case of spontaneous sub retinal haemorrhage associated with idiopathic intracranial hypertension thanuja pradeep1, chris pius2 1associate professor, department of ophthalmology, ms ramaiah medical college hospital , bangalore, india. 2junior resident, department of ophthalmology, ms ramaiah medical college hospital, bangalore, india. abstract introduction: idiopathic intracranial hypertension (iih)is defined as increase in intracranial pressure due to unspecified causes leading to headache, papilledema, and transient vision loss. usually the patients present with mild visual loss but about 25% may develop permanent visual loss due to irreversible optic disc damage. one rare cause of severe visual loss is subretinal hemorrhage (srh) due to underlying subretinal neovascular membrane. case report: we report a case of a 36-year-old man diagnosed with iih and papilloedema with sudden onset profound visual loss in his right eye. on examination, there was a large peripapillary srh superior to the disc and involving the macula.we stress the importance of recognizing this uncommon complication of papilledema and discuss the possible causes for developing srh, its most common outcome and the diagnostic as well as treatment modalities available. discussion: we stress the importance of recognizing this uncommon complication of papilledema and discuss the possible causes for developing srh, its most common outcome and the diagnostic as well as current treatment modalities available conclusion: this report highlights a rare case of spontaneous sub retinal haemorrhage in a patient with iih. measurement of optic nerve sheath diameter can be a vital tool for the diagnosis of raised intracranial pressure in this setting. keywords: papilledema, idiopathic intracranial hypertension, sub retinal haemorrhage, spontaneous sub retinal haemorrhage. cite this article: pius, chris; pradeep, thanuja. a rare case of spontaneous sub-retinal haemorrhage associated with idopathic intracranial hypertension. international journal of retina, [s.l.], v. 6, n. 1, p. 51, mar. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/223>. doi:https://doi.org/10.35479/ijretina.2023.vol006.iss001.223. introduction subretinall hemorrhage (srh) refers to the blood between the neurosensory retina and the retinal pigment epithelium (rpe). srh can arise directly from the choroidal neovascular membranes (cnv), which grows through breaks in bruch's membrane. [1] occurrence of bilateral srh in patients with pseudo tumour cerebrii is a rare occurrence and can present with sudden onset visual loss. correspondence to: chris pius, ms ramaiah medical college hospital, bangalore, india. chris.pius95@gmail.com 52 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 5; 1; we bring to light the case of bilateral subretinal haemorrhage in a patient with idopathic intracranial hypertension presenting with papilledema. [2] case report a 36 year old male presented to us with sudden onset of painless decreased vision in the right eye three days ago. he also complained that his decrease in vision predominantly affected his central visual field rather than the peripheral field. he had recently been diagnosed with type two diabetes mellitus. there was no history of hypertension or any other pre-existing ophthalmic condition. there was no history of headache or trauma. there were no neurologic symptoms. the visual acuity in the right eye was counting fingers at two meters and in the left eye, 6/6 by snellens chart testing . ishihara’s test for colour vision was performed and patient had colour vision defects in right eyewas able to read 2/38 plates .contrast sensitivity was affected in the right eye (5%). on finger confrontation test, decrease in central visual field of the right eye was noted. extra ocular movements showed no restriction and were painless. the pupil of the right eye exhibited rapd grade 3. fundus examination of the right eye showed a raised hyperaemic disc with blurring of the disc margins on all sides. a large peri-papillary sub retinal haemorrhage was seen extending 3 disc diameter superior to the disc, and 2 disc diameter temporal to disc involving the macula, 1 disc diameter inferior and nasal to the disc. retinal striae were seen extending supero-temporally from the disc.(figure1) vep recorded prolonged latency of p100 wave in the right eye. the anterior segment examination in left eye was normal. fundus examination of the left eye was relatively normal except disc hyperemia and blurring of disc margins.(figure 2) b scan showed thickening of the optic nerve head, widening of the optic nerve head shadow and an anechoic vitreous cavity in the right eye. in the left eye widening of the optic nerve head shadow was noted .optic nerve sheath diameter measured 3mm behind the globe was measured to be 8mm and 7mm in the right and left eye.(figure 3) oct scan was done which showed large sub retinal haemorrhage involving macula and extending superiorly above the macula in the right eye.the retinal thickness was 397 um at fovea, 418um at the highest point and 307um on an average.(figure 4) figure 1: colour fundus photo of the right eye showing a large peripapillary sub retinal haemorrhage. figure 2: colour fundus photo of the left eye showing disc hyperaemia and blurring of disc margins published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 53 figure 3a optic nerve sheath measurement of the right eye using ultrasound b scan. figure 3b. optic nerve sheath measurement of the left eye using ultrasound b scan. the patient was subjected to a complete neurologic examination by a neurologist which was within normal limits. the patient was then admitted to the neurology department for further evaluation. laboratory investigations were normal including complete blood count, coagulation profile, peripheral smear, serum creatinine and electrolytes plasma homocystine levels were found to be moderately elevated24.6 umol/l. mri of brain and orbit with mr venogram was reported to be normal. lumbar puncture demonstrated opening pressure of 30 cm of h2o, the normal csf opening pressure in males being < 30 cm h2o. [3] csf evaluation showed a clear colourless fluid with slightly elevated glucose (79 mg/dl), protein 57.8 mg/dl and normal chloride level. on microscopy, 100% lymphocytes were noted. csf was sent for tb cbnaat as well as cryptococcal antigen which were negative for the same. ana if, anti nmo /anti mog antibodies was also negative. he was diagnosed with idopathic intracranial hypertension and treated with iv fluids , acetazolamide tablets and paracetamol, and discharged. patient was subsequently lost to follow up as he moved overseas. figure 4: oct imaging of the right eye 54 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; discussion occurrence of spontaneous sub retinal haemorrhage in pseudo tumour cerebri is rare and fewer than 15 cases overall have been reported describing this condition.[4-12] the pathogenesis was descrcribed initially by morese et al, who stated that formation of a sub retinal neovascular membrane ,also known as choroidal neovascular membrane was often antecedent to a sub retinal haemorrhage. the swelling of the axons of the optic nerve head seen in papilloedema casues a mechanical discontinuity in the normal apposition of the chorio-retinal layers and a break in bruchs membrane . this anatomic dehiscence coupled with hypoxia as a result of the axonal swelling paves way for new vessel formation beneath the retinal pigment epithelium and the neurosensory retina leading to formation of a neovascular membrane.(7) the inner blood retinal barrier comprises of non fenestrated retinal endothelial cells in contrast to capillary beds of choroidal neovascular (cnmv)membranes which are fenestrated. these fenestrae coupled with the action of vascular endothelial growth factor (vegf) facilitates the opening of fenestrations leading to hyperpermeability and the extravasation of macromolecules from the blood vessels. (13) there are other risk factors also which make the cnv prone to haemorrhage. hypertension is one factor where increased pressure within the lumen can increase the leakage. microtrauma and anticoagulant use are other risk factors.(14) majority of the cnvm are idiopathic.(15) in this patient , sudden visual loss was most likely due to secondary to retinal detachment as a result of haemorrhage from a peripapillary neovascular membrane formation which progressed to involve the macula. various treatment modalities have been used for cnvm including argon laser photocoagulation(4,7) standard 3-port vitrectomy(10) and ppv with retinotomy(16). photocoagulation can only be performed safely when the cnv does not involve the foveola. it also carries the risk of permanent damage to the nerve fibre layer when adjacent to the disk and in the papillomacular bundle. (4,7) due to the lack of safety and proven efficacy of these methods, newer techniques can be adopted. displacement of sub retinal haemorrhage involving the macula with a 2step pars plana vitrectomy using tissue plasminogen activator (tpa) and perfluorocarbon liquid (pfcl) tamponade is shown to be a safe and efficient treatment option. (17) optic nerve sheath fenestration has also been tried, following which the papilledema improved but there was no improvement in visual function(7) troost et.al, also suggested that these membranes may not even require treatment due to the fact that they regress spontaneously with the resolution of papilloedema and carry good visual prognosis.(5,11) the value of surgically removing sub retinal hemorrhages to improve visual outcome remains unestablished.(7) shirodkar et. al evaluated the efficacy of optic nerve sheath diameter (onsd) by ultrasound as a noninvasive method for detecting raised intracranial pressure (icp). onsd was measured at 3mm behind the globe.the measurements above 4.6 mm and 4.8 mm in females and males were considered to have increased icp.in our patient,at 3mm behind the globe, onsd was measured to be 8mm and 7mm in od and os suggestive of raised icp. hence this non invasive test can be helpful in the early detection of raised icp.(18) conclusion this report highlights a rare case of spontaneous sub retinal haemorrhage in the setting of iih. measurement of optic nerve sheath diameter can be an invaluable cost effective method for the diagnosis of raised intracranial pressure. it is yet unknown whether surgical intervention in sub retinal haemorrhages can improve visual outcomes. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 55 further research on the efficacy of surgical intervention in non amd related srh is warranted. acknowledgements: we would like to thank the department of neurology,ms ramaiah memorial hospital for their help and support. references 1. hochman, m. a., seery, c. m., & zarbin, m. a. (1997). pathophysiology and management of subretinal hemorrhage. survey of ophthalmology, 42(3), 195-213. 2. sathornsumetee b, webb a, hill dl, newman nj, biousse v. subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. journal of neuro-ophthalmology. 2006 sep 1;26(3):197-9 3. ø sh, lundqvist c. cerebrospinal fluid opening pressure in clinical practice a prospective study. j neurol. 2020 dec;267(12):3696-3701. 4. jamison rr. subretinal neovascularization and papilloedema associated with pseudotumor cerebri. am j ophthalmol 1978;85:78–81. 5. troost bt, sufit rl, grand mg. sudden monocular visual loss in pseudotumor cerebri. arch neurol 1979;36:440–2. 6. morris at, sanders md. macular changes resulting from papilloedema. br j ophthalmol 1980;64:211–6. 7. morse ph, leveille as, antel jp, et al. bilateral juxtapapillary subretinal neovascularization associated with pseudotumor cerebri. am j ophthalmol 1981;91:312–7. 8. caballero-presencia a, diaz-guia e, martinezperez m, et al. ne´ovascularisation sousre´tinienne juxtapapillaire bilate´rale dans un cas de pseudotumor cerebri. j fr ophthalmol 1986;9:105–10. 9. coppeto jr, monteiro ml. juxtapapillary subretinal hemorrhages in pseudotumor cerebri. j clin neuro-ophthalmol 1985;5:45–53. 10. castellarin aa, sugino ik, nasir m, et al. clinicopathological correlation of an excised choroidal neovascular membrane in pseudotumor cerebri. br j ophthalmol 1997;81:994–1000. 11. akova ya, kansu t, yazar z, et al. macular subretinal neovascular membrane associated with pseudotumor cerebri. j neuroophthalmol 1994;14:193–5. 12. wendel l, lee ag, boldt hc, et al. subretinal neovascular membrane in idiopathic intracranial hypertension. am j ophthalmol 1996;141:573– 4. 13. dvorak hf, brown lf, detmar m, et al: vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. am j path01 146: 1029 1039,1995 14. el baba f, jarrett wh ii, harbin ts jr, et al: massive hemorrhage complicating age-related macular degeneration. ophthalmology 93:15811592, 1986 15. krill, a. e., and archer, d.: choroidal neovascularization in multifocal (presumed histoplasmin) choroiditis. arch. ophthalmol. 84:595, 1970. 16. wei y, zhang z, jiang x, li f, zhang t, qiu s, yang y, zhang s. a surgical approach to large subretinal hemorrhage using pars plana vitrectomy and 360 retinotomy. retina. 2015 aug 1;35(8):1631-9. 17. fleissig, e., barak, a., goldstein, m. et al. massive subretinal and subretinal pigment epithelial hemorrhage displacement with perfluorocarbon liquid using a two-step vitrectomy technique. graefes arch clin exp ophthalmol 255, 1341–1347 (2017). 56 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 18. shirodkar, c. g., rao, s. m., mutkule, d. p., harde, y. r., venkategowda, p. m., & mahesh, m. u. (2014). optic nerve sheath diameter as a marker for evaluation and prognostication of intracranial pressure in indian patients: an observational study. indian journal of critical care medicine: peer-reviewed, official publication of indian society of critical care medicine, 18(11), 728. this work licensed under creative commons attribution abstract case report discussion conclusion published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; 68 international journal of retina (ijretina) 2019, volume 2, number 2. p-issn. 2614-8684, e-issn.2614-8536 ocular toxoplasmosis: clinical characteristics and management ovi sofia, rizqi wahyu hariyono department of ophthalmology, faculty of medicine, universitas brawijaya, dr. saiful anwar general hospital, malang abstract introduction: ocular toxoplasmosis is a major cause of infectious posterior uveitis worldwide. there was no exact number of ocular toxoplasmosis prevalence in indonesia, but indonesia was considered to have high seroprevalence in southeast asian. this study is conducted to determine clinical characteristics and management of ocular toxoplasmosis at outpatient clinic of dr. saiful anwar general hospital in malang, east java. methods: this was retrospective study. we reviewed the medical records of patients with ocular toxoplasmosis and collected the data associated with age, sex, laterality, visual outcome, type of lesions, serum serological titers, therapeutic regimens, and complications. result: there were 48 eyes from 38 patients included in this study, mostly were female (66%) with mean age was 33,5 years. unilateral infection (71%) was more frequent than bilateral cases (39%). active lesions were found more than cicatrical lesions (56,25%). most patients with active diseases had unilateral lesion (87,5%). the most common presenting complain was blurred vision (73%). most of lesions (22 eyes; 81,4%) were located on macular region. all of patients have positive igg antitoxoplasma serum. there were 22 patients received oral trimethoprim-sulfamethoxazole and steroid. visual acuity improved in 6 patients at the end of follow-up period. complications of retinal detachment and choroidal neovascularization were found in 3 patients. conclusion: active ocular toxoplasmosis is more likely to be unilateral infection with main presenting complain is blurred vision. most of our patients show good responses to oral trimethoprim-sulfamethoxazole and steroid. keywords: ocular toxoplasmosis, retinochoroiditis toxoplasmosis, headlight in the fog, infectious uveitis, toxoplasma gondii cite this article: sofia, ovi; hariyono, rizqi wahyu. clinical characteristics and management of ocular toxoplasmosis. international journal of retina, [s.l.], v. 2, n. 2, sep. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/96>. date accessed: 18 sep. 2019. doi: https://doi.org/10.35479/ijretina.2019.vol002.iss002.96. introduction *correspondence to: ovi sofia, department of ophthalmology faculty of medicine, universitas brawijaya dr.ovisofia@ub.ac.id ocular toxoplasmosis is considered as the major cause of infectious retinochoroiditis worldwide, eventhough the prevalences may varies among countries.1 in united states, the seroprevalence of t.gondii infection is 22.5%, but the prevalence of ocular toxoplasmosis is estimated to be only 2%. in southern brazil, the seroprevalence is 85% of the population and 18% manifest evidence of retinochoroiditis.2,3 there was no exact number of ocular toxoplasmosis prevalence in indonesia, but indonesia was considered to have high seroprevalence, has been reported from 43 to 88% in some regions.4,5 the duration of active retinal infection (i.e., proliferation of tachyzoites) and the intensity of the associated inflammatory reaction appear to be the major factors accounting for variations in the characteristics of ocular toxoplasmosis. t. gondii is rarely identified in ocular tissues other than the retina. therefore, typical clinical finding of ocular toxoplasmosis gives the features of ‘headlight in the fog’, focal necrotizing chorioretinitis on the macular area 69 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; with overlying dense vitritis, usually next to or near the previous chorioretinal scar. significant visual deterioration may results from marked vitritis and macular or optic nerve involvement. atrophic macular scar or optic nerve atrophy may contributes to permanent blindness. 3,6,7 due to the limited data of the incidence of ocular toxoplasmsis in indonesia, we conducted a retrospective study to determine clinical characteristics and management of ocular toxoplasmosis in malang, east java. the data from our study may bring new perspectives regarding ocular toxoplasmosis in indonesia. methods medical records review of patients with ocular toxoplasmosis from the outpatient clinic of dr. saiful anwar general hospital, from january 2013 to december 2015, was conducted. ethical clearance was approved by hospital medical ethics committee. diagnosis was made based on characteristic clinical findings, active retinochoroiditis toxoplasmosis featured focal retinitis with overlying dense vitritis with or without presence of adjacent pigmented retinochoroidal scar, and latent lesion was described as pigmented retinochoroidal scar without active inflammation. location of lesions were also recorded. serological serum examination was performed to confimed the exposure. the data collected were age at the time of diagnosis, gender, laterality, visual acuity, disease activity, serological serum titers, regiment of treatment, and complications. visual acuity were converted into logmar. follow-up data were taken from final visit when the medications were completed or the last visit if patients were lost to follow-up. patients with incomplete medical records were excluded. categorical data were tabulated in numbers and percentages then presented by tables and graphics. results there were 48 eyes from 38 patients included in this study. demographic data for all patients were showed in table 1. ophthalmic data for all eyes at initial presentation were showed in table 2. table 1. demographic data at initial presentation. female gender 25 (66%) age (years) mean  sd 33.5  16.2 median (range) 31 (9 to 70) occupation farmer 16 (42.1%) student 9 (23.7%) civil servant 4 (10.5%) army 2 (5.3%) other 7 (18.4%) table 2. ophthalmic data at initial presentation presenting symptoms blurred vision 29 (76.3%) floaters 5 (13.2%) both 4 (10.5%) laterality (patients) unilateral 27 (71.1%) bilateral 11 (28.9%) disease activity (eyes) active lesion 27 (56.3%) retinochoroidal scar 21 (43.7%) serological serum titer positive igg 34 (89.5%) positive igm and igg 3 (7.9%) no data 1 (2.6%) systemic medicationsa antimicrobial 24 (100%) corticosteroid 23 (95.8%) anumber of patients with active lesions figure 1. classic presentation of ocular toxoplasmosis in a 50year-old female. focal necrotizing retinitis on macular region (black arrow) was noted with adjacent chorioretinal scar (white arrow) and overlying vitritis, represented ‘headlight in the fog’ appearance. patients with active lesions were divided into 2 categories, based on the location of lesion. we found 22 eyes with macular lesions and 5 eyes with extramacular lesions. initial visual acuity (logmar) for each groups were shown in figure 1. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; 70 (a) (b) figure 2. initial visual acuity of patients with (a) macular lesion and (b) extramacular lesions. all patients with active lesion received medications. besides one patient who received oral antibiotic only, all patients received oral antibiotic and steroid. antibiotics was given either as single therapy or as combination with other antibiotics. oral steroid was started 48-72 hours after antibiotics initiation at the dose of 0.5-1 mg/kgbw/day on tapered dose. the different regimens that had been given in this study were described in table 3. table 3. regimen of treatment regimen no. of pts trimethoprimsulfametoxazole, steroid 10 clindamycin, steroid 6 spiramycin, steroid 5 azithromycin, steroid 2 clindamycin 1 follow-up period ranged from 2 to 4 months, with mean 2.8 month. seven patients were lost to follow-up. resolution of lesions noted in 17 patients who received antibiotics and steroid. figure 3. extramacular lesion in a 27-year-old female. resolution was noted at 1-month follow-up (white arrow) after 3-weeks course of azithromycin along with steroid. improvement of visual acuity were achieved in 5 patients with macular lesions (22.7%) compared to 2 patients with extramacular lesions (40%). visual acuity at presentation and follow-up were shown in figure 4. (a) (b) figure 4. visual acuity improvement in patients with (a) macular lesion and (b) extramacular lesion. three patients experienced complications at the final follow-up, 2 patients had choroidal neovascularization and 1 patient had retinal detachment. 0 0,5 1 1,5 2 0 10 20 30 v is u a l a cu it y (l o g m a r ) n = 22 (eyes) 0 0,5 1 1 2 3 4 5 v is u a l a cu it y (l o g m a r ) no. (eyes) before after 0 0,2 0,4 0,6 0,8 0 2 4 6 v is u a l a cu it y (l o g m a r ) n = 5 (eyes) 0 0,5 1 1,5 2 1 3 5 7 9 11 13 15 17 19 21v is u a l a cu it y (l o g m a r ) no. (eyes) before after 71 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; discussion the most common presenting symptom in our study was blurred vision (76.3%), similar with previous study done in central java.5 this result may due to macular involvement and/or dense vitritis. most active lesions were unilateral, nonetheless 3 patients had bilateral presentation, that may suggest congenital infection. the unilateral case tends to occur more common in acquired infection, while bilateral central lesions with large atrophic scar are more frequent in congenital toxoplasmosis. but differentiating congenital and acquired ocular toxoplasmosis in adult is challenging, except there are proof of other signs of congenital infection.8,9 in our study, 21 eyes presented with retinochoroidal scar that inadvertently found during routine ophthalmoscopy examination. diagnosis of typical ocular toxoplasmosis is mainly based on clinical findings. there is no laboratory test that can differentiate the route of infection. serological serum examination is useful to confirm the exposure. negative titer may not exclude the diagnosis.1,3,7 all of our patients had increased serum igg antitoxoplasma, and 3 patients had positive igm antitoxoplasma. igg titer may increase 23 weeks after acute infection, reaching the peak at 6-8 weeks and remain positive for long period. igm antitoxoplasma reach the peak at first week of the onset of infection, and decreased 1 month after.1,6,9 all patients with ocular toxoplasmosis may have positive serum igg antitoxoplasma, but so are all individuals with seroprevalence. another laboratory tests, such as goldmann-witmer coefficient and polymerase chain reaction, are very useful to make diagnosis in atypical lesions.10,11 there are controversies regarding whether ocular toxoplasmosis should be treated, the duration of treatment, and what agent(s) should be used.12 there is lack of international guideline or consensus regarding the treatment regimen of ocular toxoplasmosis. the standard therapy has been “classic treatment” with triple drugs, sulfadiazine, pyrimethamine, and prednisone. many comparative studies have been conducted to investigate different treatment regimens for ocular toxoplasmosis. a study involving 79 uveitis specialist responders represented 9 antibiotics used in 24 different regimens. a prospective clinical trial found no significant differences between classic treatment and trimethoprim-sulfamethoxazole. trimethoprim-sulfamethoxazole is widely used as alternative treatment, due to low price, drug availability, and similar action as classic treatment. trimethoprimsulfamethoxazole had also proven to be effective in reducing the recurrence rate of recurrent retinochoroiditis.3,7,13,14 eventhough the use is still controversial, oral steroid may beneficial to limit the tissue destruction due to inflammation. however, the use of oral steroid without antibiotics coverage must be avoided, as that may cause further damage to retina. oral steroid should be commenced 72 hours after initiating antibiotics.3,7,13 from 27 patients in our study who receiving treatments, 10 patients were lost to follow-up. the mean follow-up was 2.8 months. clinical improvements that were evaluated included decreased level of vitritis, decreased size of retinal exudates, and cicatrization of active lesion. resolution of lesions were achieved in all patients receiving treatments until the end of follow-up. in group of patients with active lesions, 5 out of 22 eyes experienced visual acuity improvements, and 1 eye had decreased visual acuity due to optic nerve involvement. improvement of visual acuity were noted more in patients with extramacular lesion. this is consistent with the fact that macular lesion has poorer visual prognosis due to retinochoroidal scar formation as the final result. complications of retinal detachment and choroidal neovascularization may occur during resolution of lesion. choroidal neovascularization may arise from the edge of the retinochoroidal scar. the most common retinal detachment is rhegmatogenous type, that may due to the traction of atrophic scar to the surrounding tissues.3,7 our study has some limitations, due to the retrospective nature, limited time of data collections, and short period of follow-up. further randomized clinical study that involving larger number of patients and longer follow-up period may provide bigger perspective of ocular toxoplasmosis in indonesia. conclusion our study showed that ocular toxoplasmosis occurs more common in woman. most patients presented with blurred vision. unilateral typical lesion is the commonest cases. trimethoprim-sulfamethoxazole was most frequent antibiotics used in our study, either as single therapy or combination with other agent, and oral steroid used in coverage of antibiotics. most of our patients show good responses to the treatment regimens. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; 72 references 1. sofia o., sridharan s., biswas j. algorithm of choroiditis. world journal of retina and vitreous. 2012. vol. 2(2): 39-45. 2. holland gn. lx edward jackson memorial lecture. ocular toxoplasmosis: a global reassessment. part i: epidemiology and course of disease. am j ophthalmol 2003;136:973–988.basic and clinical science course section 9. intraocular inflammation and uveitis. american academy of ophthalmology. 2016-2017. p 298-311. 3. retmanasari a., widartono bs., wijayanti ma., artama wt. prevalence and risk factors of toxoplasmosis in middle java, indonesia. ecohealth 2017;14:162-170. 4. suhardjo, utomo pt, agni an. clinical manifestations of ocular toxoplasmosis in yogyakarta, indonesia: a clinical review of 173 cases. southeast asian j trop med public health 2003;34:291-297. 5. garweg jg, de groot-mijnes jdf, montoya jg. diagnostic approach to ocular toxoplasmosis. ocular immunology & inflammation 2011. vol.19(4): 255–261. 6. holland gn. lx edward jackson memorial lecture. ocular toxoplasmosis: a global reassessment. part ii: disease manifestations and management. am j ophthalmol 2004;137:1–17. 7. schallhorn jm., gonzales j. ocular toxoplasmosis: the treatment dilemma. journal of aapos 2013;17(5):454455. 8. fuh uc et al. clinical features and risk factors of patients with presumed ocular toxoplasmosis. journal of ophthalmic and vision research. 2016. vol.11 (1): pg. 48-53. 9. harper tw, miller d, schiffman jc, davis jl. polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis. american journal of ophthalmology. 2009. vol.147:140–7. 10. groot-mijnes jd, et al. polymerase chain reaction and goldmann-witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis. american journal of ophthalmology. 2006. pg. 313318 11. iaccheri b., fiore t., papadaki t., androudi s., janjua s., bhaila i., et al. adverse drug reactions to treatments for ocular toxoplasmosis: a retrospective chart review. clinical therapeutics 2008;30(11):2069-2074. 12. kim sj, scott iu, brown gc, brown mm, ho ac, ip ms, et al. interventions for toxoplasma retinochoroiditis. ophthalmology 2013;120:371–378. 13. felix et al. trimethoprim-sulfamethoxazole versus placebo to reduce the risk of recurrences of toxoplasma gondii retinochoroiditis: randomized controlled clinical trial. american journal of ophthalmology, 2014. vol. 157(4): 762–766. this work licensed under creative commons attribution 40 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; international journal of retina (ijretina) 2018, volume 1, number 2. p-issn. 2614-8684, e-issn.2614-8536 outcome of vitrectomy surgery in dropped nucleus at jakarta eye center referano agustiawan, soedarman sjamsoe, waldensius girsang, elvioza jec eye hospital abstract introduction: to report management and outcome of dropped nucleus in jakarta eye center methods: retrospective review of the records of 19 consecutive patients who underwent pars plana vitrectomy for retain lens fragments at jakarta eye center from january 2010 to september 2012. result: the mean age of the patient was 57 years (range 48-79). there were 10 males (53%) and 9 females (47%). 10 patients (53%) had vitrectomy within 1 day of phacoemulsification, 6(32%) within 1 week and 3(15%) after more than 1 week. eight patients (42%) achieved a final visual acuity of 0.5 or better, only 3 patients (15%) had final visual acuity 1-meter finger counting or worse. 74% patient achieved final acuity better than pre-op (14 patients). early vitrectomy group has 3 patients (30%) with complication, intermediate vitrectomy group has 33% complication and late vitrectomy has 33 % complication. posterior chamber iol were implanted in 12 patients (63%), 2 patients had scleral fixation iol, anterior chamber iol in 2 patients, and only 3 patients (16%) were left aphakic. conclusion: surgical management in cases of nucleus drop in jec showed good result with very limited complications. in most cases, vitrectomy was performed immediately after cataract surgery. early vitrectomy has no significant differences in complications and visual outcome than 1 week vitrectomy and late vitrectomy after cataract surgery. keywords: cataract surgery, pars plana vitrectomy, dropped nucleus cite this article: agustiawan, referano et al. outcome of vitrectomy surgery in dropped nucleus at jec eye hospitals. international journal of retina, [s.l.], v. 1, n. 2, aug. 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/28>. introduction *correspondence to: referano agustiawan, jec eye hospital, referanoagustiawan@gmail.com phacoemulsification is becoming increasingly popular in indonesia. jakarta eye center as a pioneer of this technique in indonesia has been performing more than 100,000 phaco surgeries since 1984. while phacoemulsification has several major advantages, nucleus and nuclear fragment dislocation is a potentially serious complication of this technique. this complication may occur during hydrodissection, phacoemulsification of the nucleus in the presence of posterior capsular tear, posterior extension of a tear in the coninous curvelinier capsulorrhexis or a zonular dialysis. the more recent literature reports incidence of this complication 0.3%2.7%. 1 retained nuclear fragment can result in severe intra ocular inflammation, vitreous hemorrhage, glaucoma, retinal detachment and may lead to loss of useful vision. the modern management of a nucleus drop requires pars plana vitrectomy by an experienced vitreoretinal surgeon. while successful removal of nuclear fragments can result in good visual recovery, the requisite instrumentation and trained personnel must be available. 2 however, only 44-69% of patients who undergo this procedure achieve a final visual acuity of 20/40 or better.3-10 the purpose of this study was to evaluate the clinical features and visual outcomes of pars plana vitrectomy in patients with nucleus drop in jakarta eye center. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 41 patients and methods a retrospective review of nucleus drop patient records from january 1, 2010 to september, 2012 at jakarta eye center was performed. the nuclear fragment drop reported here occurred in a consecutive series of 13,340 phacoemulsification performed during period of 2 years. the relevant information was retrieved from patient records. all phacoemulsification surgeries were performed by jakarta eye center doctors. when facing a nucleus drop case, the protocol in our hospital required the operating surgeon to performed a partial anterior vitrectomy. unless the clinical impression was that of a hard nucleus, the surgeon would implant iol (intra ocular lens). in case of doubt a vitreoretinal was consulted and if available depending on media clarity and state of anesthesia, the nuclear fragment was removed at the same sitting. otherwise patient were managed with an elective 3-port pars plana vitrectomy later. wire-loop vectis or similar devices were not used to retrieve sunken nucleus or nuclear fragment. a three-port pars plana vitrectomy was performed before the nuclear material was removed. cortical material covering the nucleus and small soft lens fragment removed with vitrector. when the nuclear material was difficult to fragment, it was crushed between the light pipe and vitrector and then removed. if the entire nucleus was in the vitreous, the nucleus was dragged up into the anterior chamber with or without pfcl (perfluorocarbon liquid) and removed through an extension of the original scleral tunnel incision or corneal incision. if an iol had not been implanted during the primary surgery, it was implanted at this time. the following information was noted for each patient: age, sex, risk factor for lens dislocation, visual acuity before vitrectomy, size of the dislocated lens fragment, interval between cataract surgery and vitrectomy, type of iol implant, vitrectomy methods, perioperative complication and final visual acuity. results total phacoemulsification surgery in jakarta eye center from 2010 to september 2012 were recorded 13,340. complication number were occurred in 172 cases (1.3%). nineteen nucleus dropped (0.14%) were recorded in this period. all of 19 nucleus drop cases were included in this study. the mean age of the patient was 57 years (range 48-79). there were 10 males (53%) and 9 females (47%). preexisting eye disease diabetic retinopathy (42.1%), myopic degeneration (10.5%) and previous retinal detachment (15.8%) were the most frequent preexisting eye disease (table 1) table 1. preexisting eye disease condition number % diabetes retinopathy 8 42.1 myopic degeneration 2 10.5 post retinal detachment 3 15.8 glaucoma 1 5.3 risk factors for dropped nucleus the risk factors for the dislocation of lens fragments during phacoemulsification surgery are presented in table 2. the most common risk factors included brown cataract (47.7%) and vitrectomized eye (21.1%) table 2. risk factor for dropped nucleus risk factor number % brown cataract 9 47.4 myopic eye 2 10.5 vitrectomized eye 4 21.1 shallow anterior chamber 1 5.3 42 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; table 3. distribution of age, sex, preexisting eye disease, nucleus size, bcva, and lens status in each group early vit group (10) intermediate vit group (6) late vit group (3) mean age(years) 67 56 58 range 46-79 62-73 48-64 male/female 6/4 3/3 1/2 vitrectomy type tsv 10 5 2 vit 1 1 preexisting eye disease post rd 2 1 dm 5 2 1 glaucoma 1 myopic degeneration 1 1 nucleus size whole nucleus 1 1 more than half 6 2 less than half 4 3 2 complication choroidal detachment 2 1 high iop 1 retinal detachment 1 1 iol drop 1 pre op post op pre op post op pre op post op bcva > 0.5 1 4 1 3 1 >0.1 – 0.4 1 4 1 1 1 <0.1 8 2 4 2 3 1 lens status aphakia 7 3 5 1 pc iol 3 6 1 4 2 2 ac iol 1 1 scleral fixation 2 tsv= 23 or 25 gauge transconjunctival sutureless vitrectomy; vit= 20 gaugevitrectomy ; rd= retinal detachment; dm=diabetes mellitus; iop= intra ocular pressure; iol=intra ocular lens; bcva= best corrected visual acuity; pc=posterior chamber; ac=anterior chamber timing of pars plana vitrectomy ten patients (53%) had vitrectomy within 1 day of phacoemulsification (early vitrectomy group), 6 (32%) within 1 week (intermediate vitrectomy group), and 3 (15%) after more than 1 week (late vitrectomy group). the distributions of age, sex, clinical findings at presentation, visual acuity, lens status and dropped nucleus size are shown in table 3. the visual acuity of early vitrectomy group at presentation was worse than 0.1 in 8 of 10 patients. in 6 patients the dropped nucleus size was more than half, and less than half in 4 patients. at presentation 7 of 10 patient were aphakic, and the rest was pseudophakic with posterior chamber iol in sulcus. visual acuity improvement was noted in 8 of 10 patients (80%). on the other hand, some complications were occurred in this group. choroidal detachment was noted in 2 patients (20%), iol dropped followed by retinal detachment were published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 43 noted in 1 patient (10%). all of those 3 patients were left aphakic after vitrectomy due to severe choroidal detachment (2 patients). one patient with iol dropped during vitrectomy was left aphakic after iol extraction and retinal detachment surgery. in intermediate vitrectomy group, visual acuity at presentation was worse than 0.1 in 4 of 6 patients, and between 0.1 and 0.5 in 1 patient, and 1 patient had more than 0.5. only 1 patient in this group had iol implanted at presentation, 5 of 6 were aphakic. one patient had whole nucleus dropped. in 2 patients the dropped nucleus size was more than half and 3 patients has less than half nucleus dropped in vitreous cavity. one patient (16%) had high intraocular pressure after vitrectomy and well controlled by anti-glaucoma medication, and 1 patients (16%) had choroidal detachment after vitrectomy. choroidal detachment was well resolved with steroid treatment. scleral fixation iol surgery was done in 2 patients in this group. two of 6 (33%) patient had visual acuity worse than 0.1, 3 patients (50%) had more than 0.5 visual acuity and 1 patient (17%) had visual acuity between 0.1 to 0.5. total 4 patients (67%) had visual improvement after surgery. in late vitrectomy group, all patient had visual acuity worse than 0.1 at presentation. one patient was aphakic and 2 patients were pseudophakic. whole nucleus drop was noted in 1 case in this group while 2 patients had less than half nucleus dropped posteriorly. no patient in this group was aphakic, with 1 patient had anterior chamber iol implanted. only 1 complication recorded in this group. this complication was occurred in patient with history of retinal detachment. visual acuity improvement were noted in 2 of 3 patient (67%). in general, 15 patients (79%) had improvement visual acuity after vitrectomy. fourteen of 19 patient (74%) had final visual acuity better than 0.1, with 6 patients (32%) had final visual acuity between 0.1 and 0.5 and 8 patient (42%) had visual acuity more than 0.5. complication were noted in 7 cases (34%) and 4 of those complications were well managed with medication or surgery. discussion indonesian reports on incidence and management of nucleus drop are limited. as phacoemulsification becomes the most popular technique for cataract surgery, there is an increase in the number of retained lens fragments after cataract surgery. our incidence in nucleus drop was slightly lower than those identified with mathai et al.2 they reported that nucleus drop incidence was 0.8% compare to our report (0.14%). this result might be related to the phaco surgeon. in our study, all phaco surgeon are experience surgeon of jakarta eye center while resident converting to phacoemulsification were included in mathai et al report.2 transconjunctival sutureless vitrectomy (tsv) methods was used in most cases in our hospital (89.5%). this technique is allowed us to perform efficient vitrectomy under local anesthesia with minimally trauma, minimal astigmatism post vitrectomy and faster recovery compare to conventional technique. furthermore, this technique can help surgeon to meet patient expectation. unavailability of fragmatome in 23 gauge and 25 gauges is the main limitation of this technique in nucleus drop cases. both of 20 gauge vitrectomy in our series were used in big nucleus size (whole nucleus and more than half nucleus) drop cases. most of our cases were implanted with pc-iol. scleral fixation iol was noted in 2 cases (10%), and ac-iol was noted in 2 cases (10%). this report is not too different to other series reported by chen et all.11 chen cl et al reported 13 % ac-iol and 14 % scleral fixated iol were implanted in their nucleus drop cases. this approach is dependent on multiple factors including the degree to which the capsular bag is intact and the type of intraocular lens that has been inserted. there are limited number of clinical trials comparing ac-iol with scleral-fixated iol, but the results show no significant superiority of one design over other, and therefore the choice of lens and method of fixation is still open to personal preference, availability and the individual surgeon’s skill set.12 in our study, 40% in group early vitrectomy had vision 0.5 or better, 50% in group moderate vitrectomy had vision 0.5 or better, and 33% in group late vitrectomy had vision 0.5 or better. over all we have 42% patients had visual acuity 0.5 or better. these results are not consistent with other study by chen et al11. they found that immediate vitrectomy had better visual outcome than latter vitrectomy. in their study, 76% of the patients in group a (early vitrectomy) had a final visual acuity of 6/12 or better; 45% of the patients in group b (within 1-week vitrectomy) had a final visual acuity of 6/12 or better, and 28% of the patients in group c (late vitrectomy) had a final visual acuity of 6/12 or better. complication was recorded in 7 cases (34%). complications that noted in our series were retinal detachment, iol drop, choroidal detachment, and high intra ocular pressure. in chen et all11 study, no patient in same day vitrectomy or 1-week vitrectomy experienced retinal detachment, whereas in late vitrectomy group 55% patient had retinal detachment after surgery. kapusta et al13 reported no retinal detachment in their series, attributing this to the fact that cataract surgeon in their institution are discourage from attempting to retrieve nuclear fragments from deep within the vitreous cavity. on the other hand, in our study no patient in 1-week vitrectomy (intermediate vitrectomy) had retinal detachment while 10 % patient in early vitrectomy (same day vitrectomy group) and 33% patient in late vitrectomy group experienced retinal detachment after surgery. those patients with retinal detachment has history of 44 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; vitrectomy due to retinal detachment before cataract surgery. one patient in early vitrectomy group has experienced drop iol in the end of vitrectomy. this condition was worsening to retinal detachment 1 week after vitrectomy. in this study early vitrectomy group has 3 patients (30%) with complication, intermediate vitrectomy has 33% complication and, late vitrectomy has 33 % complication. in conclusion, the results of our study demonstrate that surgical management in cases of nucleus drop in jec showed good result with very limited complications. in most cases vitrectomy was performed immediately after cataract surgery. early vitrectomy has no significant differences in complications and visual outcome than 1week vitrectomy and late vitrectomy after cataract surgery. further prospective study with higher number of cases may provide us with more insight into optimal result in nucleus drop management references 1. pande m, dabbs tr. incidence of lens matter dislocating during phacoemulsification. j cat ref surg 1996;22:737-42 2. mathai a, thomas r. incidence and management of posteriorly dislocated nuclear fragments following phacoemulsification. indian j ophthalmol 1999;47:173 3. kim je, flynn hw jr, smiddy we, murray tg, rubsamen pe, davis jl, nicholson dh:retained lens fragments after phacoemulsification.ophthalmology 1994; 101: 1827–1832. 4. vilar nf, flynn hw jr, smiddy we, murraytg, davis jl, rubsamen pe: removal of retainedlens fragments after phacoemulsificationreverses secondary glaucoma and restoresvisual acuity. ophthalmology 1997;104: 787–791. 5. ross wh: management of dislocated lens fragments after phacoemulsification surgery.can j ophthalmol 1996; 31: 234–240 6. borne mj, tasman w, regillo c, malecha m,sarin l: outcomes of vitrectomy for retained lens fragments. ophthalmology 1996; 103: 971–976. 7. margherio rr, margherio ar, pendergastsd, williams ga, garretson br, strong le,trese mt, cox ms, hassan ts: vitrectomy for retained lens fragments after phacoemulsification. ophthalmology 1997; 104: 1426–1432. 8. al-khaier a, wong d, lois n, cota n, yang yc, groenewald c: determinants of visual outcome after pars plana vitrectomy for posteriorly dislocated lens fragments in phacoemulsification. j cataract refract surg 2001; 27: 1199–1206. 9. hansson lj, larsson j: vitrectomy for retained lens fragments in the vitreous after phacoemulsification. j cataract refract surg 2002; 28: 1007–1011. 10. rossetti a, doro d: retained intravitreal lens fragments after phacoemulsification:complications and visual outcome in vitrectomized and nonvitrectomized eyes. j cataract refract surg 2002; 28: 310–315 11. chen cl, wang ty, cheng lh et al. immediate pars plana vitrectomy improves outcome in retained intravitreal lens fragments after phacoemulsification.ophthalmol 2008;222:27783 12. bastawrous a, parkes c, prasad s. choices in correction of aphakia during vitrectomy.ophthalmol 2011;226(suppl 1):46-52 13. kapusta m,chen jc, lam wc. outcomes of dropped nucleus during phacoemulsification.ophthalmology 1996; 103: 1184-7 this work licensed under creative commons attribution 16 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; international journal of retina (ijretina) 2019, volume 2, number 1. p-issn. 2614-8684, e-issn.2614-8536 characteristics of patient with macular hole after pars plana vitrectomy (ppv) and internal limiting membran (ilm) peeling in cicendo eye hospital national eye center, bandung rani pitta, rova virgana, iwan sovani, arief kartasasmita, erwin iskandar, grimaldi ihsan, made indra departement of opthamology, faculty of medicine universitas padjadjaran cicendo eye hospital national eye center abstract introduction : macular hole (mh) can cause severe visual disturbance, but remarkable progress has been achieved in surgical treatment for eyes with this condition. vitrectomy with internal limiting membrane (ilm) peeling allows a very high success rate for mh closure (approaching 90%). to compare characteristics patients with closed and unclosed macular hole after pars plana vitrectomy (ppv) surgery and internal limiting membran (ilm) peeling. method : this was retrospective study which data was obtain from patient’s medical records who underwent ppv and ilm peeling since july 1st to december 31th 2018. results : 27 eyes from 25 patients had mh surgery. 20 eyes (74%) had closed mh and 7 (26%) eyes unclosed mh after surgery. hff value before surgery was 1,34 ± 0,90 and mhi was 1,09 ± 0,81 in closed mh. meanwhile in unclosed mh, hff value before surgery 0,53 ± 0,12 and mhi was 0,75 ±0,10. mhi ≥0,5 and hff value ≥ 0,9 had a good prognostic factor. conclusion : despite of good prognostic factor from oct measurement and achieve anatomical success, foveal microstructure also important in visual recovery after mh surgery. keywords: macular hole, ilm peeling, oct macula. cite this article: omas, rani pitta. the characteristics of patient with macular hole after pars plana vitrectomy (ppv) and internal limiting membran (ilm) peeling in cicendo eye hospital national eye center, bandung. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/61>. introduction *correspondence to: rani pitta, department of ophthalmology, universitas padjadjaran, rani_pitta@yahoo.co.id a macular hole was first described by knapp in 1869. a macular hole (mh) is a full-thickness or partial-thickness defect in the macular region, and its pathogenesis can be idiopathic or result from myopia, trauma, or other causes. in most cases it is idiopathic, due to abnormal vitreofoveal traction. idiopathic macular holes occur at a rate of approximately 8 per 100,000 persons per year and have a female-to-male ratio of 2 to 1. the hallmark complaint of idiopathic macular hole formation is acute or subacute painless development of central visual distortion or blurred vision.1-3 the gass classification system explains the clinically observed appearance of macular holes in four stages and their precursor lesions. kelly and wende were the first to report that vitreous surgery can improve the visual acuity in some eyes with acute, idiopathic macular holes. since then, vitrectomy for idiopathic macular holes rapidly has become a widely performed procedure throughout the world. recent studies confirm that high rates of anatomic success (between 85% and 100%) are achievable in large series of macular holes of all stages treated with vitrectomy, with approximately two-thirds of eyes achieving 20/50 or better vision. 1,3-4 surgery for mh has undergone great developments since kelly and wendel first applied vitrectomy to treat mh. both closure rate and visual recovery have improved dramatically; internal limiting membrane (ilm) peeling in particular has significantly improved the closure rate. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 17 the use of dyes and the development of microincision surgery have reduced both the duration of surgery and the risk of damage from surgery. 1,3,5 before the introduction of vitrectomy to treat mh, the spontaneous closure rate for gass stage 3 and 4 mhs was merely 4%, while that for stage 2 mhs was 11.4% following the introduction of vitrectomy by kelly and wendel, the closure rate increased to 58%. as surgical techniques and instrumentation have improved, the closure rate has increased to as high as 90%. the purpose of this study was compared characteristics patients with closed and unclosed macular hole after pars plana vitrectomy (ppv) surgery and internal limiting membran (ilm) peeling 2,3,5 method this was a retrospective observational study involving patients who visit and underwent mh surgery from vitreoretinal unit cicendo eye hospital, bandung, indonesia, between july 1st to december 31st , 2018. inclusion criteria were patients with macular hole after pars plana vitrectomy and ilm peeling. macular hole was graded according of gass criteria stage 3–4 and etiology mh was idiopathic. exclusion criteria was macular hole with combination retinal detachment (mhrd), previous retina surgery and uncomplete data oct. in a retrospective chart research, we obtained preoperative data on onset, history of duration of symptom and visual acuity examination was done using snellen’s chart that converted to logmar, lens status, indirect opthalmoscope with +20d lens was used to evaluated the detailed fundus to examine extent and macular status. oct macula was used to evaluated. intraoperative data is the type of tamponade (silicone oil or gas) and postoperative data was visual acuity and oct macula. we evaluate macular condition after surgery. the pars plana vitrectomy with 23 gauge trocars using noncontact wideangle viewing system. trocars were placed 3-4mm from limbus that allows peripheral vitrectomy to be performed without touching the lens, and also switching between the 3 entry sites. a core vitrectomy was performed and the internal limiting membrane was removed with staining. the posterior hyaloid was elevated and trimmed in all patients. a fluid– gas exchange was carried out, and the vitreous was filled with an inert air, gas (sf6 or c3f8) or fluid. all patient were operated by five experienced posterior segment surgeons and postoperative follow-ups were made at the vitreoretinal unit cicendo eye hospital national eye center, bandung, indonesia. all of this patient medical records that used for this study has already approved by cicendo hospital medical comittee. data in this study was analyzed using microsoft excel 2016. result the total of 27 eyes from 25 patients had mh surgery (pars plana vitrectomy and ilm peeling). baseline characteristics in this study was described in table 1. the mean age of this study was 62±6,92 years old with sex occur distributin of this study female 76% and male 24%. indications for surgery includes stages 3 and 4 regarding to gass classification. we examined stage of macular hole. there are 6 eyes (22%) with stage iii and 21 eyes (78%) with stage 4. there were 7 eyes (33%) of stage iv didn’t closed after surgery. table 1. baseline characteristic characteristic mean ± sd n(%) range sex male 6 (24%) female 19 (76%) age 62±6,92 46-76 y.o 40-49 y.o 1(4%) 50-59 y.o 8(32%) 60-69 y.o 14(56%) >70 y.o 2(8%) lens status phakic 21(78%) pseudophakic 6(22%) stage macular hole iii 6(22%) iv 21(78%) 18 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; we examined visual acuity in patients after macular surgery (ppv + ilm peeling). there were 20 eyes (74%) had closed mh and 7 eyes (26%) unclosed mh after the surgery. for closed mh, mean uncorrected va (visual acuity) before surgery was 0.73 ± 0.24 log and after surgery 0,65 ± 0,25 log. for unclosed mh, mean uncorrected va before surgery was 1,30 ± 0,31 log and after surgery 1,165 ± 0,165 log. there were 27 eyes underwent pars plana vitrectomy and ilm peeling. there were 19 eyes used sf6 as a tamponade and 1 eye with air in closed mh. there were 6 eyes used sf6 as a tamponade in unclosed mh. we also examined mhi (macular hole index) and hff (hole form factor) from oct macula patients as a prognostic factor. if mhi value ≥ 0.5 and hff ≥ 0,9, the patient has a good prognosis. we found mean hff value before surgery was 1,34 ± 0,90 and mhi was 1,09 ± 0,81 in closed mh. meanwhile in unclosed mh, hff value before surgery 0,53 ± 0,12 and mhi was 0,75 ±0,10. discussion a macular hole is an anatomic discontinuity of the neurosensory retina that develops in the center of the macula or fovea. typically, the patient will experience metamorphopsia and decreased visual acuity. most investigators believe that macular holes are caused by pathologic vitreoretinal traction at the fovea.1-4 tabel 2. characteristics after macular surgery characteristics mean±sd n (eyes) mean±sd n (eyes) closed mh unclosed mh total 20 7 duration of symptoms 8,34 ± 7,43 11,42 ± 5,42 uncorrected va before surgery 0,73 ± 0,24 1,30 ± 0,31 uncorrected va after surgery 0,65 ± 0,25 1,165 ± 0,165 follow up (weeks) 9,65 ± 7,76 4±0,00 oct macula stage mh pre-op iii 6 0 iv 14 7 hff (hole form factor) 1,34 ± 0,90 0,53 ± 0,12 mhi (macular hole index) 1,09 ± 0,81 0,75 ±0,10 tamponade sf6 19 7 air 1 the beijing eye study is a population-based crosssectional study of 4346 subjects that found a prevalence of macular holes of 0.09 ± 3.04%. eye disease casecontrol study group wrote the majority (72%) of idiopathic macular holes occurred in women; more than 50% of holes were found in individuals 65 to 74 years of age and only 3% in those under the age of 55. in this study, mean age of was 62±6,92 years old with sex distributin of this study 6 male (24%) and 19 female (76%)1,-4 the duration of a patient’s symptoms is an important predictor of anatomic macular hole closure and visual improvement. kelly and wendel reported that visual outcomes were best for those with symptoms existing for less than 6 months. in this study, duration of symptoms mean 8,34 ± 7,43 weeks for closed mh and 11,42 ± 5,42 weeks for unclosed mh2-4 for decades, macular holes (mh) have been classified in four stages, as first described by donald gass in 1988. williamson et al reported that among 351 cases, the stage 2, 3, and 4 closure rates were 95.8%, 73.0%, and 56.3%, respectively, and this difference was significant. in this study, 7 eyes with unclosed mh were stage iv mh.3,5-6 optical coherence tomography (oct) has enhanced our understanding of mh by providing an objective and reproducible way of visualizing the macula. oct has revolutionized macular imaging and also allows quantitative measurements of many anatomic parameters. the anatomic parameter could be used in prognostic factor in macular hole surgery. the anatomic parameter can help predicted postoperative anatomic and visual outcome. the diameter of the macular hole measured by oct at the level of the retinal pigment epithelium and the minimum diameter seem to provide a published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 19 prognostic factor for postoperative visual outcome and anatomical success of macular hole surgery.6-8 the hole form factor (hff) is the first calculated oct index used as a prognostic factor. the hff is the quotient of the summation of the left and right arm lengths divided by the basal hole diameter. puliafito et al found an 80% anatomical success rate in patients with hff greater than 0.9. hff value ≥ 0.9 had better prognosis. in this study mean hff value in closed mh was 1,34 ± 0,90 before surgery (n=20) and in unclosed mh hff value was 0,53 ± 0,12 (n=7). 6-8 mh index (mhi) is an intuitive predictor for visual outcome following mh surgery. the mhi is defined as the ratio of the hole height to the basal hole diameter and is reported to be positively correlated to the postoperative visual acuity in several studies. mhi value ≥ 0.5 had better visual acuity than those with an mhi value <0.5. in this study, we found that mhi value in closed mh before surgery was 1,09 ± 0,81µm (n=20) and compare to unclosed mhi 0,53±0,15µm (n=7) after surgery.7-9,10 the ilm is the basal lamina of the inner retina and is thought to be a scaffold for proliferation of fibrocytes, myofibroblasts, and retinal pigment epithelial cells. ilm peeling increases the likelihood of successful macular hole closure, but, because the ilm also plays a role in the structural integrity of the retina, it has been postulated that removal of this membrane could be functionally damaging to the retina.3,7,10 cochrane review found that ilm peeling achieves higher anatomical success with a reduced need for additional surgical interventions when compared to nonpeeling in treating patients at stages 3, and 4. in this study, there were 27 eyes underwent vitrectomy and ilm peeling and only 1 eye need additional surgical intervention because of re-open. we found in oct mhi value : 0,23 and hff 0,426 from this patient (reopen).3.6,10 kelly and wendel reported that 73% patients who underwent vitrectomy resulting in successful macular reattachment experienced an improvement in visual acuity of two lines or better. in this study, va not improve enough. we analyze because patients didn’t get corrected va, some patients had cataract, unclosed mh, or in closed mh still had irregular closure so it can limited visual recovery. 6,8,10 photoreceptor defects were correlated with postoperative bcva. there are four distinct hyperreflective lines that can be viewed by sd-oct: the photoreceptor inner segment/outer segment (is/os) junction, the external limiting membrane (elm), the cone outer segment tips (cost), and the retinal pigment epithelium (rpe). the international nomenclature oct consensus refers to the is/os junction as the ellipsoid zone. it has also been demonstrated that the integrity of the elm and ellipsoid zone is the most important factor related to postoperative visual acuity. 6,8,10 retinal tamponade may be created using different agents at the conclusion of macular hole surgery to achieve anatomic closure of the macular hole. tamponade options include the use of air (days), sf6 (2 to 4 weeks), c3f8 (1 to 3 months), or silicone oil (long term). commonly used long-lasting gases include sulfur hexafluoride (sf6) and perfluoropropane (c3f8). no significant differences in anatomic success or visual outcomes have been reported between these. in this study we found that 19 eyes used sf6 and 1 eye using air in closed mh. in unclosed mh, there were 7 eyes used sf6.3,10-11 conclusion macular hole (mh) is a round full-thickness opening in the foveal center. macular hole surgery consists of vitrectomy with internal limiting membrane (ilm) peeling. ilm peeling for macular holes rapidly has high rates of anatomic success are achievable. despite of good prognostic factor from oct measurement and achieve anatomical success, foveal microstructure also important in visual recovery after mh surgery. reference 1. ryan sj. retina. sixth ed. china: elsevier; 2018. 557-68 2. cantor.b. american academy of opthalmology. basic and clinical science course. retina and vitreous. 2016-2017 3. olsen t.w. et al. idiopathic macular hole : retina/vitreous preferred practice pattern development process and participants. 2014. 1-33 4. zhang p, shang q, ma j, hao y, ye c. correlation between postoperative area of high autofluorescence in macula and visual acuity after macular hole closure. european journal of ophthalmology. 2017. 781–5 5. kang sw. types of macular hole closure and their clinical implications. british journal of ophthalmology. 2013. 1015–9. 6. zhao p, wang s, liu n, shu z, zhao j. a review of surgical outcomes and advances for macular holes. 2018. hal 1–10 7. goldberg ra, waheed nk, duker js. optical coherence tomography in the preoperative and postoperative management of macular hole and epiretinal membrane. british journal of ophthalmology. 2014. 20–3 8. tao lw, wu z, guymer rh, luu cd. ellipsoid zone on optical coherence tomography: a review: ellipsoid zone on optical coherence tomography. clinical & experimental ophthalmology. 2016. 422–30 20 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 9. j. r, c. r. application of optical coherence tomography and macular holes in ophthalmology. optical coherence tomography. intech. 2013 10. rizzo s, et al. internal limiting membrane peeling versus inverted flap technique for treatment of full-thickness macular holes: a comparative study in a large series of patients. retina. 2018. 73–8. 11. casini g, loiudice p, de cillà s, radice p, nardi m. sulfur hexafluoride (sf6) versus perfluoropropane (c3f8) tamponade and short term face-down position for macular hole repair: a randomized prospective study. international journal of retina and vitreous. 2016. 1-6 this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 27 international journal of retina (ijretina) 2020, volume 3, number 1. p-issn. 2614-8684, e-issn.2614-8536 comparison of oral rifampicin with observation alone in treatment of acute central serous chorioretinopathy anum badar1, sadaf khan1, sobia usman shah2, muhammad tahir3, saman babree1 1lrbt eye hospital lahore 2combined military hospital lahore, 3combined military hospital rawalakot abstract introduction: a randomized control trial to compare efficacy of oral rifampicin in terms of drying of macula and decrease macular thickness with observation alone in patients of acute central serous chorioretinopathy done in layton rahmatulla benevolent trust (lrbt) free eye and cancer hospital, lahore from january 2017 to june 2017 methods: after getting approval from hospital ethical committee 140 patients of csr were included in the study. the demographic details were noted and patients were randomized by lottery methods in two groups (group a& b). group-a was observed for spontaneous resolution, routine treatment started if no improvement noted after 6 weeks of observation alone. group b was given oral rifampicin 600mg per day for four weeks with liver function tests being done before commencement of treatment and after 2 weeks. oral rifampicin was stopped if patient developed deranged liver function tests. patients were followed up at 4 weeks for macular dryness and decrease macular thickness on optical coherence tomography(oct). all the readings were carried out and noted by single person in order to minimize bias. results: a total of 140 patents, 70 in each group, were included in study with mean age 38.77+7.74 in group-a and 39.14+7.97 years in group-b. regarding gender distribution 65.71 %(n=46) in groupa and 613.43%(n=43) in group-b were male. comparison of outcome of treatment of acute central serous chorioretinopathy with oral rifampicin vs observation showed that 18.57 %(n=13) in groupa and 41.43%(n=29) in group-b had dry macula. conclusion: we concluded that there is a significant difference in drying of macula in acute central serous chorioretinopathy with rifampicin versus observation alone. keywords: acute central serous chorioretinopathy, oral rifampicin, drying of macula cite this article: badar, anum et al. comparison of oral rifampicin with observation alone in treatment of acute central serous chorioretinopathy. international journal of retina, [s.l.], v. 3, n. 1, feb. 2020. issn 26148536. available at: https://www.ijretina.com/index.php/ijretina/article/view/103 date accessed: 22 feb. 2020. doi: https://doi.org/10.35479/ijretina.2020.vol003.iss001.103. introduction *correspondence to: anum badar, lrbt eye hospital lahore, pakistan, dranumbadar@gmail.com central serous chorioretinopathy (cscr) is defined as a serous detachment of the neurosensory retina over an area of leakage from the choriocapillaries through the retinal pigment epithelium (rpe).1 https://www.ijretina.com/index.php/ijretina/article/view/103 https://doi.org/10.35479/ijretina.2020.vol003.iss001.103 28 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; incidence of visual loss in young adult men due to central serous chorioretinopathy is approximately z1/10,0002 which is 1.74-fold higher than females.3 with a recurrence rate of 19.41%.4 risk factors include exogenous steroid, type a personality, pregnancy, smoking, cushing syndrome, h.pylori infection and systemic lupus erythematosis.5 central serous chorioretinopathy is thought to be caused by an impaired automatic response due to elevating circulating cortisol and epinephrine level which in turn affect the auto regulation of the choroidal circulation. specific psychological and personality profiles have been associated with cscr but the exact link between anxiety-sensitive personalities and steroid biology has not been elucidated. all this considered, it is clear that complex links between cscr and corticosteroids are yet to be described. in this context, we have investigated and identified the mineralocorticoid receptor as a potential player in cscr pathogenesis. this review will focus on recent findings that have furthered the epidemiology, the clinical understanding and the management of cscr and will detail the possible role of the mineralocorticoid pathway in cscr pathogenesis and treatment. as central serious chorioretinopathy mainly effects young working male population, this novel treatment strategy would be tremendously beneficial in terms of early return to their activities and less socio-economic loss. confirmation of efficacy of rifampicin opens the doors for this newer treatment modality. methods this randomized control trial was done at layton rahmatulla benevolent trust (lrbt) free eye and cancer hospital, lahore from january 2017 to june 2017. ethical approval was taken from hospital ethical committee and written consent was taken from all the participants. sample size was calculated considering 80% power of test (1-beta). sample was collected by non-probability consecutive sampling. the patients with age ranging from 20 to 50 presenting within 3 weeks of symptoms onset were included as we were looking for role of rifampicin in acute csr. all those patients with disease duration of more than 6 months, recurrent disease, having another ocular pathology and deranged liver function tests were excluded from study. demographic information such as name, age, gender was noted at the time of recruitment. preoperative assessment including visual acuity, slit lamp examination, ffa and macular thickness on oct were carried out and patients were randomly assigned to group a or group b by using lottery methods. to avoid bias one experienced ophthalmologist who has done at least five hundred independent oct performed all the oct. group a was observed (there was no ethical issues as observation alone is considered for spontaneous resolution up to 6 months before commencement of treatment). group b was given oral rifampicin 600mg per day for four weeks. if there is no improvement after 6 weeks in group a, they were given the usual treatment. liver function tests were repeated after two weeks in group-patient having deranged liver function tests were excluded from the study and oral rifampicin was stopped. patients were followed up at 4 weeks to see decrease in macular thickness. all the readings were carried out and noted by single person in order to minimize bias. spss-21 was used for statistical analysis. quantitative variables like age and bcva were presented as mean and standard deviations while qualitative variables like gender, efficacy in terms of macular dryness were presented as frequency and percentage. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 29 chi square test was used to compare the qualitative outcomes i.e. efficacy (in terms of macular dryness) as per operational definition in both groups. post stratification chi square test was applied. the p-value of ≤0.05 was considered significant. results a total of 140 cases, (70 in each group), fulfilling the inclusion/exclusion criteria were enrolled in study. age distribution of the patients shows that 41.43%(n=29) in group-a and 40%(n=28) in groupb were between 20-35 years of age whereas 58.57%(n=41) in group-a and 60%(n=42) in groupb were between 36-50 years of age, mean+ sd was calculated as 38.77+7.74 in group-a and 39.14+7.97 years in group-b. table 1. age distribution (n=140) age (in years) group-a (n=70) group-b (n=70) no. of patients % no. of patients % 20-35 29 41.43 28 40 36-50 41 58.57 42 60 total 70 100 70 100 mean+sd 38.77+7.74 39.14+7.97 gender distribution shows that 65.71%(n=46) in group-a and 613.43%(n=43) in group-b were male while 34.29%(n=24) in group-a and 38.57%(n=27) in group-b were females.mean bcva was calculated as 0.17+0.10 in group-a and 0.15+0.12 in group-b table 2. mean bcva (n=140) bcva group-a (n=70) group-b (n=70) mean sd mean sd 0.17 0.10 0.15 0.12 comparison of efficacy of oral rifampicin in terms of drying of macula with observation alone in patients of acute central serous chorioretinopathy shows that 18.57%(n=13) in group-a and 41.43%(n=29) in group-b had efficacy whereas 81.43%(n=57) in group-a and 58.57%(n=41) in group-b had no findings of efficacy, p value was 0.03 showing a significant difference. effect modifiers like age, gender, visual acuity (pretreatment bcva), duration of disease was controlled through stratification. post-stratification chi square test was applied. p value of <0.05 was considered significant. table 3. comparison of efficacy of oral rifampicin in terms of drying of macula with observation alone in patients of acute central serous chorioretinopathy (n=140) efficacy group-a (n=70) group-b (n=70) no. of patients % no. of patients % yes 13 18.57 29 41.43 no 57 81.43 41 58.57 total 70 100 70 100 30 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; table 4. stratification for efficacy with regards to age (n=140) age: 20-35 years group efficacy p value yes no 0.03 a 6 23 b 13 15 age: 36-50 years group efficacy p value yes no 0.03 a 7 34 b 16 26 table 5. stratification for efficacy with regards to gender (n=140) male group efficacy p value yes no 0.01 a 10 36 b 20 23 female group efficacy p value yes no 0.08 a 3 21 b 9 18 discussion poor visual outcome and frequent exacerbations are the features of central serous retinopathy (csr). very few therapies exist for csr, and the existing therapies are often ineffective. some investigators believe that initial choroidal vascular compromise subsequently leads to secondary dysfunction of the overlying rpe they proposed that choroidal hyper permeability causes serous detachments of the rpe, which can induce a rip or decompensation of the rpe. alterations in choroidal circulation may also cause choroidal ischemia. an alternative theory suggests that csc results from dysfunction of the rpe. this occurs following an undefined insult. it results in either a few impaired rpe cells or even a single rpe cell, which causes a reverse in fluid movement in a chorioretinal direction. this, in turn, leads to leakage of fluid in the subretinal space and finally to the development of a neurosensory retinal detachment. the relation between cscr and corticoids is probably one of the most intriguing aspects of the disease. glucocorticoids efficiently reduce macular edema of many origins, even when associated with subretinal fluid,15 but glucocorticoids can aggravate subretinal fluid accumulation in cscr patients.. but high-dose intraocular injection of glucocorticoids, routinely administered for the treatment of macular edema, has not been associated with increased incidence of cscr. such discrepancies reflect the still non-elucidated complexity of steroids regulation on ocular physiopathology. specific psychological and personality profiles have been associated with cscr but the exact link between anxiety-sensitive personalities and steroid biology has not been elucidated and the full ocular and systemic steroid hormonal profile of cscr published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 31 patients has been only partially explored. more determinants should be now considered in light of recent discoveries linking stress, corticosteroids, epigenetic modifications and cardiovascular risk factors. life style modification is advised to reduce the circulating cortisol levels with stopping of exogenous glucocorticoids. patients are observed for the period of three months for spontaneous resolution. focal laser, photodynamic therapy and intravitreal bevacizumab was previously considered mainstay of treatment. newer advances in treatment of central serous chorioretinopathy include systemic anti glucocorticoids e.g. mifepristone, ketoconazole, rifampicin, eplerenone etc.6-7 rifampicin is an anti-tuberculous medication which is thought to facilitate catabolism of endogenous steroids. it causes a proliferation of the smooth endoplasmic reticulum and an increase in the cytochrome p-450 content in the liver, thus affecting the metabolism and bioavailability of endogenous corticosteroids, consequently aiding in resolution of cscr and improving its symptomatology.75,76 however, care is to be taken as hepatotoxicity can develop as a side effect while being treated for cscr.77 a study published in iranian journal of ophthalmology evaluated therapeutic effects of rifampicin in acute central serous chorioretinopathy. results showed significant drying of macula in treatment group 45.5% than control group 24.9%. as central serious chorioretinopathy mainly effects young working male population, this novel treatment strategy would be tremendously beneficial in terms of early return to their activities and less socio-economic loss. confirmation of efficacy of rifampicin opens the doors for this newer treatment modality. figure 1. acute central serous chorioretinopathy with asymptomatic involvement of the contralateral eye 32 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; figure 2. acute central serous chorioretinopathy in two cases, with increased and normal choroidal thickness in our study, out of 140 cases (70 in each group), 41.43%(n=29) in group-a and 40%(n=28) in groupb were between 20-35 years of age whereas 58.57%(n=41) in group-a and 60%(n=42) in groupb were between 36-50 years of age, mean+sd was calculated as 38.77+7.74 in group-a and 39.14+7.97 years in group-b, 65.71%(n=46) in group-a and 613.43%(n=43) in group-b were male while 34.29%(n=24) in group-a and 38.57%(n=27) in group-b were females. comparison of efficacy of oral rifampicin in terms of drying of macula with observation alone in patients of acute central serous chorioretinopathy shows that 18.57%(n=13) in group-a and 41.43%(n=29) in group-b had efficacy whereas 81.43%(n=57) in group-a and 58.57%(n=41) in group-b had no findings of efficacy, p value was 0.03 showing a significant difference. we compared our results with a study published in iranian journal of ophthalmology evaluated therapeutic effects of rifampicin in acute central serous chorioretinopathy. results showed significant drying of macula in treatment group than control group. macula was dried in 45.5% of treatment group and 24.9% control group.8 our findings are in agreement with the above study. zac b. ravage and others80 evaluated the efficacy of oral rifampin for the treatment of csc. they recorded that the follow-up was 8 weeks for two patients and 12 weeks for three patients. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 33 one patient self-discontinued rifampin after 3 weeks of treatment. one patient developed choroidal neovascularization after 2 months, treated with iva and excluded from further analysis. reported side effects of treatment include headache in 1 patient and nausea in 1 patient. mean change in central macular thickness (cmt) from baseline oct was -99 (sd±167) µm at week 1, -102 (sd±215) µm at week 8 and -93 (sd±91) µm at week 12. change in cmt for each patient was -440, -217, -64, 1 and 118 µm. 3 patients gained 0 lines of vision, 2 patients gained ≥ 3 lines of vision. they concluded that rifampin may be of potential benefit to patients with csc. acute cases appear to respond most favorably. sub-retinal fluid may decrease with treatment, while sub-rpe fluid often persists. these early findings suggest a novel method for the treatment of chronic csc and warrants further study. the findings of our study confirms the efficacy of rifampicin and opens the doors for this newer treatment modality which would speed and recovery with high response rate, conclusion we concluded that there is a significant difference in efficacy in terms of drying of macula in acute central serous chorioretinopathy with rifampicin versus observation alone. references 1. fruschelli m, denaro r, esposti g, frezzotti p, torchia r, esposti pl. new diagnostic and therapeutic strategies in acute and chronic central serous chorioretinopathy. acta ophthalmologica 2013;91(252):0. 2. liew g, franzco gq, franzco mg, franzco sf. central serous chorioretinopathy: a review of epidemiology and pathophysiology. clinical & experimental ophthalmology 2012;41:201-4. 3. tsai d, chen s, huang c, chou p, chung c, huang p. epidemiology of idiopathic central serous chorioretinopathy in taiwan 2001-2006: a population-based study; 2013;8:e66858. 4. elias a, goplakrishnan m, nair d, bhatt s, gudapati r, annantharaman g. a 10 year study of central serous chorioretinopathy: recurrence rate and factors affecting recurrence. wjorv 2011;1:69-74. 5. daruich a. central serous chorioretinopathy: recent findings and new physiopathology hypothesis.[accessed on june 21, 2015] 6. howard f, michael d, seenu m. current concepts in managing central serous chorioretinopathy. osli 2014;45:9-13. 7. pitcher jd, cscr: diagnosis and treatment. [accessed on june 21, 2015] 8. sabouri mr, kazemnezhad e. evaluation of therapeutic effect of rifampicin for acute central serous chorioretinopathy. iranian journal of ophthalmology 2014;26:102-7. 9. lehmann m, wolff b, vasseur v, martinet v, manasseh n, sahel ja, mauget-faÿsse m. retinal and choroidal changes observed with “en face” enhanced-depth imaging oct in central serous chorioretinopathy br. j. ophthalmol., 1997;97:1181–6. 10. kitzmann as, pulido js, diehl nn, hodge do, burke jp. the incidence of central serous chorioretinopathy in olmsted county, minnesota, 1980-2002. ophthalmology. 2008;115(1):169-73. 11. liew g, quin g, gillies m, fraser-bell s. central serous chorioretinopathy: a review of epidemiology and pathophysiology. clin experiment ophthalmol. 2012 jul 12. 12. tewari hk, gadia r, kumar d, venkatesh p, garg sp. sympathetic-parasympathetic activity and reactivity in central serous chorioretinopathy: a case-control study. invest ophthalmol vis sci. 2006;47(8):3474-8. 34 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 3; 1; 13. carvalho-recchia ca, yannuzzi la, negrao s. corticosteroids and central serous chorioretinopathy. ophthalmology. 2002;109(10):1834-7. 14. cotticelli l, borrelli m, d'alessio ac. central serous chorioretinopathy and helicobacter pylori. eur j ophthalmol. 2006;16(2):274-8. 15. prunte c, flammer j. choroidal capillary and venous congestion in central serous chorioretinopathy. am j ophthalmol 1996;11:26–34. 16. spitznas m. pathogenesis of central serous retinopathy: a new working hypothesis. graefe’s arch clin exp ophthalmol 1986;224:321–24. 17. yannuzzi la. type-a behaviour and central serous chorioretinopathy. retina 1987;7:111–30. 18. mansuetta cc, mason jo, swanner j, feist rm, white mf, thomley ml, mcgwin g, emond tl. an association between central serous chorioretinopathy and gastroesophageal reflux disease am. j. ophthalmol., 2004;137:1096– 1100 19. wu zh, lai ry, yip yw, et al. improvement in multifocal electroretinography after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy: a randomized placebo-controlled trial. retina. 2011;31: 13781386. 20. steinle nc, gupta n, yuan a, singh rp. oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. br j ophthalmol. 2012;96(1):10–13. 21. nelson j, saggau dd, nielsen js. rifampin induced hepatotoxicity during treatment for chronic central serous chorioretinopathy. retin cases br rep. 2014;8(1):70–72. 22. ravage zb, packo kh. rifampin for treatment of central serous chorioretinopathy. investigative ophthalmology & visual science 2011;52:2137. 48 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; international journal of retina (ijretina) 2020, volume 3, number 2. p-issn. 2614-8684, e-issn.2614-8536 sequential applied benzalkonium chloride and insulin eye drops reduces ocular central macular thickness and improves vision of diabetics and non-diabetics herman c.i. themen1, jerry r. toelsie2, jerrel c. pawiroredjo1, dinesh jiawan1, robbert bipat2 1 suriname eye center, academic hospital of paramaribo and department of ophthalmology, faculty of medical science, anton de kom university of suriname 2 department of physiology, faculty of medical science, anton de kom university of suriname abstract introduction: macular edema is a rather disabling condition that can be the consequence of several disorders of the eye. most of the time it occurs in patients suffering from diabetic retinopathy. the exact pathophysiological mechanism of this condition is not clear, but it is probably the result of inflammatory processes or structural and mechanical disturbances of the vitreomacular tissue. due to this obscure pathophysiological mechanism, a targeted efficient treatment is still lacking. however, accumulating evidence is suggesting that local application of insulin might reduce the structural and functional defects of this disorder. the aim of this study is to assess the effects of sequential applied benzalkonium chloride and insulin eye drops on the visual acuity and central macular thickness of eyes suffering from macular edema. methods: patients refractive to or refusing treatment with anti-vegf agents were selected. their visual acuity and central macular thickness were measured immediately before and until six months after treatment. the treatment consisted of twice a day application of specially prepared benzalkonium chloride and insulin eye drops. results are expressed as mean ± sd. the procedures followed were all in line with the guides for ethics of the hospital and were not in conflict with the declaration of helsinki. result: after six months, the mean visual acuity increased significantly from 0.28±0.17 to 0.53±0.27 (p = 0.002) and the central macular thickness decreased from 393±122 µm to 250±72 µm (p = 0.0005). conclusion: sequential applied benzalkonium chloride and insulin eye drops improve visual acuity and reduce central macular thickness in eyes suffering from macular edema. large scale studies to confirm and to elucidate the exact mechanism of action are necessary. apart from this, the use of these drops may prove to be a cheaper and more efficient method to treat the rather disabling condition. keywords: macular edema, insulin, visual acuity, central macular thickness cite this article: themen, herman c.i. et al. sequential applied benzalkonium chloride and insulin eye drops reduces ocular central macular thickness and improves vision of diabetics and non-diabetics. international journal of retina, [s.l.], v. 3, n. 2, sep. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/105 introduction *correspondence to: herman c.i. themen, suriname eye care center hcithemen48@gmail.com macular edema is a consequence of a number of ocular diseases which include, but is not limited to diabetic retinopathy, retinal vascular occlusions, postsurgical conditions, and uveitic diseases.1 the main pathophysiologic mechanism is an accumulation of fluid in the various layers of the central retina.2 the disabling disorder allegedly starts with a disturbance in the bloodretinal-barrier and is probably the result of inflammatory processes, surgical and nonsurgical vitreomacular structural and published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 49 and mechanical disturbances frequently accompanied by visible macular adhesion of posterior hyaloid, and an increase in capillary permeability3–5. this rather complex pathophysiologic mechanism makes it difficult to treat the disorder. current therapeutic strategies include primarily the application of non-steroidal anti-inflammatory eye drops, corticosteroids and inhibitors of carbonic anhydrase especially in patients with diabetes6,7. in refractory cases photo-coagulation of retinal tissues and intra-vitreal injection of agents like crystalline steroids, vegf antagonists, ocriplasmin with or without cannulation of occluded retinal vein and surgical vitreoretinal release of traction are applied. apart from the maintenance of a well-controlled blood glucose level being the main approach up till now, the last mentioned options are all invasive measures that may accompany a range of collateral tissue damage, which may lead to a significant formation of scar in healthy retinal tissues6–9. in addition frequent anti-vegf injections may block the physiologic actions of vegfa on normal neural and retinal cells and thus prevent adequate functional wound healing and visual function in time10,11. finally, intra-vitreal crystalline steroid harbors the potential to damage the optic nerve through steroid-induced glaucoma if not treated adequately.12 consequently, the search for a less invasive, safe and overall long-term effective drug strategy with the main goal of preservation and maintenance of adequate central vision is ongoing13,14. local application of insulin to the eye and skin of both animals as well as humans showed healing of corneal epithelial defects and skin wounds in both diabetics and non-diabetics 15–17. moreover, sequentially applied surfactant and insulin eye drops were currently tested in animals and humans for systemic regulation of blood glucose.18,19a decrease of insulin receptors and glucose transporters in ocular tissue of diabetics20,21, might hint towards a chronic local ocular insulin deprivation, perhaps even before the development of systemic diabetes mellitus. these reasons justify the evaluation of early started insulin eye drops sequentially applied after a surfactant to address the affliction of the blood-retinal barriers in the pigment epithelium and retina in macular edema. since the effect of insulin eye drops in humans on macular edema has not yet been evaluated, we aimed to evaluate the effects of insulin eye drops sequentially applied after a surfactant (0.01% benzalkonium chloride eye drops) on macular edema found in patients with ocular disorders in this study. methods patient selection patients were selected from subjects reporting at the department of ophthalmology of the academic hospital of paramaribo in suriname in the period of january 2016 until august 2016. they had been diagnosed with macular edema. a number of 30 patients initially reported with macular edema with or without macular hole on oct. out of this group, only patients who had been treated previously with anti vegf (bevacizumab) and had shown no long term regression of the edema and patients who had refused treatment with anti vegf were selected. a number of 15 patients met these criteria. six patients refused to participate in the study mostly because they had minimal macula edema and still a good visual acuity. the remaining 9 patients participated with 12 eyes suffering from macular edema of which 4 also had a macular hole. one subject was refractory to intra-vitreal anti-vegf, in both eyes. the remaining 8 subjects had no intra-vitreal antivegf, retinal laser, pharmacological vitreolysis or cannulation of occluded retinal vein or surgical release of vitreo-macular traction immediately before or during the study. seven of these were diabetics, while the remaining two did not suffer from this metabolic disorder. of all 9 subjects 7 had diabetes and 2 were nondiabetic. all patients were informed that they could withdraw at any moment from the study without consequences. procedure the ophthalmologist meticulously informed the participants about the procedures, possible adverse effects and outcomes and supplied them with all necessary data before receiving their oral and written consent to participate in this study. the departments of ophthalmology and the emergency room of the hospital were available for 24/7 in case of emergency and unexpected adverse effects until three months after completion of the study. all procedures were in line with the hospital’s policy on ethics and 50 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; complied with the declaration of helsinki. the board of executives of the faculty of medicine of the university gave approval for publication of the results. immediately before the treatment was started, visual acuity and central macular thickness were classically determined with the snellen eye chart and optical coherence tomography (zeiss cirrus hd oct model 5000) respectively. this was considered as the pretreatment baseline value. patients regularly received supplies of benzalkonium chloride 0.01% and mixtard insulin (novolin 70/30, 100 iu/ml) eye drops for at least three months. these had been prepared by the hospital pharmacist. in brief the insulin was transferred from the flacons to a dropper bottle under sterile conditions in a laminar flow hood. under the same conditions benzalkonium chloride was diluted from the available stock to the appropriate concentration and then titrated into a dropper bottle. the benzalkonium and insulin were both sequentially applied with a gap of 30 minutes twice a day to the affected eyes. participants were monitored for a period of up to one year. visual acuity and central macular thickness were assessed every month during the treatment. three of the subjects in this study had binocular macular edema of which in the first month the most affected eye was treated. they asked to treat the second eye accordingly in the second month. statistics obtained raw data were processed with graphpad prism 8.4.2. data of individual eyes are graphically presented. for the pretreatment and treatment, the best visual acuity and the thinnest central macular thickness were registered. because of the small sample size, wilcoxon matched-pairs signed rank test was used to assess the difference. when p<0.05, they were considered significantly different. the power of the studies was calculated with an on-line tool (http://onlinestatbook.com/2/calculators/power_calc.ht ml) and was 0.77 for the visual acuity and 0.95 for the central macular thickness. results figure 1. optical coherence tomography of the macular area of representative patient with diabetes. a decrease of central macular thickness was observed after treatment of both eyes. http://onlinestatbook.com/2/calculators/power_calc.html http://onlinestatbook.com/2/calculators/power_calc.html published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 51 figure 1 shows a scan of the retina before and after treatment. figure 2 presents the maximum obtained visual acuity within 6 months after treatment was started. the mean visual acuity increased significantly from 0.28±0.17 to 0.53±0.27 (p = 0.002). figure 3 presents the smallest thickness of central macula that had been obtained in the same period. the mean central macular thickness decreased from 393±122 µm to 250±72 µm (p = 0.0005). thus, a clear improvement of both visual acuity and central macular thickness in the post-treatment period were observed. figure 2. visual acuity of individual eyes before and after treatment with insulin. *p = 0.001 vs pretreatment figure 3. minimum thickness of central macula area before and after treatment with insulin. *p = 0.0001 vs pretreatment 52 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; figure 4: optical coherence tomography of binocular macular edema in a patient with a defect (arrow) in the central macula of the right eye. there is a clear reduction of thickness after treatment in both eyes, however, the visual acuity of the rig ht eye did not improve significantly. figure 4 shows a scan of a patient with macular edema of both eyes and a clear defect in the central macula of the right eye. this is one of the four eyes with macular holes showing a significant decrease of macular thickness, however without significant improvement of visual acuity. for this reason, in this small number of cases, the mean improvement of macular thickness was allegedly better than the observed improvement of visual acuity. however, in the 8 remaining eyes without macular hole, the main visual acuity was better than the main edema reduction in all 12 eyes. figure 5 is a representative scan of a non-diabetic with macular edema before and after treatment with the insulin. figure 5: optical coherence tomography of a non-diabetic patient with macular edema in the left eye before and after treatment, also showing improvement of the central macular thickness. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 53 discussion this study shows that sequentially applied surfactant and insulin eye drops reduces central retinal thickness and improves visual acuity in eyes of patients suffering from macular edema. this observation is peculiar, since systemic insulin probably does not affect glucose metabolism of retinal nerve tissue directly.22,23 therefore, the effects observed in this study can be the result of other local actions of this hormone. for instance, it has been shown that the function of sodium potassium atpase in the retinal tissue is reduced in eyes of diabetic animals and might be one of the pathophysiologic mechanism leading to macular edema.24,25 insulin stimulates the action of the abovementioned ion-pump in murine corneal endothelial cells.26 the resulting volume reduction with stimulation of this ion pump can explain a reduction in retinal thickness and hence an improved visual acuity. another study showed that insulin stabilizes the microvascular endothelial barrier.27 since disruption of the blood retinal barrier plays a role in the development of macular edema28, this action of insulin may contribute to the reduction of macular thickness and improvement of visual acuity. conclusion an additional mechanism could also be the stimulation of glucose uptake by the surrounding tissue near the external blood retinal barrier or pigment epithelium. the resultant reduction of glucose in the retinal tissue cells will lead to a reduced cell volume through osmotic processes.23 finally, as mentioned before, insulin inactivates the endothelial contractile machinery and enhances cell celladhesions in rat coronary microvascular endothelial monolayers.27 regardless of the abovementioned mechanisms, this study shows both a reduction of macular thickness and improvement of visual acuity. whatever the mechanism, the observations in this study warrant further investigation in large scale preclinical and clinical studies and eventually may lead to an alternative, less invasive early started therapeutic strategy, not only for macular edema but also in diabetics as a preventive strategy for drp, in an effort to treat the metabolic pathway upstream, next to downstream consequences. references 1. scholl s, augustin a, loewenstein a, et al. general pathophysiology of macular edema. european journal of ophthalmology 2011; 21 suppl 6:s10-9. 2. scholl s, kirchhof j, augustin aj. pathophysiology of macular edema. ophthalmologica 2010; 224:8–15. 3. das a, mcguire pg, rangasamy s. diabetic macular edema: pathophysiology and novel therapeutic targets. ophthalmology 2015; 122:1375–94. 4. romero-aroca p, baget-bernaldiz m, pareja-rios a, et al. diabetic macular edema pathophysiology: vasogenic versus inflammatory. journal of diabetes research 2016:1–17. 5. kaiser pk, riemann cd, sears je, et al. macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction. american journal of ophthalmology 2001; 131:44–9. 6. kessel l, tendal b, jørgensen kj, et al. post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops. ophthalmology 2014; 121:1915–1924. 7. wolfensberger tj. (1999) the role of carbonic anhydrase inhibitors in the management of macular edema. kluwer academic publishers. 8. schatz h, madeira d, mcdonald hr, et al. progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. archives of ophthalmology (chicago, ill. : 1960) 1991; 109:1549–51. 9. maeshima k, utsugi-sutoh n, otani t, et al. progressive enlargement of scattered photocoagulation scars in diabetic retinopathy. retina (philadelphia, pa.) 2004; 24:507–11. 10. nishijima k, ng ys, zhong l, et al. vascular endothelial growth factor-a is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. american journal of pathology 2007; 171:53–67. 11. galiano rd, tepper om, pelo cr, et al. topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting 54 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; bone marrow-derived cells. the american journal of pathology 2004; 164:1935–1947. 12. phulke s, kaushik s, kaur s, et al. steroid-induced glaucoma: an avoidable irreversible blindness. journal of current glaucoma practice 2017; 11:67–72. 13. gaudana r, ananthula hk, parenky a, et al. ocular drug delivery. the aaps journal 2010; 12:348–60. 14. abcouwer sf, gardner tw. diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. annals of the new york academy of sciences 2014; 1311:174–90. 15. bastion mlc, ling kp. topical insulin for healing of diabetic epithelial defects?: a retrospective review of corneal debridement during vitreoretinal surgery in malaysian patients. the medical journal of malaysia 2013; 68:208–16. 16. xuan b, mcclellan da, moore r, et al. alternative delivery of insulin via eye drops. diabetes technology & therapeutics 2005; 7:695–698. 17. wang al, weinlander e, metcalf bm, et al. use of topical insulin to treat refractory neurotrophic corneal ulcers. cornea 2017; 36:1426–1428. 18. liu sx, chiou gc. feasibility of insulin eyedrops for human use. journal of ocular pharmacology 1994; 10:587–90. 19. pillion dj, wang p, yorks j, et al. systemic absorption of insulin and glucagon applied topically to the eyes of rats and a diabetic dog. journal of ocular pharmacology and therapeutics 1995; 11:283– 295. 20. naeser p. insulin receptors in human ocular tissues. immunohistochemical demonstration in normal and diabetic eyes. upsala journal of medical sciences 1997; 102:35–40. 21. kumagai ak, glasgow bj, pardridge wm. glut1 glucose transporter expression in the diabetic and nondiabetic human eye. investigative ophthalmology & visual science 1994; 35:2887–94. 22. fort pe, losiewicz mk, reiter cen, et al. differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance. lo acy, ed. plos one 2011; 6:e26498. 23. de moraes g, layton cj. therapeutic targeting of diabetic retinal neuropathy as a strategy in preventing diabetic retinopathy. clinical & experimental ophthalmology 2016; 44:838–852. 24. macgregor lc, matschinsky fm. altered retinal metabolism in diabetes. ii. measurement of sodiumpotassium atpase and total sodium and potassium in individual retinal layers. the journal of biological chemistry 1986; 261:4052–8. 25. ottlecz a, garcia ca, eichberg j, et al. alterations in retinal na+, k+-atpase in diabetes: streptozotocininduced and zucker diabetic fatty rats. current eye research 1993; 12:1111–1121. 26. hatou s, yamada m, akune y, et al. role of insulin in regulation of na+-/k+-dependent atpase activity and pump function in corneal endothelial cells. investigative ophthalmology and visual science 2010; 51:3935–3942. 27. gündüz d, thom j, hussain i, et al. insulin stabilizes microvascular endothelial barrier function via phosphatidylinositol 3-kinase/akt-mediated rac1 activation. arteriosclerosis, thrombosis, and vascular biology 2010; 30:1237–1245. 28. shin es, sorenson cm, sheibani n. diabetes and retinal vascular dysfunction. journal of ophthalmic & vision research 2014; 9:362–73. this work licensed under creative commons attribution published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; 80 international journal of retina (ijretina) 2019, volume 2, number 2. p-issn. 2614-8684, e-issn.2614-8536 challenges in cytomegalovirus (cmv) retinitis management denisa rosati1, sauli ari widjaja1,2, ima yustiarini1,2, randi montana1,3, wimbo sasono1,2, muhammad firmansjah1,2, ady dwi prakosa1,2, moestidjab1,2, gatut suhendro1,2 1 department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia 2 vitreoretinal division, department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia 3 infection immunology division, department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia abstract introduction: hiv infection can manifest in a variety of ways in and around the eyes and it is most commonly due to retinal microvasculopathy, neoplasm and also opportunistic infection. those usually occur associated with a significantly reduced cd4 t-cell counts. in this era of highly active anti retroviral therapy (haart) has caused a major decreasing of the ocular involvement prevalence itself. case report: a 31 year-old-male came with blurred vision on the right eye, which has started 3 years ago and slowly worsened. central scotoma also presented previously. patient was an hiv-aids, that placed him on haart. cd4+ t-lymphocyte count was 3 cells/mm3. the initial visual acuity was light perception and fundus examination showed roth spots, massive exudates and hemorrhages covering the optic disc and decreased foveal reflex. laboratory examination revealed positive rubella and anti-cmv immunoglobuling (igg). he also suffered from lung tuberculosis and took tuberculosis medication regularly. patient was diagnosed with cytomegalovirus (cmv) retinitis based on history of illness, fundus examination as well as laboratory testing and given oral induction valganciclovir 900 mg once daily for 3 weeks followed by maintenance dosage. result: after valganciclovir induction, there was significant changes with decreased peripapillary exudates, hemorrhages and vasculitis, but the optic disc appeared pale. the patient also had bicytopenia due to valganciclovir therapy that complicate his condition and passed away after 3 months follow up. conclusion: cmv retinitis is reported to occur in patient with extreme cd4 count usually less than 50 cells/mm3. the sooner of proper treatment would likely following better outcome. making diagnosis of immunosuppresed patient with ocular manifestations was challenging so that comprehensive eye examination in hiv-infected individuals should be conducted. oral valganciclovir could give satisfactory response to decrease the progression of retinitis but risk of blindness may still occur. keywords: cytomegalovirus, cmv retinitis, valganciclovir, hiv-aids, cd4+ t-lymphocyte cite this article: rosati, denisa. challenges in cytomegalovirus (cmv) retinitis management. international journal of retina, [s.l.], v. 2, n. 2, sep. 2019. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/91 https://doi.org/10.35479/ijretina.2019.vol002.iss002.91 introduction *correspondence to: denisa rosati department of ophthalmology, faculty of medicine universitas airlangga, dr. soetomo general academic hospital surabaya, indonesia denisarosati88@gmail.com human immunodeficiency virus (hiv) remains a major public health problem with 56,000 new hiv infections per year in the united states.1 in indonesia, hiv/aids reported case was 3,679 in 2016.2 it is estimated that about 70 to 80% of adult hiv/aids patients will experience ocular complication during their illness.3 the majority of ocular involvement in hiv is hiv retinopathy and cytomegalovirus (cmv) retinitis. hiv retinopathy is a non-infectious microvascular disorder characterized by cotton wool spots, microaneurysms, retinal hemorrhages, roth spots and telangiectatic vascular changes.4 https://www.ijretina.com/index.php/ijretina/article/view/91 https://doi.org/10.35479/ijretina.2019.vol002.iss002.91 81 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; the most common manifestation of this disorder is cotton wool spots. unlike infective lesion, cotton wool spot in hiv retinopathy are transient, not visually threatening and tend to disappear within 6-12 weeks.5 retinal hemorrhages are seen less frequently in approximately 30% of patients with advanced hiv/aids.6 it may appear as flame-shaped areas when they affect the nerve fiber layer and as dot-and-blot patterns when they affect the deeper layers of the retina.7 it can be differentiated from cmv retinitis by the presence of fewer hemorrhages and the absence of subtle iritis or vitritis. cmv retinitis is the most common ocular opportunistic infection that potentially blinding of patients with hivaids. this disease occurred in up to one-third of hivinfected patients before the invention of highly active anti retroviral therapy (haart) and significantly associated with cd4+ t-lymphocyte cell count <50 cells/mm3.8,9 the incidence of cmv retinitis in the post-haart era is estimated to be at most 5.6 cases/100 persons/year.10 cmv retinitis is characterized by typical white, crumbly areas of retinal necrosis and hemorrhage which is sight threatening if originate in posterior pole. cotton wool spot is an early manifestation of cmv retinitis.9 the lesions tend to enlarge and coalesce over time, forming large, wedge-shaped areas of involvement.11 the clinical forms of cmv retinitis divided as typical form which appear as white spots with many hemorrhages, atypical form which appear as a zone of thinned retina and small dot infiltrate without hemorrhages, perivascular form or “frosted branch angiitis” and optic neuropathy which has the worst prognosis.12 patient with vision disturbance may have irreversible vision loss because of direct damage to the macula and optic nerve, retinal detachment even after cmv retinitis has resolved and immune recovery uveitis.13 cmv retinitis can be treated with ganciclovir or foscarnet, administered systemically or intravitreally.14 another drug of choice is valganciclovir, an orally administered monovalyl ester prodrug of ganciclovir. induction therapy typically 900 mg once daily for 2-3 weeks followed by maintenance therapy 450 mg once daily.10 case report a 31-year-old man referred to the outpatient clinic with painless visual loss on the right eye since three years ago, started with black dot in the center of his vision, that slowly worsening by time. patient had been diagnosed with hiv since 4 years and treated with highly active anti retroviral therapy (haart) such as emtricitabine/tenofovir and lopinavir/ritonavir. this patient also suffered from lung tuberculosis and had taken anti-tuberculosis fixed-dose combinations (fdcs) for five months. discrete painless papulo-nodular lesions found over face and neck, assessed as pruritic papular eruption and molluscum contagiosum (figure 1). figure 1. discrete papulonodular lesions (pruritic papular eruption and moluscum contagiosum) the visual acuity was light perception on the right eye with mid-dilated pupil, and relative afferent pupillary defect (rapd) was present at presentation. there was no inflammatory sign on anterior segment. funduscopy examination revealed massive soft exudates and hemorrhages in posterior pole covering the optic disc, roth’s spot, necrotic lesion due to vasculitis and also reduced foveal reflex (figure 2). the left eye was within normal limit. laboratory test showed low cd4 count of 3 cells/mm3, anemia 8.5 g/dl, positive igg rubella and anticmv. chest x-ray revealed infiltrates with suspicious of lung tuberculosis. figure 2. fundus photograph both eyes before oral valganciclovir therapy. right eye showed massive soft exudates and hemorrhages in posterior pole the patient was diagnosed with cytomegalovirus (cmv) retinitis and treated with oral valganciclovir, 900 mg once daily for 3 weeks induction therapy and followed by 450 mg once daily for maintenance therapy. funduscopy examination was done at the end of induction therapy, showed significant changes with decreased peripapillary exudates, hemorrhages and vasculitis, but the optic disc appeared pale (figure 3). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; 82 optical coherence tomography (oct) examination showed macular thickening, intraretinal and subretinal fluid (figure 4). shortly after the end of induction therapy, patient was admitted at department of internal medicine ward due to chronic diarrhea and bicytopenia. hemoglobin decreased to 6.5 g/dl and white blood cells (wbc) count was 1.430. he had to get prc transfusion and at that time, considering his weak condition, internal medicine department suggested to postpone valganciclovir maintenance therapy since it appeared to be the underlying cause of his bicytopenia. during hospitalized, visual acuity decreased to no light perception. figure 3. fundus photograph both eyes after oral valganciclovir induction therapy. right eye showed significant decreasing of exudates and hemorrhages figure 4. macular oct both eyes before valganciclovir induction therapy (4a) and after valganciclovir induction therapy (4b) one week after, valganciclovir maintenance therapy was continued. during one week follow up, there was no changes in visual acuity, funduscopy showed a pale optic disc, necrotic lesion and decreased exudates with minimal hemorrhages. patient passed away after 3 months evaluation with remained ocular condition. discussion hiv/aids is undoubtedly a multi systemic disease and ocular involvement occurs in up to 70% of cases during the natural history of infection. ocular manifestations of hivassociated spectrum are very broad and extend from a simple blepharitis to blindness.12 the two most common posterior segment ocular manifestations of hiv/aids are hiv retinopathy and cytomegalovirus (cmv) retinitis. in this case, the patient complained of gradually painless visual loss with central scotoma and also massive exudates and hemorrhages on funduscopy. hiv retinopathy itself is an occlusive microangiopathy,15 which presents as cotton wool spots, microaneurysms and retinal hemorrhages. however, cotton wool spot associated with hiv retinopathy are usually superficial, smaller lesions that resolve within few months.16 patients with hiv retinopathy rarely have immediate vision loss but there may be damage to the retinal nerve fiber layer, decrease colour vision and also visual field defect.17 on the other hand, cmv lesions tend to enlarge and coalesce over time to form larger areas of involvement. some individuals may complain of blurred vision, scotomas, flashlights or floaters. however, approximately 15% of infected patients are often asymptomatic despite the presence of extensive or vision threatening cmv retinitis.18 cmv retinitis is the most common cause of blindness in patient with hiv-aids. the location of infected retina, determine the risk for vision loss. posterior retinitis threatens the macula and optic nerve and anterior retina increases the risk of retinal detachment.15 in this case, the infected retina was posteriorly, which include macula and optic nerve. hence, the risk of vision threatening was greater. the patient also developed permanent and irreversible visual impairment. laboratory tests showed a severe decline of cd4+ cell count to only 3 cells/μl. cd4+ cell count of less than 50 cells/μl of patient with hiv/aids is a major risk factor for having active cmv retinitis infection.(19,20) data from the longitudinal study of the ocular complications of aids (lsoca) showed that 90% patients with cmv retinitis had a recent cd4+ cell count of <50 cells/μl and 85% was using anti retroviral therapy (art) prior to cmv diagnosis.21 conducting routine ophthalmology examinations especially funduscopy on patients presenting for art initiation with advanced disease is very important.21,22 before haart, treatment of cmv retinitis was a lifelong treatment with specific anti cmv therapy that likely to relapsing of retinitis after two until three weeks of discontinuation.23 4a 4b 83 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 2; in this haart era, immune function that is improved by haart make the cessation of all anti-cmv therapy without reactivation of cmv retinitis possible.24 despite such reports, anti-cmv chemotherapies are still involved especially ganciclovir, foscarnet and cidofovir.25,30 in this case, patient was given oral valganciclovir as induction and maintenance therapy. it was the only drug of choice that was available in our center. historically, the most utilized antiviral agent has been intravenous ganciclovir. in an attempt to make an oral preparation with convenient dosing that has the safety profile, efficacy and bioavailability comparable to ganciclovir, the prodrug was developed.26 a randomized control trial study in 2002 showed that valganciclovir, the valine ester of ganciclovir, was found to be as effective as intravenous ganciclovir in more convenient way. in this study, the participants were given oral valganciclovir 900 mg twice daily as induction therapy and the remaining received intravenous ganciclovir 5 mg/kg for three weeks.27 the main adverse effects of both drugs were diarrhea (30%), neutropenia and anemia (20%).28 this patient also had been admitted to internal medicine ward due to chronic diarrhea and bicytopenia. so that, patient on oral valganciclovir therapy must undergo complete both ophthalmic and systemic evaluations periodically. depending the medication used, complete blood count, chemistries and intraocular pressure must be checked. also dilated eye examinations should be performed daily to weekly initially, then 2 weeks after induction therapy. patients should be undergone cd4 counts and viral load studies. as well. the other reliable treatment for cmv retinitis is intraocular sustained release ganciclovir implants, which have been very effective in treating cmv retinitis but it is not readily available.29 in cmv retinitis management, it is often hard to choose the best therapy for the patient considering the side effects. oral valgancyclovir has been a favourite because it doesn’t need iv administration and hospitalization. on the other hand, the cost of the drug is very high, longterm therapy needs strictly good compliance and it causes some toxicities that worsen the condition of immunosuppresed patient. in a point that the patient get remarkable decrease of myelosuppression, sometimes we need to postpone therapy. consequences, the infection might relapse or remain. it should be avoided if hemoglobin is <8 g%, absolute neutrophil count is less than 500 cells/l, and the platelet count is less than 25,000/l.30 in this case, we needed to postpone valganciclovir maintenance therapy due to bicytopenia. delay of therapy administration bothered the evaluation of medication result. patient’s visual acuity did not improve after 3 weeks maintenance therapy. besides, patient got sight-threatening lesions that close to the macula and optic nerve head. the choice of therapy of this condition is injection of 2 mg gancyclovir or 2.4 mg foscarnet. those medications were not available in our center. on the follow up examination after valganciclovir induction therapy, fundus evaluation showed a remarkable changes. exudates and hemorrhages were significantly decreased and the optic disc was easier to evaluate. a pale disc with sclerotic vascularities appeared and his visual acuity was no light perception. as optic atrophy had already set in the vision did not improve even though the chorioretinitis patches had resolved.31 visual loss adds to the overwhelming social and economic burden not only for the patient and family itself but also society. we support routine funduscopic examination that has to be included in the standard who care package for hiv-infected patients with advanced disease.32 conclusion ocular involvement in hiv/aids infected patients is very common with broad spectrum of manifestations including non infectious, infectious and neoplasm. cmv retinitis with involvement of posterior pole or owing retinal detachment is the major factor that causes blindness. as cmv retinitis still exists in the haart 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5; 1; international journal of retina (ijretina) 2022, volume 5, number 1 p-issn. 2614-8684, e-issn.2614-8536 remarkable result towards retinopathy associated autoimmune hemolytic anemia rofa husnul khuluqi1, nadia artha dewi1, susanto nugroho2, lely retno wulandari1 1 department of ophthalmology, universitas brawijaya, dr. saiful anwar general hospital, malang, east java, indonesia 2department of pediatrics, universitas brawijaya, dr. saiful anwar general hospital, malang, east java, indonesia abstract introduction: to present the clinical findings of autoimmune hemolytic anemia (aiha) retinopathy and its rapid resolutions following treatment with steroid. case report: a 14-year-old female patient presented with decreased vision in the left eye. there was history of aiha. visual acuity was 1/60 in le and 6/6 in re. there was conjunctival pallor, and the other anterior segment were unremarkable. fundus examination of left eye revealed flame shaped and dot blot hemorrhage, roth’s spots, optic disc swelling, venous turtuosity, and elevated macula. there were afferent pupil defect, red green deficiency, and contrast sensitivity decline. hematological evaluation revealed anemia. a mri head and orbital examination were unremarkable. discussion: this patient was assessed with le anemic retinopathy due to aiha. the patient’s visual acuity improved as the retinopathy resolved after 1 month of oral steroid therapy. conclusion: anemia may play a role in the occurrence of retinopathy. the diagnosis of retinopathy can be made by linking ophthalmic fndings with positive serological test. accurate comprehensive examination can establish the systemic diagnosis, and control of systemic parameters will improve retinopathy, reverse vision loss, and avoid permanent blindness keywords: autoimmune hemolytic anemia, pediatric aiha, retinal hemorrhage cite this article: khuluqi, rofa husnul. remarkable result towards retinopathy associated autoimmune hemolytic anemia. international journal of retina, [s.l.], v. 5, n. 1, p. 53, feb. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/190>. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss001.190. correspondence to: rofa husnul khuluqi, department of ophthalmology, universitas brawijaya, indonesia rofakhuluqi@gmail.com introduction anemia is characterized by decrease level of hemoglobin in blood. autoimmune hemolytic anemia (aiha) is one type of anemia, which erythrocytes are attacked by the patient's own antibodies.1,2 etiology of autoimmune response is unknown, but it may include idiopathic, viral infections, autoimmune disease, blood malignancy, immune deficiency, bone marrow transplant, history of previous blood transfusion, and use of certain drugs.1,3 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 63 autoimmune hemolytic anemia is a rare etiology of hemolytic anemia in children with an incidence of approximately 0.2 – 0.4 per 100,000 people in the group of ages 11-20 years. despite of it’s etiology, anemia is accompanied by many ocular manifestations. pale conjunctiva is the most common ocular manifestation that found in 98% of cases, followed by retinopathy which occurred in 42% of cases and pallor of posterior pole in 39% case. 4.5 study by carraro et al revealed that anemia can causes retinopathy in 28% cases, and increase to 38% cases when there is coexisting thrombocytopenia.6 manifestations of anemic retinopathy may include retinal hemorrhage, whitecentered retinal hemorrhages (roth spots), subhyaloid and vitreous hemorrhages, venous and arteriolar turtuosity, cotton wool spots, macular stars and edema papil. increasing severity of anemia, directly proportional to increased risk of retinopathy, especially when level hemoglobin (hb) below 6 grams/ dl.3.7 the prevalence of anemic retinopathy is 83% of cases, among patients with severe anemia (<8gr/dl).3 here, we present a case of retinopathy in children which is related to aiha and it’s rapid resolution after anemia treatment. case presentation a 14-year-old girl was consulted to ophthalmology department by pediatrician in saiful anwar hospital with sudden painless blurred vision in her left eye for 3 days duration, during hospital admission for autoimmune hemolytic anemia. she also complained about dizziness and weakness, nausea and signs of bleeding in the other part of body. patient has been diagnosed with aiha since 1.5 years ago with previous positive coombs test. the patient received therapy from pediatric involved of intravenous methylprednisolone 35 mg three time a day, intravenous metamizole 500 mg three time a day and oral sucralfate 15 mg three time a day. ophthalmological examination revealed visual acuity of 6/6 in the right eye and 1/60 in the left eye. anterior segment examination revealed pallor on the conjunctiva of both eyes and positive rapd examination on left eye. other anterior segments examination and intraocular pressure measurement were unremarkable on both eyes. dilated fundus examination revealed segmental optic nerve head swelling, dot blot hemorrhages, flame-shaped hemorrhage and venous turtoisity, only in left eye. optic nerve function examination showed red green deficiency with ishihara plate in her left eye. amsler grid examination revealed metamorphopsia in central of left eye. optic nerve head and macular optical coherence tomography (oct) examination showed left intraretinal hyperreflection, retina and macular thinning, and peripapilary rnfl thickening, figure 1. (a) fundos photograph of the right eye compared to (b) left eye on first examination. right eye are normal findings, while the left eye revealed, segmental papilledema (pink arrow), venous turtoisity (green arrow), dot blot (black arrow) and flame shaped hemorrhage (blue arrow). 64 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; her hemoglobin level was markedly low (7.0 g/dl) but the leucocyte and platelet counts were normal. the peripheral blood smear revealed hypochromic microcytic anemia. the patient was treated with oral steroid provided by pediatrician. the patient had worsening symptoms 5 days after initial treatment. her left visual acuity was decrease to counting finger at half meter without new abnormal findings on her anterior segment. only left rapd was detected, while the other optic nerve function test such as isihara, amsler grid, contrast sensitivity and confrontation tests were dificult to assess due to poor visual accuity. posterior segment examination showed marked left optic disc swelling with dot blot hemorrhage, flame shaped hemorrhage, roth's spot, arteriovenous turtoisity, retinal edema and macular edema. optic nerve and macular oct examination of the left eye showed blurred disc margin and exudation in subretina respectively. the patient was consulted to the neuroophthalmologist (no) due to worsening left papilledema and then was suspected with left infiltrative optic neuropathy. patient were planned for head and orbita mri examination and complete blood count. steroid treatment with methylprednisolone 32 mg three time a day orally, was continued according to pediatrician’s advice. figure 2. optic nerve head oct (left) and macular oct (right) at first examination. there were intraretinal hyperreflective, retinal and macular thinning, and peripapillary thickening of the left eye. right eye showed normal findings. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 65 twenty days later (or 1 month after onset of symptoms) the patient reported subjective improvement in her symptoms. visual acuity of left eye has improved to 2/60. anterior segment examination showed normal findings, with relative afferent pupillary defect, decreased contrast sensitivity, and metamorphopsia of left eye. figure 3. funduscopic photo (a) of the right eye compared to (b) left eye at 5 day after initial treatment. the left eye revealed disc swelling (pink arrow), vein turtoisity (green arrow), dot blot hemorrhage (black arrow), flame shaped hemorrhage (blue arrow), roth's spot (yellow arrow), retinal edema and macular edema (white arrows). oct examination (c) showed left exudation of the macula and subretinal, and marked disc swelling. right eyes was unremarkable 66 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; other optic nerve function test of left eye, isihara and confrontation examination were unremarkable. dilated fundus examination revealed significant regression of optic nerve swelling and retinal hemorrhage, with minimally exudate surrounding macula. optic coherence tomography examination showed improvement of retinal thickening and macular thinning with the absent of subretinal hyporeflective. head & orbital mri and repeat blood test were done, and the result were normal (hb 12.4 g/dl). oral ethylprednidolone was tappered to 16 mg tid according to pediatrician’s advice, figure 4. funduscopic photo (a) of the right eye and (b) left eye at 20 days after progression of symptoms (or 1 months after initial symptoms). left eye showed regression of disc edema (pink arrow), exudate (white arrow), and complete resolution of arteriovenous turtoisity, flame shaped hemorhages, dot blots, roth's spots, and macular elevation. peripapillary and macular oct examination (c), also revealed improvement. right eye was unremarkable. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 67 at the 4 months and 6 months follow-up after onset of symptoms, the patient’s best corrected visual acuity of her left eye improved to 6/24, anterior and posterior segments were unremarkable, figure 5. examination at 4 month follow-up after onset of symptoms. fundus photograph of both eyes was normal (a) & (b), left macular oct (c) showed macular thinning, and humphrey visual field test (d) showed arcuate defect with central figure 6. examination at 6 month follow-up after onset of symptoms. fundus photograph of both eyes was normal (a) & (b), left macular oct (c) showed macular thinning, and humphrey visual field test (d) showed arcuate defect with central scotoma on the left eye 68 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; but the optic nerve function remains altered. there were relative afferent pupillary defect, red green deficiency, decreased contrast sensitivity, and metamorphopsia on central. humphrey visual field test revealed arcuate defect with central central scotoma. peripapillary oct examination showed normal results of both eyes , macular oct of left eye showed thinning of the macula. discussion anemia is a very common haematological disorder, which provides various ocular manifestations. research conducted by garg and argawal, pale conjunctiva is the most common ocular manifestation of anemia, seen in 100% of cases. retinal hemorrhage occupies second most common of ocular manifestation seen in 35% of cases. while the decrease of vision takes third order of ocular manifestation, seen in 29% of cases.8 study by satish s. et al, concluded that pale on conjunctiva is the most common finding and seen in all patients. flame shaped hemorrhage is second most common findings, seen in 37.50% of patients. posterior pole pallor is the third most common finding that seen in 31.25% of cases. other less common eye manifestations such as edema of eyelids, subconjunctiva bleeding, papilledema, macular star and cotton wool spot.9 sigh et al, on his study concluded that retinopathy only occurs in patients with severe anemia.7 retinal changes that common to all anemia include the findings of retinal haemorrhage (flame shape hemorrhage and dot blot hemorrhage), cotton wool spots, roth spots, retinal edema, hard exudate, change of blood vessels and optic nerve.7,10 decline of visual acuity can be rare in anemia because most cases are asymptoms. hemorrhage, edema, or hard exudate in macula can cause visual impairment. decreased visual acuity can also occur due to disc edema or optic neuropathy.10,11 incidence and severity of retinopathy is always proportional to severity of anemia. therefore, improvements of anemia will be followed by improvements of ocular manifestation.8,9,10 decrease of visual acuity in this patient occurs rapidly due to low hemoglobin level that causes bleeding on the retina, macular edema and hipoxaemia associated papilledema or microvascular insufficiency.12 this explains the findings on macular oct of the left eye, where the hypoxaemic area showed improvement of thickness and reflectivity in the inner retinal layer corresponds to improvement of retinal oedema. beside, increasing in contour is also seen in irregular macules due to edema caused by ischemia. hyperreflexivity in inner retinal layer causes optical shadowing signal of outer retinal layer and retinal pigment epithelium/choriocapillaris complex resembling retinal edema.13 funduscopic examination in this case show retinal changes in the form of general findings that can be occurs in all types of anemia including retinal hemorrhage, cotton wool spots, retinal edema, vascular changes and optic nerve changes. in this case, retinal hemorrhage occurs in the form of flame shaped hemorrhage, dot and blot hemorrhages and roth spots. bleeding that occurs in anemic retinopathy can appeared in the form of superficial bleeding i.e. flame shaped haemorrhage located in the nerve fiber layer of retina (retinal nerve fiber layer/ rnfl). the bleeding in some cases can appeared as dot and blot haemorrhage which located in the deeper retinal layer. rare form of bleeding are subhyaloid and vitreous bleeding. white centered retinal hemorrhages or roth spots are also not uncommon. white lesion in the middle of the roth spot can be caused by infiltration of inflammation, fibrin and platelets, neoplastic cells, or areas of ischemia.12 retinal haemorrhage and retinal edema in suspected anemia related with endothelium cell dysfunction originating from ischemia, reactive retinal vasodilation and improved flow dynamics associated retinal vasculature with hypoxemia.14 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 69 retinal hypoxia may causes increase in transmural pressure associated with hypoproteinemia and may causes microtrauma of blood vessels wall, and then causes macular retinal edema and bleeding on the retina.8 cotton wool spots are superficial white lesions that represent rnfl infarcts caused by anemic retinal hypoxia. retinal edema in anemic retinopathy is caused by hypoxemia which triggers an increase in retinal blood vessel flow dynamics and microtrauma on the vessel wall, thereby increasing transmural pressure and causing leakage. hard exudates occur as a result of retinal oedema that undergoes repair. if it is severe enough and is located in the macula, then a macular star will appear. vascular changes occurring in anemic retinopathy include turtuosity, weakness and pallor of arteries and veins. this finding is more pronounced as the severity of anemia increases. optic nerve changes may present as papilledema or as papillary atrophy at a later stage.10 in addition to anemic retinopathy, the patient also had ischemic optic neuropathy. in this case, the patient had persistent optic nerve dysfunction including dyschromatopsia, decreased contrast sensitivity, rapd, and arcuate visual field defect with central scotoma. this is consistent with optic nerve ischemia and macular disorders. in anterior ischemic optic neuropathy (aion), monocular vision loss may be painless, and may develop over hours to days. visual acuity may be reduced, but visual field defects are always present. visual field defects can vary in the form of altitudinal defects, arcuate defects, and other defects. relative afferent pupilary defect can be seen, unless optic nerve neuropathy occurs in both eyes. optic disc edema develops at onset and may precede visual disturbances.15 in addition to the hypertension, diabetes mellitus and nocturnal hypotension that have long been associated with aion, acute anemia has also been shown to be associated with the incidence of shockinduced ischemic optic neuropathy following massive gastrointestinal bleeding and major surgical procedures. anemia that contributes to the initiation of non-arteritic ischemic optic neuropathy through delayed organ hypoxia and/or microvascular insufficiency can lead to impaired axoplasmic outflow and subsequent disc oedema.12 neuroimaging using ct scan and mri is performed in cases of optic nerve swelling to rule out infiltrative optic neuropathy, intracranial masses or spaceoccupying lesions, including intraorbital lesions that can cause optic nerve head swelling.12 magnetic resonance imaging (mri) was performed in this patient and showed normal results, no intracranial mass was detected. other examination in anemic retinopathy are indicated only for treatment concideration. fluorescein angiography may show delayed arteriovenous transit time in the presence of venous occlusion. optical coherence tomography (oct) is useful in cases of vascular occlusion to demonstrate macular edema. because anemic retinopathy can be seen in oncology patients and in infectious endocarditis or autoimmune disease, a complete blood count with peripheral blood smear is mandatory. bone marrow biopsy may be indicated in myeloproliferative cases.12 other tests performed on these patients included macular and optic nerve head oct, blood tests, and mri of the head and orbits. examination of the macular and optic nerve head oct showed optic disc edema and macular edema which worsened at the second visit compared to the other visits. a study conducted by carraro et al., proved that anemia can cause retinopathy, especially when there is thrombocytopenia. this also proves that an increase in the severity of anemia and a decrease in platelet levels are associated with an increase in the severity of retinopathy. 70 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; this patient's blood test showed a decrease in hemoglobin with normal platelet levels. on subsequent blood tests, it was found that the hemoglobin and platelet levels had improved. it is known that the patient delayed her blood test due to worsening of general condition. therefore progression of retinal findings in this patient could not be demonstrated to be associated with decreased hemoglobin and platelet levels. glucocorticoids are the gold standard for aiha treatment with 60% responding well to this therapy and 20% providing complete resolution. in the patients who have a good response to this therapy, glucocorticoids must be tappered down slowly for 23 months. but relapses are frequent and the patient should be monitored closely. if the patient does not respond to this therapy, other therapies should be considered. second-line treatment includes splenectomy and anti-cd20 mab.16 our patient received oral treatment for aiha with moderatedose steroids, oral prednisone 32 mg tid given by the pediatrician. most cases of anemia retinopathy require only treatment of the underlying etiology of the anemia and retinopathy usually resolves on its own.10 conclusion anemia regardless of its etiology is the cause of retinopathy which include retinal hemorrhages, roth spots, subhyaloid and vitreous hemorrhage, cottonwool spots, vascular tortuosity, optic disc edema, macular edema and ischemic neuropathy. severity of the retinopathy corespond with the severity of anemia. the lower the hemoglobin level, the severe the anemia and, the severe the retinopathy. therefore, complete blood examination with peripheral blood smear in patients with retinopathy are very recommended. on the other hand, in anemic patients, it is better to do fundoscopy examination to evaluate anemic retinopathy, because in most cases anemic retinopathy are asymptomatic. references 1. oner a, ozkiris a, dogan h, erkilic k, karakukcu m. bilateral macular hemorrhage associated with autoimmune hemolytic anemia. retina. 2005 dec 1;25(8):1089-90. 2. chew fl, tajunisah i. retinal phlebitis associated with autoimmune hemolytic anemia. ocular immunology and inflammation. 2009 dec 1;17(6):394-5.g 3. thomas as, walter sd, fekrat s. bilateral prefoveal subinternal limiting membrane hemorrhage in autoimmune hemolytic anemia. ophthalmic surgery, lasers and imaging retina. 2016 dec 16;47(12):1151-3. 4. reddy vs, samayam p, ravichander b, bai u. autoimmune hemolytic anemia: mixed type—a case report. indian journal of hematology and blood transfusion. 2011 jun 1;27(2):107-10. 5. sankaran j, rodriguez v, jacob ek, kreuter jd, go rs. autoimmune hemolytic anemia in children: mayo clinic experience. journal of pediatric hematology/oncology. 2016 apr 1;38(3):e120-4. 6. carraro mc, rossetti l, gerli gc. prevalence of retinopathy in patients with anemia or thrombocytopenia. european journal of haematology. 2001 oct;67(4):238-44. 7. singh b, gupta m, ahmad e, srivastava s, ranjan r, prabhakar t. retinal changes in anaemia: an observational study. 8. garg p, agrawal a. ocular manifestations in patients with anaemia. j. evid. based med. healthc. 2017;4(79):4646-9. 9. satish sc, tapan jp. ocular manifestations in patients with nutritional anaemia. indian j of basic and applied med research 2014;3(4):8994. 10. shah g, modi r. anemic retinopathy: case reports and disease features. retina today. 2016 may published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 71 11. goel n. the “double-ring sign” in anemic retinopathy evaluated by spectral domain optical coherence tomography. retinal cases and brief reports. 2018 jul 1;12(3):247-50. 12. varner p. isolated unilateral disk edema. clin optom. 2011;3:13-55. 13. badaró e, novais e, prodocimo lm, sallum jm. spectral-domain optical coherence tomography for macular edema. the scientific world journal. 2014;2014. 14. mansour am, lee jw, yahng sa, kim ks, shahin m, hamerschlak n, belfort rn, kurup sk. ocular manifestations of idiopathic aplastic anemia: retrospective study and literature review. clinical ophthalmology (auckland, nz). 2014;8:777. 15. american academy of ophthalmology. basic and clinical science course section 5. neuroophthalmology. usa: american academy of ophthalmology 2016-2017. 16. bass gf, tuscano et, tuscano jm. diagnosis and classification of autoimmune hemolytic anemia. autoimmunity reviews. 2014 apr 1;13(4-5):560-4. this work licensed under creative commons attribution abstract published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 1 international journal of retina (ijretina) 2019, volume 2, number 1. p-issn. 2614-8684, e-issn.2614-8536 the effect of citicoline on electroretinography abnormalities in patients with non-proliferative diabetic retinopathy anna nur utami 1,3, elvioza 1,3, m. sidik 1,3, aria kekalih 2,3 1 department of ophthalmology, universitas indonesia, depok, indonesia 2department of community, universitas indonesia, depok, indonesia 3cipto mangunkusumo hospital, jakarta, indonesia abstract introduction: to determine the effect of citicoline 1000 mg oral supplementation given for 4 weeks on electroretinography abnormalities in patients with npdr (non-proliferative diabetic retinopathy). methods : prospective, double blind, randomized clinical trial. thirty-eight patients who matched the inclusion and exclusion criteria were randomized into two groups: the placebo (p-npdr) and citicoline (c-npdr). in the end, there were 18 eyes in citicoline group and 16 eyes in placebo group. the primary outcome was p50 and n95 amplitude in perg within group and intergroup which were taken at the baseline and 4 weeks after treatment. results : at the end of treatment, the n95 amplitude in c-npdr showed improvement, 4.85 (1.9-10.3) µv, before treatment to 5.7 (1.9-17.1) µv, after treatment with p = 0.04. median p50 amplitude improved in both groups, with c-npdr: 3.1 µv to 3.8 µv (p = 0.89), and p-npdr: 3.5 µv, to 4.5 µv (p = 0.10). delta ∆n95 amplitude is higher in c-npdr, while delta ∆p50 amplitude is higher in p-npdr, with p values 0.35 and 0.45. conclusion : oral citicoline may induce a significant improvement in mean n95 amplitude before and after the treatment. p-npdr showed positive trend in p50 amplitude while in c-npdr showed positive trend in n95 amplitude, but these values were not statistically significant (p = 0.45; p= 0.35). keywords: citicoline, non-proliferative diabetic retinopathy, pattern electroretinography, p50-n95 amplitude. cite this article: utami, anna nur. the effect of citicoline on electroretinography abnormalities in patients with nonproliferative diabetic retinopathy. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/53>. introduction *correspondence to: anna nur utami, department of ophthalmology, universitas indonesia, dr.annanurutami@gmail.com diabetes mellitus (dm) is a metabolic disorders caused by hyperglicemia.1 in 2000, at least 172 million people or 2.8% of world population had diabetes. diabetic retinopathy is one of microvascular complication of dm. approximately, 25-50% of type 1 diabetes patients have retinopathy after 10 years, while in type 2 patients, 23% will have retinopathy. who reported that diabetic retinopathy is responsible for 4.8% of the 37 million cases of blindness in the world.2 the retinal changes in diabetic retinopathy are a consequence of a damage in retinal microvasculature. the retinal cells involved in diabetic retinopathy are endothelial cells and neuronal cells. studies around these days showed that significant neuronal damage is an earlier event that vascular damage.3 diabetes can caused neural apoptosis by several mechanisms, include: ischemia, oxidative stress, glutamate excitotoxity, neuroinflamation, and increased activity of aldose reducatse.4 ganglion cells, in the inner layer of the retina, are the most involved cells in the pathological process in diabetes.5 citidine diphosphocoline (cdp-choline or citicoline) cdp-choline is an essential intermediate in the synthesis of structural phospholipids of cell membranes, phosphatidylcholine.6 after neural death process, exogen citicoline will participate in the phospholipid synthesis at the neuronal membrane cells. several studies also reported that citicoline also have neuroprotective effect in retinal ganglion cells and promotes nerve regeneration in vitro.7 2 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2;1; electroretinography examination is an electric functional examination that aims to evaluate the retina function. pattern electroretinography (perg) is a retinal biopotential evoked by a patterned checkerboard stimulus. there are two components in perg, which are p50 and n95 amplitudes. perg can provide information about the macular and retinal ganglion cell function.8 these retinal ganglion cells are influenced by oral citicoline. the management of diabetic retinopathy in the early phase is limited by risk factors controlled, such as hiperglycemia, hypertension, and dyslipidemia. while in diabetes mellitus, the ischemia caused by the gyperglicemia activates a number of proinflammatory pathways, and cause a long-lasting persistent effect even after the blood glucose is normal (hyperglicemic memory).9 thus, the aim of this study is to evaluate the effect of oral citicoline on electroretinography in patients with npdr. methods this study was a prospective, double blind, randomized clinical trial study, and held in vitreoretina and neuroophthalmology division kiranacipto mangkunkusumo hospital from march to july 2016. ethical approval and informed consent were obtained. the inclusion criteria was patients in moderate / severe npdr which has not been treated by prp, aged 20-65 years old, and hba1c < 8%. patients will be excluded if the bestcorrected visual acuity < 20/50, significant media opacity (moderate severe), macular / optic nerve disease other than diabetic retinopathy, and previous antioxidant / neuroprotective treatment within 2 weeks. patient with worsen progressitivity of the disease who needs the prp treatment, having a protocol violation, or loss to follow up will be dropped out from this study. consecutive sampling was done and subjects were randomized (block randomization) into 2 groups: placebo and citicoline. only one eye which met the criteria included in the study. subject who met inclusion and exclusion criteria underwent bca examination using edtrs chart, funduscopy with 78d lens, fundus photograph, and erg examination (perg and full-field erg). all electrophysiological examinations were performed using an iscev standard. the subjects under examination were seated in an acoustically isolated semi-dark room in front of a display surrounded by a uniform field (120 · 120 degree) of luminance (5 cd/m2). the visual stimuli were checkerboard patterns (contrast was 93 %, mean luminance 100 cd/m2) generated on a television monitor and reversed in contrast at the rate of 4 reversals per second. the electrode used was dtl-plus. the pharmacologic treatment was given for 4 weeks in a daily intraoral dose of 1000 mg citicoline or placebo. the primary outcome in this study was p50 amplitude and n95 amplitude, with bcva as a secondary outcome. evaluation was done in 4 weeks post intervention. the side effect of the drugs was also recorded, statistical analysis was performed using spss 21.0. the numeric data is analyzed with t test or mannwhitney test. paired t-test was used to compare mean amplitude p50 and n95 amplitude within group. result there were 38 eyes included in the beginning of the study. 4 subjects were dropped out because of 2 subjects had gastrointestinal discomfort and 2 subjects were loss to follow up. thirty-four eyes were analyzed, with 18 eyes in citicoline group and 16 eyes in placebo groups. table 1 shows the baseline characteristic of patients in the study include: age, gender, hba1c, duration of dm, dyslipidemia, hypertension, and degree of retinopathy with or without macular edema. baseline characteristics of the subjects in both groups were similar (p > 0.05). table 2 shows the baseline data before the intervention in two groups; include p50 amplitude, n95 amplitude, and bcva. the statistical analysis from the two groups were p > 0.05, which can be concluded that all data from both groups were similar. the p50 and n95 amplitude was assessed at day-0 (baseline) and 4 weeks post intervention. clinically, the result in citicoline groups showed improvement in all variables. median p50 amplitude before treatment, 3.1 µv, increased to 3.8 µv (p = 0.89), median n95 amplitude increased from 4.85 µv to 5.7 µv (p = 0.04), and median bcva logmar improved from 0.13 logmar to 0.10 logmar (p = 0.02). in placebo group, only p50 amplitude improved from 3.5 µv to 4.5 µv (p = 0.10). figure 1 and 2 show the comparison in p50 and n95 amplitude post intervention between two groups. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2;1; 3 table 3 exhibited a comparison in delta examination after the intervention in both groups. delta examination results were obtained from the amplitude difference between the pre and post intervention. delta n95 amplitude was higher in citcioline group (p = 0.35) while the delta p50 amplitude was higher in the placebo group (p = 0.45). total subjects in this study were 38 subjects. there were four-drop outs. after the randomization table was openned, we found that these subjects were from placebo groups. table 1. baseline characteristics variable placebo citicoline p subjects (n) 16 18 age (years) 55.56 ± 7.85* 56.83 ± 6.93* 0.6a gender (%) • female 9 (56.2%) 10 (55.6%) 0.97b • male 7 (43.7%) 8 (44.4%) duration dm (years) • < 10 years 7 (43.7%) 10 (55.6%) 0.49b • > 10 years 9 (56.2%) 8 (44.4%) hba1c (%) 7.5 (4-8.1)** 7 (6-8)** 0.76c hipertension • yes 2 (12.5%) 7 (38.9%) 0.08d • no 14 (87.5%) 11 (61.1%) dyslipidemia • yes 5 (31.2%) 7 (38.9%) 0.64b • no 11 (68.8%) 11 (61.1%) diagnosis • moderate npdr 9 (56.2%) 14 (77.8%) 0.27b • severe npdr 7 (43.8%) 4 (22.2%) • with macular edema 7 (43.8%) 7 (38.8%) 0.77b • without macular edema 9 (56.2%) 11 (61.1%) a: t-test; b: chi square; c: mann-whitney test; d: fisher test, *: mean ± sd, **: median (min-max) table 2. baseline data before the intervention in two groups variable placebo citicoline p amplitude p50 (µv) 3.6 ± 1.5* 3.8 ± 2.9* 0.80a amplitude n95 (µv) 4.4 ± 1.9* 5.3 ± 2.5* 0.28a bcva (logmar) 0.21 ± 0.16* 0.17 ± 0.16* 0.29a bcva : best corrected visual acuity; a: t-test ; *: mean ± sd; table 3. comparison of delta ∆ evalution post-intervention between the two groups variable placebo citicoline p ∆ amplitude p50 (µv) 0.90 ± 2.1* 0.21 ± 3.1* 0.45a ∆ amplitude n95 (µv) 0.03 ± 2.4* 0.81 ± 2.3* 0.35a ∆ bcva (logmar) 0.0 (-0.10 – 0.42)** 0.0 (-0.18 – 0.30)** 0.08b a: t-test; b: mann-whitney test *: mean ± sd; **: median (min-max) 4 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1 figure 1. comparison of p50 amplitude preand post intervention between the two groups figure 2. comparison of n95 amplitude preand post intervention between the two groups discussion variables included in the baseline characteristics were gender, age, hbaa1c, duration of dm, hypertension, dyslipidemia, and degree of retinopathy. the proportion of the gender in this study is almost equal between the female and male, with percentages of 56% female and 44% male. similar data was reported by yau et al10, that the prevalence of diabetic retinopathy in women (52%) and men (48%) are the same. the mean age of the subjects in this study was 56.24 ± 1.25 years old. this characteristics was similar to epidemiological studies conducted in 22.896 subjects of american, australian, european, and asian, with mean age of 58.1 years old.10 this study included only subjects with hba1c levels < 8%. david md, et al11 reported that the risk of progression in diabetic retinopathy is associated with hba1c levels in one’s blood. study from raman12 also reported that the levels of hba1c > 8% was significantly associated with the incidence of sight-threatening diabetic retinopathy (severe npdr, proliferative diabetic retinopathy and clinically significant macular edema). diabetic retinopathy is a multifactorial microvascular complications associated with hyperglycemia, hypertension, and high lipid levels in the blood. the proportion of subjects with hypertension in this study was 26.5%. wisconsin study also reported that the prevalence of hypertension in type 1 diabetes was 17.3% and 25.9% after 10 years of diabetes.13 chew et al14 in the early treatment diabetic retinopathy study (edtrs) reported patients with elevated levels of total cholesterols and high ldl may exacerbate the occurance of retinopathy and the formation of hard exudates. one of the purposes of this study was to evaluate the results of the examination before and after the intervention within group. p50 amplitude was clinically improved in both groups before and after treatment, but these values were not statistically significant (p> 0.05). p50 amplitude was increased higher in the placebo group. the p50 component is more specific to be an indicator of macular function.15 improvement in the p50 amplitude could be caused by improvement of subject’s risk factors, such as hypertension and dylipidemia that lead to reduction in hard exudates and intraretinal hemorrhages in the macula. all subjects in this study were consulted to the internist at the first visit. idiculla et al16 reported that serum lipids has a significant connection with the formation of hard exudates, clinically significant macular edema (csme), and loss of visual acuity in type 2 diabetes. study by rusenberg17 reported that diabetes could cause swelling and beading on the dendrites and axons of retinal ganglion cells. n95 in perg is a component that reflects the retinal ganglion cell layer. several studies reported that n95 amplitude is directly related to the volume of retinal ganglion cells. exogenous citicoline can increase the formation of phosphatidylcholine (ptdcho) and phospholipids, stabilizes the intracellular conditions of neuronal cells, decrease the activity of phospholipase a2 enzyme (pla2), and antipoptosis in mitochondria pathway.18-23 figure 2 shows that preand postintervention n95 amplitude only inrease in citicoline group. there was an increase in the median of n95 amplitude before treatment, 4.85 µv, to 5.7 µv after treatment, which statistically significant (p=0.04) in citicoline group. previous study regarding the used of citicoline in glaucoma and naion also reported similar ideas. parisi24 reported that the administration of intramuscular citicoline in 1000 mg/day for 60 days in patients with glaucoma might improve the visual function as suggested by the increase in p50-n95 amplitude and n75-p100 vep. parisi25 also had research on citicoline administration in patients with naion. in his research, citicoline given in 1600 mg/diem for 60 day p = 0.04 p = 0.68 p = 0.89 p = 0.1 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1 5 improved the perg and vep in patients. the secondary outcome of this research is bcva variable. the bcva improved by 0.03 logmar in citicoline group, with p value of 0.02. this finding is consistent with previous study that also reported that citicoline can improve visual acuity. citicoline is a neuroprotective agent, which plays an important role in the synthesis of phospholipid in cell membrane. additional functions of phospholipid in neuronal membrane is to impulse conduction of nerve cells and neurotransmitter.6 another objective of this study was to look at the differences in test results preand post-intervention in both groups (intergroup). table 3 shows that the n95 amplitude in citicoline group had better improvement that the placebo group, but unfortunately from the statistically analysis, the p value was > 0.05. this value could be explained by several reasons, such as: distribution value was abnormal in both groups, which made the standard deviation was quite large. standard deviation entered in the calculation of the sample in this study was 0.7 µv, while the standard deviation obtained from the results is 1.9 µv. wide variation in this study is probably because of differences in visual acuity. severity of retinopathy, and large variations in duration of dm. total subject in this research is 38. only 2 subjects had gastroinstetinal complaint after the intervention. these two subjects were from placebo group. there was zero person from the citicoline group. this result is similar to other studies that reported citicoline are safe and the side effects that are attributable to this drug are rare. the side effect consist mainly of headache and gastrointestinal discomfort (5.01%).6 conclusion daily dose 1000 mg of citicoline given in 4 weeks may induce a significant improvement in mean n95 amplitude before and after the treatment. in placebo group, there was a positive trend in p50 amplitude while in citicoline group showed positive trend in n95 amplitude, but these values were not statistically significant. references 1. miranda m, sanches mv, alvares r, vilela c, romero fj. electroretinogram alteration in diabetes. electroretinograms. dr. gregor belusic (ed.) intech; 2011. [cited 2015 december]. available from: http://intechopen.com. 2. prevention of blindness from diabetes mellitus: report of a who consultation in geneva [internet]. switzerland: world health organization; 2005 nov [cited 2015 des]. 7p. available from: http://who.int. 3. matteucci a, dkk. primary retinal cultures as a tool for modeling diabetic retinopathy: an overview. hindawi. biomed research international. 2015. 4. m. seki, t. tanaka, h. nawa et al. involvement of brainderived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. diabetes. 2004;53:241219. 5. bikbova g, oshitari t, yamamoto s. diabetes mellitus and retinal vein occlusion as risk factors for open angle glaucoma and neuroprotective therapies for retinal ganglion cell neuropathy. j clinic experiment ophthalmol. 2012. s3:002. 6. secades jj. citicoline: pharmacological and clinical review, 2010 update. rev neurol 2011; 52 (suppl 2): s1-62. 7. oshitari t, fujimoto n, adachi-usami e. citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. neuroreport 2002; 13: 2109-11. 8. bach m, hoffmann m. update on the pattern electroretinogram in glaucoma. optom vis sci. 2008;85:386–95. 9. giacco f, brownlee m. oxidative stress and diabetic complications: circ res.2010;107(9):1058-70. 10. yau dkk. global prevalence and major risk factors of diabetic retinopathy. diabetes care. 2012; 35(3): 556-64. 11. davis m, fisher m, gangnon r, et al. risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early treatment diabetic retinopathy study report #18. invest ophthalmol vis sci.1998;39:233-52. 12. raman r, verma a, pal s, gupta a, vaitheeswaran k, sharma t. influence 
of glycosylated hemoglobin on sight-threatening diabetic retinopathy:a 
population-based study. diab res clin pract. 2011:1-6. 13. klein r, knudtson md, lee ke, gangnon r, klein be. the wisconsin epidemiologic study of diabetic retinopathy: xxii the twent-five-year progression of retinopathy in persons with type 1 diabetes. ophthalmology. 2008; 115(11):1859-68. 14. chew dkk. association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. early treatment diabetic retinopathy study (etdrs) report 22. arch ophthalmol. 1996 sep; 114(9):1079-84. 15. kreuz ac, oyamada mk, hatanaka m, montero ml. the role of pattern-reversal electroretinography in the diagnosis of glaucoma. arq biras oftalmol. 2014;77(6):40310. 16. idiculla j, nithyanandam s, joseph m, ajoy mohan vk, vasu u, sadiq m. serum lipids and diabetic retinopathy: a cross-sectional study. indian j endocrinol metabl. 2012. 16(2): s492-4. http://intechopen.com/ http://who.int/ 6 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1 17. rusenberg bm, pavlidids m, stupp t, thanos s. pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy. graefe's archive for clinical and experimental ophthalmology. 2006. 245(7): 1009-18. 18. grieb p, redjak r. pharmacodynamics of citicoline relevant to the treatment of glaucoma. journal of neuroscience research. 2002;67:143–8. 19. seki m, tanaka t, nawa h, et al. involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocininduced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. diabetes 2004; 53: 241219. 20. siesjo b. k. pathophysiology and treatment of focal cerebral ischemia ii: mechanisms of damage and treatment. j. neurosurg. 1992;77:337–54. 21. park ch, kim ys, lee hk, kim yh, choi my. citicoline reduces upregulated clusterin following kainic acid injection in the rat retina. current eye research. 2007;32:1055–106. 22. alberghina m, giuffrida-stella am. changes of phospholipidmetabolizing and lysosomal enzymes in hypoglossal nucleus and ventral horn motoneurons during regeneration of craniospinal nerves. j neurochem. 1988;51:15-20. 23. lynch ma, voss kl. arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue. j neurochem. 1990; 55: 215-21. 24. parisi v. electrophysiological assesment of glaucomatous visual dysfunctiin during treatment with cytidine-5-diphosphocholine (citicoline): a study of 8 years of follow-up. documenta ophthalmologica. 2005;110: 91– 102. 25. parisi v, coppola g, ziccardi l, gallinaro g, falsini b. cytidine 5-diphosphocoline (citicoline): a pilot study in patients with non-arteritic ischemic optic neuropathy. european journal of neurology 2008,15: 465–474. this work licensed under creative commons attribution http://link.springer.com/journal/417 http://link.springer.com/journal/417 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 11 international journal of retina (ijretina) 2019, volume 2, number 1. p-issn. 2614-8684, e-issn.2614-8536 evaluation of silicon oil evacuation procedure in cipto mangunkusumo hospital indonesia triwijayanti 1, ari djatikusumo 2, andi arus victor 2, elvioza2, gitalisa andayani adriono2, anggun rama yudantha2, mario marbungaran hutapea2 1 rumah sakit umum daerah tarakan, jakarta, indonesia 2 vitreoretina division, department of ophthalmology, faculty of medicine universitas indonesia cipto mangunkusumo hospital, indonesia abstract background: injection of silicon oil (so) is a standard procedure for vitreous replacement in vitrectomy procedure for retinal detachment cases. it acts as a great tamponading agent for reattachment of retinal breaks or retinal detachment. despite its minor side effect, so could cause several complications such as cataract, endothelial decompensation, increased intraocular pressure, and secondary glaucoma. thus needed to be evacuated after the retinal reattachment is stabilized. following the evacuation procedure, visual acuity is known to be significantly improved. however, some cases show decreased of visual acuity due to retinal redetachment, optic nerve damage due to secondary glaucoma, hypotony, vitreous hemorrhage, expulsive hemorrhage, and cornea abnormality. methods: a retrospective descriptive study of retinal detachment patients underwent so evacuation procedure in cipto mangunkusumo hospital, indonesia from september 2017 until january 2018. results: there were seventy-seven cases of retinal detachment undergoes so evacuation within the period of september 2017-january 2018. there was an improvement of visual acuity (greater than 6/60) after one month of so evacuation. anatomical retinal reattachment was successfully observed in 91% patient. the most occurring complication after so evacuation includes secondary glaucoma and retinal redetachment. conclusion: so evacuation is a standard procedure following a vitrectomy in retinal detachment cases. the evacuation procedure yields in positive benefit for patient in term of visual acuity and anatomical structure. keywords: silicon oil evacuation, retinal detachment, surgical complication cite this article: triwijayanti, triwijayanti et al. the evaluation of silicon oil evacuation procedure in cipto mangunkusumo hospital indonesia. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/58>. background *correspondence to: andi arus victor, department of ophthalmology, universitas indonesia, arvimadao@yahoo.com silicon oil (so) was introduced by cibis et al in 1962 as a tamponading agent to manage retinal detachment then haut et al combined so with vitrectomy.1, 2 nowadays, pars plana vitrectomy with so injection becomes the standard procedure for retinal detachment notably for complex cases of retinal detachment including proliferative vitreoretinopathy, giant tear, tractional retinal detachment, and trauma. 3-6 so is an inert and stable polymer with minimal toxicity reaction and high surface adherence which makes it a good vitreous replacement. in retinal detachment cases, so covers the surface of detached retina, holds and prevents the fluid to enter the subretinal space.7 so used for vitreoretina surgery has viscosity of 1000 cst or 5000 cst and specific gravity of 0.97 which is less than aqueous humor and vitreous humor thus so tends to float in vitreous cavity. 8 the application of so as a tamponading agent has more benefit compared to gas. several studies shows that using so has higher surgical outcome compared to gas. so is also the more preferable tamponading agent for patients who are a frequent travel and unable to position their head after surgery. 9, 10 so tamponade has several complications and these are endothelial decompensation, cataract, elevated intraocular pressure, and secondary glaucoma. 12 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; therefore, so is evacuated after the retinal condition has been stabilized or emulsification has occurred.11 evacuation procedure is associated with improvement of visual acuity. however, some studies also found a reduction of visual acuity following evacuation procedure due to retinal redetachment, optic nerve damage due to secondary glaucoma, hypotonic eye, vitreous bleeding, expulsive hemorrhage, and cornea abnormality. 12, 13 methods this is a retrospective descriptive study of retinal detachmnet patients in cipto mangunkusumo hospital, indonesia who underwent vitrectomy with so injection and followed by so evacuation procedure from the period of september 2017 until january 2018. written informed consent was obtained from each patient prior to all procedures of silicone oil evacuation in this study. the inclusion criteria are all retinal detachment patients who underwent so evacuation in september 2017 until january 2018. the exclusion criteria are patients with unattached retina after vitrectomy with so injection and patient who has history of past surgical procedure including scleral buckling or gas vitrectomy. the data was collected from patient’s medical record. the collected data are patient’s base characteristics, details on so evacuation procedures, visual acuity pre so injection and post so evacuation, intraocular pressure pre so injection and post so injection, and complication post so evacuation. examination of patient’s visual acuity and intraocular pressure was done one month post so evacuation. the collected data were then processed descriptively and all variables presented in the table. result there were eighty-one retinal detachment cases which underwent so evacuation in the period of september 2017-january 2018. four cases were excluded from the study due to the previous history of gas vitrectomy or scleral buckling. there were seventy-seven cases were included in the study. distribution of patient’s characteristics is shown on table 1. the majority of retinal detachment patients are male 67.53% meanwhile female contributes only 32.47%. patient tends to be in age >50 years old (53.25%) and only a small number of patients are in age <30 years old (6.49%). there were 23.38% of patients who have high myopia status prior to surgery. patient’s status lens prior to so injection was found to be phakic in 92.21% of patients and only 6 patients (7.79%) who possessed pseudophakic lens table 1. patient's characteristics variable frequency (n) percentage (%) gender (n=77) male 52 67.53 female 25 32.47 age (n=77) <30 5 6.49% 30-50 31 40.26% >50 41 53.25% high myopia 18 23.38 lens status (n=77) phakic 71 92.21 pseudophakic 6 7.79 table 2 summarized the indications for so evacuation procedure. the main indication for so evacuation was emulsification which occurs on 44 cases (57.14%). the second most common indication was stable retina reattachment found in 23 cases (29.87%). the other indication was secondary glaucoma (3 cases) and cataract (9 cases). table 2. indication for so evacuation procedure so evacuation indication frequency (n) percentage (%) so emulsification 44 57.14% secondary glaucoma 3 3.89% cataract 7 9.1% retina reattached (>6 months) 23 29.87% table 3 describes the so evacuation procedure and additional surgical procedure. additional procedures in conjunction with so evacuation include phacoemulsification, intraocular lenses, endolaser, so exchange, and vitrectomy. there were 46 patients who underwent so evacuation only. table 3. so evacuation and additional surgical procedure procedure frequency (n) percentage (%) evacuation 43 55.84% evacuation+phaco emulsification+iol 24 31.16% evacuation+el 3 3.9% evacuation+el+ phacoemulsifi cation+iol 3 3.8% so exchange+ vitrectomy+el 4 5.2% total 77 100% *el= endolaser published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 13 there were 4 (5.2%) cases of retinal redetachment found upon so evacuation procedure thus needing so exchange, vitrectomy, and endolaser procedure to be done. table 4. visual acuity before and after so evacuation visual acuity pre so injection one month post so evacuation loss of follw up 9 (11.69%) 1/300 26 (33.77%) 11 (14.29%) 0.5/60 19 (24.68%) 15 (19.48%) 1/60-3/60 23 (29.87%) 22 (28.57%) >6/60 9 (11.69%) 20 (25.97%) changes in visual acuity are described in table 4. there were 26 patients (33.77%) who had a visual acuity of 1/300 prior to so injection. this number decreased at one month post so evacuation to be only 11 patients (14.29%). patients visual acuity >6/60 increases from 9 patients to 20 patients. there were 9 patients who were lost to follow up. table 5. intraocular pressure (iop) before and after so evacuation intraocular pressure pre so injection (n, %) one month post so evacuation loss of follow up 10 (12.98%) <8 13 (16.88%) 8 (10.39%) 9-21 52 (67.53% 44 (57.14%) >21 2 (2.59%) 15 (19.48%) intraocular pressure (iop) measurement was done prior to so injection and post so evacuation presented on table 5. prior to so injection, the majority of patients have iop between 9-21 mmhg 67.53% and this number relatively constant after one month post so evacuation (57.14%). however, the number of patients who possessed iop >21 mmhg increases become 15 patients (19.48%) (table 5). 10 patients were lost to follow up or no iop recorded on the medical record. anatomical successability of so usage was evaluated during so evacuation procedure and was found to be highly successful retinal reattachment at 91% of the cases and only 9% of cases had persisted retinal detachment. table 6. complication occuring post so evacuation complication after so evacuation frequency (n) percentage (%) retinal redetachment 8 10.39% vitreous hemorrhage 3 3.8% choroidal detachment 1 1.3% secondary glaucoma 13 16.88% toxic anterior segment syndrome (tass) 1 1.3% endophthalmit is 1 1.3% table 6 records the complication occurring after so evacuation. the most common complication is secondary glaucoma (16.88%) followed by retinal redetachment (10.39%) and vitreous hemorrhage (3.8%). the three cases of vitreous hemorrhage leads to other complications including retinal redetachment and non-clearing vitreous hemorrhage. patient who suffered from vitreous hemorrhage and retinal redetachment underwent vitrectomy procedure and so tamponade. the non clearing vitreous hemorrhage underwent two different treatment approaches vitrectomy combined with endolaser and conservative treatment of semifowler position. other complication such as choroidal detachment, tass and endophtalmitis were found only in one patient for each complication. discussion a descriptive retrospective study was done in 77 retinal detachment in cipto mangunkusumo hospital, indonesia who underwent so evacuation to evaluate the outcome of the procedure. on this study, patient’s characteristics were found to be predominantly male ages >50 years old and had phakic lens. according to lam et al, those variables tend to vary among healthcare facilities and do not act as a prognostic factor in determining anatomical successability following so evacuation.14 high myopia status found on 18 cases (23.38%) and one of them experienced retinal redetachment after so evacuation. scholda et al found that high myopia state has been associated with higher retinal redetachment following so evacuation.15 meanwhile, lam et al studies found the axial length of the eye above 27 mm is a risk factor for low anatomical successability after a so evacuation. 14 our evaluation recorded the predominant indication for so evacuation was emulsification and stable retinal reattachment for more than 6 months. this finding is in concordant with a study by teke et al where emulsification is the most common complication occurring in tamponading with so.16 on the other hand, choudary et al reported that the main indication for so evacuation was high iop. 17 the available literature regarding the best timing for so evacuation vary among studies from 8 weeks to 1 year. however, it is strongly suggested to perform evacuation procedure when emulsification is evident or after the stable 14 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; retinal reattachment has occurred and persisted for more than 6 months.18, 19 the emulsification of so triggers inflammation process, induces proliferative vitreoretinopathy, secondary glaucoma, and keratopathy. moreover, there is not enough evidence that suggest the longer duration of maintaining so inside the eye leads to a better outcome. 20, 21 there were 24 patients (31.07%) who underwent so evacuation combined with phacoemulsification. the high number of this procedure was due to cataract formation. the prolonged contact between so and the posterior capsule of the lens which triggers epithelial proliferation hence cataract formation. the combination of these procedures has been found to be safe and proven to yield a better visual outcome. 22, 23 there was a pronounced improvement in the group of visual acuity >6/60 within one month post so evacuation from 9 patients to 20 patients. furthermore, the number of patients who has visual acuity of 1/300 markedly decreases after the evacuation procedure by 9%. a study by goezinne et al reported a 45% improvement of at least two snellen lines and 36% remained stable or improve at least one snellen lines after so evacuation.24 on contrary, several studies found decreased visual acuity post so removal from 1-30% of the cases. this was hypothesized due to neuronal apoptosis triggered by a sudden change in retinal flux ionic, phototoxicity of so which has the capability to dissolve lutein and zeaxanthin, and retinal toxicity.25-27 elevated iop >21mmhg occurs in 15 (19.48%) patients post so evacuation. meanwhile, goezinne et al recorded 8.5% elevated iop occurs post so evacuation.24 elevated iop has been found to be the most common complications in so usage due to droplets remains obstructing the trabecular meshwork. this study discovered 3 cases of secondary glaucoma which requires surgical therapy including trabeculectomy and or pmma implants.28 hypotonic eyes were also recorded in 8 patients post so evacuation. gonvers et al found that this number tends to be higher reaching for 20% for iop 1-5 mmhg and 55% below 11mmhg.29 hypotonic eyes are associated with choroidal detachment and considered to be a rare case according to caswell et al.13 in this study, there was one case of choroidal detachment with iop of 11 mmhg. retinal redetachment is one of complication post so evacuation. retinal redetachment can arise due to retinal break as an intraoperative complication or due to the elimination of the so tamponade.14 in our study, 8 retinal redetachment cases were recorded upon so evacuation. based on a recent study, the number of retinal redetachment associated with so evacuation varies from 0-20%.18 meanwhile, chouldhary et al only report 3.46% cases of retinal redetachment. the low number in their study is thought due to the advanced surgical technique such as maximum vitreous base shaving, retinotomy, adequate so tamponade, and laser, hence complication minimization. 17 vitreous hemorrhage was reported in 3 eyes (3.8%). jonas et al stated that presence of vitreous hemorrhage within 3 days post so evacuation is associated with a possible retinal tear or retinal redetachment.30 the three cases of vitreous hemorrhage underwent different therapy approach including conservative semi-fowler position, vitrectomy, and vitrectomy with sol tamponade. other complication documented in this study includes endophthalmitis and toxic anterior segment syndrome (tass) which each accounts for 1.3%. endophthalmitis occurred 4month post so evacuation and was treated with evisceration. meanwhile, the patient with tass was found to suffer from macular edema and was treated with oral methylprednisolone and triamcinolone acetonide intravitreal injection. tass was commonly found in the patient who underwent a surgical procedure on anterior segment such as cataract surgery, hence a combination of so evacuation with phacoemulsification could be the triggering factors for anterior segment inflammation.31 however, moisseiev et al argue that the use of so triggers inflammation reaction at the anterior segment of the eye.32 conclusion evacuation of so is a standard procedure following so injection. the procedure results in an improvement of visual acuity and also normal intraocular pressure. however, the patient should be regularly monitored post-evacuation procedure to minimize the complication. acknowledgement the author would like to express his gratitude to all parties who have aided the making of this manuscript. references 1 .cibis pa, becker b, okun e, canaan s. the use of liquid silicone in retinal detachment surgery. arch ophthalmol. 1962;68:590-9. 2. haut j, ullern m, van effenterre g, chermet m. [use of intraocular silicone in 200 cases]. bull soc ophtalmol fr. 1979;79(8-9):797-9. 3. castellarin a, grigorian r, bhagat n, del priore l, zarbin ma. vitrectomy with silicone oil infusion in severe diabetic retinopathy. br j ophthalmol. 2003;87(3):318-21. 4. schwartz sg, flynn hw, jr., lee wh, wang x. tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy. cochrane database syst rev. 2014(2):cd006126. 5. shen yd, yang cm. extended silicone oil tamponade in primary vitrectomy for complex retinal detachment in proliferative diabetic retinopathy: a long-term follow-up study. eur j ophthalmol. 2007;17(6):954-60. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 15 6. shunmugam m, ang gs, lois n. giant retinal tears. surv ophthalmol. 2014;59(2):192-216. 7. hans‐heinrich moretto ms, gebhard wagner. silicones. ullmann's encyclopedia of industrial chemistry. 7 ed2000. 8. saxena s mc, ohji m, akduma l. long-term intraocular tamponade with silicone oil. vitreoretinal surgery. 2012;p.64. 9. vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. silicone study report 2. arch ophthalmol. 1992;110(6):780-92. 10. vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. silicone study report 1. arch ophthalmol. 1992;110(6):770-9. 11. federman jl, schubert hd. complications associated with the use of silicone oil in 150 eyes after retina-vitreous surgery. ophthalmology. 1988;95(7):8706. 12.franks wa, leaver pk. removal of silicone oil-rewards and penalties. eye (lond). 1991;5 ( pt 3):333-7. 13. casswell ag, gregor zj. silicone oil removal. ii. operative and postoperative complications. br j ophthalmol. 1987;71(12):898-902. 14. lam rf, cheung bt, yuen cy, wong d, lam ds, lai ww. retinal redetachment after silicone oil removal in proliferative vitreoretinopathy: a prognostic factor analysis. am j ophthalmol. 2008;145(3):527-33. 15. scholda c, egger s, lakits a, walch k, von eckardstein e, biowski r. retinal detachment after silicone oil removal. acta ophthalmol scand. 2000;78(2):182-6. 16. teke my, balikoglu-yilmaz m, yuksekkaya p, citirik m, elgin u, kose t, et al. surgical outcomes and incidence of retinal redetachment in cases with complicated retinal detachment after silicone oil removal: univariate and multiple risk factors analysis. retina. 2014;34(10):1926-38. 17. choudhary mm, choudhary mm, saeed mu, ali a. removal of silicone oil: prognostic factors and incidence of retinal redetachment. retina. 2012;32(10):2034-8. 18. hutton wl, azen sp, blumenkranz ms, lai my, mccuen bw, han dp, et al. the effects of silicone oil removal. silicone study report 6. arch ophthalmol. 1994;112(6):778-85. 19. jonas jb, budde wm, knorr hl. timing of retinal redetachment after removal of intraocular silicone oil tamponade. am j ophthalmol. 1999;128(5):628-31. 20. scholda c, egger s, lakits a, haddad r. silicone oil removal: results, risks and complications. acta ophthalmol scand. 1997;75(6):695-9. 21. k j. retinal redetachment after silicone oil removal pak j opthalmol.28:127-31. 22. loncar vl, petric i, vatavuk z, bencic g, andrijevicderk b, mandic z. phacoemulsification and silicone oil removal through the planned posterior capsulorhexis. coll antropol. 2005;29 suppl 1:63-6. 23. krepler k, mozaffarieh m, biowski r, nepp j, wedrich a. cataract surgery and silicone oil removal: visual outcome and complications in a combined vs. two step surgical approach. retina. 2003;23(5):647-53. 24. goezinne f, la heij ec, berendschot tt, liem at, hendrikse f. risk factors for redetachment and worse visual outcome after silicone oil removal in eyes with complicated retinal detachment. eur j ophthalmol. 2007;17(4):627-37. 25. roca ja, wu l, berrocal m, rodriguez f, alezzandrini a, alvira g, et al. un-explained visual loss following silicone oil removal: results of the pan american collaborative retina study (pacores) group. int j retina vitreous. 2017;3:26. 26. newsom rs, johnston r, sullivan pm, aylward gb, holder ge, gregor zj. sudden visual loss after removal of silicone oil. retina. 2004;24(6):871-7. 27. kirchhof b, tavakolian u, paulmann h, heimann k. histopathological findings in eyes after silicone oil injection. graefes arch clin exp ophthalmol. 1986;224(1):34-7. 28. ni c, wang wj, albert dm, schepens cl. intravitreous silicone injection. histopathologic findings in a human eye after 12 years. arch ophthalmol. 1983;101(9):1399-401. 29. gonvers m. temporary silicone oil tamponade in the management of retinal detachment with proliferative vitreoretinopathy. am j ophthalmol. 1985;100(2):239-45. 30. jonas jb, knorr hl, rank rm, budde wm. retinal redetachment after removal of intraocular silicone oil tamponade. br j ophthalmol. 2001;85(10):1203-7. 31. cetinkaya s, dadaci z, aksoy h, acir no, yener hi, kadioglu e. toxic anterior-segment syndrome (tass). clin ophthalmol. 2014;8:2065-9. 32. moisseiev e, barak a. toxic anterior segment syndrome outbreak after vitrectomy and silicone oil injection. eur j ophthalmol. 2012;22(5):803-7. this work licensed under creative commons attribution 28 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; international journal of retina (ijretina) 2022, volume 5, number 1. p-issn. 2614-8684, e-issn.2614-8536 clinical characteristics of vitrectomy patients in the case of rhegmatogen retina detachment in prof dr r d kandou central general hospital, manado ade john nursalim1, vera sumual1, eugeni sumanti1, irene rumampuk1, stevanus loho1, christian komaling1 1 ophthalmology department rsup prof dr r d kandou, medical faculty sam ratulangi university, indonesia. abstract introduction: rhegmatogenous retinal detachment (rrd) is an ophthalmology urgency that can cause blindness if treated late. incidence of rrd has increased overtime. we describe the clinical characteristics of vitrectomy patients in rrd cases at dr. r. d. kandou hospital, north sulawesi province, manado city, indonesia. methods: the study was conducted based on a retrospective search on the medical record data of 72 rrd patients who underwent vitrectomy within june 2018 until june 2020. result: most of the participants were male, with total of 43 patients (59.70%) where the majority of the samples were from age group 51-60 years (33 patients). moreover, the eyes affected by rrd were mostly right eyes as many as 41 patients (56, 9%) with the location of the break was mainly the superotemporal area in 28 patients (38.9%). furthermore, the status of the macula was dominantly macular off counted as 44 patients (61.10%) the anesthesia used was local anesthesia in 69 patients (95.80 %), meanwhile, the time taken for the procedure was quiet long with more than 1 month for all patients. conclusion: the clinical characteristics of rrd patients at dr. r. d. kandou hospital are mostly consistent with previous studies in several places in the world. older age as well as male patients were more susceptible to rrd. however, time to do vitrectomy need to be evaluated and corrected to improve visual prognosis. keywords: rhegmatogenous retinal detachment cite this article: nursalim, ade john. clinical characteristics of vitrectomy patients in the case of rhegmatogen retina detachment in prof dr r d kandou central general hospital, manado. international journal of retina, [s.l.], v. 5, n. 1, p. 19, feb. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/188>. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss001.188. correspondence to: ade john nursalim, medical faculty sam ratulangi university, indonesia. dr.adejn@gmail.com introduction retinal detachment is the detachment of the retinal neurosensory tissue from the underlying layer. rhegmatogenous retinal detachment (rrd) is a type of retinal detachment characterized by a tear in the retina. rrd is a condition that can lead to blindness if not treated.1 rrd is an eye urgency that requires immediate treatment. surgery performed on the rrd eye with high visual acuity has better outcome in compared to the low visual acuity ones.2 . published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 29 the incidence of rrd in the world reaches 10.9 cases per 100,000 population in asia, lower than 13.3 cases per 100,000 population in europe. the median age of rrd cases is 50 years in men and women in asia and 60-70 years in europe. 3, 4 the incidence of rrd has also increased over time.5 simple rrd is characterized by a small tear in the peripheral retina followed by good visualization of the fundus. rrd complex consist of the following signs of extensive detachment either subtotal or total with multiple tears, posterior tears, presence of retinal dialysis or major tears, vitreous hemorrhage, eye trauma or proliferative vitreoretinopathy. 6 there are a few therapeutic procedures for rrd cases such as pars plana vitrectomy, scleral buckle and pneumatic retinopexy.7 these therapeutic options for rrd have their advantage and disadvantages. pars plana vitrectomy is currently the most popular procedure to treat rrd compared to scleral buckle and pneumatic retinopexy right now. this procedure involves removal of the vitreous to remove traction continued with gas bubble or silicone oil injection as a tamponade to ensure attachment of the retina. similar to pneumatic retinopexy, patient then have to maintain particular head position to ensure tamponade function adequately. unfortunately, silicone oil will need further surgery for the evacuation while gas bubble will have certain period to resorb. pneumatic retinopexy as mentioned before is a minimal invasive procedure relying on gas tamponade. however, this procedure still access the intraocular space. scleral buckle procedure on the other hand uses silicone explants which are sutured to the external sclera. this procedure done without accessing intraorbital space. thus, this procedure preserves crystalline lens and does not need positioning after surgery compared to ppv or pneumatic retinopexy. 8-10 the choice of therapeutic option is still debatable. primary rhegmatogenous retinal detachment outcomes randomized trial (pivot) found that ppv excel in showing great success in 12 months postsurgery for 93,2% patients while pneumatic retinopexy only achieve 80,8%.8 ppv also have a greater success rate compared to scleral buckle. this comparison referred to 90,8% in scleral buckle and 93,1% in ppv.9 methods this study is a retrospective descriptive study on medical record data in the retinal subdivision of the prof dr r d kandou central general hospital, manado. the research subjects were all medical record data of patients with a diagnosis of rhegmatogen retinal detachment (rrd) who underwent vitrectomy in the period of june 2018 to june 2020. the exclusion criteria in this study are medical records that are incomplete and indecipherable. the variables observed are both gender; male and female, age in years, laterality to the right or the left eye, the location of the break, and the location of retinal tear. the location of the break is divided into four locations: no break found, inferior, superotemporal and superonasal. the break that is included in the assessment is a primary break and is not an iatrogenic break that may occur during the operation. while the macula status is classified into macula on (attached macula) and macula off (detached macula). the results of the study are described in the form of a data frequency distribution table to the describe the clinical characteristic. results this study found 72 medical record files that met the research criteria the results (table 1) showed that the most genders included in the criteria as seen on this study were male as many as 43 people (59.7%), and female 29% (40.3%), the most age was in the age range of 51 to 60 years old as many as 33 people (45,83%), followed by the age range of 61-70 years old as many as 15 people (20,83 %). laterality of rrd cases was dominated by right eye for 41 people (56.90%) and 31 people (43.10%) for left eye. most of the break locations were in the superotemporal area as many as 28 people (38.90%), inferior as many as 22 people (30.60%), superonasal as many as 13 people (18.1%) and no break was found in 9 people (12, 5%). macula on status was found in 28 people (38.9%) and macula off in 44 people (61.10%). 30 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; the type of anesthesia used consisted of local anesthesia in 69 people (95.8%), general anesthesia in 3 people (4.20%). time of surgery was 72 people (100%) were done after 1 month. table 1. study result figure 1. distribution of 72 patients with rhegmatogenous retinal detachment in different age groups male group dominates the overall age group of rrd patients except in the age group below 30, 3040 and above 70. figure 2. age distribution for each break location. the age distribution for each break location was dominated by superotemporal at the age range of 51-60 years, inferior at the age of 41-50 years, superonasal at the age above 70 years. discussion the study showed that most of the gender were male, with a male to female ratio of 1.48:1. this dominance was also found in almost all age groups of rrd patients (figure 1). this finding is consistent with previous studies in several area of the world.5, 1114 the majority of rrd cases in male is associated with longer axial length of the eyeball in comparison to female eyeball and the higher risk of trauma in daily activitiy. 15, 16 most of the ages in this study were dominated by the age group 51-60 years old and age group 61-70 years old and the trend decline on population older than 70 years old. this finding is in line with other studies.15 one explanation for this finding is the process of vitreous liquefaction and the occurrence of a posterior vitreous detachment process. 17 the vitreous liquefaction process is known to begin at the age of 40 years to 70 years with an average rate of 55 years.18 1 2 0 6 0 01 1 6 10 3 11 1 3 13 6 40 1 0 4 6 2 0 5 10 15 <30 30-40 41-50 51-60 61-70 >70 not found inferior superotemporal superonasal variable frequency (n) percentage (%) gender male 43 59.70% female 29 40.3% age (year) <30 3 4,17% 30-40 5 6,94% 41-50 9 12,50% 51-60 33 45,83% 61-70 15 20,83% >70 7 9,72% laterality right 41 56,90% left 31 43,10% break location not found 9 12,50% inferior 22 30,60% superotemporal 28 38,90% superonasal 13 18,10% macula status macula on 28 38,90% macula off 44 61,10% anaesthetic type local 69 95,80% general 3 4,20% surgery time < 1 month 0 0,00% > 1 month 72 100,00% 1 5 7 19 8 32 0 2 14 7 4 0 5 10 15 20 <30 30-40 41-50 51-60 61-70 >70 male female published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 31 this study showed that rrd was more common in the right eye than the left eye with a ratio of 1.33:1. this result is in accordance with several other studies. 5, 19, 20 the right eye is often the dominant eye and is also more often in a myopic state. 19, 21 this laterality might be related to the fact that the non-dominant eye is known to tend to blink more. this causes, the dominant eye tends to get more solar radiation than the non-dominant eye. 20, 22 long-term exposure to sunlight can increase the risk of retinal detachment. 23 the right eye also tends to be larger, so it has a greater risk of rrd than the left eye. this is also related to the condition of myopia experienced by the patient.19, 21 in addition, differences in the vasculature of the right and left eyes related to the flow of the left carotid vessels which are direct branches of the aorta are also possible but this is still debated.20 the break location in this study was dominated by the superotemporal and inferior regions followed by the superonasal in almost all age groups, especially in the age range of 51 -60 years (figure 2) which in line with the previous study conducted in 844 patients. this might be related with the sequential process of posterior vitreous detachment which starting in superotemporal quadrant.24 the break in the superotemporal area is also associated with a lower success rate of the operation than breaks in other areas. there is no evidence support the cause of this rate but it might be related with gravity.25 we have known that retina attached strongest in ora serrata, optic nerve and macula. if we take this into consideration, the distance between ora serrata and optic nerve has its longest distance in superotemporal quadrant. this put superotemporal quadrant into the weakest point of retinal attachment especially in long axial length. a total of 12.5% of eyes with rrd in this study had an unidentified break on ophthalmological examination. another study reported also reported similar findings that 11.6% of rrd patients did not have a retinal tear at the time of examination.26 peripheral retinal degeneration might be the reason why the break cannot be found on fundus examination. this micro break is one of the risk factors for rrd is difficult to be identified on fundus examination. however, peripheral retinal degeneration such as lattice degeneration, retinoschisis, cyctic retinal tufts, and zonular traction tufts can lead to rrd. 27 this study shows that most rrd patients have macular off status. macular off status is associated with poor visual acuity prior to surgery as well as poor post procedural prognosis and visual acuity. this disorder can be in the form of metamorphopsia or binocular double vision. 28-30 anesthesia used for pars plana vitrectomy were mostly general anesthesia. along with the development of surgical techniques and instruments, the trend of using general anesthesia is decreasing and being replaced by a trend of local anesthesia. local anesthesia on the other hand has several advantages over general anesthesia such as shorter duration of surgical preparation, rapid recovery period, less need for operating room facilities like recovery room and intensive care unit following procedure, and cost efficient. 31-33 the total cost for a vitrectomy procedure in indonesia is known to be reduced by up to 46.6% with the use of local anesthesia compared to general anesthesia.33 this study showed that the timing of the procedure for all rrd patients occurred after one month. the time at which rrd is treated is an important predictor of surgical success and restoration of vision. surgery is expected to be performed less than 72 hours after the initial symptoms. surgery taken during this period give better prognostic results than after.2 this study did not get data on the reasons why the time for all of the surgeries were more than 1 month. delayed surgery can occur in several stages of the process starting from the initial process depending on the patient's ability to recognize first signs such as floaters, seeing flashes of light, or loss of visual field. awareness of these first symptoms is accompanied by the time required to report this incident to the doctor, the referral process to an ophthalmologist, the process of preparing for surgery, and the surgery itself.34 32 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; conclusion the clinical characteristics of rhegmatogenous retinal detachment patients who went on vitrectomy at prof dr r d kandou hospital are in accordance with other studies that has been conducted. most of the surgeries are performed using local anesthesia which can lead to cost efficiency. overall 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scupola a, viggiano d, sammarco mg, de turris s, romano mr, et al. incidence and factors influencing retinal displacement in eyes treated for rhegmatogenous retinal detachment with vitrectomy and gas or silicone oil. investigative ophthalmology & visual science. 2017;58(6):bio191-bio9. 31. riaz s, khan mt, ahmad m, butt nh, chaudhary s. shifting paradigm: from general anesthesia to local anesthesia in posterior segment surgeries. pakistan journal of ophthalmology. 2020;36(3). 32. marova n, vasilyev yi, klyushnikova e, kononov a, polyakova t. local anesthesia for vitreo-retinal surgery. regional anesthesia and acute pain management. 2018;12(1):24-9. 33. simanjuntak gw, djatikusumo a, adisasmita a, nadjib m, mailangkay h, hussain n. cost analysis of vitrectomy under local versus general anesthesia in a developing country. clinical ophthalmology (auckland, nz). 2018;12:1987. 34. eijk es, busschbach jj, timman r, monteban hc, vissers jm, van meurs jc. what made you wait so long? delays in presentation of retinal detachment: knowledge is related to an attached macula. acta ophthalmologica. 2016;94(5):434-40. this work licensed under creative commons attribution abstract introduction methods results discussion conclusion 48 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; international journal of retina (ijretina) 2022, volume 5, number 1. p-issn. 2614-8684, e-issn.2614-8536 retinal impairment associated with long-term use of ritonavir among hiv patients: a systematic review for primary eye care practice zakirunallah karunia 1, ivana beatrice alberta 2, salsha alyfa rahmani 3 1 general practitioner at pelabuhan hospital, jakarta 2 general practitioner at bhayangkara pusdik brimob hospital, pasuruan 3 general practitioner at kemayoran district general hospital, jakarta abstract introduction: ritonavir as part of highly active antiretroviral therapy (haart) is a potent inhibitor of hiv protease that have been reported causing retinal impairment in the long term use. primary eye care (pec) is an integral part of primary health care that provides an early screening for drug induced retinal toxicity, by using a funduscopy examination. this study proposed to review and analyze some case reports conducted on long-term use of ritonavir that affects retinal impairment among hiv patients, in primary eye care practice. method: pubmed and google scholar were used to perform a systematic review of retinal impairment associated with long-term use of ritonavir among hiv patients. using prisma 2020 guidelines, nine case reports and one case series were included in this review and only focus on simple funduscopic examination for primary eye care practice. result: funduscopy mainly showed bilateral retinal pigment epithelium (rpe) atrophy with hypertrophy or mottling. two cases found bilateral crystalline deposits with pigment disruption. one case showed rounded hypopigmented lesion. bilateral subtle annular pattern of rpe was found in one case. bilateral retinitis pigmentosa-like appearance found in one case while another found unilateral hyperemic lesion at the left fovea. conclusion: retinal impairment detected on funduscopy occurred in hiv patients on long-term use of ritonavir. keywords: ritonavir, retinal impairment, hiv, primary eye care cite this article: karunia, zakirunallah -; alberta, ivana beatrice; rahmani, salsha alyfa. retinal impairment associated with long-term use of ritonavir among hiv patients: a systematic review for primary eye care practice. international journal of retina, [s.l.], v. 5, n. 1, p. 39, feb. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/179>. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss001.179. introduction retinal impairment that associated with longterm use of ritonavir as antiretroviral therapy for hiv patients is uncommonly reported. ritonavir is an inhibitor of the human immunodeficiency virus type 1 (hiv-1) protease and is now used in combination in highly active antiretroviral therapy (haart). the adverse effects of ritonavir may cause disadvantageous on the eyes, especially on the retina. rare cases of retinopathy have been reported in the literature since 2011 with heterogeneous phenotypes ranging from macular atrophy, intraretinal cysts, macular telangiectasia4 to retinitis pigmentosa-like presentation5 in the long term use of ritonavir. *correspondence to: zakirunallah karunia, pelabuhan hospital, jakarta indonesia, zakirunallahk@gmail.com published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 49 primary eye care (pec) is a facility which accessible and give comprehensive care for patients’ eye care treatment in a competent manner. pec provides the patient with the first contact for eye care as well as a lifetime of continuing care6. pec is the primary health care (primary health care) to help undertake the prevention of eyes diseases which some lead to blindness and it should be a vital part of phc. the ophthalmologist is certainly suitable and costeffective provider of pec6. although in some conditions, pec can be provided by general practitioners at basic health units and rural health centers8 with limited resources. we conducted a systematic review of the published case and serial case reports describing the clinical features associated with ritonavirinduced retinal toxicity. in this review, we focus on pec practice to diagnosing the effect of haart use earlier. hiv associated with retinopathy a. pathophysiology human immunodeficiency virus (hiv) are divided into two types, hiv-type 1 (hiv-1) and hiv-type 2 (hiv-2), the main agent of aids is hiv-19. the pathogenesis of hiv infection and the progression to aids are a result of the infecting virus isolate and the host’s immune response to the virus9. hiv is able to enter the body via intact mucous membranes, eczematous or injured skin or mucosa and by parenteral inoculation. hiv attaches first to dendritic cells or macrophages/monocytes. hiv is taken by macrophages and replicated as shown for m cells in the mucosa11. after a day or two the virus can be detected in regional lymphatic tissue and within 5–6 days in regional lymph nodes. after 10–14 days postinfection hiv can be detected in the whole body, including the nervous system11. most of the infected individuals present symptoms resembling flu-like illness, as fever, pharyngitis, oral ulcers, lymphadenopathy, arthralgia, myalgia, weight loss, and malaise. during acute hiv-1 infection, the number of cd4+ t-cells dramatically declines before the onset of antiviral immune response9. b. hiv retinopathy the eye is infected to hiv virus either directly or indirectly by numerous opportunistic infections. hiv retinopathy is an ocular affection occurring especially in hiv positive patients with deep immunodeficiency. hiv-related ophthalmic manifestations are extensive and may affect any part of eye. dry eye and hiv retinopathy were the most common ocular manifestations found in patients12. in the pre-haart era, cmv retinitis was the most common hiv-associated retinopathy that occurred in 20%-40% of patients. cmv retinitis occurs only after cd4 t lymphocyte counts drop below 50 cells/ul. if left untreated cmv retinitis leads to retinal necrosis that may result in rhegmatogenous retinal detachment (rd) in three to six months of diagnosis. ritonavir overview a. ritonavir profile ritonavir as a part of haart acts as a potent inhibitor of hiv protease4. ritonavir prevents the cleavage process of viral polyprotein precursors into mature and functional proteins, hence interrupting the production of new viral particles14. the inhibition of hiv protease results in the release of immature non-infectious virions that halt the spread of the virus to uninfected cells. ritonavir has been shown to be 98% to 99% protein-bound, and its primary site of metabolism is in the liver. b. side effect the most common side effects found in patients with ritonavir treatment are general weakness, peripheral paresthesia, nausea, vomiting, diarrhea, rash, and fatigue, and 50 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; with long-term use it’s possible to find hyperlipidemia and lipodystrophy. visual symptoms are rare but have been reported in some studies that described the long-term effects of protease inhibitors, including ritonavir, in hivpositive4. visual change can be detected and identified by eye examination such as funduscopy fundus autofluorescence (faf), fluorescein angiogram (fa), spectral domain-optical coherence tomography (sd-oct), electroretinogram (erg), and humphrey visual field. in indonesia, based on standar kompetensi dokter indonesia (indonesian doctor competency standars) 2019, general practitioners must be able to do funduscopy independently. funduscopy is included as a competence that must be achieved at the time of graduation as a doctor16 although in fact not all general practitioners are able to perform funduscopy due tu limited resources. therefore general ophthalmologists must also emphasize this for early detection of retinal toxicity on hiv patients. fundus examination showed hypopigmented annular lesions in the macular region corresponding to the retinal pigment epithelium (rpe) atrophy1,3-4,17-20 and parafoveal opacification in the macula4 (figure 1.) corresponding to the crystal and pigment deposit15 (figure 2.) some studies also showed scattered bone spicule-like pigment changes on the midperipheral retina5 and slightly hyperemic lesion centered at the fovea21 (figure 3.) figure 1. fundus photograph: hyperthrophic and atropic changes in the rpe in macula as well as parafoveal opasification4 figure 2. fundus photograph: crystalline (yellow arrow) and pigment deposits (blue arrow) in the macula15 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 51 methods a. study selection pubmed and google scholar were used to conduct a literature review. we searched for case report studies that evaluate the effect of ritonavir on the retina. the search query included ritonavir and (retina or retinal or ocular) and (toxicity or impairment or damage). the following were the inclusion criteria for each study: (1) documented retinal impairment due to ritonavir treatment, (2) conducted in human eyes, and (3) published in the last 10 years. we adhered to the preferred items for systematic reviews and meta-analyses (prisma) 2020 guidelines. (figure 4.) all the reports were critically appraised by 3 independent reviewers based on joanna briggs institute (jbi) critical appraisal checklist for case report. b. study eligibility criteria the population-intervention-comparatoroutcomes-study design (picos) framework was used to identify eligible cases, as follows: ● population. only human patients, with no restrictions on age or other demographics ● intervention and comparator. long-term use of ritonavir on hiv patients. we excluded the drug combinations used. no comparator was required. ● outcomes. retinal impairment showed on eye examination. in this study, we limit the examination on funduscopy which mostly primary health care had. ● study design. we included only case reports and case series published in full text. based on who-umc causality assessment system, long-term use of ritonavir categorize into “possible” cause to retinal impairment that showed by abnormality on funduscopic examination with reasonable time relationship to drug intake, but it might also be explained by patient’s underlying disease or other drugs that patients already take. in this case, rechallenge was not necessary because discontinuation or interruption of ritonavir as part of haart may result in viral rebound, immune decompensation, and clinical progression which can harm patients. figure 3. fundus photograph: scattered bone spicule-like pigment changes on the mid-peripheral retina5 52 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; after assessing studies for risk of bias using cochrane risk-of-bias tool, we found no risk of bias in random sequence generation, allocation concealment, blinding of participants and personnel, and incomplete outcome data. however there is an unclear risk of bias for blinding of outcome assessment since there is a difference between the ritonavir dose taken by participants and half of the studies didn’t include the ritonavir dose. we used subgroup analysis to explore possible causes of heterogeneity among study results. results the literature search identified total of 10 case reports. from the 10 case reports which were included in this review, 9 of them were single case reports and 1 was a case series including 3 patients. ritonavir was administered ranging from 100 mg daily or twice daily but few reports didn’t state the dose taken by the patients. the patients were all male and the mean age of the patients was 41 years, ranging from 30-59. the overall average treatment duration was 93 months, ranging from 19 to 216 months treatment duration. some authors included the presence of liver dysfunction. our outcome is to find retinal impairment showed on eye examination in hiv patients. in this study, we limit the examination on funduscopy which mostly primary health care have to visualize the retina. as described, the retinotoxicity mostly presented in bilateral macular, while 3 cases presented in bilateral retinal and macular1,5,19, and 1 case only involved in unilateral macular21. figure 4. flow diagram of the study selection process published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 53 funduscopy examination mainly showed bilateral rpe atrophy with hypertrophy or mottling. two cases found bilateral crystalline deposits with pigment disruption. bilateral subtle annular pattern of retinal rpe was found in one case. another author found bilateral retinitis pigmentosa-like appearance of the fundus with scattered bone specula pigmentation. tu et al. found unilateral hyperemic lesion centered at the left fovea. to monitoring the further implication of ritonavir treatment, some authors reported the follow-up examination ranging from 6 to 24 months. some authors reported the follow-up examination of the ritonavir side effect. roe and biancardi et al report the decreasing of visual acuity with significantly larger rpe hypertrophy and atrophy after 24 and 8 months of follow-up. some reported the bilaterally stable of visual acuity and clinical appearance of the patients after cessation of ritonavir, in nearly or more than 24 months1,15 and 6 months21 of follow-up. discussion we have concluded some publication suggested that ritonavir causes retinotoxicity. however, there are some limitation of the evidence included in the review which are not explained on all the publication, such as the doses of drugs and abnormalities finding after several period of followup time. roe et al. published the first case series in 2011 describing retinal anomalies in hiv-positive individuals treated with ritonavir. they documented three patients with varying degrees of bilateral macular rpe atrophy, macular telangiectasia, cystic gaps, and parafoveal intraretinal crystals4. it's worth noting that these three individuals, like another instance by louie, bunod, and tu, had a history of liver dysfunction1,3,21. because ritonavir is predominantly removed through the hepatobiliary system in humans, it's probable that liver failure in these patients inhibited ritonavir removal, resulting in higher circulating drug levels5. table 1. result 54 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; another possible factor determining the degree of retinal damage, in addition to the length of exposure to the medication, is its serum concentration. this was observed in investigations by tu et al and pinto et al, implying that hepatic lesions in ritonavir users would raise the compound's serum levels, increasing the risk of retinal damage and aggravation. after stopping ritonavir, one patient's visual acuity improved, according to tu et al17,21. ritonavir toxicity studies in mice, rats, and dogs were undertaken. the liver and retina were the main organs targeted. repeated high oral doses of ritonavir cause phospholipidosis in rodents, resulting in retinal degeneration and hypertrophy of the retinal pigment epithelium, as seen in histology and electron microscopy examinations of amorphous granular inclusion bodies in the liver and retina. with higher liver enzymes, the phospholipidosis was more pronounced in the retina than in the liver. phospholipidosis is a typical occurrence following the treatment of amphiphilic cationic drugs that may alter phospholipid metabolism22. all studies of persistent ritonavir toxicity have a few clinical symptoms in common. pigmentary alterations in the macula are a common finding45,15,17-21. a granular appearance of the retinal pigment epithelium in the macula has been documented in several cases5,15,18, few in a bull'seye pattern20,22 and others with a less particular pattern of pigment defects3-15,18-19,21. non et al. and pinto described a bull's-eye pattern that included retinal epithelial alterations, macular atrophy, and annular macular pigmentation, which looked similar to bull's eye maculopathy, a condition traditionally associated with chloroquine toxicity17,21. according to a study by papavasileou et al, ritonavir can simulate retinitis pigmentosa. retinopathy phenocopying retinitis pigmentosa can be caused by a variety of causes (pseudoretinitis pigmentosa). it's critical to distinguish these illnesses from rp since, unlike rp, these conditions are usually curable5. ritonavir-related retinal toxicity appears to arise only after long-term use4-5,15,17-21. in documented cases, the shortest period of therapy before diagnosis was 19 months. this case's 7-year history of ritonavir use before to diagnosis is consistent with earlier accounts. the loss of vision caused by this toxicity can be worse4,15,19,21, and there have been reports of advancement even after the medicine has been stopped. early detection and withdrawal of ritonavir use are critical, as one case was reported to be reversible in a patient with acute and symptomatic illness21. furthermore, vadlapatla et al. discovered that ritonavir inhibits hypoxia-inducible factor 1 (hif1) and vascular endothelial growth factor (vegf) in retinal pigment epithelial cells in vitro. inhibition of vegf causes choriocapillaris and photoreceptor degradation in nonhypoxic mice's retinas23. vegf may also have a direct neurotrophic effect on photoreceptors, according to kurihara et al. as a result, it's possible that ritonavir's persistent reduction of vegf synthesis could deplete neurotrophic factors important for photoreceptor health or create choriocapillaris vascular malfunction, affecting both the retinal pigment epithelium and the photoreceptors24. needless to say, further study is indicated to better characterize the pathophysiology of this toxicity. conclusion despite the fact that case studies discussing ritonavir’s adverse effects on the retina have been rare in the last decade, we continue to elaborate on those reports comprehensively. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 55 this systematic review summarizes findings of retinal toxicity alterations related with long-term ritonavir usage. it might be beneficial to raise primary eye care practitioners' awareness of the importance of early diagnosis of sight-threatening side effects associated with hiv patients' ritonavir therapy, so that they can refer to a retina specialist for further medical examination and research to gain a better understanding of ritonavir's potential side effects. references 1. louie ak, jones hn. case report: retinal toxicity secondary to ritonavir. optom vis sci. 2019;96(5):376-381. 2. pereira m, ferreira l, horta a, carvalho ac. exogenous cushing's syndrome as a result of ritonavir–budesonide interaction – a case report. hiv & aids review. 10.1016/j.hivar.2016.03.002. 2016;15(2);91-93. 3. bunod r, miere a, zambrowski o, girard p, surgers l, eric h. ritonavir associated maculopathy-multimodal imaging and electrophysiology findings. american journal of ophthalmology case reports. 2020;19(9). 4. roe rh, jumper jm, gualino v. retinal pigment epitheliopathy, macular telangiectasis, and intraretinal crystal deposits in hiv-positive patients receiving ritonavir. retina. 2011;31(3);559-565. 5. papavasileiou e, younis s, zygoura v, quijano c, jackson tl. ritonavir-associated toxicity mimicking retinitis pigmentosa in an hiv-infected patient on highly active antiretroviral therapy. retinal cases & brief reports. 2016;0(0);1. 6. aao (american academy of ophthalmology), policy statement definition of primary eye care, san fransisco: american academy of ophthalmology. 2014;3-6. 7. ceh (community eye health) / international centre for eye health, who can carry out primary eye care, london: community eye health. 1998;11(28). 8. ceh (community eye health) / international centre for eye health, development of primary eye care as an integrated part of comprehensive health care, london: community eye health. 1998;11(28).20 non l, jeroudi a, smith bt, and parsaei s. bull’s eye maculopathy in an hiv-positive patient receiving ritonavir. antiviral therapy. 2016;21(4);365-367. 9. fanales-belasio e, raimondo m, suligoi b, buttò s. hiv virology and pathogenetic mechanisms of infection: a brief overview. ann ist super sanità 2010;46(1):5-14. 10. vidya vijayan kk, karthigeyan kp, tripathi sp, hanna le. pathophysiology of cd4+ t-cell depletion in hiv-1 and hiv-2 infections. front. immunol. 2017;8(850). 11. seitz r. human immunodeficiency virus (hiv). transfusion medicine and hemotherapy2016;43(3):203–222. 12. saini m. and potash m. chronic, highly productive hiv infection in monocytes during supportive culture. current hiv research 2014;12(5):317–324. 13. goldberg de, smithen lm, angelilli a, freeman wr. hiv-associated retinopathy in the haart era. retina 2015;25(5):633–649. 14. cozzupoli gm, savastano mc, falsini b, savastano a, rizzo s. possible retinal impairment secondary to ritonavir use in sars-cov-2 patients: a narrative systematic review. j ophthalmol. 2020;2020:5350494. 15. faure c, paques m, audo i. electrophysiological features and multimodal imaging in ritonavirrelated maculopathy. doc ophthalmol. 2017;135(3):241-248. 16. konsil kedokteran indonesia. standar nasional pendidikan profesi dokter indonesia. 2019:170. 56 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 17. pinto r, vila-franca m, oliveira afonso c, ornelas c, and santos l. ritonavir and bull’s eye maculopathy: case report. gms ophthalmol cases. 2013;3;1-4. 18. biancardi al, curi al. retinal toxicity related to long-term use of ritonavir. retina: the journal of retinal and vitreous disease. 2016; 36(1):229-231. 19. mesquita lrc, da fonseca mlg, da silva rm, morizot, eh. panretinal ritonavir-induced retinopathy. retinal cases & brief reports. 2018;0(0);1. 20. non l, jeroudi a, smith bt, and parsaei s. bull’s eye maculopathy in an hiv-positive patient receiving ritonavir. antiviral therapy. 2016;21(4);365-367. 21. tu y, poblete rj, freilich bd, zarbin ma, bhagat n. retinal toxicity with ritonavir. int j ophtalmol 2016;9(4):640-642. 22. medicines agency european, “norvir: epar scientific discussion,” 2005, https://www.ema.europa.eu/en/documents/scienti fic-discussion/norvir-epar-scientificdiscussion_en.pdf 23. vadlapatla rk, vadlapudi ad, pal d, mukherji m, and mitra ak. ritonavir inhibits hif-1α-mediated vegf expression in retinal pigment epithelial cells in vitro. eye. 2014;28(1);93-101. 24. kurihara t, westenskow pd, bravo s, aguilar e, and friedlander m. targeted deletion of vegfa in adult mice induces vision loss. journal of clinical investigation. 2012; 122(11);4213-4217. this work licensed under creative commons attribution 1 general practitioner at pelabuhan hospital, jakarta 2 general practitioner at bhayangkara pusdik brimob hospital, pasuruan published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 45 international journal of retina (ijretina) 2018, volume 1, number 2. p-issn. 2614-8684, e-issn.2614-8536 the difference of visual field defect on diabetic retinopathy patients treated with panretinal laser photocoagulation with 20-milisecond and 100-milisecond duration nova herdana, ak ansyori, ramzi amin, irsan saleh department of ophthalmology, universitas sriwijaya, palembang, indonesia abstract introduction: panretinal laser photocoagulation (prp) is a standard treatment for severe nonproliferative and proliferative diabetic retinopathy. twenty-milisecond duration prp show same effectiveness with 100-ms standard prp in inhibit neovascularization progression. this shorter pulse tend to minimize retinal neuronal defect and visual field defect. this study aim to analyze the difference of visual field defect in diabetic retinopathy (dr) patients treated with 20-ms prp compared with 100-ms prp in moh. hoesin hospital palembang. methods: a clinical trial with single blinding on severe-very severe npdr and early pdr eyes treated with prp between june and august 2016. forty eyes (25 patients) were randomized into two groups. twenty eyes were treated with 20-ms prp, and other 20 eyes treated with 100-ms prp. visual field defect was evaluated using humphrey field analyzer 30-2 sita standard at baseline and 2 weeks follow-up. result: unpaired t-test showed significant difference in mean deviation (md) after laser on npdr eyes (p=0.042, p<0.05), meanwhile there was no significant difference in early pdr eyes (p=0.17, p>0.05). in npdr eyes, more md improvement was found in 20-ms prp group (0.79±0.93 db) than in 100-ms group (-0.04±0.61 db). in early pdr eyes, md improvement was bigger (1.0±0.88 db) in 20-ms prp group than in 100-ms group (0.10±1.47 db). there was no significant difference in pattern standard deviation (psd) on both group at any dr grade (p=0.208; p=0.201; p>0.05). conclusion: after 2 weeks, 20-ms prp caused more improvement and lesser visual field defect (p=0.042, p<0.05) on npdr eyes. there was no significant difference in psd on both groups. keywords: diabetic retinopathy, panretinal laser photocoagulation, visual field defect. cite this article: herdana, nova et al. the difference of visual field defect on diabetic retinopathy patients treated with panretinal laser photocoagulation with 20-milisecond and 100-milisecond duration. international journal of retina, [s.l.], v. 1, n. 2, aug. 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/35>. introduction *correspondence to: nova herdana, department of ophthalmology, universitas sriwijaya. nouv.nice2@gmail.com panretinal laser photocoagulation (prp) remains the gold standard treatment to inhibit progression and reduce the risk of severe visual loss in proliferative diabetic retinopahy (pdr). the goal of prp is to destroy ischemic retina and increase oxygen tension in the eye so it can regress the neovascularization.1,2 the thermal effect of the laser coagulates surrounding photoreceptors and retinal pigment epithelium (rpe) cells and immediately creates laser burns within outer retinal layer. after photocoagulation, the photoreceptors were shifting from adjacent areas into the lesion, mediated by mueller cells, form glial matrix filling the lesion in the photoreceptors layer in 1 weeks, and reestablish synapses to neurons in the inner nuclear layer (inl). this process restore light sensitivity and local activation of the bipolar and ganglion cells in the former lesion.3,4 46 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; the laser scar expansion in the retina may be associated with photoreceptor loss, rpe hyperthrophy, and visual field loss. longer pulse durations and greater laser energy have caused collateral damage not only in the outer but also into the inner retina. blankenship reported that laserinduced damage within retinal ganglion cells results in the loss of nerve fiber layer and thinning within peripapillary nerve fiber layer zones. heijl and henricsson (1994) reported visual field sensitivity was often depressed even before treatment with mean md -4.3 (-1, -11.6) db, but it significantly lower 2 weeks after prp with mean md -8.6 db.2,3 conventional photocoagulation using a single application of laser energy per shots is usually delivered as a 100-200 ms duration burns. early treatment diabetic retinopathy study (etdrs) recommends aplication of up to 2000 visible end-point burns on the retina. a new laser method of pattern scan laser (pascal) photocoagulation using a shorter pulse (10-20-ms) duration was introduced in 2005 to reduce collateral retinal injuries. the laser burns are localized in outer retina so that it reduce rnfl loss and minimize visual field defect after laser.5,6 the use of 1500 20-ms burns in a single session was shown to be a safe regimen in the manchester pattern scan laser study (mapass) trial. this shorter pulse duration prp resulted in similar regression of diabetic retinopathy compared to conventional prp.6 this study aim to assess the difference of visual field defect in dr patients treated with 20-ms prp compared with 100-ms prp. methods a clinical trial study with single blinding was conducted. it included 40 eyes of 25 type 2 dm patients with dr who attended vitreoretina subdivision at mohammad hoesin hospital between june and august 2016. written informed consent was taken from all patients for the procedure. information was collected on age, sex, involving eye, duration of diabetes (years), and gradation of dr. inclusion criteria were patients with type 2 dm who had severe-very severe npdr, early pdr, who underwent laser prp; normal intraocular pressure (10-21 mmhg), had ability to perform accurate humphrey visual field test. exclusion criteria were posterior segment abnormality which is not severe-very severe npdr and early pdr, previous laser or intravitreal injection, glaucoma, and eyes with media opacity that prevent fundus examination and prp laser treatment. prp was done with argon laser from visulas 532s (carl zeiss meditec), with spot size 200 µm and power was adjusted untill received grey-white burn according to etdrs guidelines, with one half burn width apart. an average 1200 to 2000 burns were given. the study sample was randomized into two groups. twenty eyes were treated with 20-ms duration prp, and other 20 eyes treated with 100-ms duration prp. visual field defect was evaluated using humphrey field analyzer 30-2 sita standard at baseline and 2 weeks follow-up. we recorded visual acuity (va), visual field index (vfi), mean deviation (md), and pattern standard deviation (psd) before and 2 weeks after prp treatment. we performed statistical analyses using spss version 21 with t-test, wilcoxon and mann whitney test to analyze the difference of visual field among the two groups. the null hypothesis was rejected for p-values < 0.05. results a total of 40 eye samples obtained from 25 diabetic patients (mean age 51.76 years; range 39-63) were treated with prp. in 20-ms prp group, the mean age was 52.65±7.54 years and in 100-ms prp group was 51.75±7.59 (p=0.709). all included 16 female (64%) and 9 male (36%) eye samples. the characteristics of the subjects are described in table 1. table 1. characteristics of the subjects in the study characteristics number (%) sex male female age <40 years 40-49 years 50-59 years > 60 years laterality bilateral right eye left eye duration of dm (years) < 5 years 5-10 years >10 years dr gradation severe npdr very severe npdr early pdr 9 (36) 16 (64) 1 (4) 8 (32) 10 (40) 6 (24) 15 (60) 6 (24) 4 (16) 7 (28) 7 (28) 11 (44) 15 (37.5) 2 (5) 23 (57.5) published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 47 the mean duration of diabetes was 9.24 years (range 315 years) with 11 (44%) subjects had diabetes for more than 10 years. seven (28%) subjects had diabetes for 5-10 years and less than 5 years, respectively. the distribution of dr gradation were 23 (57.5%) early pdr eyes, 15 (37.5%) severe pdr, and 2 (5%) very severe pdr eyes. fifteen (65.2%) of all early pdr eyes had diabetes for more than 5 years, and 13 (76.5%) of all npdr eyes either. the relation of dr gradation with duration of dm are shown in table 2. in severe-very severe npdr eyes, paired t-test show no significant difference in va before and after prp on both group with p=0.351 for 20-ms prp and p=0.121 for 100ms prp group (p>0.05). the same results were obtained in early pdr eyes (p>0.05). there was no significant difference on both group at any dr gradation. see table 3. table 2. relation of dr gradation with duration of dm duration of dm dr gradation p* severe-very severe npdr early pdr < 5 years 4 (23.5%) 8 (34.8%) 0.505 ≥ 5 years 13 (76.5%) 15 (65.2%) total 17 (100%) 23 (100%) *chi square test (p<0.05) table 3. comparison of visual acuity on both group to dr gradation dr gradation prp duration visual acuity (logmar) p* p** before after improvement severevery severe npdr 20-ms 0.48+0.34 0.44+0.24 -0.04+0.10 0.351 0.130 100-ms 0.60+0.22 0.53+0.12 -0.07+0.10 0.121 early pdr 20-ms 0.74+0.27 0.68+0.24 -0.06+0.03 0.101 0.918 100-ms 0.72+0.27 0.67+0.24 -0.05+0.03 0.135 *paired t-test (p<0.05); **unpaired t-test (p<0.05) table 4. comparison of visual field index (vfi) on both group to dr gradation dr gradation prp duration visual field index (vfi) p+ p++ before after improvement severevery severe npdr 20-ms 94.5 (77-99) 94 (90-99) -0.05 1.000 0.074 100-ms 92 (76-100) 92 (77-95) 0 0.592 early pdr 20-ms 84.5 (34-93) 87.5 (59-95) 3 0.037 0.853 100-ms 88 (45-98) 88 (58-95) 0 0.574 +wilcoxon test (p<0.05); ++mann whitney test (p<0.05) 48 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; table 5. comparison of mean deviation (md) on both group to dr gradation dr gradation prp duration mean deviation (md) p* p** before after improvement severe-very severe npdr 20-ms -7.48+2.72 -6.69+1.79 0.79+0.93 0.560 0.042 100-ms -8.77+2.71 -8.81+2.10 -0.04+0.61 0.954 early pdr 20-ms -11.25+4.48 -10.25+3.60 1.0+0.88 0.138 0.719 100-ms -10.86+4.51 -10.76+3.04 0.10+1.47 0.928 *paired t-test (p<0.05); **unpaired t-test (p<0.05) table 6. comparison of pattern standard deviation (psd) on both group to dr gradation dr gradation prp duration pattern standard deviation (psd) p* p** before after improvement severevery severe npdr 20-ms 3.39+1.80 3.30+1.57 -0.09+0.23 0.953 0.208 100-ms 4.45+2.54 4.30+1.93 -0.15+0.61 0.860 early pdr 20-ms 6.16+1.92 6.19+2.24 0.03+0.32 0.863 0.201 100-ms 5.14+2.17 4.99+2.44 -0.15+0.27 0.650 *paired t-test (p<0.05); **unpaired t-test (p<0.05) visual field index (vfi) at 2 weeks after prp, there was a significant vfi improvement in early pdr treated with 20-ms duration prp (p=0.037), but not in 100-ms prp group (p=0.574). however, the difference between both laser laser group was insignificant in npdr and pdr group (p=0.074 and p=853, respectively). these comparison can be seen in table 4. mean deviation (md) before the treatment, there was a significant difference in md between dr gradation. the mean md in early pdr (-11.06±4.40) was reduced more than in severe-very severe npdr eyes (-8.16±2.71) with p=0.021 (p<0.05). at npdr eyes follow up, we found more md improvement (0.79±0.93, p=0.560) in 20-ms prp and less improvement in 100-ms prp (-0.04±0.61, p=0.954). unpaired t-test showed a significant difference between both group (p=0.042, p<0.05). at early pdr eyes, we found less md improvement both in 20-ms prp and 100-ms prp group (1.0±0.88 and 0.10±1.47, respectively) than in npdr eyes. this result also showed no significant difference in between both group (p=0.719). these comparison are outlined in table 5. pattern standard deviation at baseline, there was a significant difference in psd between dr gradation. the mean psd in early pdr (5.68±2.06) was reduced more than in severe-very severe npdr eyes (3.95±2.22) with p-value =0.016 (p<0.05). compared to the baseline, we found psd difference was insignificant between 20-ms and 100-ms prp in npdr eyes (p=0.953 and 0.860) and pdr eyes (0.863 and 0.650). unpaired t-test also found no significant difference between these laser group (p=0.208). the similar result was also found in pdr eyes follow up, with p=0.201 (p>0.05) between both laser group. see table 6. discussion diabetic retinopathy is one of the most prevalent cause of legal blindness in patients aged 20-64 years. with aging population, this prevalence is expected to rise. in our study, the mean age in 20-ms prp and 100-ms prp group was 52.65±7.54 years and 51.75±7.59 years, respectively. the highest prevalence was at age range 50-59 years (40%). these results were close to a study performed by park (2012), which obtained mean age of dr patients were 55.3 years. al-amer (2008) found a mean age 57.8 years with highest prevalence at age range 56-65 years. meanwhile, boesoirie (2005) reported that highest prevalence of dr was at age range 41-50 years and 51-60 years (36.84%, equally). 7,8,9 all patients included 16 (64%) female and 9 ( 36%) male eyes. wang et al (2013) also reported that the prevalence of dr in female (64.5%) were more than male (35.5%). meanwhile, tajunisah et al (206) reported that prevalence of dr in male (57.4%) was bigger than female. these published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 49 differences could probably due to different size of sample, population characteristics, and duration of the study.10,11 the wisconsin epidemiologic study of diabetic retinopathy (wesdr) reported that the duration of dm was directly associated with an increased prevalence of dr in both type 1 and type 2 dm.1 al-amer (2008) reported that the chance to have dr increase 21% per year duration of dm.8 jee et al (2013) reported the prevalence of dr was 2.8% in new dm patients, increase to 33.2% in patients having dm for > 10 years.12 he et al (2012) the mean duration of dm was 8.05±6.71 years, with pdr group (10.58±6.98) was longer than npdr group (6.99±6.29).13 in our study, fifteen (65.2%) of all early pdr eyes had diabetes for more than 5 years, and 13 (76.5%) of all npdr eyes either (table 2). most of our patients did not realize that they had diabetic, so they would go for examination only if they already had visual disturbance. there was no significant difference in va before and after prp on both laser group at any dr gradation (p=0.130 for npdr group and p=0.918 for early pdr group). cho et al (2013) reported no significant difference in va between before and after 20-ms prp (0.09±0.24, p=0.18). the thickening of the subfoveal choroid may indicate choroidal effusion produced by a disruption of the choriocapillaris caused by laser photocoagulation. the damage to the choroid induced transudation in 59-90% eyes after prp, with the associated ciliochoroidal effusion resolving completely in 7-14 days.14 at 2 weeks after prp, there was a significant vfi improvement in early pdr treated with 20-ms duration prp (p=0.037), but not in 100-ms prp group (p=0.574) and both laser group npdr gradation (table 4). vfi has focused on central visual field. therefore, the decrease in vfi can be detected if the visual field change were at central, not peripheral visual field. marvasti et al (2013) revealed that vfi has linear correlation with retinal ganglion cell (rgc) numbers.15 this fact gives us an early information that 20-ms prp cause lesser damage in rgc more improvement than 100-ms prp. mean deviation (md) is the average elevation or depression of the patient’s overall field compare to the normal reference field. a significant md may indicate that the patient has an overall depression, or that there is significant loss in one part of the field and not in others. before the treatment, the mean md in early pdr (11.06±4.40) was significantly reduced more than in severe-very severe npdr eyes (-8.16±2.71) with p=0.021. a similar result also found in pattern standard deviation (psd). psd is a measurement of the degree to which the shape of the patient’s measured field departs from the normal, age-corrected reference field. psd reflects irregularities in the field caused by localized defects. the mean psd in early pdr (5.68±2.06) was significantly reduced more than in severe-very severe npdr eyes (3.95±2.22) with p-value = 0.016 (p<0.05). henricsonn and heijl (1994) reported that there was no evidence of visual field loss in eyes with mild disease, but clear visual field defects in eyes with more advanced disease. significantly reduced sensitivity was often correlated with retinal nonperfusion and it tend to be in the midperiphery than paracentrally.16 kiss and miller reported that shorter duration pulse are confined more to the outer retina with less energy spread laterally or in the direction of the choroid or nerve fiber layer.5 this theory supports our study results. at npdr eyes follow up, we found more md improvement (0.79±0.93) in 20-ms prp and less improvement in 100ms prp (-0.04±0.61). unpaired t-test showed a significant difference between both group (p=0.042, p<0.05). an unsignificant difference was obtained in early pdr group between both laser group with p-value 0.719. however, md improvement in 20-ms prp (1.0±0.88) was bigger than 100-ms prp (0.10±1.47) group. this results give us an early information that shorter pulse laser give more improvement effect to visual field defect. in our study, the irregularities in the field caused by localized defects has not change yet at 2 weeks after prp. at follow up, psd difference was insignificant between 20ms and 100-ms prp in npdr and pdr eyes. unpaired ttest also found no significant difference between these laser group in both dr gradation. wang et al (2013) reported psd improvement from 3.26±1.56 db to 2.84±1.38 db after 12 weeks with 20-ms prp treatment.10 sher (2013) and paulus (2008) reported that laser scar was formed in 1 weeks and get complete resolution in 2-4 months.4,17 the difference result is due to our shorter follow-up time and lesser sample size. conclusion after 2 weeks, 20-ms prp caused more improvement and lesser visual field defect (p=0.042) on npdr eyes. although statistically insignificant, the study reported that md and psd improvement were bigger in 20-ms prp than 100-ms prp. further study with larger sample size and longer follow-up is needed to assess the visual field difference after treatment between these difference laser duration. references 1. skuta gl, cantor lb, weiss js, et al. retina and vitreous. american academy of ophthalmology 2014-2015. 2. muqit mmk, wakely l, stanga pe, et al. effect on conventional argon panretinal photocoagulation on retinal nerve fiber layer and driving visual fields in diabetic retinopathy. eye. 2009: 1-7. 3. henriccson m, heijl a. the effect of panretinal photocoagulation on visual acuity, visual field and on subjective visual imapirment in preproliferative and early proliferative diabetic retinopathy. acta ophthalmologica (copenh). 1994; 72(5):570-5. 50 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 4. paulus ym, jain a, gariano rf, et al. healing of retinal photocoagulation lesions. iovs. 2008, vol 49: 5540-5. 5. kiss s, miller jw. the pattern scanning laser (pascal) photocoagulator for diabetic retinopathy. us ophthalmic view. 2011; 94-95. 6. muqit mmk, marcellino gr, henson db, et al. pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy : manchester pascal study report 4. eye (25). 2011;1447-1456. 7. park, et al. prevalence and risk factor for diabetic in koreans with type ii diabetes : baseline characteristics of seoul metropolitan city-diabetes prevention program (smc_dpp). bjo. 2012;96:151-155. 8. al-amer, et al. prevalence and risk factors of diabetic retinopathy among jordanian patients with type 2 diabetes. digital journal of ophthalmology. vol 14. 2008. 9. boesoirie sf. keberhasilan terapi fotokoagulasi laser pada pasien retinopati diabetik di rumah sakit cicendo bandung. 2005. 10. wang j, zhang r, chen rp, et al. prevalence and risk factors for diabetic retinopathy in a high-risk chinese population. bmc public health. 2013;13:633. 11. tajunisah i, et al. prevalence and risk factors for diabetic retinopathya study of 217 patients from university of malaya medical centre. med j malaysia. vol 61 (4). 2006:451-6. 12. jee d, lee wk, kang s. prevalence and risk factors for diabetic retinopathy: the korean national health and nutition examination survey 2008-2011. iovs vol 54. 2013:6827-33. 13. he, et al. factors associated with diabetic retinopathy in chinese patient with type 2 diabetes mellitus. international journal of endocrinology. 2012;53:115663. 14. cho ge, cho hy, yt kim. change in subfoveal choroidal thickness after argon laser panretinal photocoagulation. int j ophthalmol. vol 6. 2013:505509. 15. marvasti ah, et al. the relationship of a new visual field index, the vfi, with mean deviation (md) in 30-2 and 24-2 treshold tests examined by humphrey field analyzer. gujarat medical journal, vol 60. 2014. 16. henricsson m, heijl a. visual field at different stages of diabetic retinopathy. acta ophthalmologica. 1994:72(5):560-9. 17. sher a, et al. restoration of retinal structure and function after selective photocoagulation. j. neurosci. april 2013. 33(16):6800-6808. this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 9 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 is 360° intraoperative laser retinopexy after primary pars plana vitrectomy worthwhile to prevent recurrent retinal detachment? marouane maslik, younes abaaqil, sarah belghmaidi, ibtissam hajji, abdeljalil moutaouakil mohammed 6 university hospital, marocco abstract introduction: to determine if performing 360° laser retinopexy anterior to the equator during surgery is a viable option to prevent recurrent retinal detachment following a primary pars plana vitrectomy for rhegmatogenous retinal detachment methods: a consecutive case series of 142 patients with retinal detachment who underwent vitrectomy by a single surgeon in mohammed vi university hospital marrakech hospital between january 2020 and december 2021. a comparison was made between a group of consecutive patients who underwent 360° laser retinopexy and a control group of patients who did not receive the treatment (39). patient demographic and clinical information was gathered from medical records. both groups were analyzed and compared in terms of baseline characteristics and the risk of recurrent retinal detachment over time. result: prophylactic intraoperative 360° laser treatment was performed on 103 rrd cases (52 years) and compared to a control group of 39 rrd cases (56.8 years). the rate of the incidence of recurrent retinal detachment at six months after surgery was 12.6%( 13/103 eyes) in the 360° laser group and 28.2%(11/ 39 eyes) in the control group. conclusion: intraoperative 360° laser retinopexy performed after primary pars plana vitrectomy led to a substantial decrease in the rate of recurrent retinal detachment post-surgery. keywords: 360° laser ; rhegmatogenous ; retinal detachment ; prevention ; reccurence cite this article: maslik, marouane et al. is 360° intraoperative laser retinopexy after primary pars plana vitrectomy worthwhile to prevent recurrent retinal detachment?. international journal of retina, [s.l.], v. 6, n. 1, p. 9, feb. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/213>. date accessed: 28 feb. 2023. doi: https://doi.org/10.35479/ijretina.2023.vol006.iss001.213 correspondence to: marouane maslik, mohammed 6 university hospital, marocco marouane.maslik.2@gmail.com introduction rhegmatogenous retinal detachment (rrd) repair is a common vitreoretinal surgical procedure. despite good surgical techniques and less-invasive technologies, up to 10% of cases may still require additional interventions to repair an eventual recurrent retinal detachment. this may be due to surgical technique and the presence of remaining peripheral vitreous, which can lead to traction on the peripheral retina and retinal detachment. . https://doi.org/10.35479/ijretina.2023.vol006.iss001.213 10 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; to prevent this, careful peripheral retinal examination, proper treatment of retinal breaks, and prophylactic scleral buckling or cryopexy have been used[1,2,3]. however, there is a need for a less-invasive alternative. we hypothesize that 360°intraoperative laser retinopexy anterior to the equator can reduce the incidence of retinal breaks and detachment by creating strong chorioretinal adhesion and preventing the progression of retinal detachment, similar to demarcation laser treatment. this study aims to evaluate the effect of intraoperative 360° prophylactic laser retinopexy on the incidence of retinal detachment after vitrectomy in rrd cases using a case-control design. methods this study retrospectively reviewed the medical records of patients who underwent primary pars plana vitrectomy for rhegmatogenous retinal detachment (rrd) by two surgeons at mohammed vi university hospital in marrakech between january 2020 and december 2021. the patients were part of a consecutive case series cohort and were divided into two groups based on whether or not they received intraoperative prophylactic 360° laser retinopexy. the study was approved by the institutional review board and all patients provided informed consent. the preoperative evaluation included a detailed examination and the collection of patient information such as age, gender, systemic disease, previous ocular surgery, and associated eye diseases. postoperative evaluations were conducted at various intervals up to six months after surgery. patients with previous ocular surgery, giant tears, retinal dialysis, trauma, proliferative vitreoretinopathy grade c or higher, retinal detachment with macular hole, or round hole detachment without associated pvd were excluded from the study. surgical technique after local or general anesthesia, phakic patients underwent cataract surgeries. sclerotomies were created 3.5 mm from the limbus and the posterior cortical vitreous was removed up to the vortex vein. the eyes underwent 360° scleral depression to trim the vitreous base [conventional 23-gauge ppv done]. after fluid-air exchange, the causal retinal breaks were treated with a focal endo-laser. in the treatment group, 360° laser retinopexy was performed by placing three rows of white burns anteriorly to the vortex vein level, towards and beyond the equator with burns approximately one burn width apart using the endo-laser system.sutures of the sclerotomies were made with 8.0 vicryl. retinal detachment patients with superior breaks were positioned upright, while those with nasal, temporal, or inferior breaks were positioned on the contralateral cheek. statistical analysis additionally, multivariate regression analysis was performed to determine the independent effect of prophylactic 360° intraoperative laser on the rate of retinal detachment after vitrectomy, while controlling for other baseline and intra-operative factors that could impact the rate of re-detachment. the odds ratio and 95% confidence interval were calculated to determine the effect size of prophylactic 360° intraoperative laser on the rate of re-detachment. the results of the statistical analysis were used to evaluate the efficacy and safety of prophylactic 360° intraoperative laser in reducing the rate of retinal detachment after vitrectomy in patients with rrd. results baseline characteristics of the study cohort 142 rrd cases were included . demographics and clinical data are summarized in table 1. intraoperative circumferential laser was performed on 142 rrd cases (72.5%) and compared to a control group of 39 rrd cases (27.5%). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 11 table 1: patients characteristics incidence of retinal detachment in the study, the rate of retinal re-detachment in the control group (28.2%) was significantly higher (p=0.045) compared to the 360° laser group (12.6%) (table 2). this suggests that the use of prophylactic 360° intraoperative laser leads to a reduction in the incidence of retinal re-detachment in patients treated with ppv for rrd. the results demonstrate that prophylactic 360° intraoperative laser is an effective method for reducing the risk of retinal redetachment in patients with rrd. other complications the results of the study showed that there was a significant reduction in the rate of retinal redetachment in the 360° laser group compared to the control group. however, the proportions of erm, macular hole, cystoid macular edema, and vitreous hemorrhage did not show a statistically significant difference between the two groups. the postoperative erm occurred in 6.8% of the eyes from the 360° laser group and 5% from the control group, and there was no statistically significant difference between the groups. no patient developed a macular hole, and the incidence of cme and vitreous hemorrhage was low and comparable in both groups. overall, the results indicate that the prophylactic 360° laser did not increase the risk of postoperative erm or other complications in rrd cases. retinal detachment 360° laser group control group p number 103 39 age(year) 52 ±10 56.8 ± 9.5 0.756 gender(m/f) 75/28 12/27 0.434 lens status (phakic, pseudophakic ) 71/32 27/12 macula status(on/off) 21/82 9/30 0.346 axial length 24.4 ± 2.4 24.7 ± 2.8 0.688 preop va 20/86 20/75 0.297 retinal break(single/multiple) 31/72 8/31 0.523 localization of breaks (n: nasal, sup: superior, inf: inferior, t: temporal) n: 11 t:32 sup:36 inf:24 n: 2 t:17 sup:12 inf:8 breaks size (clock hours ) (grt excluded) <1:84 1≤bs<2: 17 ≥2:2 <1:32 1≤bs<2: 5 ≥2:2 preop pvr (c or higher excluded ) a:16 b:87 a:7 b:32 lattice degeneration(+/-) 91/12 32/7 0.784 tamponade(sf6/c2f8/c3f8) 5/81/17 3/35/1 0.972 12 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; table 2: complications visual acuity between the 360° laser group and the control group. both groups showed a similar level of improvement in visual acuity after surgery (log mar; the 360° laser group: 0.10 ± 0.25 compared to the control group: 0.06 ± 0.28, p = 0.193) (table 3). table 3 visual acuity retinal detachment 360° laser group control group p preoperative va 20/86 20/75 (log mar) 0.61 ± 0.84 0.58 ± 0.90 0.688 postoperative va 20/28 20/24 (log mar) 0.10 ±0.25 0.06 ± 0.28 0.193 discussion vitreoretinal traction caused by vitreous adhesion is a significant element in the occurrence of rrd , as it can form retinal breaks and create a tractional force that allows vitreous fluid to enter the subretinal space[4,5]. therefore, surgical interventions such as ppv (pars plana vitrectomy), scleral buckling (sb), or a combination of these techniques are typically performed to relieve vitreoretinal traction, seal retinal breaks, and drain subretinal fluid. [6] scleral buckling is an effective technique for relieving vitreous traction, as it indents the eye wall and enhances proximity between the retinal pigment epithelium and detached retina by displacing subretinal fluid and closing retinal breaks. [7,8]. however, there are postoperative complications associated with scleral buckling that may lead some surgeons to choose ppv over sb (refractive changes, globe ischemia, buckle extrusion, strabismus, and diplopia, serous choroidal detachment) [9,10] on the other hand, the ppv technique also has limitations, including difficulties in overcoming vitreoretinal tractional forces at the vitreous base, particularly in phakic patients which limits access to the peripheral vitreous. shaving the peripheral vitreous is a controversial issue, with some surgeons recommending it and others suggesting that it is not necessary for success. [11,12] proliferative vitreoretinopathy, locating all retinal breaks failure, and occurrence of new breaks secondary to vitreous base traction forces are important causes of retinal detachment recurrence. retinal detachment 360° laser group total n=103 control group total n=39 p retinal re-detachment new breaks ( peripheral / posterior ) opening of older breaks pvr 13(12.6%) 3/0 4 6 11(28.2%) 5/1 2 3 0.092 epiretinal membrane 7(6.8%) 2(5%) 0.230 macular hole 0 (0%) 0 (0%) 0.274 cystoid macular edema 1(1%) 1(2.5%) 0.669 vitreous hemorrhage 1(1%) 0(0%) 0.885 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 13 peripheral retinopexy is proposed as a solution to these issues by creating a “second” ora serrata, but the effectiveness of 360° prophylactic laser retinopexy in patients with rrd remains a topic of controversy. [11,13] performing 360° endo laser as an extra procedure during ppv for rrd treatment has not been extensively studied. some reports exist about its use for reducing the retinal detachment rate, but these are mostly related to the treatment of macular diseases [14, 15, 16], or before silicon oil removal [17]. however, there are not many studies about the efficiency of 360 laser in ppv for rrd. in terms of demographics, initial retinal detachment characteristics, and clinical data, there were no significant differences between the two groups. this study is a retrospective cohort study of 142 cases of rrd treated with primary ppv. the baseline demographic data, including age, sex, duration of symptoms, and lens and refractive status, was not significantly different between the 360° laser group and the control group. both groups were wellbalanced regarding the retinal detachment characteristics the results of the study showed that the rate of re-detachment in the total population was 16%. this falls within the range reported in the current literature (4 to 20%). [18,19]. the rate of re-detachment in the 360° laser group was 12.6%, while it was 28.2% in the control group. the use of 360° laser as an extra procedure was associated with a 55% decrease in the odds of recurrent rd compared to focal retinopexy. previous studies have shown the use of 360° laser photocoagulation in patients undergoing vitrectomy for macular or vitreal diseases, such as epiretinal membrane (erm) and macular hole (mh). these studies have shown a reduction in the incidence of retinal detachment, with koh et al. reporting a threefold reduction in incidence, from 13.3% to 3.5%, in a case series of 220 patients undergoing ppv. yang et al. showed a significant reduction in the redetachment rate in the 360° laser group, from 2.6% to 0%, in a cohort of 618 patients undergoing ppv for a non-rd indication[16]. however, a study by garg et al. found no advantage for rrd prevention in a 176 patients cohort undergoing 360° laser. [20]. the study by iwase about prophylactic 360° laser after phaco vitrectomy in patients with macular holes (mh) and retinal detachment (rd) [15],compared this modality to focal retinopexy. in the cohort of patients with mh, the 360° ilr group showed a significant decrease in the rate of detachment at 12 months (0% vs. 5.7%). however, no statistically significant decrease in the rate of re-detachment was noted in rd’s cases. another study by bilgin et al., (prospective randomized) included 50 patients with rd. 25 in the experimental group (360° laser), and 25 in the control group. [1] the rate of re-detachment was 4% in the exp group compared to 12% in the control group, but the results were not statistically significant. the incidence of epiretinal membrane was 16% in both groups. in a similar way, barrada et al. studied 80 patients with rd treated with primary ppv. the redetachment rate decreased from 32.5% to 25% with the use of a prophylactic 360° laser, but the results were not statistically significant [21]. it is important to note that retinal detachment characteristics in these studies may differ from the current study, such as the presence of macula on detachments and the duration of symptoms/detachment. 14 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; previous studies have shown that 360° laser as an additional procedure after silicone oil removal, has been associated with a reduction in the rate of retinal re-detachment. ( 58% in avitabile et al’s clinical trial) [17]. the incidence of erm formation after 360° laser retinopexy was reported in the study by chaturvedi et al. as 3.2%, suggesting that the procedure may increase the risk of erm formation[22,23]. however, the results of our study did not show a significant increase in erm formation after 360° ilr, with an incidence of 6.8% in the laser group and 5% in the control group. this is in accordance with the current papers on post rd surgery erm formation, as reported by katira et al. which showed an incidence of 12.8% in eyes undergoing ppv for retinal detachment with laser or cryo [11]. the limitations of the study are: • the groups are different in the number of macula off cases and the number of pseudophakic patients, which could add up to the differences between the groups. • the sample size was not large enough to analyze additional co-factors in a multivariate regression model. • the study did not control for all baseline and intra-operative characteristics, which could affect the results. conclusion in summary, the study suggests that prophylactic 360° intraoperative laser during primary ppv for rrd can lead to an important decrease in post-operative re-detachment rate and does not enhance the erm formation risk . the results suggest the performing of 360° laser in patients with rrd treated with ppv and call for a larger randomized controlled trial to further confirm these findings. conflict of interest: none references 1. bilgin, a.b., dogan, m.e., aysun, b. et al. pars plana vitrectomy with or without intraoperative 360° peripheral endo laser for rhegmatogenous retinal detachment treatment. int ophthalmol 39, 1687–1694 (2019). https://doi.org/10.1007/s10792018-0986-z 2. nagpal m, et al. management of recurrent rhegmatogenous retinal detachment. indian j ophthalmol. 2018;66:1763 3. dirani a, antaki f, rheaume ma, et al. 360degree intra-operative laser retinopexy for the prevention of retinal re-detachment in patients treated with primary pars plana vitrectomy. graefes arch clin exp ophthalmol 2020;258:249-56. 4. kuhn f, aylward b. rhegmatogenous retinal detachment: a reappraisal of its pathophysiology and treatment. ophthalmic res 2014;51:15-31. 5. mitry d, fleck bw, wright af, et al. pathogenesis of rhegmatogenous retinal detachment: predisposing anatomy and cell biology. retina 2010;30:1561-72. 6. saw sm, gazzard g, wagle am, et al. an evidence-based analysis of surgical interventions for uncomplicated rhegmatogenous retinal detachment. acta ophthalmol scand 2006;84:606-12. 7. schwartz sg, flynn hw. primary retinal detachment: scleral buckle or pars plana vitrectomy? curr opin ophthalmol 2006;17:245-50. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 15 8. oster sf, mojana f, freeman wr. spectraldomain optical coherence tomography imaging of postoperative scleral buckles. retina 2011;31:1493-9. 9. znaor l, medic a, binder s, et al. pars plana vitrectomy versus scleral buckling for repairing simple rhegmatogenous retinal detachments. cochrane database syst rev 2019;3:cd009562. 10. papakostas td, vavvas d. postoperative complications of scleral buckling. semin ophthalmol 2018;33:70-4. 11. chaturvedi v, basham rp, rezaei ka. scleral depressed vitreous shaving, 360 laser, and perfluoropropane (c3f8) for retinal detachment. indian j ophthalmol 2014;62:804-8. 12. tabandeh h, london nj, boyer ds, flynn hw jr. outcomes of small-gauge vitreoretinal surgery without scleraldepressed shaving of the vitreous base in the era of wide-angle viewing systems. br j ophthalmol 2019;103:1765-8. 13. park sh, yang sc, lee jj, et al. fortified barrier laser on the vitreous base in vitrectomy for rhegmatogenous retinal detachment. clin ophthalmol 2019;13:2127-33. 14. koh hj, cheng l, kosobucki b, freeman wr (2007) prophylactic intraoperative 360 degrees laser retinopexy for prevention of retinal detachment. retina 27(6):744–749. https://doi.org/10.1097/iae.0b013e318030e bd7 15. iwase t, jo yj, oveson bc (2013) effect of prophylactic 360 degrees laser treatment for prevention of retinal detachment after phaco vitrectomy: (prophylactic 360 degrees laser treatment for prevention of retinal detachment). bmc ophthalmol 13:77. https://doi.org/10.1186/ 1471-2415-13-77 16. yang hs, kim yj, kim jg (2016) new prophylactic intraoperative septated circumferential barrier laser in macular surgery. can j ophthalmol 51(2):102–107. https:// doi.org/10.1016/j.jcjo.2015.12.013 17. laidlaw da, karia n, bunce c, aylward gw, gregor zj (2002) is prophylactic 360-degree laser retinopexy protective? risk factors for retinal redetachment after removal of silicone oil. ophthalmology 109(1):153–158 18. adelman ra, parnes aj, ducournau d, european vitreo-retinal society retinal detachment study g (2013) strategy for the management of uncomplicated retinal detachments: the european vitreoretinal society retinal detachment study report 1. ophthalmology 120(9):1804–1808. https://doi.org/10.1016/j. aphtha.2013.01.070 19. lindsell lb, sisk ra, miller dm, foster re, petersen mr, riemann cd, hutchins rk (2017) comparison of outcomes: scleral buckling and pars plana vitrectomy versus vitrectomy alone for primary repair of rhegmatogenous retinal detachment. clin ophthalmol 11:47–54. https://doi.org/10.2147/opth.s112190 20. garg a, chang js, tosi gm, esposti p, chen rw, horowitz j, hoang qv, schiff wm, barile gr, chang s (2018) prophylactic preoperative laser retinopexy does not reduce the occurrence of rhegmatogenous retinal complications in macular surgery. retina 38(9):1707–1712. https://doi.org/10.1097/iae. 0000000000001780 16 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 21. barrada o, nabih m, khattabm a, nosseir a (2015) 360&#176; laser retinopexy in preventing retinal re-detachment after 23gauge vitrectomy for primary repair of retinal detachment. egyptian retina journal 3(1):1–9. https://doi.org/10.4103/23475617. 179339 22. zhou c, qiu q (2015) 360 degrees versus localized demarcation laser photocoagulation for macular-sparing retinal detachment in silicone oil-filled eyes with undetected breaks: a retrospective, comparative, interventional study. lasers surg med 47(10):792–797. https://doi.org/10.1002/lsm.22430 23. katira rc, zamani m, berinstein dm, garfinkel ra (2008) incidence and characteristics of macular pucker formation after primary retinal detachment repair by pars plana vitrectomy alone. retina (philadelphia, pa) 28(5):744–748. https://doi.org/10.1097/iae.0b013e318162b 031 this work licensed under creative commons attribution abstract introduction methods surgical technique results incidence of retinal detachment other complications discussion conclusion published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 1 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 post-evacuation of silicone oil complications in rhegmatogenous retinal detachment patients who underwent pars plana vitrectomy at tertiary hospital in bali, indonesia ari andayani1, i made dwi surya wibawa2, ni made ari suryathi1, anak agung mas putrawati triningrat1, ida bagus putra manuaba1 1 ophthalmology departement faculty of medical and health sciences udayana university-prof dr. i.g.n.g ngoerah hospital bali 2 resident of ophthalmology department faculty of medical and health sciences udayana university-prof dr. i.g.n.g ngoerah hospital bali abstract introduction: pars plana vitrectomy with silicone oil injection has become a standard procedure to treat retinal detachment with complex cases. considerations related to the use of silicone oil are the need for additional surgical procedures to remove silicone oil after the retinal condition is declared stable or because emulsification of silicone oil has occurred. methods: an analytical observational study with a cross-sectional approach. data were collected retrospectively by collecting medical records of patients who underwent silicone oil evacuation in 2021. result: the research subjects were 23 people, where 52.2% of the subjects were women with a median age of 51 years. most of the subjects (65.2%) had no complications, with the most complications occurring were secondary glaucoma (13%) and redetached retina (13%). there was no statistically significant difference between visual acuity before and after the evacuation of silicone oil with a p value of 0.202 and there was no statistically significant difference between iop before and after evacuation of silicone oil with a p value of 0.132. conclusion: evacuation of silicone oil is a follow-up action after ppv with so tamponade. complications which may arise are detach dan glaucoma. there was no significant difference in visual acuity and iop before and after so evacuation. keywords: evacuation of silicone oil, rhegmatogenous retinal detachment, postoperative complications cite this article: andayani, ari. post-evacuation of silicone oil complications in rhegmatogenous retinal detachment patients who underwent pars plana vitrectomy at tertiary hospital in bali, indonesia. international journal of retina, [s.l.], v. 6, n. 1, p. 1, feb. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/221>. date accessed: 28 feb. 2023. doi: https://doi.org/10.35479/ijretina.2023.vol006.iss001.221. 2 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; correspondence to: ari andayani, udayana university, prof i.g.n.g ngoerah hospital bali aldianahalim@yahoo.com introduction rhegmatogenous retinal detachment (rrd) is the detachment of the sensory retinal layer from the retinal pigment cell layer which is marked by a break. pars plana vitrectomy (ppv) is a surgical therapy in rrd cases which was first introduced by robert machemer in 1972 from his previous therapy, namely the sclera buckle. ppv has several advantages compared to the sclera buckle so that until now it has become a standard procedure in treating rrd, but the sclera buckle is still chosen in some cases. one of the drawbacks of the ppv procedure is the use of intraocular gas or silicone oil (so) tamponade after vitrectomy surgery which can accelerate the occurrence of cataracts in fachia patients. 1 so (polydimethylsiloxane) was first introduced by cibis et al in 1962 as a tamponade agent for the treatment of retinal detachment which was later by haut et al combined with vitrectomy. ppv accompanied by injection of so is a standard procedure for treating retinal detachment in complex cases such as proliferative vitreoretinopathy (pvr), giant tears, tractional retinal detachment and trauma.2 so considered a better tamponade than gaseous sulfur hexafluoride (sf6) and perfluopropane (c3f8) in eyes with pvr cases, both for anatomical and functional recovery. in addition, so also does not prevent patients from traveling or staying in certain positions for some time. so can cause long-term complications, including endothelial decompensation, cataracts, increased eye pressure and secondary glaucoma. another consideration related to the use of so is the need for additional surgical procedures to remove so after the retinal condition has been declared stable or because emulsification of the retina has occurred so.3 evacuation of so is associated with improved vision, but there are also those who say that decreased vision can occur during evacuation of so associated with repeated retinal detachment, damage to the optic nerve due to glaucoma, hypotonia in the eye, vitreous hemorrhage, and corneal abnormalities.4 based on the description above, retinal detachment patients undergoing ppv surgery and evacuation so may experience sharp changes in vision and some accompanying manifestations. until now there is still not much data regarding the impact of evacuation measures so in bali, therefore the author wants to do more research on complications after evacuation of so in rhegmatogenous retinal detachment patients undergoing pars plana vitrectomy at prof. dr. igng ngoerah denpasar in 2021. methods this research is an analytic observational study with a cross-sectional approach. data was collected retrospectively by recording the characteristics and medical record data of rhegmatogenous retinal detachment patients who underwent pars plana vitrectomy surgery and so evacuation from january to december 2021 at prof dr. i.g.n.g ngoerah hospital denpasar. the research data included: gender, age, lens status, laterality, visual acuity before and after the so evacuation procedure, intraocular pressure (iop) before and after the so evacuation procedure, indications for silicone oil (so) evacuation, additional actions during silicone oil evacuation and complications that occurred after the evacuation of silicone oil. this study meets declaration of helsinki, published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 3 and it has received an ethical clearance certificate from the research ethics committee of the faculty medicine, udayana university no. 2421/uni4.2.2.vii.14/lt/2022. all data obtained were entered into work tables and analyzed using ibm® spss® statistics 26.0 (international business machines (ibm) corporation, armonk, ny, usa). subject characteristic data were analyzed descriptively. nominal and ordinal categorical scale data are displayed in the form of frequencies and percentages while for numerical scale data in the form of the mean for normally distributed data and the median if the data is not normally distributed. the normality test uses shapiro-wilk because the number of research samples is less than 50. based on the results of the normality test, the research data is not normally distributed so that the analysis of differencesvisual acuity and iop pre and post so evacuation using the non-parametric wilcoxon sign rank test. results during the period of january 1st 2021 to december 31st 2021 there were 23 patients who underwent silicone oil evacuation at prof. dr. igng ngoerah hospital denpasar. the characteristics of the research subjects are shown in table 1 patients were dominated by female at 52.2%. description of the age of research subjects with a median value of 51 years. as many as 69.6% of research subjects live in bali. the status of phakic and pseudophakic lenses with the same amount is 47.8%. as many as 73% of study subjects with laterality in the left eye. as many as 69.6% of the study subjects had visual acuity <3/60 for pre-evacuation and 1 month postevacuation of so so that the data distribution was not normal. the iop in the study subjects was the median value of 14 mmhg for pre-evacuation and the mean± sd 14 mmhg ± 6.42 mmhg for 1 month post evacuation of so. the indication for so evacuation in this study was retina reattached >3 months as much as 73.9%. the actions taken were 47.8% in the form of evacuating only so without any other action. in the subjects of this study, 65.2% did not experience complications after so evacuation and 13% of subjects experienced complications in the form of redetached retina and secondary glaucoma. table 1. characteristics of research subjects characteristics of research subjects n(%) age (median (min-max)) 51.00(17.00-62.00) 12-25 yrs 5 (21.7%) 26-45 yrs 6 (26.1%) 46-65 yrs 12 (52.2%) >65 yrs 0 (0%) gender man 11 (47.8%) woman 12 (52.2%) address bali 16 (69.6%) outside bali 7 (30.4%) lens status phakic 11 (47.8%) pseudophakic 11 (47.8 %) aphakic 1 (4.3 %) laterality right eye 6 (26.1 %) left eye 17 (73.9 %) 4 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; va pre evacuation so <3/60 16 (69.6 %) 3/60 <6/60 1 (4.3 %) 6/60 <6/18 4 (17.4 %) 6/18 <6/12 1 (4.3 %) >6/12 1 (4.3 %) va 1 month post evacuation so <3/60 16 (69.6 %) 3/60 <6/60 5 (21.7 %) 6/60 <6/18 2 (8.7 %) 6/18 <6/12 0 (0 %) >6/12 0 (0 %) iop pre evacuation so (median (min-max)) 14.00 (7.00-37.00) <10 mm hg 1 (4.3 %) 10-21 mm hg 21 (91.3 %) >21mmhg 1 (4.3 %) iop 1 month post evacuation so (mean ± sd) 14.00±6.42 <10 mm hg 7 (30.4 %) 10-21 mm hg 14 (60.9 %) >21mmhg 2 (8.7 %) so evacuation indications reattached retina > 3 months 17 (73.9 %) redetached retina 4 (17.4 %) so emulsification 1 (4.3 %) secondary glaucoma 1 (4.3 %) additional surgery so evacuation only 11 (47.8 %) so evacuation + phaco + iol 8 (34.8 %) so evacuation + retamponade 4 (17.4 %) complications without complications 15 (65.2 %) redetached retina 3 (13.0 %) remaining so in bmd 2 (8.7 %) secondary glaucoma 3 (13.0 %) the normality test for visual acuity data using the shapiro-wilk found that the data were not normally distributed, so a different test was carried out using the wilcoxon signed rank test. based on the results of the wilcoxon signed rank test calculation, a p value of 0.202 was obtained, which indicated that there was no statistically significant difference between visual acuity before and after silicone oil evacuation. table 2. differences between visual acuity before and after silicone oil evacuation means std. deviation z p.s va pre evacuation so 1.6957 1.18455 -1,276 .202 va 1 month post evacuation so 1.3919 .65638 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 5 the normality test for iop data using shapiro-wilk found that the data were not normally distributed, so a different test was carried out using the wilcoxon signed rank test. based on the results of the wilcoxon signed rank test calculation, a p value of 0.132 was obtained, where this shows that there is no statistically significant difference between intraocular pressure before and after evacuation of silicone oil. table 3. differences between intra ocular pressure before and after silicone oil evacuation means std. deviation z p.s tio pre evacuation so 2.0000 .30151 -1,508 .132 tio 1 month post evacuation so 1.7826 .59974 discussion this study was an observational study with a cross-sectional approach, with data obtained retrospectively from january 1st to december 31st 2021, 23 rrd patients who underwent so evacuation were assessed and the complications and characteristics of the patients who underwent the procedure were assessed. data on the characteristics of the research sample as a whole can be seen in table 1. the research sample was grouped based on gender, found that there were more women, namely 52.2%. this is in line with research by leeuwen, et al (2020) where the incidence of rhegmatogenous retinal detachment is higher in women. research conducted by yu et al (2016), obtained more male samples, but not too different from women, namely 53%, meanwhile, another study by jia et al (2020) found a male sample of 62.7%. this difference can be caused by several factors including geographical conditions, ethnicity, and also the size of the study sample. based on age, the median age of the sample was 51 years with an age range of 46-65 years of 52.2%.this was also reported by triwijayanti, et al (2019) of the 77 cases included in the study, 53.25% of the samples were dominated by people over 50 years of age who underwent so evacuation. it is known that retinal detachment is more common in people over 50 years of age, and 66% of retinal detachment patients are older than 50 years, with the highest rate in the age range of 50-59 years. 5,6,7,8 lens status in the subjects of this study obtained the same number of phakic and pseudophakic, namely 47.8% with the most laterality in the left eye of 73.9%. research conducted by lam et al, (2008) stated that the proportion of patients with pseudophakia did not differ much from fachia, namely 37.4% compared to 38.8%. the pseudophakic condition during the so evacuation procedure can be caused by the possibility that the patient's lens condition has advanced cataracts, requiring cataract extraction when performing a vitrectomy.9,10 the visual acuity in this study that we describe is the visual acuity before and after the silicone oil evacuation procedure. 69.6% had visual acuity <3/60 both in the subject before the action or after the silicone oil evacuation was carried out. from research conducted by ghoraba, et al (2021) it was found that 54% of the sample had visual acuity <1/60 before the so evacuation was carried out and 65% in the range of 1/60 to 3/60. in this study, there was no statistically significant difference in visual acuity between before and after so evacuation. this was also reported by ghoraba, et al (2021) where there was no significant relationship between visual acuity before and after so evacuation. the condition of visual acuity that did not differ between before and after so evacuation was probably caused by several things, including the long waiting time for surgery, the condition of retinal damage which was quite severe when the pars plana vitrectomy was to be performed. the same results were also reported by soheilian et al (2006) where visual acuity before evacuation of so <3/60 was 71% and 6 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; after evacuation with visual acuity <3/60 so was 66%.11 for intraocular pressure in this study, a median value of 14 mmhg was obtained in the subjects before the silicone oil evacuation was carried out and with an average value of 14 mmhg in the subjects after the silicone oil evacuation was carried out. triwijayanti, et al (2019) reported for intraocular pressure before evacuation of silicone oil with a range of 9-21 mmhg of 67.53%. one month after the evacuation of silicone oil, 57.14% did not experience a change in iop. in this study, there was no significant difference between intraocular pressure between before and after evacuation of silicone oil. goezinne, et al (2007) reported that 8.5% increased intraocular pressure after evacuation of silicone oil. budenz, et al (2001) found that patients who underwent so evacuation alone for the reason of lowering iop had a tendency for iop to remain high after evacuation and even required additional glaucoma surgery. there are several factors that can cause iop to remain high after so evacuation. first, there is edema in the trabecular meshwork due to postoperative inflammation. second, the mechanical impact of the balanced salt solution (bss) during the so evacuation action can divide the so droplet into smaller droplets, which are more likely to obstruct the trabecular meshwork.5,12,13,14 the indications for evacuation of so may vary in each case. in this study, for the most indications, retina reattached > 3 months was 73.9%, while triwijayanti, et al (2019) reported that for the most indications that so evacuation was done, there was so emulsification of 57.14%. another study by choudary, et al (2012) reported that an increase in iop was the most indication for so evacuation. so evacuation is usually done wisely to avoid complications that can occur. usually scheduled 3-6 months after so implantation. however, in some cases so evacuation can be associated with hypotonia or redetachment. this becomes complex and requires further evaluation. in line with this research, where the retina reattached for more than 3 months is one of the indications for so evacuation.4,5,15,16 when evacuation of so is carried out, other additional measures can also be taken. in this study, 47.8% were evacuated only from so, 34.8% were accompanied by phacoemulsification and intraocular lens implantation, and 17.4% were accompanied by retamponade due to the subject's retina being redetached. this is in line with research from triwijayanti, et al (2019), namely 55.84% of cases were only evacuated by so and 31.16% were evacuated by so accompanied by phacoemulsification and intraocular lens implantation. the longer the duration of so implantation in the eye, the risk of developing cataracts and glaucoma will increase. in some cases, the short-term duration of so can also cause cataracts either due to the mechanical or toxic effects of so. in this study, there were samples that underwent so evacuation and phacoemulsification at the same time, but the researchers did not discuss the status of the lens's cloudiness level due to limitations with data and analysis of the lens's cloudiness level.5 each action of course can cause complications. in this study, the most complications that we experienced were retinal redetached and secondary glaucoma. retinal redetached was diagnosed based on the results of posterior segment examination using a 78d lens on a slit lamp. the secondary glaucoma was diagnosed when an iop >21mmhg measured by a handheld tonometer. both of this complications were evaluate 1 month after the so evacuation. but in this study, most of the so evacuation procedures did not cause complications, namely 65.2%. the most complications experienced were retinal redetached and secondary glaucoma, each of 13.0%. this was also reported by triwijayanti, et al (2019), published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 7 where 65.03% did not experience complications and the most reported complication was secondary glaucoma (16.88%). a meta-analysis study by he, et al (2018) states that the condition of pvr before vitrectomy surgery and os implantation is not a risk of redetached, but the formation of pvr after evacuation of so can be the main cause of redetached retina. this is in line with this study which found the condition of redetached retina, but indeed the researchers did not assess the degree of pvr in this study.5,17 conclusion the research subjects in this study had an age with a median of 51 years with the majority of subjects being in the age range of 46-65 years, female and living in bali with the majority of phakic and pseudophakic lens status. most of the subjects only had so evacuation performed without any other additional measures. the most complications that arise are redetached retina (13.0%) and secondary glaucoma (13.0%), however most patient did not experience any complications at all (65.2%). there was no significant difference in visual acuity and iop between before and after so evacuation. demographic factors such as occupation and clinical characteristics such as the type of so, lens opacities status and longer follow-up time to determine patient progress to minimize complications that may occur. references 1. 1. american academy of opthalmology staff. 2019-2020. retina and vitreous. aao. san fransisco. p. 451-459. 2. schwartz sg, flynn hw, jr., lee wh, wang x. tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy. cochrane database syst rev. 2014(2):cd006126. 3. issa, r., xia, t., zarbin, m.a., bhagat, n. 2019. silicone oil removal: post-operative complications. eye. 2020(34) 537-543. https://doi.org/10.1038/s41433-019-0551-7. 4. choudhary mm, saeed mu, ali a. removal of silicone oil: prognostic factors and incidence of retinal redetachment. retina. 2012;32(10):20348. 5. triwijayanti et al. the evaluation of silicon oil evacuation procedure in cipto mangunkusumo hospital indonesia. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 26148536. 6. leeuwen, r. v., haarman, a.e.g., put, m.a.j., klaver, c.c.w., los, l.i. association of rhegmatogenous retinal detachment incident with myopia prevalence in the netherlands. jama ophthalmol. 2021; 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(eds) cutting-edge vitreoretinal surgery. springer, singapore. https://doi.org/10.1007/978-981-33-4168-5_40 11. ghoraba hh, leila m, shebl m, abdelhafez ma, abdelfattah hm. long-term outcome after siliconee oil removal in eyes with myopic retinal detachment associated with macular hole. clin ophthalmol. 2021 mar 8;15:10031011. doi: 10.2147/opth.s298565 12. goezinne f, la heij ec, berendschot tt, liem at, hendrikse f. risk factors for redetachment and worse visual outcome after silicone oil removal in eyes with complicated retinal detachment. eur j ophthalmol. 2007;17(4):62737. 13. pastor s (2001) cyclophotocoagulation: a report by the american academy of ophthalmology. ophthalmology 108(11):2130– 2138 14. budenz dl, taba ke, feuer wj et al (2001) surgical management of secondary glaucoma after pars plana vitrectomy and silicone oil injection for complex retinal detachment. ophthalmology 108:1628-1632 15. choudhary mm, choudhary mm, saeed mu, ali a. removal of silicone oil: prognostic factors and incidence of retinal redetachment. retina. 2012;32(10):2034-8 16. abu-yaghi, n. e.,gharbieh, y. a. a., al-amer, a. m., alryalat, s. a. s., nawaiseh, m. b., darweesh, m. j., alkukhun, l. r., abed, a. m., saleh, o. a., ababneh, o. h. 2020. characteristics, fates and complications of long term silicone oil tamponade after pars plana vitrectomy. bmc ophthalmology. 20:336. https://doi.org/10.1186/s12886-020-01608-5 17. he, y., zeng, s., zhang, y., zhang, j. 2018. risk factors for retinal redetachment after silicone oil removal: a systemic review and metaanalysis. opthalmic surgery, lasers & imaging retina. 49(6):416-424). doi: 10.3928/2325816020180601-06 this work licensed under creative commons attribution https://doi.org/10.1007/978-981-33-4168-5_40 https://doi.org/10.1186/s12886-020-01608-5 abstract introduction methods results discussion conclusion 102 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; international journal of retina (ijretina) 2022, volume 5, number 2. p-issn. 2614-8684, e-issn.2614-8536 central macular thickness reduction after intravitreal injection of bevacizumab compared to intravitreal ketorolac in naive diabetic macular edema agung saputro1, angela nurini agni1, supanji1 1 department of ophthalmology, faculty of medicine, public health and nursing, universitas gadjah mada/dr. sardjito general hospital yogyakarta, indonesia abstract introduction: diabetic macular edema (dme) is a debilitating complication of the diabetic eye. vascular endothelial growth factor (vegf) was found to be responsible for this disease entity, and anti-vegf remains the main treatment of dme. inflammatory processes occur in diabetic eye, with some researchers postulates the role of them in the making of dme. this study’s objective is to search for anti-vegf alternative using non-steroid anti-inflammatory drugs (nsaid), ketorolac tromethamine. methods: we conducted a double blind, randomized clinical trial in dme patients using intravitreal injection of bevacizumab and ketorolac. central macular thickness (cmt) was assessed pre-treatment and one-month post-treatment. best corrected visual acuity (bcva) and intraocular pressure (iop) were also assessed. wilcoxon tests were performed to evaluate changes in cmt, visual acuity, and iop. result: we enrolled 50 treatment-naïve dme patients from march 2020 to march 2021. twentyfive patients were allocated for each group. there is a statistically significant difference in cmt at one-month follow-up between the two groups (p:0.001) and a markedly reduced cmt between the groups (p:0.001), with the reduction higher in bevacizumab group. bcva changes significantly in bevacizumab group (p:0.01), but there is no statistically significant difference between the two groups (p:0.07). there’s a marked difference of iop in 1 hour after injection in both groups, with higher transient iop elevation in ketorolac group (p:0.02), but there is no marked difference in one-month follow-up (p:>0.05). the perceived pain right after intravitreal injection is not different between bevacizumab and ketorolac group. conclusion: intravitreal injection of ketorolac found to be inferior compared to bevacizumab in reducing cmt of dme. meanwhile, there’s no differences in visual acuity, intraocular pressure (one-month follow-up) and pain after injection between two groups. keywords: dme, ketorolac, nsaid, bevacizumab, cmt cite this article: supanji, supanji; agni, angela nurini. central macular thickness reduction after intravitreal injection of bevacizumab compared to intravitreal ketorolac in naive diabetic macular edema. international journal of retina, [s.l.], v. 5, n. 2, sep. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/203>. date accessed: 26 sep. 2022. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss002.203.. https://www.ijretina.com/index.php/ijretina/article/view/203 https://doi.org/10.35479/ijretina.2022.vol005.iss002.203 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 103 introduction diabetic macular edema (dme) is a major complication of diabetic retinopathy (dr), which leads to severe visual disturbance. dme prevalence is around 4.3-7.9% in type 1 diabetes and 1.4-12.8% in type 2 diabetes. cumulative incidence of dme in type 2 diabetes is 6.1% in 6-year followup, while some other reports found 1.4% in 4-year follow-up.1 expression of intercellular adhesion molecule (icam)-1 becomes increased in endothelial cells in diabetics. this will cause accumulation of leukocytes in retinal capillary walls, which in turn will release cytokines, chemokines, pro-inflammatory and proangiogenic factors in the retina. inflammatory mediators will disrupt tight junctions between endothelial cells, therefore increase the vascular permeability. the cumulative response causes a disruption of blood-retinal barrier and development of intraretinal edema.2 anti-angiogenic therapy is becoming the standard management of dme and replacing laser therapy. anti-vascular endothelial growth factor (anti-vegf) targeting angiogenic activity, binds to vegf protein and prevents activation or interaction with its receptors. anti-vegf reduces vascular permeability.3 this anti-vegf treatment has some systemic complications. some proportions of patients also were reported to not respond well to this standard therapy. out of ten people, only three or four people respond well to anti-vegf treatment.4 other than patients’ resistance and various response to this therapy, anti-vegf availability in some areas in developing countries has also encouraged us to expand more options. steroid therapy is an alternative, which targets inflammatory cascade resulting in dme. steroid use, for instance intravitreal triamcinolone acetonide, can lead to cataract formation (46%) and raise intraocular pressure (iop) (16%). nsaids can be an alternative candidate for therapy of dme, targeting the same cascade, most importantly cyclooxygenase blockade.2 ketorolac and diclofenac are nsaids that are readily available as intravenous solutions. some researchers have reported their use as therapy of dme.5–8 in this study, we aimed to find evidence of noninferiority of ketorolac as an nsaid compared to standard therapy (bevacizumab) in treating naïve diabetic macular edema. methods this was a double blind, randomized clinical trial in dme patients using intravitreal injection of bevacizumab and ketorolac. central macular thickness (cmt) was assessed pre-treatment and one-month post-treatment.9 we enrolled 50 treatment naïve dme patients from march 2020 to march 2021. they were randomly assigned to two groups, 25 patients in bevacizumab group and 25 others in ketorolac group. complete ophthalmological status including visual acuity, iop and central macular thickness using optical coherence tomography (oct) were collected. systemic disease status was also collected (systemic hypertension and hba1c levels). patients completed informed consent forms prior to participation in this study. the inclusion criteria were as follows: patients diagnosed as having dme by retina specialist, age >18 years, and patients with no prior treatment of dme (including laser, anti-vegf and steroid). the exclusion criteria were patients with visual axis opacities, patients with inflammation/infection in either anterior or posterior segment, patients underwent intraocular procedures during the study period, and patients with systemic medications of steroid/nsaids. correspondence to: supanji, ophthalmology department vitreoretina consultant universitas gadjah mada/ dr.sardjito hospital,, supanji@ugm.ac.id mailto:supanji@ugm.ac.id mailto:supanji@ugm.ac.id mailto:supanji@ugm.ac.id mailto:supanji@ugm.ac.id 104 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; all patients received a single intravitreal injection of bevacizumab (1.25 mg in 0.05 ml) or ketorolac (3000µg in 0.1 ml) by a retina specialist who was masked about the two agents. pain scores using visual analog scale (vas) were measured right after injection. transient iop data were collected in an hour period after intravitreal injection. one week after injection, patients came to the retina clinic to be evaluated for adverse events after injection. in the one-month follow-up period, complete ophthalmological status, visual acuity, iop and oct findings were collected as end points. data were collected and analyzed using the spss 22 program (ibm corp., armonk, ny). statistical analyses were performed using wilcoxon tests for changes in cmt, visual acuity, and iop within the group. mannwhitney analyses were performed for cmt reduction, best corrected visual acuity (bcva) changes, iop increase and vas score between two groups. non-inferiority was analyzed using a noninferiority graph. this clinical trial has been approved by the medical and health research ethics committee of the faculty of medicine, public health and nursing universitas gadjah mada. results a total of 50 patients were enrolled in this study. one patient in the active control group (bevacizumab) and one patient in ketorolac group did not complete the one-month follow-up periods. another patient in the ketorolac group opted out from further analysis as the diabetic retinopathy status progressed and the oct could not be performed. table 1 below describes the baseline characteristics of the two groups table 1. distribution of baseline characteristics in each treatment group no variab le ketorolac (n=25) bevacizumab (n=25) p value 1 age (ye ars ± sd) 56.80 ± 6.31 57.52 ± 6.34 0 .31 2 se x male 56% 24% 0 .0 42 fe m ale 44% 76% 3 systolic b lood p re ssure (m m hg) 142.36 ± 61.41 149.58 ± 45.18 0 .96 4 hb a1c (%) 8.6 ± 1.85 8.89 ± 1.58 0 .54 5 duration of d iab e te s (ye ars) 6.90 ± 5.69 9.0 8 ± 6.0 1 0 .20 6 cmt (µm ) 452.52 ± 144.0 8 422.36 ± 142.36 0 .48 7 bcva (logmar) 0 .71 ± 0 .50 0 .99 ±0 .64 0 .13 8 iop (m m hg) 14.47 ± 4.0 3 15.96 ± 4.0 7 0 .25 ab b re viations: sd = stand ard de viation, hb a1c = glycated he m oglob in, cmt = ce ntral macular thickne ss, bcva = be st corre cte d visual acuity, logmar = lo garithm of the minim um angle of re solution, iop = intraocular pre ssure . table 2 shows the reduction of cmt from baseline, which was seen in the bevacizumab group, reduced from 422.36 ± 142.36 µm to 117.96 ± 170.60 µm (p<0.001). meanwhile in the ketorolac group, the reduction was relatively low, from 452.52 ± 144.08 µm to 431.82 ± 137.28 (p=0.86). at the one-month follow-up visit, cmt levels in bevacizumab group were lower than in ketorolac group (p=0.001). there was a marked difference in the cmt reduction between the two groups (p=0.001). meanwhile it’s a different case with visual acuity (bcva) changes in the two groups. bcva changes were getting better in both groups. the improvements at one-month follow-up were marked in bevacizumab group (p<0.05). bcva levels were also improved in the ketorolac group, but it was not statistically significant (p=0.62). comparing the two groups, bcva at one-month and overall bcva improvement were better in the bevacizumab group but both results were not statistically significant. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 105 table 2. mean ± standard deviations (sd) of cmt reduction and bcva improvement at 1 month follow-up no variab le ketorolac bevacizumab p value cmt red uction 1 base line cmt (µm ) 452.52 ± 144.0 8 422.36 ± 142.36 0 .48 2 cmt in 1 m onth (µm ) 431.82 ± 137.28 30 4.40 ± 92.14 0 .0 0 1* 3 cmt re d uction (µm ) 8.52 ± 64.24 117.96 ± 170 .60 0 .0 0 1* p value (p re and p ost) 0 .86 <0 .0 0 1* bcva imp rovement 1 base line bcva (logmar) 0 .71 ± 0 .50 0 .99 ± 0 .64 0 .13 2 bcva at 1 m onth 0 .62 ± 0 .51 0 .72 ± 0 .60 0 .72 3 bcva change s 0 .0 3 ± 0 .28 0 .26 ± 0 .47 0 .0 7 p value (p re and p ost) 0 .62 0 .0 1* ab b re viations: sd = stand ard de viation, cmt = ce ntral macular thickne ss, bcva = be st corre cte d visual acuity, logmar = logarithm of the minim um angle of re solutio n. figure 1 describes the non-inferiority graph of the two groups. the non-inferiority margins were plotted at 25.3 µm. the difference of the cmt reduction between the two groups (ketorolac – bevacizumab) was -109.43±36.5 µm, in favor of bevacizumab. the upper bound of the confidence interval (ci) was -33.25, not exceeding the noninferiority margin (-∆). this graph shows that we cannot prove the non-inferiority of ketorolac in reducing cmt compared to the active standard (bevacizumab) figure 1. non-inferiority of ketorolac compared to active control (bevacizumab). 106 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; table 3 shows transient iop surge after intravitreal injection. both groups showed transient iop elevation at 1 hour after injection. this elevation was greater in the ketorolac group. the iop levels were getting normal after one-month period. there were no differences between the two groups. pain levels right after injection measured by vas scores were shown to be comparable between the two groups. there were no adverse events found in both groups table 3. mean ± sd of transient iop elevation, iop in 1 month follow-up, vas score after injection no variab le ketorolac bevacizumab p value 1 base line iop (m m hg) 14.47 ± 4.0 3 15.96 ± 4.0 7 0 .25 2 iop 1 hour afte r inje ction 24.80 ± 1.27 (p :0 .0 0 3) 18.37 ± 4.79 (p :0 .0 0 9) 0 .0 2* 3 iop in 1 m onth 14.21 ± 2.94 (p :0 .77) 15.32 ± 4.0 1 (p :0 .31) 0 .34 4 vas score right afte r inje ction 3.41 ± 2.34 3.33 ± 2.58 0 .92 ab b re viations: sd = stand ard de viation, iop = intraocular pre ssure , vas = visual analo g scale . discussion in our study on naïve dme, we found a slight reduction in mean cmt in ketorolac group after onemonth of follow-up but is not significant statistically. significant reduction found in bevacizumab group. in refractory dme treated with ketorolac, a study by maldonado et al. found cmt reduction at 15 days after injection but no reduction after thirty days of injection.5. the half-life of bevacizumab in vitreous after single injection ranging from 3 to 6 days,10 while ketorolac only has a half-life of 3 hours after single injection.11 this can be the explanation for the only slight reduction of cmt found in the one-month follow-up after ketorolac injection. response to intravitreal injection in dme depends on local factors in the macula itself. morphological type of edema affects its response to therapeutic agents. sponge-like diffuse retinal thickening have better response, followed by cystoid type, while serous detachment type has the lower response.12 cystoid type edema were more likely responsive to triamcinolone acetonide, since this agent prevents swelling of muller cells.13 patients with sponge-like diffuse retinal thickening respond well to bevacizumab.14 anti-inflammatory agents will be more suitable for serous detachment type of dme.15 in this study, the morphological profiles of macular edema were not taken into account. this may be one of the factors for some non-responders found in the two groups. hba1c is a systemic factor that influences response to intravitreal injection. lipid profile, vegf serum, kidney function marker and systolic blood pressure were not found to be related to the response.16 overall bcva changes between two groups in our study are not significantly different. however, bcva changes in one-month follow-up in the bevacizumab group were markedly different. soheilian et al. showed improvement in visual acuity after injection of diclofenac in naïve dme. unlike our study, this improvement was not accompanied with improvement of cmt. improvement of retinal perfusion with injection of nsaid can explain this visual acuity improvement.6 functional improvement after intravitreal injection depends on baseline acuity and anatomical factors in the macula. ellipsoid zone disruption and losing of external limiting membrane in serous detachment limit the functional improvements.15 foveal avascular zone exceeding 1000 µm2 in oct-angiography is a marker of macular ischemia and related to worse outcome.14 our study showed marked transient iop elevation after injection of ketorolac, which can be explained by the higher volume injected compared to bevacizumab (0.1 ml vs 0.05 ml). iop will gradually lower after a single intravitreal injection. diagnosis of glaucoma, ocular hypertension and history of retinal vein occlusion are some factors associated with sustained iop elevation after intravitreal injection.17 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 107 in our study, iop became stable after one-month of follow-up. kidde et al. showed that increased volume after intravitreal injection is responsible for the transient iop surge.18 iop elevation can exceed 45.8 mmhg right after injection. after injection of bevacizumab (0.05 ml), 2.9% of patients had iop more than 25 mmhg, compared to 7.1% in triamcinolone group (0.1 ml). elbendary and shahin showed no iop increase after injection of 0.1 ml of diclofenac a day after injection.19 there are several factors associated with severity of transient iop increase after intravitreal injection: absence of subconjunctival reflux, smaller needle, tunneled injection technique, smaller vitreous volume, and prior glaucoma diagnosis.17 our study showed there was no difference in pain score between the two groups. hwan shin et al. showed vas score 2.7 ± 1.4 after intravitreal injection of anti-vegf and 3.5 ± 1.1 after intravitreal injection of dexamethasone. there are several factors influencing pain after injection: gender, age, paracentesis procedure, needle size, anesthetic agent, and injection location.20 in this study, both groups received one injection with the 30 g needle and the same anesthetic agent (tetracaine). none of the patients underwent paracentesis procedures, and unfortunately, we did not collect location of injection data. there are several limitations in this study. as mentioned above, other anatomical factors of macular edema were not taken into account, for instance; vitreomacular traction, hard exudates, and other types of macular edema morphology. macular ischemic factors were also not included in our study. conclusion this study shows that intravitreal ketorolac is not as effective as bevacizumab in reducing cmt in naïve dme. this finding highlights the dominance of the permeability factor in dme addressed by anti-vegf. further study needs to consider morphological type and other anatomical factors inside the macula in analyzing cmt changes. on the other hand, the overall bcva changes were not significantly different between the two groups. the iop changes after one month show no difference between the two groups. pain scores measured by vas were also comparable between the two groups. most importantly, there were no adverse events found in both groups. acknowledgement the authors would like to acknowledge hibah dana masyarakat universitas gadjah mada for funding this research with letter id 260/un1/fkkmk/pp/pt/2020. references lee r, wong ty, sabanayagam c. epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. eye vis. 2015;2(1):1–25. doi: 10.1186/s40662-015-0026-2 2. semeraro f, morescalchi f, cancarini a, russo a, rezzola s, costagliola c. diabetic retinopathy, a vascular and inflammatory disease: therapeutic implications. diabetes metab. 2019;45(6):517– 27. doi: 10.1016/j.diabet.2019.04.002 3. imazeki m, noma h, yasuda k, motohashi r, goto h, shimura m. anti-vegf therapy reduces inflammation in diabetic macular edema. ophthalmic res. 2021;64(1):43–9. doi: 10.1159/000508953 4. virgili g, parravano m, jr e, gordon i, lucenteforte e. anti-vascular endothelial growth factor for diabetic macular oedema : a network meta-analysis ( review ). cochrane database syst rev. 2017;(6). doi: 10.1002/14651858.cd007419.pub5 5. maldonado rm, vianna rng, cardoso gp, de magalhães av, burnier mn. intravitreal injection of commercially available ketorolac tromethamine in eyes with diabetic macular edema refractory to laser photocoagulation. curr eye res. 2011;36(8):768–73. doi: 10.3109/02713683.2011.585734 6. soheilian m, karimi s, ramezani a, montahai t, yaseri m, soheilian r, et al. intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial. int ophthalmol. 2015;35(3):421–8. doi: 10.1007/s10792-0149967-z https://doi.org/10.1186/s40662-015-0026-2 https://doi.org/10.1016/j.diabet.2019.04.002 https://doi.org/10.1159/000508953 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bevacizumab in patients with diabetic macular edema (dme). thesis: 2021. 10. schmidt-erfurth u, garcia-arumi j, bandello f, berg k, chakravarthy u, gerendas bs, et al. guidelines for the management of diabetic macular edema by the european society of retina specialists (euretina). ophthalmologica. 2017;237(4):185–222. doi: 10.1159/000458539 11. tsilimbaris m, tsika c, kymionis gd. intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery. ther clin risk manag. 2016;(12):177–82. doi: 10.2147/tcrm.s97342 12. shimura m, yasuda k, yasuda m, nakazawa t. visual outcome after intravitreal bevacizumab depends on the optical coherence tomographic patterns of patients with diffuse diabetic macular edema. retina. 2013;33(4):740–7. doi: 10.1097/iae.0b013e31826b6763 13. kim tk, shin hy, kim sy, lee yc, lee my. factors influencing intravitreal bevacizumab and triamcinolone treatment in patients with diabetic macular edema. eur j ophthalmol. 2017;27(6):746–50. doi: 10.5301/ejo.5000974 14. usui-ouchi a, tamaki a, sakanishi y, tamaki k, mashimo k, sakuma t, et al. factors affecting a short-term response to anti-vegf therapy in diabetic macular edema. life. 2021;11(2):1–9. doi: 10.3390/life11020083 15. parravano m, costanzo e, querques g. profile of non-responder and late responder patients treated for diabetic macular edema: systemic and ocular factors. acta diabetol. 2020;57(8):911–21. doi: 10.1007/s00592-02001496-7 16. wong wm, chee c, bhargava m, chai c, lin h, zhao p, et al. systemic factors associated with treatment response in diabetic macular edema. j ophthalmol. 2020;2020. doi: 10.1155/2020/1875860 17. bracha p, moore na, ciulla ta, wudunn d, cantor lb. the acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: a review. surv ophthalmol. 2018;63(3):281–95. doi: 10.1016/j.survophthal.2017.08.008 18. kiddee w, trope ge, sheng l, beltran-agullo l, smith m, strungaru mh, et al. intraocular pressure monitoring post intravitreal steroids: a systematic review. surv ophthalmol. 2013;58(4):291–310. doi: 10.1016/j.survophthal.2012.08.003 19. elbendary am, shahin mm. intravitreal diclofenac versus intravitreal triamcinolone acetonide in the treatment of diabetic macular edema. retina. 2011;31(10):2058–64. doi: 10.1097/iae.0b013e31822a042a 20. shin sh, park sp, kim y-k. factors associated with pain following intravitreal injections. korean j ophthalmol. 2018;32(3):196. doi: 10.3341/kjo.2017.0081 this work licensed under creative commons attribution https://doi.org/10.1007/s10792-016-0335-z http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5787025/ https://doi.org/10.1159/000458539 https://doi.org/10.2147/tcrm.s97342 https://doi.org/10.1097/iae.0b013e31826b6763 https://doi.org/10.5301/ejo.5000974 https://doi.org/10.3390%2flife11020083 https://doi.org/10.1007/s00592-020-01496-7 https://doi.org/10.1007/s00592-020-01496-7 https://doi.org/10.1155/2020/1875860 https://doi.org/10.1016/j.survophthal.2017.08.008 https://doi.org/10.1016/j.survophthal.2012.08.003 https://doi.org/10.1097/iae.0b013e31822a042a https://doi.org/10.3341%2fkjo.2017.0081 abstract introduction methods results conclusion 22 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; international journal of retina (ijretina) 2018, volume 1, number 1. p-issn. 2614-8684, e-issn.2614-8536 giant retinal tear management at refferal eye hospital mia purnama, iwan sovani, arief s kartasasmita, erwin iskandar, rova virgana, grimaldi ihsan universitas padjadjaran/cicendo national eye hospital abstract introduction: to report the characteristics, management and outcome in giant retinal tear (grt) associated retinal detachment patients at cicendo eye hospital methods: this retrospective study was performed on medical records who had undergone retinal detachment surgery between january 2014 and march 2017. age, sex, etiologies, size of grt, quadrant involvement, lens status, proliferative vitreo-retinopathy (pvr), managements and outcomes were evaluated in association with giant retinal tears result: twenty-six patients (23 males, 3 females) age between 11-59 years with follow up from 2 months to 18 months were enrolled in this study. twenty-five eyes have retinal detachment with macular involvement and 11 patients had high myopia. majority of patients had 90 of grts. most retinal tears were located at temporal quadrant (73%). nineteen patients had undergone pars plana vitrectomy (ppv) and 7 patients had combined ppv with encircling buckle. fifteen patients had used heavy liquid, 24 patients had silicon oil and 2 had gas tamponade. intraoperative complications included lens trauma, retinal slippage and choroidal detached were found in 1 eye respectively. fourteen eyes had recurrent retinal detachment. at the last follow up, 14 patients had anatomically attached retina. twelve patients had total retinal detachment and marked pvr. five fellow eyes were treated with prophylactic laser. visual acuity improved in 11 eyes. conclusion: giant retinal tears were more common in patients with high myopia. management of grt currently with ppv and ppv combined with encircling buckle. the success rate of anatomy and visual acuity was less than other previous studies keywords: giant retinal tear, proliverative vitreo-retinopathy, pars plana vitrectomy cite this article: purnama, mia et al. giant retinal tear management at referral eye hospital. international journal of retina, [s.l.], v. 1, n. 1, sep. 2017. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/5 introduction *correspondence to: arief f kartasasmita, universitas padjadjaran, cicendo national eye hospital a.kartasasmita@unpad.ac.id giant retinal tear (grt) is a full-thickness retinal break extending circumferentially for 90 degrees or greater of the retina associated with vitreous detachment. their management poses significant challenges due to the many complications and technical difficulties involved for unfolding and sealing the retinal tear.1-4 although grt can occur spontaneously, they are often associated with a number of conditions; this include ocular trauma, high myopia, pseudophakia, hereditary conditions, for example, marfan syndrome, stickler syndrome, extensive lattice degeneration and young age.5,6 with such a large tear, the anterior insertion of the retina no longer offers peripheral support and the retina folds back on itself. the retina also tends to roll due to the absence of vitreous attachment.7 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 23 a wide range of techniques have been used with varying degrees of success. recently, common techniques used to treat grt include primary vitrectomy with expansile gas or silicon oil tamponade, and combined scleral buckle-vitrectomies. the use of heavy liquid as an adjunctive tool has made unfolding and stabilization of the retina easier. the use of silicon oil has also been proven to be more effective in early visual rehabilitation and is also safer to exchange with perfluorocarbons.7 proliverative vitreo-retinopathy (pvr) is one of the late complications of grt, and the leading cause of surgical failure. increased access to the exposed retinal pigment epithelium (rpe) allows greater spillage of cells and pigment into the vitreous cavity and on the retinal surface, thereby increasing the risk of pvr.8 giant retinal tears in pediatric patients (younger than 16 years) are more likely to be associated with pvr which may be due to a delay in diagnosis or the greater wound healing response in children.8 other mechanism predisposing to pvr include the presence of vitreous hemorrhage and breakdown of the blood-ocular barrier leading to production of cytokines which could further stimulate cellular proliferation.8,9 since grt can adversely affect the prognosis of retinal detachment surgery, we decided to report patients who were operated for retinal detachment with grt at our center and evaluate etiology, management and outcomes. patients and methods this is a retrospective study of 26 eyes of 26 patients between the ages of 11 and 59 years. these patients underwent surgery to repair rhegmatogenous retinal detachment due to grt between january 2014 and march 2017 at the cicendo eye hospital. patients were included and all patients had more than 2 months of follow up. giant retinal tear was defined as a retinal tear of 90or greater confirmed intraoperatively or by clinical examination. of the excluded eyes, 2 had initial vitreous surgery elsewhere, 1 had undergone previous pars plana vitrectomy (ppv), and 1 had less than 1 month of follow up. all case notes were then reviewed. age, sex, address, etiology, lens status, size of grt, quadrant involvement, macular involvement, pvr, and surgical procedure, usage of heavy liquid, tamponade, complications, length of follow up and prophylactic laser of fellow eye. outcome variables included visual acuity, rates of retinal re-attachment and incidence of pvr. the operating surgeon selected the surgical approach for the individual patient, and there was no defined protocol in this study. complete anatomical success was defined as complete retinal attachment after silicone oil removal at the 2th or more postoperative month, while incomplete success was considered in eyes were the retina remained detached under silicon oil or redetached after silicon oil removal. results there were 26 eyes of 26 patients with rhegmatogenous retinal detachment associated with grt. of these, 23 were males and 3 females, with 14 right eyes and 12 left eyes being affected. their age ranged between 11 and 59 years with a mean of 38.39 years (sd: 13.67). in all, 23 patients were coming from west java, 2 were from central java, and 1 from aceh. postoperative follow-up period ranged from 2 months to 18 months (mean 6,58 months4,86). the location of most retinal tears was temporal quadrant (69%) of 18 eyes. in all, 25 eyes (96%) had a retinal detachment involving the macula with a significant drop in visual acuity. altogether 11 eyes (42%) had etiology of high myopia, 6 eyes (23%) had history of blunt trauma, 7 eyes (27%) of idiopathic, 1 eye (4%) was marfan’s syndrome and 1 eye (4%) was extensive lattice degeneration. a total of 14 eyes (54%) affected right eye and 12 (46%) left eye. visual acuity of hand motion were 19 eyes (73%), 5 eyes (19%) were light perception, 1 eye (4%) was 1meter counting finger, 1eye (4%) was 0,4. lens status of phakic eye were 19 eyes (73%), pseudophakic eye with posterior chamber intraocular lens were 7 eyes (27%). figure 1. initial management for patients undergoing surgery for giant retinal tear-associated retinal detachment in all, 13 eyes (50%) had grt that extended 90 circumferentially, with 11 eyes (42%) had grt that extended between 90 and 180 circumferentially and 2 eyes (8%) had grt greater than 180. at the first presentation, there were 17 eyes (65%) with no pvr, 6 eyes (23%) had pvr grade b, and 3 eyes (11,5%) had pvr grade c. at the last surgeries found that incidence rate of pvr grade b was 23% (6 eyes) and incidence rate of pvr grade c increased to 42% (11 eyes). 0 10 20 30 40 50 60 70 80 90 100 p e rc e n ta g e o f p a ti e n ts 24 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; a total of 19 eyes had undergone pars plana vitrectomy (ppv) and 7 eyes had undergone combined ppv with encircling scleral buckle. attachment of retina after initial surgery of ppv were 42 % (8/19 eyes) of cases and eyes after initial surgery of ppv with encircling buckle were 57 % (4/7 eyes) of cases. table 1. baseline characteristics of patients undergoing surgery for giant retinal tearrelated retinal detachments baseline parameter n = 26 mean age, years (sd) 38.39 (13.67) age, years (range) 11 59 gender, n (%) male 23 (88) female 3 (12) mean followup, months (sd) 6.58 (4.86) length of follow up, months (range) 2-18 etiologies, n (%) high myopia 11 (42) idiopathic 7 (27) trauma 6 (23) extensive lattice degeneration 1 (4) marfan's syndrome 1 (4) visual acuity pre-operative, n (%) hand motion 19 (73) light perception 5 (19) 1 meter counting finger 1 (4) 0.4 1 (4) lens status, n (%) phakic 19 (73) pseudophakic 7 (27) quadrant involvement, n (%) temporal 18 (69) inferior 5 (19) superior 2 (8) nasal 1 (4) macular involvement, n (%) off 25 (96) on 1 (4) proliferative vitreo-retinopathy, n (%) no proliferative vitreo-retinopathy 17 (65) b 6 (23 ) c 3 (12) size of giant retinal tear, n (%) 90 13 (50) 90 180 11 (42) > 180 2 (8) retinal re-detachment after initial surgery of ppv were 58 % (11/19 eyes) of cases and eyes after initial surgery of ppv with encircling buckle were 43 % (3/7 eyes). lensectomy were performed on 4 eyes due to lens opacity, the rest were not done lensectomy. the use of heavy liquid in this study were obtained in 15 eyes and 11 eyes did not use heavy liquid. eyes with grt in this study were given tamponade of silicon oil (so) as much as 24 and 2 eyes were gases. the use of silicon oil in this study include the viscosity of 1000 centistoke given to 13 eyes, viscosity of 5000 centistoke given to 9 eyes and heavy so given to 2 eyes. gases tamponade that has been used in this study were sf6 and c3f8, both patient given this gasses tamponade experienced redetached retina and performed reoperation. eyes with redetached retina after being given so tamponade with viscosity of 1000 centistoke as much as 7 eyes, so viscosity of 5000 centistokes were 5 eyes and heavy so was 1 eye. table 2. intraoperative data for patients with giant retinal tear-related retinal detachments intraoperative parameter number (%) tamponade sf6 1 (4) c3f8 1 (4) silicon oil 1000 cs 13 (50) silicon oil 5000 cs 9 (34) heavy silicon oil 2 (8) complication no complication 23 (88) lens touch 1 (4) slippage retina 1 (4) choroidal detached 1 (4) retinal condition at the end of initial surgery attached retina perfectly 21 (81) attached retina imperfectly 5 (19) various types of complications that had occurred intraoperative in this study include, lens touch in 1 eye, slippage in 1 eye with encircling buckle, and choroidal detached in 1 eye. retinal condition at the end of surgery were obtained with 21 eyes were perfectly attached retina and 5 eyes were imperfectly attached retina due to the rest of subretinal fluid. visual acuity at the end of follow up varies from hand motion of 13 eyes, 1 until 6 meter counting finger were 10 eyes and more than 0.1 were 3 eyes. at the end of follow up period visual acuity improved in 11 (42%) eyes, did not change in 14 (54%) eyes and worsened in one (3.8%) eye. a total of 12 eyes (46%) have no re-operation. reoperation 1 time on 10 eyes (38%) and re-operation 2 times on 4 eyes (15%). last retinal condition at the end of follow up found 14 eyes (54%) attached retina and 12 eyes (46%) redetached published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 25 retina. prophylactic laser of fellow eye performed 5 eyes and the rest is not performed. discussion giant retinal tear associated retinal detachment are relatively uncommon. these patients present a surgical challenge because of the high incidence of pvr and redetachment rate. of the 1233 documented clinical encounters with retinal detachment underwent retinal reattachment surgery identified during the current study period, only 26 (2%) patients were identified as having giant retinal tear. giant retinal tears comprise about 1.5% of rhegmatogenous retinal detachments. the average age of incidence is 42 years. there is usually a higher incidence in males than females, with males comprising 72% of cases. about 54% of grts are idiopathic, 12.3% result from trauma, 25% result from high myopia, and 14% result from other hereditary conditions such as marfan’s, stickler‐wagner, and ehrler danlos syndromes.10 in the current study, a history of high myopia was the single most identifiable etiology in the study population (42%). marco et al., reported the grt associated retinal detachment study with the greatest etiology of extensive lattice degeneration in 24 eyes (30 %) and high myopia were 21 eyes (27%) of 79 cases.5 gonzalez and flyyn reported that trauma was a common associated factor in patients presenting with grt associated retinal detachment.11 in addition to ppv, the use of encircling scleral buckle has been a point of controversy among vitreo-retinal surgeons. scleral buckles are supposed to aid in reduction of traction within the vitreous base, thereby ensuring that the grt do not extend or re-open. this reduces the chances of recurrence of retinal detachment due to the formation of fresh anterior retinal breaks or pvr.3, 12 however this procedure has also been implicated in complicating the closure of grt due to distortion of the shape of the eye, fish-mouthing and tendency to increase ‘slippage’ of the retina posteriorly and the possible induction of pvr due to additional trauma.3,8 conversely, other surgeons prefer adjunctive buckling in as a primary procedure aiming to reduce the failure rate. their rationale was that scleral buckling reduces the early and late tractional forces and supports areas of un-detected retinal breaks.5 meanwhile, other surgeonsreserve scleral buckling only for second intervention.3 in this study, we found that retinal re-attachment was successful with combine ppv with encircling buckle in 4/7 eyes (57%) and ppv alone was 42% (8/19 eyes). ambresin et al., reported the success rate of management of grt with vitrectomy, internal tamponade, and peripheral 360 degrees photocoagulation of the retina without scleral buckle is high (94.4%).13 proliferative vitreo-retinopathy has an incidence of up to 40-50% in association with grt. this suggest that, unless these eyes have adequate management of pvr, there will be a high failure rate.1,2 an incidence of pvr at the first presentation in this study were 34% (9 eyes) and at the end of surgery were 65% (17 eyes). dabour reported ppv combined with scleral buckle, 360 laser photocoagulation and postoperative silicon oil tamponade is effective 83.3% (20/24 eyes) in the management of grt more than 180.14 on the other hand, in a prospective randomized comparative study conducted by sharma et al., they used 360° degree 9 mm silicone band buckle in 10 cases and none in 11 cases. they reported that the primary success was 100% in sclera buckle group as compared to 37.5% in non sclera buckle group, and that re-operation were required in 8 out of 11 cases in nonscleral buckle group. the final visual acuity was better in eyes treated with scleral buckle. controversy remains whether lens extraction is necessary or not in the management of fresh giant tears. the advantage of lens removal is the better visualization of vitreous base. in this study, it was found that lens removal was not necessary and may minimize the surgical trauma in such complex procedure. in addition, intraocular lens power calculation is often inaccurate in eyes with grt when the macula is off. moreover, the use of wide angle viewing systems coupled with indentation for giant tear surgery improves the ability to see the peripheral retina in phakic and pseudophakic eyes and makes thorough vitreous base shaving feasible.1,3,9 in this table 3 anatomic and visual acuity outcomes of patients undergoing surgery for giant retinal tear-related retinal detachments outcomes parameter number (%) retinal attachment rates, n (%) vitrectomy 8 (42) vitrectomy combined encircling buckle 4 (57) recurrent retinal detachment 14 (54) re-operation 1 time 10 (38) re-operation 2 times 4 (16) last retinal condition at last follow-up attached retina 14 (54) re-detached retina 12 (46) final visual acuity hand motion 13 (50) 16 meter counting finger 10 (38) > 0.1 3 (12) visual acuity at last follow up improved 11 (42) did not change 14 (54) worsened 1 (4) 26 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; study, lensectomy performed on 4 eyes due to lens opacity. sharma et al., considered lens removal only in cataractous eyes, subluxated lenses or the presence of pvr are the main indications for lens removal in grt. also, many eyes with grt are often highly myopic and the pars plana region is often wide and broad. this anatomic variation allows adequate exposure of the vitreous base with less risk of lens touch.15 however, the initial surgery for grt should not be compromised to preserve the lens. in the current study, developed cataract in phakic eyes and lens extraction was done during silicon oil removal thus avoiding disadvantages of multiple surgeries. heavy liquids (perfluorocarbons) have revolutionized grt surgery. they allow hydraulic manipulation of the retina. their high specific gravity enables the retinal flap to be unrolled, and displacement of subretinal fluid in a posterior to anterior direction allows surgery to be performed with the patient in a supine position. due to their high surface tension, retinal breaks can be closed internally, without the heavy liquid flowing into the subretinal space.1-3 in this study, where at initial surgeries heavy liquid were used in 15/26 cases (57%), 7 eyes had re-detachment (47%). in the 11 eyes where heavy liquid was not used. the re-detachment rate was 64% (7/11). these results are in keeping with previous studies advocating the use of heavy liquid in the management of grt. expansile gases and silicone oil have been used as tamponade in grt surgery. since the first report of the use of silicone oil for the treatment of retinal detachment in 1962, this agent has been increasingly used as a tamponade in managing complex retinal detachments including those resulting from grt. the silicon oil study has shown that, in eyes with complex retinal detachment, the retinal re-attachment rates, visual acuity outcomes, and complication rates are better with silicon oil compared to sulphur hexafluoride gas as an internal tamponade, and comparable with c3f8.16 in this study, the use of silicone oil may have contributed to the anatomical success rate 50% (12/24 eyes), expansile gases has re-detachment rate was 100% (2/2). garcia et al., said that superior grt with retinal detachment and without pvr, prefer to use a mixture of sf6 gas. if there is pvr and tears at any location except for 5, 6, and 7 o’clock they use a mixture of c3f8. these patients should be able to position for at least 1 week. finally, in detachments with severe pvr or tears in areas near 6 o’clock, they use 1000 centistoke so. they do not support the frequent use of heavy so tamponades, such as liquids and per fluorinated oils, because they provide inadequate protection against superior tears, are difficult to remove, and are toxic to the photoreceptors in the lower sectors of the retina.17 in this study, the success rate with primary procedure was 42% (11/26 eyes), which increased to 54% (14/26) with multiple surgeries. visual acuity at the end of follow up period visual acuity improved in 11 (42%) eyes. our final retinal re-attachment rate was less than reported in some of the other studies. this was due to recurrent retinal detachment in 15 cases, resulting from severe pvr (42%). shunmugam et al, reported primary and final retinal re-attachment rates are achieved in 88% and 95% of patients respectively.6 even when the retina remains attached, however, visual recovery may be limited. prophylactic treatment of the fellow eye is controversial. some authors suggest that fellow eyes of those with non-traumatic grt should be treated prophylactically.18 in this study, prophylactic laser of the fellow eye in nontraumatic cases of grt was 5/20 eyes (25%). conclusion in this study, the more common etiology grt was high myopia, the majority gender was males. mostly grt size was 90 with the most location was at temporal quadrant. the management were ppv alone and combined ppv with encircling scleral buckle. anatomical success was 54%, and visual acuity outcome in our case series were variable, the most was no change (54%). this is a lack in our study, which should be measured is best corrected visual acuity. references 1. beroccal mh, chenworth ml, acaba la: management of giant retinal detachments. j ophthalmic vis res 2017, 12(1):93-97 2. nagpal m. giant retinal tears: size does matter. retina today 2013, 26-28. 3. adelman ra, parnes aj, sipperley jo, ducournau d: strategy for the management of complexretinal detachments: the european vitreo-retinal society retinal detachment study report 2. ophthalmology 2013, 120:1809-1813 4. mehdizadeh m, afarid m, hagigi ms. risk factors for giant retinal tears. j ophthalmic vis res 2010, 5:246-249. 5. gonzalez ma, flynn hw jr, smiddy we, albini ta, tenzel p: surgery for retinal detachment in patients with giant retinal tear: etiologies, management strategies and outcomes. ophthalmic surg laser imaging retina 2013, 44(3):232-237. 6. shunmugam m, ang gs, lois, n. giant retinal tears. surv ophthalmol 2014, 59:192-216. 
 7. ghosh yk, banarjee s, savant v, kotamarthi v, benson mt, scott rah and tyagi ak. surgical treatment and outcome of patients with giant retinal tears. eye 2004, 18:996-1000 8. chang s, lopez jm. giant retinal tears and proliferative vitreoretinopathy. in: ryan sj, ed. retina. 4th ed. st. louis: mosby; 2006: 2345-2351. 9. gopal l, sharma t, bhende ps. complicated published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 27 forms of retinal detachment: giant retinal tear. in: ryan sj, ed retina. 5th ed. st. louis: mosby; 2013: 1844-1851 10. ang gs, townend j, lois n. epidemiology of giant retinal tears in the united kingdom: the british giant retinal tear epidemiology eye study (bgees). retina 2010, 51:4781-4787. 11. gonzalez ma, flynn h. retinal detachment caused by giant retinal tears: etiologies, tchniques and outcomes. investigate ophthalmology & visual science 2012, 53:58085810 12. lee sy, ong sg, wong dwk, ang cl. giant retinal tear management: an asian experience. eye (lond). 2009, 23(3):601-605 13. ambresin a, wolfensberger tj, bovey eh. management of giant retinal tears with vitrectomy, internal tamponade, and peripheral 360 retinal photocoagulation. retina 2003, 23(5):622 14. dabour sa: the outcome of surgical management for giant retinal tear more than 180. bmc ophthlmology 2014, 14:86 15. sharma y, reddy p, azad r: 60 degree scleral buckling in vitreous surgery for giant retinal tears without proliferative vitreoretinopathy changes.
dulles, usa: american academy of ophthalmology; 2000. 16. vaziri k, schwartz sg, kishor ks, flynn jr hw. tamponade in the surgical management of retinal detachment. clinical ophthalmology 2016, 10:471-476 17. garcia rag, arencibia od, martinez fe. surgery for retinal detachment with giant retinal tears: an update on surgical approaches. retina today 2014, 61-64 18. kazahaya m. prophylaxis of retinal detachment. semin ophthalmol 1995, 10:79-86 this work licensed under creative commons attribution 94 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; international journal of retina (ijretina) 2022, volume 5, number 2. p-issn. 2614-8684, e-issn.2614-8536 clinical manifestations and cd4 count characteristics of patients with cytomegalovirus (cmv) retinitis yunneke renna xaverina1, ovi sofia1 1department of ophthalmology, universitas brawijaya, dr. saiful anwar general hospital, malang, east java, indonesia abstract introduction: to describe the clinical manifestations and cd4 count characteristics of patients with cytomegalovirus (cmv) retinitis. methods: this is a retrospective study of patients diagnosed with cmv retinitis at the ophthalmology outpatient clinic at dr. saiful anwar general hospital, malang, between january 2016 to december 2019. the patients’ characteristics and clinical data including gender, age, visual acuity, slit lamp biomicroscopy, indirect ophthalmoscope, and laboratory findings were collected from medical records. result: twenty-one eyes from thirteen patients with cmv retinitis were enrolled. the mean age was 30.9 ± 7.12 years, with 54% of them male. bilateral lesions were observed in 62% of the patients, and the mean visual acuity during the initial visit was 1.50 ±1.07 log mar. all patients presented with the classic form of cmv retinitis. mean cd4 count when commencing treatment was 62.23 ±11.82 cells/µl with 77% below 50 cells/µl. patients with cd4 count < 50 cells/µl mostly presented with posterior uveitis, bilateral lesion, and visual acuity ≤1.00 logmar. ten patients were given oral valganciclovir and antiretroviral therapy. retinal detachment condition was noted at seven eyes. candidiasis was the most presenting opportunistic infection. conclusion: cytomegalovirus retinitis was found in patients infected with aids with low cd4 counts. in this study, patients with cd4 counts of below 50 cells/µl tend to have more severe clinical presentations. keywords: cytomegalovirus, retinitis, aids, valganciclovir, cd4 count cite this article: xaverina, yunneke renna; sofia, ovi. clinical manifestations and cd4 count characteristics of patients with cytomegalovirus (cmv) retinitis. international journal of retina, [s.l.], v. 5, n. 2, sep. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/201>. date accessed: 26 sep. 2022. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss002.201. correspondence to: yunneke renna xaverina, dr. saiful anwar general hospital, malang, indonesia, yunnekerenna@gmail.com introduction cytomegalovirus (cmv) retinitis is frequently found in immunocompromised patients, but it can also be present in immunocompetent individuals.1 this opportunistic infection usually takes place in patients with a low cd4 count at around 50 cells/µl.2 marked with hemorrhage and necrosis located according to the retinal vessel arcades. this condition can threaten vision due to its location at the posterior pole. https://www.ijretina.com/index.php/ijretina/article/view/201 https://doi.org/10.35479/ijretina.2022.vol005.iss002.201 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 95 cotton-wool spots may act as the early manifestation of cmv retinitis, with the lesion growing larger and accumulating as time goes by. more than half of all patients with cmv retinitis show no symptoms and abnormalities may be identified once funduscopic screening is undertaken. common findings include a decline in visual acuity, floaters, or scotoma.2-4 antiretroviral therapy in patients with hiv has been reported to reduce the incidence of cmv retinitis in developed countries up to 80–90%. however, in developing countries, patients are diagnosed at a late stage with a low cd4 count, which indicates that cmv retinitis remains a major problem.3 this also takes place in southeast asia, including indonesia, wherecmv retinitis is still prevalent in patients with aids and is the leading cause of blindness.5 researchers in singapore in 2012 pointed out that > 90% of patients with cmv retinitis are male and are, at the time, undergoing arv. the median cd4 count of patients upon being diagnosed with cmv retinitis is 38 cells/µl where they saw declines in their cd4 count compared with when they were first diagnosed with hiv.6 a study in vietnam in 2013 reported the prevalence of cmv retinitis to be 7% with a mean age of 32 years, 77% of whom were male, a median cd4 count at the time of examination to be 47 cells/µl, and 62% undergoing antiretroviral therapy.7 another study conducted in bandung, indonesia, in 2018 showed a mean age of 38.3 years with a higher prevalence in males, all of them received antiretroviral therapy (art) and treatment provided to the patient is intravitreal ganciclovir.8 one study carried out in myanmar in 2019 revealed the prevalence of patients with aids and a cd4 count <100 cells/µl diagnosed with cmv retinitis was 10.7%.9 the recommended therapy for cmv retinitis is oral valganciclovir due to its ability to treat systemic cmv infections, easier administration route, and minimal side effects. in addition to the oral route, therapy for cmv retinitis can also be given intravenously or intravitreally. the therapies of choice via intravenous route consist of ganciclovir, foscarnet, or cidofovir; meanwhile, the intravitreal route may use ganciclovir implant or injection.10 administering valganciclovir therapy can begin with an induction dose of 900 mg twice daily for 2–3 weeks, followed by 900 mg once a day as a maintenance dose.4 the prognosis of cmv retinitis is determined by the location of lesions, retinal detachment, and the general condition of the patient.11 a possible complication that may arise aside from retinal detachment is the appearance of immune recovery uveitis (iru) in patients receiving therapy.10 to date, research discussing the characteristics of clinical manifestations and cd4 count in patients with cmv retinitis in indonesia has been meager. thus, our study attempts to collect data on patients with cmv retinitis through their medical records in order to identify clinical manifestations and cd4 count also follow up characteristics in patients with cmv retinitis in dr. saiful anwar general hospital, malang. methods design this is a retrospective study conducted at the eye polyclinic of the infection and immunology division at dr. saiful anwar general hospital (rssa), malang. research samples were collected using the consecutive sampling method, involving data of new patients diagnosed with cmv retinitis obtained from the outpatient medical record data at the eye polyclinic within the span of 4 years from 1 january 2016 to 31 december 2019. 96 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; diagnostic criteria diagnosis is established when clinical examination indicates lesions that are characteristic of cmv retinitis on the retina, which may be classic, granular, perivascular form. demographic data demographic data include the age and sex of the patients. clinical data the symptoms are defined as the complaints reported by the patients upon admission, which may comprise declining visual acuity (blurriness), photopsia (flashes), floaters (squiggly lines across one’s vision) or a combination of those. the patient’s clinical data comprise examination results on visual acuity, anterior segment, and posterior segment. visual acuity refers to the result of testing a patient’s sharpness of vision upon admission, which was then converted into logmar. slit-lamp biomicroscopy examination was undertaken on the anterior segment of the eye to identify any indications of inflammation in the anterior chamber and the vitreous (based on the standardization of uveitis nomenclature criteria)12 or any other abnormalities. the posterior segment was examined using an indirect funduscopy to identify any signs of necrotizing retinitis, which may include hemorrhage and necrosis according to the vascular arcades or other retinal abnormalities. the adjunct test involves the patient’s cd4 count upon commencing therapy and every month for the next 6 months. the systemic status includes other opportunistic infections present in the patient, such as candidiasis, tuberculosis, genital ulcer, herpes zoster, or toxoplasmosis identified during the examination at the internal medicine polyclinic. treatment is the type of medication therapy provided, which can be arv only or arv with oral valganciclovir. complications may present as retinal detachment, immune reactive uveitis (iru), or optic neuropathy on the affected eye, and an evaluation is to be done on the other eye (fellow eye). follow-ups span 6 months after therapy, taking note of whether or not the patients come each month for their follow-up. research data are presented in the form of descriptive data, while the research subjects’ characteristics are displayed in tables and diagrams. inclusion and exclusion criteria the inclusion criteria comprise all patients diagnosed with cmv retinitis on classic, granular, or perivascular form; on the other hand, the exclusion criteria consist of incomplete or missing medical record data. research ethics this study has been approved by the committee of medical research ethics of dr. saiful anwar general hospital, malang with number 400/261/k.3/302/2020. results based on the 4-year long medical record, this study found that the number of patients diagnosed with cmv retinitis is 21 eyes from 13 patients. table 1. the patients’ demographic data and clinical results. variable frequency age (mean ±sd) 30.9 ± 7.12 years age group 20–29 years 5/13 (39%) 30–39 years 6/13 (46%) > 40 years 2/13 (15%) sex male 7/13 (54%) female 6/13 (46%) complaint initial visit blurred vision 13/13 (100%) glare 1/13 (8%) laterality unilateral 5/13 (38%) bilateral 8/13 (62%) visual acuity (mean ±sd) 1.50 ±1.07 logmar visual acuity group ≤1.00 logmar 7/21 (33%) >1.00 logmar 14/21 (67%) uveitis type posterior 17/21 (81%) panuveitis 4/21 (19%) table 1 illustrates the demographic data and clinical examination results of the patients. the mean age of the 13 patients is 30.9 ± 7.12 years, and most of them were 30-39 years old, which were 6 patients. there are more male patients than female patients. while all of them complained of blurred vision upon published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 97 admission to the polyclinic, more patients had bilateral lesions than unilateral lesions. the mean visual acuity of the patients in this study is 1.50 ± 1.07 logmar with most of them having a visual acuity of >1.00 logmar or below 20/200. of the examination results using indirect funduscopy, all patients show the classic form. figure 1. a fundus photo of a patient with cmv retinitis. a 30-year-old patient with a cd4 count of 34 cells/µl in which we found a classic-form feature. all patients diagnosed with cmv retinitis demonstrated immunocompromised condition with aids. the mean cd4 count upon arriving at the outpatient clinic is 62.23 ± 11.82 cells/µl, where 10 patients (77%) have a cd4 count <50 cells/µl. according to the cd4 count test, only 3 patients have >50 cells/µl (58, 130, and 418 cells/µl). table 2. cd4 count of patients with cmv retinitis. variable frequency <50 cells/µl ≥50-100 cells/µl >100 cells/µl initial visit 10/13 (77%) 1/13 (8%) 2/13 (15%) lesion laterality unilateral 4/13 (30%) 1/13 (8%) bilateral 6/13 (46%) 1/13 (8%) 1/13 (8%) according to lesion laterality, in the 10 patients with a cd4 count of 50 cells/µl, there is more bilateral lesion than unilateral lesion (46%). table 3. cd4 count of eyes with cmv retinitis. variable frequency <50 cells/µl ≥50-100 cells/µl >100 cells/µl uveitis type posterior uveitis 13/21 (62%) 2/21 (9,5%) 2/21 (9,5%) panuveitis 3/21 (14%) 1/21 (5%) visual acuity ≤1.00 logmar 4/21 (19%) 1/21 (4,5%) 2/21 (9,5%) >1.00 logmar 12/21 (57%) 1/21 (4,5%) 1/21 (4,5%) in patients with a cd4 count < 50 cells/µl, there are more eyes with posterior uveitis than those with panuveitis, which is 62%. the results of the visual acuity test on the 16 patients with a cd4 count < 50 cells/µl indicate that most of them have a visual acuity > 1.00 logmar (57%). opportunistic infections may emerge in patients with cmv retinitis while also posing risks of concurrent infections. oral candidiasis is the most prevalent opportunistic infection in this study, which involves 5 patients (38%), followed by 3 patients having genital ulcer, pulmonary tuberculosis, or diarrhea, and 2 patients with cerebral toxoplasmosis. retinal detachment as a complication of cmv retinitis was observed in 7 eyes (33%) of the 13 patients in this study. figure 2. opportunistic infections in patients with cmv retinitis. figure 3. a fundus photo of retinal detachment. the fundus photo of retinal detachment in a 40-year-old male patient with cmv retinitis with bilateral lesion and a cd4 count of 34 cells/µl. of the 31 patients diagnosed with cmv retinitis, 10 patients receive arv therapy + valganciclovir. of the 10 patients, 4 patients lost to follow-up. consequently, only 6 patients have complete followup data throughout the 6 months. 12% 19% 19% 31% 19% cerebral toxoplasmosis genital ulcer pulmonary tuberculosis oral candidiasis diarrhea 98 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; figure 4. a follow-up fundus photo of a patient. the follow-up fundus photo of a 30-year-old male patient (a) before initiating therapy, with a cd4 count of 34 cells/µl, and (b) after receiving arv therapy + valganciclovir for 3 months, with a cd4 count of 85 cells/µl. figure 5. follow-up data of the cd4 count of patients with cmv retinitis undergoing arv therapy + valganciclovir. of the 6 patients having complete follow-up data for 6 months, there are 2 patients receiving complete valganciclovir therapy until cd4 count >100 cells/µl for 3 consecutive months. throughout the follow-up period, all patients do not experience any change in visual acuity and there was no involvement of the fellow eye. discussion according to the study results, the mean patient age is 30.9 ± 7.12 years, and there are more people who were 30–39 years old and more male patients (54%) than female patients. similar findings were also reported in a study by singh et al.3 in india, leenasirimakul et al.5 in thailand, colby et al.7 in vietnam, and sovani et al.8 in indonesia, where the mean age of patients with cmv retinitis ranged from 30 to 40 years, and > 50% of them were male. all of the patients diagnosed with cmv retinitis in this study are patients with aids. h this is supported by data from the center of data and information, indonesian ministry of health (infodatin) stating that, in 2019, the number of people with aids in indonesia was 7,036, and east java province places third with 958 people. most of the cases involve people in their productive age, which is 25–49 years, with men having a higher prevalence (68.6%) than women.13 0 50 100 150 200 250 300 0 1 2 3 4 5 6 cd 4 co un t ( ce lls /µ l) months (after commencing therapy) patient 1 patient 2 patient 3 patient 4 patient 5 patient 6 patient 7 patient 8 patient 9 patient 10 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 99 in this study, all patients came with a complaint of blurred vision, with bilateral lesion slightly more common (62%) than the unilateral lesion. the mean visual acuity is 1.50 ±1.07 logmar. patients with cmv retinitis often complained of blurred vision, floaters, or scotoma. research conducted by singh et al.3, sovani et al.8, and adeiza et al.14 also pointed out that blurred vision is the commonest complaint reported by patients. this is in accordance with the findings related to decreased visual acuity and bilateral lesion in these studies. in developing countries, patients will likely be seeking help to hospitals or ophthalmologists only when their condition has gotten worse or when manifestations appear on both eyes. in other words, they will come to healthcare facilities when their condition has grown serious and therapy can be very challenging. several reasons that may explain these issues are the possibility that there are still a large number of people lacking the necessary education, people with an inadequate economic condition, and people finding difficulties in accessing health care. screening can be performed on patients with a cd4 count < 100 cells/µl. because cmv retinitis may not display symptoms, it’s still highly recommended that patients undergo screening early to receive the necessary therapy immediately and to prevent blindness.3, 9, 14 factors that may affect the visual acuity of patients with cmv retinitis include macular involvements, retinal detachment, or the condition of the optic nerve.15 a study by iu et al.16 argued that significant macular involvement is a factor in poor prognosis of visual acuity with visual acuity test < 20/200. the majority of retinitis lesions will turn into areas of retinal atrophy. macular involvement will entail permanent visual impairment with poor visual acuity. all eyes in patients with cmv retinitis demonstrate the classic-form feature, in which 67% are posterior uveitis. this finding is similar to that of a study by sovani et al.8 in which the classic form is the dominant clinical finding. the classic or fulminant form is a clinical feature of cmv retinitis with its characteristic pizza pie or cottage cheese with ketchup appearance.17 however, the lesions of cmv retinitis may also manifest in a granular or perivascular form. they can also present with or without inflammation of the aqueous or vitreous humor. retinitis lesions can be unifocal or multifocal based on the perivascular distribution. usually, there are signs of mild to moderate inflammation of either the aqueous or vitreous humor.15 in this study, all patients with cmv retinitis also have aids with a mean cd4 count upon admission at 62.23 ± 11.82 cells/µl. there are 11 patients (85%) with a cd4 count < 100 cells/µl. similar findings are reported by ho et al.15 and singh et al.3 in their study, where the mean cd4 count of patients when they first arrived was 50–100 cells/µl. a cd4 count <100 cells/µl poses greater risks of cytomegalovirus infection, which oftentimes manifests in the eye as retinitis.18 some patient in our study have cd4 >50 cells/µl at initial visit, in our limitation we don’t know the initial cd4 count when the patient have symptom because the patient already have scar lesion. an examination result of cd4 count < 50 cells/µl poses a risk of cmv retinitis infection in patients with aids. the longitudinal study of ocular complication of aids (lsoca) describes that a cd4 count < 50 cells/µl is the sole crucial risk factor in the development of cmv retinitis.19, 20 of the 13 patients with cmv retinitis in this study, 10 of whom have a cd4 count of < 50 cells/µl. therefore, these 10 patients receive arv and valganciclovir therapy. in indonesia, the use of valganciclovir therapy during the era of indonesian healthcare and social security agency is limited to those with a cd4 count <50 cells/µl. a precondition of providing therapy for patients with cmv retinitis is that there has to be a clinical finding of lesion typical of cmv retinitis upon indirect funduscopy examination.10, 21 the current recommended therapy calls for the administration of valganciclovir at a dose of 900 mg two times a day throughout the induction phase (2–3 weeks), followed by 900 mg once daily for the maintenance phase. valganciclovir administered via oral route has the same efficacy and bioavailability with intravenous ganciclovir. systemic delivery of therapy may become an option to treat extraocular cmv diseases, prevent contralateral eye involvement, and mitigate mortality. should the patient’s cd4 count reach > 100 cells/µl by 3–6 months with inactive lesion, then the therapy can be stopped.10, 20, 22 100 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; in this study, oral candidiasis is the commonest (38%) opportunistic infection, followed by pulmonary tuberculosis, genital ulcer, diarrhea, and cerebral toxoplasmosis. multicenter research undertaken in korea from 2006 to 2013 also concluded that candidiasis, particularly oral candidiasis, is the most frequently encountered opportunistic infection in patients with aids, the second being tuberculosis. the opportunistic infections likely to be found in conditions where the cd4 count is < 500 cells/µl are tuberculosis, bacterial pneumonia, herpes zoster, oral candidiasis, salmonellosis, kaposi's sarcoma, and non-hodgkin lymphoma.18, 23 there are 7 eyes (33%) showing retinal detachment as a complication in this study. a study by singh et al.3 also described that the prevalence of retinal detachment was 21.8%. retinal detachment is one of the reasons causing declining visual acuity in patients with cmv retinitis. rhegmatogenous, which is a type of retinal detachment, emerges from the retinal break in a necrotic retina. risk factors of retinal detachment consist of retinitis over a wide area, bilateral lesion, and active retinitis near the vitreous base.8, 19 this is a retrospective study that collects data from the patients’ medical records, which has a number of limitations, such as limited number of samples, incomplete medical records, patients who are lost to follow-up and the indonesian healthcare and social security agency policy regarding the duration of therapy and limit of cd4 count who are eligible to receive oral valganciclovir. conclusion cytomegalovirus (cmv) retinitis was found in patients infected with aids with low cd4 counts. patients with a cd4 count < 50 cells/µl exhibit more severe clinical symptoms, including posterior uveitis, bilateral lesion, and visual acuity >1.00 logmar. this study recommends further research using the prospective study design, ideally with a larger sample and a longer research duration so that evaluations can be made regarding therapy efficacy and fellow eye involvement in patients with cmv retinitis. references miyazaki d, shimizu d, shimizu y, inoue y, inoue t, higaki s, et al. diagnostic efficacy of real-time pcr for ocular cytomegalovirus infections. 2018;256(12):2413-20. 2. chiotan c, radu l, serban r, cornăcel c, cioboata m, anghel ajjom, et al. cytomegalovirus retinitis in hiv/aids patients. 2014;7(2):237. 3. singh sr, dogra m, kaur s, bajgai p, tigari b, handa s, et al. spectrum of newly diagnosed cytomegalovirus retinitis in a developing country in the haart era. 2018. 4. rosati d, widjaja sa, sasono w, firmansjah m, yustiarini i, prakosa ad, et al. challenges in cytomegalovirus (cmv) retinitis management. 2019;2(2). 5. leenasirimakul p, liu y, jirawison c, khienprasit n, kamphaengkham s, ausayakhun s, et al. risk factors for cmv retinitis among individuals with hiv and low cd4 count in northern thailand: importance of access to healthcare. 2016;100(8):1017-21. 6. teoh sc, wang px, wong epjio, science v. the epidemiology and incidence of cytomegalovirus retinitis in the hiv population in singapore over 6 years. 2012;53(12):7546-52. 7. colby dj, vo dq, teoh sc, tam nt, liem nt, lu d, et al. prevalence and predictors of cytomegalovirus retinitis in hiv-infected patients with low cd4 lymphocyte counts in vietnam. 2014;25(7):516-22. 8. sovani i. clinical characteristics and management of cytomegalovirus retinitis with hiv in cicendo eye hospital national eye centre, bandung. 2018;1:2. 9. ei wlss, pyar soe k, hilbig a, murray j, heiden d, editors. routine immediate eye examination at the point of care for diagnosis of aids-related cytomegalovirus retinitis among patients with a cd4 count< 100 in myanmar. open forum infectious diseases; 2019: oxford university press us. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 101 10. dunn jmd. cmv retinitis, johns hopkins hiv guide. 2011. 11. kim dy, jo j, joe sg, kim j-g, yoon yh, lee jyjr. comparison of visual prognosis and clinical features of cytomegalovirus retinitis in hiv and non-hiv patients. 2017;37(2):376-81. 12. ophthalmology sounwgjajo. standardization of uveitis nomenclature for reporting clinical data. results of the first international workshop. 2005;140(3):509-16. 13. kemenkes rjkkr, jakarta. infodatin, pusat data dan informasi kementerian kesehatan ri, hiv aids 2020. 2020. 14. adeiza m, habib ajnjocp. a cross-sectional study of cytomegalovirus retinitis in hiv-1 infected adults in nigeria. 2019;22(3):293. 15. ho m, invernizzi a, zagora s, tsui j, oldani m, lui g, et al. presenting features, treatment and clinical outcomes of cytomegalovirus retinitis: non-hiv patients vs hiv patients. 2019. 16. iu lp, fan mc, lau jk, chan ts, kwong y-l, wong iyjajoo. long-term follow-up of cytomegalovirus retinitis in non-hiv immunocompromised patients: clinical features and visual prognosis. 2016;165:145-53. 17. tabbara kf, el-asrar ama, khairallah m. ocular infections: springer; 2014. 18. singh n, kumar l, singh dn, kumar v. frequency of opportunistic infection in pl hiv and its role in monitoring of art 1 failure. 2020. 2020;7(7):8 %j international journal of advances in medicine. 19. port ad, alabi ro, koenig l, gupta mpjcor. cytomegalovirus retinitis in the post-cart era. 2018;6(2):133-44. 20. stewart mwjco. optimal management of cytomegalovirus retinitis in patients with aids. 2010;4:285. 21. huang jj, gaudio pa. ocular inflammatory disease and uveitis manual: diagnosis and treatment: lippincott williams & wilkins; 2012. 22. schachat ap, wilkinson cp, hinton dr, wiedemann p, freund kb, sarraf d. ryan's retina e-book: elsevier health sciences; 2017. 23. kim yj, woo jh, kim mj, park dw, song j-y, kim sw, et al. opportunistic diseases among hivinfected patients: a multicenter-nationwide korean hiv/aids cohort study, 2006 to 2013. 2016;31(5):953. this work licensed under creative commons attribution abstract introduction cytomegalovirus (cmv) retinitis is frequently found in immunocompromised patients, but it can also be present in immunocompetent individuals.1 this opportunistic infection usually takes place in patients with a low cd4 count at around 50 cells/µl.2 ma... methods results conclusion published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 21 international journal of retina (ijretina) 2019, volume 2, number 1. p-issn. 2614-8684, e-issn.2614-8536 levels of hypoxia inducible factor-1α (hif-1α) and intercellular adhesion molecule-1 (icam-1) after intravitreal bevacizumab in proliferative diabetic retinopathy ressa yuneta 1, tjahjono darminto gondhowiardjo1, rahayuningsih dharma2, sri widia a. jusman3, joedo prihartono4, andi arus victor1 1 department of ophthalmology, faculty of medicine, universitas indonesia cipto mangunkusumo hospital, indonesia 2 department of clinical pathology, faculty of medicine, universitas indonesia 3 department of biochemistry, faculty of medicine, universitas indonesia 4 department of community health, faculty of medicine, universitas indonesia abstract introduction: to assess the levels of hypoxia-inducible factor-1α (hif-1α) and intercellular adhesion molecule1 (icam-1) in vitreous of proliferative diabetic retinopathy patients which were given intravitreal bevacizumab (ivb), as well as its relation to the central macular thickness (cmt) measured prior to vitrectomy. methods: thirty-two eyes were randomized into two groups, one that received an ivb injection at 1-2 weeks previtrectomy and the control group which did not receive any injection. measurement of hif-1α and icam-1 was conducted using enzyme-linked immunosorbent assay (elisa). the cmt were measured at the initial visit, prior to vitrectomy, and at follow up time (2, 4, and 12 weeks postoperatively) using stratus oct. results: the mean levels of hif-1α vitreous (ng/mg protein) in the control group and ivb respectively 0.020 (0.006; 0.077) and 0.029 (0.016; 0.21). vitreous levels of icam-1 (ng /ml) in control group and ivb group were 20.10 (3.41; 40.16) and 23.33 (0.63; 68.5). the mean levels of hif-1α and icam-1 vitreous obtained did not differ significantly between the two groups. conclusion: the levels of hif-1α and icam-1 in pdr patients do not decrease after one injection of intravitreal bevacizumab 1-2 weeks prior to vitrectomy. the concentration of vitreous hif-1α and icam-1 are not directly related to the cmt. keywords: proliferative diabetic retinopathy, hif-1α, icam-1, intravitreal bevacizumab cite this article: yuneta, ressa et al. levels of hypoxia inducible factor-1α (hif-1α) and intercellular adhesion molecule-1 (icam-1) after intravitreal bevacizumab in proliferative diabetic retinopathy. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/60>. introduction *correspondence to: andi arus victor, department of ophthalmology, universitas indonesia, arvimadao@yahoo.com diabetic retinopathy (dr) is a complication of diabetes mellitus (dm) on the retina caused by uncontrolled high blood glucose levels in long term. proliferative diabetic retinopathy (pdr) is the advanced form of dr characterized by the formation of new blood vessels in the retina which increases the risk of visual loss.1, 2 diabetic retinopathy is the most commonly found retinal vascular disorder in the vitreoretina policlinic at cipto mangunkusumo hospital.3 in 20042009, there were 3988 dr visits and 38.3% of them were pdr. the percentage of pdr visits was increased to 47.9% in 2010-2012.4 damage to the structure of the retina as a result of long term hyperglycemia is the main pathogenesis of dr. pdr begins from retinal ischemia due to microvascular occlusion and retinal capillary nonperfusion . 22 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; it results in increased production of vascular endothelial growth factor (vegf), which stimulates the formation of neovascularization. the new vessels are fragile and can lead to the buildup of lipoproteins and bleeding in the retina and vitreous.5, 6 research with therapy focusing on biomolecular activity is expected in order to prevent the pathological retinal response to hypoxia.3, 7 recent studies have shown that elevated hif-1α and icam-1 levels affect the dr progression in pdr patients.3, 8-13 hif-1α is a protein that plays a major role as a transcription factor in vegf regulation, in which its accumulation was induced by retinal hypoxia.3, 10, 13, 14 vegf will increase retinal vascular permeability, microvascular occlusion, teleangiectasia, microaneurysms and retinal ischemia. retinal ischemia leads to hypoxia that will stimulate the formation of hif1α, which in turn triggers more vegf.15, 16 icam-1 is an adhesion molecule that plays a role in inflammatory mechanisms of blood vessel’s wall. vascular endothelial growth factor is known to corelate with icam-1 in the neovascularization process.17-19 methods this study is a prospective, post-test only, open-labeled randomized clinical trial. the subjects of this study were 32 eyes of 32 pdr patients which were evaluated from january to november 2016 at vitreoretina policlinic of cipto mangunkusumo hospital. subjects were divided into two groups, each group consisted of 16 subjects. the control group was treated with vitrectomy only, whereas bevacizumab group received ivb injection 1-2 weeks prior to vitrectomy. inclusion criterias were dm patients aged more than 18 years, with vitreomacular traction or nonclearing vitreous haemmorhage, who are willing to participate in the study, and with signed informed consent. patients with a previous history of vitrectomy surgery, intravitreal anti-vegf or laser photocoagulation, and patients without central macular thickness (cmt) measurement before vitrectomy were excluded from this study. a volume of 0.5-1 ml vitreous sample was retrieved with 1 ml syringe connected to vitrectomy cutter before running intravenous fluids during vitrectomy. the concentrations of hif-1α and icam-1 from the sample were measured in biochemistry and clinical pathology laboratory at cipto mangunkusumo hospital. using sandwich-type enzyme-linked immunosorbent assay (elisa). the hif-1α level was recorded in each 1 mg of protein (ng/mg protein). elisa kit for hif-1α (elabscience) and elisa kits for icam-1 ((r&d systems) was performed based on the recommendations of the manufacturer. stratus oct (carl zeiss meditec, dublin, ca) was used to measure cmt. all subjects were measured for their cmt and visual acuity (va) at 2nd, 4th, and 12th week postoperatively. spss version 17.0 was used for analysis, based on the intention to treat analysis. this clinical study was approved by the ethical clearance committee of faculty of medicine, universitas indonesia based on the declaration of helsinki, with ethical clearance number of 229/un2.f1/ethics/2015. results table 1: distribution of demographic data variable group p control ivb age 46.5±10.2 50.62±6.25 0.180a gender male female 6 10 3 13 0.433b duration of dm (year) 6.50 (1;20) 7 (1;20) 0.746c total cholesterol (mg/dl) 242.8±56.8 226.6±67.5 0.469a systolic blood pressure (mmhg) 147.5±19.6 141.31±22.7 0.403a diastolic blood pressure (mmhg) 83.7±12.3 76.1±10.1 0.067a hba1c (%) 8.96±2.1 9.43±1,40 0.450a mean initial cmt (μm) 507 (116;1673) 741 (233;1471) 0.522c mean cmt prior to vitrectomy (μm) 507 (177;1673) 600 (193;1363) 0.797c mean initial visual acuity (logmar) 1.8±0.3 1.9±0.1 0.248a mean visual acuity prior to vitrectomy (logmar) 1.8±0.4 1.9±0.3 0.540a a independent t-test, b fisher exact test, c mann whitney the level of hba1c, duration of diabetes, and initial cmt were higher in the ivb group, but these differences were not statistically significant (p> 0.05) published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 23 table 2: the levels of hif-1α dan icam-1 in both study groups variable groups p control ivb level of hif-1α (ng/mg protein) 0.020 (0.006; 0.077) 0.029 (0.016; 0.21) 0.172* level of icam-1 (ng/ml) 20.10 (3.41; 40.16) 23.33 (0.63; 68.5) 0.777* *mann whitney test the levels of vitreous hif-1α and icam-1 in the ivb group are higher than the control group, but not statistically significant (p> 0.05). table 3: mean cmt of each group at baseline, prior to vitrectomy and at 2nd, 4th, and 12th weeks postoperative cmt (µm) groups p control ivb initial 507 (116;1673) 741 (233; 1471) 0.434* prior to vitrectomy 507 (177; 1673) 600 (193; 1363) 2nd week postoperative 267 (120; 693) 328 (230; 545) 4th week postoperative 274 (129; 724) 320 (193; 1275) 12th week postoperative 275.5 (169; 1473) 323 (201; 575) *anova 2 way with general linear model there is no statistically significant difference in cmt measurement between two groups at every measurement time (p> 0.05). table 4: mean cmt at pre and post ivb injection in the ivb group ivb group time of measurement p pre ivb injection post ivb injection cmt (μm) 741 (233;1471) 600 (193;1363) <0.002* *wilcoxon test the decrease of the cmt between pre-ivb injection (baseline) and post ivb injection (pre-vitrectomy) was statistically significant (p <0.002). . figure 1: correlation between hif-1α concentration with cmt prior to vitrectomy in (a) control group (spearman; r=0.038 dan p=0.888) and (b) ivb group (spearman; r=-0.280 dan p=0.332). a μ m b μ m 24 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; figure 2: correlation between icam-1 concentration with cmt prior to vitrectomy in (a) control group (spearman; r=0.041 dan p=0.879) and (b) ivb group (spearman; r=-0.004 dan p=0.990). scattered diagrams at figure 1 and 2 above shows that there were no correlations between hif-1α and icam-1 on cmt value prior to vitrectomy in both groups. the subject of this research consists of pdr patients with vitreomacular traction on most subjects, so this might affect the value of cmt in this study. statistical tests were conducted in 26 subjects (14 control group and 12 ivb group) who had a complete va data at every follow-ups. table 5: visual acuity in both groups at baseline, prior to vitrectomy and at 2, 4, and 12 weeks post-operation *anova 2 way with general linear model only 26 subjects had a complete data of va at all followups period and were included for the va analysis, 14 from the control group and 12 from the ivb group. postoperative va in the ivb group was worse than in the control group at all measured time frames. these differences in va between the two groups were statistically significant. post-operative complications appeared to be almost equal in proportion between the two groups. postoperative vitreous hemorrhage in ivb group was found in subjects without silicone oil. hyphema occured in the control group with poor blood pressure and blood sugar control (hba1c: 11mg/dl). table 4.6 postoperative complications discussion this study shows that the difference between the levels of hif-1α and icam-1 in both groups is not statistically significant (p> 0.05). these results might be influenced by several factors such as the baseline levels of hif-1α and icam-1, inadequate decreased of vegf level in the ivb group, or a change in inflammatory mediators after ivb injection. decreased levels of hif-1α and icam-1 could not be seen if the baseline levels were higher in the ivb group. however in this study, the measurement of hif-1α and icam-1 before vitrectomy could not be obtained. anti-vegf binds to vegf molecules, hence, preventing the vegf to bind to its receptors. bevacizumab works by holding on to all isoforms of vegf-a. it has a longer halflife time and higher molecular weight than ranibizumab.20, 21 victor et al22 reported that pdr patients who had an ivb injection prior to vitrectomy had twice as low vegf levels than the group that did not receive ivb. han et al23 studied the effects of ivb injection 6 days prior to vitrectomy to the level of hif-1α through immunohistochemical examination of the fibrovascular membrane obtained during vitrectomy. expression of hif1α in dr group that had been given ivb injection was found to be lower than that of the control group. the visual acuity (logmar)±sd groups p control ivb initial 1.81±0.36 1.93±0.13 0.013* prior to vitrectomy 1.83±0.36 1.90±0.26 2nd week postoperative 1.99±0.31 1.93±0.26 4th week postoperative 1.69±0.65 1.98±0.08 12th week postoperative 1.61±0.74 2.00±0.00 complications groups (∑) total control ivb postoperative vitreous hemmorhage 3 3 (9.38%) hyphema 2 2 (6.25%) retinal redetachment 1 1 2 (6.25%) cataract 2 2 4 (12.5%) glaucoma 3 3 (9.38%) a b published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 25 subjects in the study were pdr with vitreous hemmorhage, traction, or macular edema. however, some patients in the study group also received laser photocoagulation before vitrectomy. han et al32 also discovered that laser photocoagulation prior to vitrectomy, prevents further ischemia and decreases the hif-1α concentration. inadequate reduction of vegf level in the ivb group could also affect the hif-1α result in the ivb group. victor et al22 report that the lowest levels of vegf found in the group that received a combination of laser photocoagulation and ivb injection. the levels of vegf in the combination therapy were found to be 5 times lower compared to the control group. the similar hif-1α levels between the case and the control group could be caused by the severe pdr subjects who require laser photocoagulation and ivb combination therapy, to achieve a significant ischemia inhibition effect to reduce levels of hif-1α. another factor that can contribute to the rising hif-1α concentration in this study is the change in inflammatory mediators after the ivb injection. an increased inflammatory mediator is a response from vegf blockade, but the details are not completely understood. some researchers reported inflammatory mediators change after ivb injection.24, 25 forooghian et al25 reported a significant increase in inflammatory mediators such as il8 and tgf-β2 in the aqueous humor of pdr patients at 10 days after ivb administration. stilla et al26 report the effects of inflammatory mediators on hif-1α. in inflammation, ang-ii, thrombin, tgf-β2 (transforming growth factor-β2), il-1β (interleukin-1β), tnf-α (tumor necrosis factor-α), nf-κb, and other factors contribute to the accumulation of hif-1α. increased tgf-β2 is expected to affect the expression of hif-1α in inflammatory processes.26 icam-1 can be induced by other inflammatory mediators such as il-1 and tnf-α, which can be induced by tgf-β.27 yan et al28 reported the post-injection effect of ranibizumab on levels of icam-1 for before and after 7 days. the study reported that the level of icam-1 in the group injected with ranibizumab one week prior to vitrectomy was higher than the control group. in the group who received ranibizumab injection for more than 1 week before vitrectomy, the level of icam-1 was lower than the control group. these results demonstrate that administration of intravitreal anti-vegf can increase the icam-1 concentration in the initial period. however, our study uses bevacizumab which is a heavier anti vegf molecule, and persist for a longer periode in the vitreous when compared to ranibizumab. hence, the inflammation effect after ivb is expected to last longer than that of ranibizumab. hif-1α affects the progression of macular edema in pdr. there was no correlation between the levels of hif1α and icam-1 on cmt prior to vitrectomy. cmt is affected by inflammation and also by vitreomacular traction of the fibrovascular membrane. the traction located at the optic disc area or along the vascular arcades will cause antero-posterior traction in the macular area.29 the mean baseline va in this study was 1.81 ± 0.36 in the control group and 1.93 ± 0.13 in the ivb group. the poor baseline va in the ivb group might have certain effects on the also poor postoperative va. this finding was similar to a study by kaiser et al30 that reported the patient with poor initial va (logmar> 1) have a settled va within 1 year after vitrectomy. abdelhakim et al31 also found that va in the subject with ivb injection 7 days prior to vitrectomy was not improved, even in patients with va more than logmar=1 or slightly better. the decrease in macular thickness happened in most of the subjects. this is consistent with a study by arevalo32 that found that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and va, even though cmt improvement is not always followed by va improvement.33 recurrent vitreous hemorrhage occurred in three patients from ivb group without silicone oil tamponade. yeung et al34 reported that intraocular tamponade is more effective than ivb injection to prevent recurrent postoperative vitreous hemmorhage. silicone oil has tamponade and compression effect on the blood vessels of the retina. retinal redetachments occurred in two subjects, 1 subject in each group. it happened due to fibrovascular reproliferation or intraoperative atrophicretina-related retinal tears.35 hyphema was found in two subjects with glaucoma. it occurred in the control group who had poor blood sugar and blood pressure control. this study is the first study that assesses both the vitreous levels of hif-1α and icam-1 in pdr patients who received ivb injection. baseline measurement of the hif1α and icam-1 levels are not possible is found to be limitations of this study. greater number of subjects and examinations of other proinflammatory cytokines that may affect the levels of hif-1α and icam-1 such as vegf, interleukin, tnf-α, and tgf-β can be done in relation to this study. conclusion the levels of hif-1α and icam-1 in pdr patients do not decrease after one injection of intravitreal bevacizumab 12 weeks prior to vitrectomy. the concentration of vitreous hif-1α and icam-1 are not directly related to the cmt. 26 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; ethics and consent to participate written informed consent was obtained from the patient. the ethical clearance approval (no: 229/un2.f1/etik/2015) was obtained from the health research ethics committee of faculty of medicine, universitas indonesia and a copy of it was submitted to the editor of this journal. conflict of interests all authors hereby declare no conflicts of interest. acknowledgement authors would like to express their gratitude to all parties who have aided the making of this manuscript. references 1. retinal vascular disease : diabetic retinopathy. san fransisco: american academy of ophthalmology 2014-2015. 2. kanski j, bowling b. diabetic retinopathy in: kanski j, bowling b, editors. clinical ophthalmology: a systematic approach. 7 ed. united kingdom: elsevier; 2011. 3. arjamaa o, nikinmaa m. oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. experimental eye research. 2006;83(3):473-83. 4. sasongko mb, widyaputri f, agni an, wardhana fs, kotha s, gupta p, et al. prevalence of diabetic retinopathy and blindness in indonesian adults with type 2 diabetes. american journal of ophthalmology. 2017;181:79-87. 5. fletcher e cn. vaughan & asbury’s general ophthalmology. 17th ed ed. mcgraw hill ed. london 2007. 6. besirli cg, johnson mw. proliferative diabetic retinopathy. mayo clinic proceedings. 2009;84(12):1054-. 7. girgis cm, cheng k, scott ch, gunton je. novel links between hifs, type 2 diabetes, and metabolic syndrome. trends in endocrinology and metabolism: tem. 2012;23(8):372-80. 8. adamiec-mroczek j, oficjalska-mlynczak j. assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes--role of the inflammatoryimmune process in the pathogenesis of proliferative diabetic retinopathy. graefe's archive for clinical and experimental ophthalmology = albrecht von graefes archiv fur klinische und experimentelle ophthalmologie. 2008;246(12):1665-70. 9. adamiec-mroczek jo-m, misiuk-hojło m. proliferative diabetic retinopathy—the influence of diabetes control on the activation of the intraocular molecule system. . diabetes research and clinical practice 2008;. 2008(84):46-50. 10. antonetti dk, r. gardner, t. . mechanism of disease diabetic retinopathy : review. n engl j med 2012(366):1227-39. 11. khalfaoui t, lizard g, beltaief o, colin d, ben hamida j, errais k, et al. immunohistochemical analysis of cellular adhesion molecules (icam-1, vcam-1) and vegf in fibrovascular membranes of patients with proliferative diabetic retinopathy: preliminary study. pathologiebiologie. 2009;57(7-8):513-7. 12. limb ga, webster l, soomro h, janikoun s, shilling j. platelet expression of tumour necrosis factoralpha (tnf-alpha), tnf receptors and intercellular adhesion molecule-1 (icam-1) in patients with proliferative diabetic retinopathy. clinical and experimental immunology. 1999;118(2):213-8. 13. zhang x, bao s, hambly bd, gillies mc. vascular endothelial growth factor-a: a multifunctional molecular player in diabetic retinopathy. the international journal of biochemistry & cell biology. 2009;41(12):2368-71. 14. okur v, cetin o, cetin e, tepeli e, bulgu y, yildirim c. hif1a as a major vascular endothelial growth factor regulator: do its polymorphisms have an association with age-related macular degeneration? clinical & experimental ophthalmology. 2015;43(1):47-53. 15. tolentino mj, miller jw, gragoudas es, jakobiec fa, flynn e, chatzistefanou k, et al. intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. ophthalmology. 1996;103(11):1820-8. 16. tolentino mj, mcleod ds, taomoto m, otsuji t, adamis ap, lutty ga. pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate. american journal of ophthalmology. 2002;133(3):373-85. 17. kima i, moona s-o, kima sh, kimb hj, koha ys, koh gy. vegf stimulates expression of icam-1, vcam-1 and e-selectin through nuclear factor-κ b activation in endothelial cells. the american society for biochemistry and molecular biology. 2000. 18. radisavljevic z, avraham h, avraham s. vascular endothelial growth factor up-regulates icam-1 expression via the phosphatidylinositol 3 ohkinase/akt/nitric oxide pathway and modulates migration of brain microvascular endothelial cells. the journal of biological chemistry. 2000;275(27):20770-4. 19. lu m, perez vl, ma n, miyamoto k, peng hb, liao jk, et al. vegf increases retinal vascular icam-1 expression in vivo. investigative ophthalmology & visual science. 1999;40(8):1808-12. 20. simo r, hernandez c. intravitreous anti-vegf for diabetic retinopathy: hopes and fears for a new therapeutic strategy. diabetologia. 2008;51(9):1574-80. 21. salam a, mathew r, sivaprasad s. treatment of proliferative diabetic retinopathy with anti-vegf agents. acta ophthalmologica. 2011;89(5):405-11. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 2; 1; 27 22. victor aa, gondhowiardjo td, waspadji s, wanandi si, bachtiar a, suyatna fd, et al. effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress. med j indones. 2014;23(2):79-86. 23. han xx, guo cm, li y, hui yn. effects of bevacizumab on the neovascular membrane of proliferative diabetic retinopathy: reduction of endothelial cells and expressions of vegf and hif-1α. molecular vision. 2012;18:1-9. 24. jeon s, lee wk, jung y. changes in the intraocular cytokine levels after intravitreal bevacizumab in uveitic macular edema. ocular immunology and inflammation. 2012;20(5):360-4. 25. forooghian f, kertes pj, eng kt, agrón e, chew ey. alterations in the intraocular cytokine milieu after intravitreal bevacizumab. investigative ophthalmology & visual science. 2010;51(5):2388-92. 26. frede s, berchner-pfannschmidt u, fandrey j. regulation of hypoxia-inducible factors during inflammation. methods in enzymology. 2007;435:405-19. 27. elmarakby aa, sullivan jc. relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. cardiovascular therapeutics. 2012;30(1):4959. 28. yan y, zhu l, hong l, deng j, song y, chen x. the impact of ranibizumab on the level of intercellular adhesion molecule type 1 in the vitreous of eyes with proliferative diabetic retinopathy. acta ophthalmologica. 2016;94(4):358-64. 29. bhagat n, grigorian ra, tutela a, zarbin ma. diabetic macular edema: pathogenesis and treatment. survey of ophthalmology. 2009;54(1):1-32. 30. kaiser rs, maguire mg, grunwald je, lieb d, jani b, brucker aj, et al. one-year outcomes of panretinal photocoagulation in proliferative diabetic retinopathy. american journal of ophthalmology. 2000;129(2):178-85. 31. abdelhakim ma, macky ta, mansour ka, mortada ha. bevacizumab (avastin) as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case series. ophthalmic research. 2011;45(1):23-30. 32. arevalo jf, garcia-amaris ra. intravitreal bevacizumab for diabetic retinopathy. current diabetes reviews. 2009;5:39-46. 33. browning dj, glassman ar, aiello lp, beck rw, brown dm, fong ds, et al. relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. ophthalmology. 2007;114(3):525-36. 34. yeung l, liu l, wu wc, kuo yh, chao an, chen kj, et al. reducing the incidence of early postoperative vitreous haemorrhage by preoperative intravitreal bevacizumab in vitrectomy for diabetic tractional retinal detachment. acta ophthalmologica. 2010;88(6):635-40. 35. sima p, zoran t. long-term results of vitreous surgery for proliferative diabetic retinopathy. documenta ophthalmologica advances in ophthalmology. 1994;87(3):223-32. this work licensed under creative commons attributio management of late spontaneous iol-capsular bag complex dislocation with low corneal endothelial cell density: a case report 32 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 international journal of retina (ijretina) 2019 volume 02, number 01 p-issn. 2614-8684, e-issn.2614-8536 a rare case of unilateral retinitis pigmentosa: challenges in making a diagnosis elyas aditya1, syntia nusanti1, muhammad sidik1, ari djatikusumo1 1 department of ophthalmology, faculty of medicine universitas indonesia, cipto mangunkusumo national central general hospital, jakarta, indonesia abstract introduction: retinitis pigmentosa (rp) is a hereditary disorder that diffusely involve photoreceptor and retinal pigment epithelial (rpe). it is characterized by progressive visual field loss and abnormal erg. unilateral rp is a rare condition that is usually sporadic. clinical presentation and ancillary test results are similar to bilateral rp, with only one eye affected. in making the diagnosis of unilateral rp, clinicians must be able to rule out secondary causes, document a normal erg in the unaffected eye, and follow-up the patient for at least 5 years to rule out bilateral but highly asymmetric disease. the aim of this case report is how to diagnose a rare case unilateral rp from clinical examination and ancillary tests. methods: we report a case of a 33-year-old female with slowly progressive restriction of visual field of the left eye in the last one year before admission. ophthalmological examination of the left eye revealed bone spicules spreading to peripheral fundus. visual field examination revealed severely constricted visual field of the left eye. the multifocal electroretinogram (mferg) examination showed severely depressed erg function with reduced foveal responses. the fellow eye was within normal limit. results: patient was diagnosed with unilateral rp and must be followed-up for at least five years to rule out bilateral yet asymmetric disease. making diagnosis of unilateral rp become one of the challenging case. clinicians must be able to rule out the secondary causes that also have unilateral pigmentary retinal degeneration. conclusion: with a good clinical examination and some simple ancillary tests, we could correctly diagnose unilateral rp. however, in this case we still need five years follow up to rule out bilateral rp but highly asymmetric disease. key words: unilateral retinitis pigmentosa, unilateral pigmentary retinal degeneration, multifocal electroretinogram cite this article: nusanti, syntia et al. a rare case of unilateral retinitis pigmentosa. international journal of retina, [s.l.], v. 2, n. 1, feb. 2019. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/52> introduction *correspondence to: syntia nusanti, department of ophthalmology, universitas indonesia, syntia_nusanti@hotmail.com retinitis pigmentosa (rp) is a hereditary disorder that diffusely involve photoreceptor and retinal pigment epithelial (rpe), and is characterized by progressive visual field loss and abnormal erg.1 in early 1855, familial retinal degeneration with intraneural retinal pigmentation was first described by donders. 2 nowadays, it is well known that the majority of rp cases have a genetic basis and cause photoreceptor cell death through apoptosis.2,3 the prevalence of primary photoreceptor degeneration is 1: 3000 to 1: 5000. 4 prevalence of recessive retinitis pigmentosa is approximately 1:100. 5 patient with rp usually complains about “night blindness”, and tunnel vision (visual field loss).2 in ocular examination there are several key features of rp such as “bonespicule” intraneural retinal pigment, thinning and atrophy of the rpe in the midand farperipheral retinal, relative preservation of the rpe in the macula, glitotic “waxy pallor” of the optic nerve head, and attenuation of the retinal arterioles.2 unilateral rp is a rare condition that is usually sporadic. clinical presentation and ancillary test findings are similar to bilateral rp, but only affect one eye. however, the vast majority of unilateral pigmentary retinal degenerations are likely to have an acquired origin like a history of vascular occlusion, history of trauma, uveitis, and infection. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01; 33 in making the diagnosis of unilateral rp, clinicians must be able to rule out such secondary causes, document a normal erg in the unaffected eye, and run a routine follow-up of the patient for at least 5 years to rule out bilateral but highly asymmetric disease. this case report will discuss about the challenges in making diagnose of unilateral retinitis pigmentosa. methods a 33-years-old female came to the ophthalmologist with progressive restricted visual field of the left eye in the last one year before admission. there was no complaint of diminished visual acuity in the night. patient went to an eye center and performed some ancillary test such as optical coherence tomography of the optic nerve, fundus fluorescein angiography (ffa), orbital ct scan, and laboratory test. the patient was referred to aini hospital, and the multifocal electroretinogram (meerg) examination was performed subsequently. there was no history of hearing disorder, neuromuscular disorder, gastrointestinal disorder, renal disorder, dermatologic disorder, mental disorder, diabetic, and hypertension. there was no history of using retinal toxic drug (chloroquine, phenothiazine, etc), trauma, and eye redness. there was no history of similar complains in her family. ophthalmological examination revealed the uncorrected visual acuity was 6/12 on the both eyes, and 6/6 with correction (spheris -1.00) on the right eye and 6/6 f1 with correction (spheris -1.00) on the left eye. the intra ocular pressure was 10.0 mmhg on the right eye, and 9.7 mmhg on the left eye. there was no limitation of the ocular movement. palpebral, conjunctiva bulbi, cornea, and anterior chamber of both eyes were within normal limits. figure 1a figure 1b the funduscopic examination of the right eye was normal (figure 1a). meanwhile, fundus examination of the left eye showed cup-to-disc ratio was 0.3-0.4 and there were narrowing retinal vessels, depigmented rpe on macular region, and bone spicules spreading to peripheral fundus (pointed by arrow). (figure 1b). the ishihara test was within normal limits. fundus fluorescein angiography (ffa) examination revealed the right eye was within normal, but the left eye showed hyper fluorescein areas surround the optic nerve and peripheral fundus (pointed by arrow). (figure 2). figure 2. fundus fluorescein angiography (ffa) examination 34 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 visual field testing with humphrey field analyzer showed there was no visual field defect of the right eye (figure 3a). on the other hand, there was severely depressed visual field on the left eye (figure 3b). figure 3a. visual field testing of the right eye. figure 3b. visual fieldtesting of the left eye optical coherence tomography (oct) examination of optic nerve head showed both optic nerve head were within normal limit. cup-to-disc ratio and mean retinal nerve fiber layer (rnfl) thickness of both optic nerve head were within normal limit. (figure 4a and 4b). figure 4a. oct examination of optic nerve head of the figure 4b. oct examination of optic nerve head of the right eye left eye laboratory examination revealed non-reactive antitoxoplasma igm, antirubella igm, anti-cmv igm, anti-hsv i igg, anti-hsv i igm, anti-hsv ii igg, antihsv ii igm and non-reactive anti-hiv tittered, but reactive antitoxoplasma igg, antirubella igg, and anti-cmv igg tittered. another laboratory examinations such as ureum levels, creatinine, and hba1c levels were within normal limit. orbital and brain coherence tomography scan (ct scan) showed there were no abnormality of orbital structures nor intracranial space occupying lesion (sol). multifocal electroretinogram (meerg) examination showed the erg function of the right eye was within normal limit. on the other hand, the erg function of the left eye was extremely depressed with reduction of foveal responses. (figure 5a and 5b). published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 35 figure 5a. meerg examination of the right eye. figure 5b. meerg examination of the left eye. result patient was diagnosed as unilateral rp and must be followed up for at least five years to rule out bilateral but highly asymmetric disease. discussion in making diagnose of unilateral retinitis pigmentosa become one of the challenging case. clinicians must rule out the secondary causes that also have unilateral pigmentary retinal degeneration such as a previous vascular occlusion, trauma, uveitis, infection, or retained metallic intraocular foreign body.1 the term retinitis pigmentosa (rp) refers to disorders that affect the photoreceptors and retinal pigment epithelium (rpe) diffusely across the entire fundus but begin with initial geographic involvement in either the periphery or the macula.2 it is now understood that the majority of cases have a genetic basis and involve photoreceptor cell death through apoptosis. 2 rp could be seen in isolation (typical rp) or in association with systemic disease (syndromic rp). the prevalence of typical rp is approximately 1:5000 worldwide. prevalence of rp is approximately 1:7000 in switzerland, 1:4016 in china, and 1:4500 in israel. the prevalence of syndromic rp is less well documented. in example, the prevalence of usher syndrome (rp with congenital deafness) is estimated to be 1:6000.6 patient with typical retinitis pigmentosa has some typical symptoms such as nyctalopia, visual field loss, central vision loss, color vision defects, and photopsia.6 patients with typical rp usually complains night vision difficulties in the first or second decade of life. people with rp have narrow visual field in the dark and may get easily disoriented on dim light. 6 the second hallmark feature of rp is an insidious, progressive loss of peripheral visual field. for many types of rp, visual field deficits are usually found first, and are most severe in the superior visual field. (figure 6) this reflects the early involvement of the inferior retina in rp. 36 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 figure 6. superior visual field deficits due to early involvement of the inferior retina in retinitis pigmentosa6 in typical rp, visual field loss is usually progressing slowly (years or decades). however, visual fields may change dramatically over a few months or years. the visual field loss may be unnoticeable, if the central field remains clear.6 patient complained restriction of visual field in the last one year before admission. visual field loss is caused by initial involvement of photoreceptors which leads to subsequent damage to inner retinal cells.6 the patient didn’t notice as the visual field defect was slowly progressing from the peripheral side. there was no diminished visual acuity in the night (night blindness). the night blindness may be unnoticeable due to the unilateral involvement of the disease; therefore, this complaint may be compensated by the other eye. typical fundus findings in rp include arteriolar narrowing, optic nerve head pallor, and intraretinal bone spicule pigmentation.1,6 (figure 7) intraretinal bone spicule pigment formations represent migration of pigment into the retina from disintegration of rpe cells with accumulation in the interstitial spaces surrounding retinal vessels.6 fundus examination of the left eye in this patient revealed there were narrowing of retinal vessels, depigmented retinal pigment epithelium (rpe) on macular region, and bone spicules spreading to peripheral fundus (figure 7). figure 7. typical fundus findings in rp (left picture)6. fundus examination on patient’s left eye (right picture) published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 37 based on the patient’s chief complain, several diseases that have similar complaints (visual field defect) such as glaucoma, retinal disease, or a neuroophthalmologic entity should be considered.7 as we know, enlargement of the cup may be the earliest change detected in glaucoma. this enlargement can be difficult to be noticed unless previous photographs or diagrams are available. confocal scanning laser ophthalmoscopy can be used to create a 3d image of the optic nerve head. parameters such as cup area, cup volume, rim volume, cdr, and peripapillary nerve fiber layer thickness are then calculated. 8 this examination was performed to our patient and the results were within normal limit (figure 8). there was no neuroretinal thinning, cdr and mean rnfl thickness were within normal limit. based on these results, we can exclude glaucoma as the etiology of visual field constriction in this patient. figure 8. confocal scanning laser ophthalmoscopy of glaucomaotus optif nerve (left picture)8. confocal scanning laser ophthalmoscopy of patient’s left eye (right picture) one of neuro-ophthalmologic disorder that we have to be concern in patient complaining unilateral field defect is compressive optic neuropathies.7 compressive optic neuropathies (con) are diseases of the optic nerve that can cause visual loss secondary to pressure on the optic nerve, either within the orbit, inside the optic canal or intracranially.9 the highly specific clinical characteristics for a compressive lesion are age less than 50 years, optic nerve pallor and cupping, visual field defects at the vertical meridian, unilateral field defects, and visual acuity less than 20/40. 7 we can exclude con as the etiology of unilateral field defect, because the visual acuity was 6/6 with correction, there were no pallor and cupping optic nerve, and the orbital and brain coherence tomography scan (ct scan) showed there were no abnormality of orbital structures nor intracranial space occupying lesion (sol). multifocal ergs (mferg) examination in patient with rp reveals a normal amplitude in macular area, but the topographic map of the multifocal ergs shows an extremely reduced periphery, indicating marked reduction of the peripheral responses (figure 9). 10 mferg examination showed the erg function of the right eye was within normal limit. in contrast, the erg function of the left eye was extremely depressed with reduction of foveal responses. the rods and cones components of the left eye at peripheral side were nearly undetectable and focal macular ergs stimulus of the left eye was smaller than the right eye (figure 9). based on this mferg result, we can conclude that the left eye was in the advanced stage of the disease. majority form of retinitis pigmentosa initially leads to death of the rod photoreceptors.2 severe cone involvement occurs in the end stage of the disease,when total vision loss happens. 2 this conclusion was supported by a “tunnel vision” visual field test which indicate the disease had been in the advanced stage. 38 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 figure 9a. mferg examination of normal eye (left picture). mferg examination of patient with rp (right picture) 10 figure 9b. mferg examination of patient’s left eye in making the diagnosis of unilateral rp, we must rule out the secondary causes that show unilateral pigmentary retinal degeneration, such as previous vascular occlusion, trauma, uveitis, infection (diffuse unilateral subacute neuroretinitis), or retained metallic intraocular foreign body. 1 based on anamnesis, there were no history of trauma, nor retained metallic intraocular foreign body. we can directly rule out the history of trauma and retained metallic intraocular foreign body as the etiology of unilateral pigmentary retinal degeneration. in diagnosing unilateral rp, we have to rule out the history of vascular occlusion in this patient, because it can reveal unilateral pigmentary degeneration like we find in unilateral rp. 1 patients with history vascular occlusion usually complain about sudden painless loss of vision. the visual field defect is usually isolated to one eye and may be partial (branch retinal artery occlusion and cilioretinal artery occlusion) or complete (central retinal artery occlusion and ophthalmic artery occlusion). in the ophthalmological examination, patient with long standing central retinal artery occlusion (crao) will reveal neovascularization of the iris and attenuated retinal arteries (figure 10). 11 figure 10. attenuated retinal arteries in crao (left picture). neovascularization of the iris in crao (right picture)11 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 39 in crao, despite the extremely constricted visual fields and poor visual acuity, the ergs in the affected eye is relatively well preserved. although the b/a ratio in the affected eyes is lower than that of fellow eye, none of the ergs from the affected eyes has a negative configuration. (figure 11) these results suggest that the function of the retinal layer related to the erg can recover to some degree following recovery of the retinal circulation, as demonstrated by fluorescein angiography. 12 figure 11. full-field erg examination on eye with crao12 based on anamnesis, ophthalmological examination, and multifocal electrophysiology exam, we can exclude prior artery occlusion in this patient. the patient did not complain about sudden, painless vision loss, only visual field restriction. in ophthalomogical examination, there were no neovascularization of the iris found. ergs in the crao is relatively well preserved. in contrast, the erg function of the patient’s left eye was depressed with reduction of foveal responses. in diagnosing rp, we have to rule out uvetis as the secondary causes that can reveal pigmentary retinal degeneration.1 congenital or acquired syphilis can present as pigmentary retinopathy that resembles advanced retinitis pigmentosa.13 (figure 12). pseudoretinitis pigmentosa can be found in ocular acquired syphilis. this finding can be found in secondary syphilis with other manifestations include apulosquamous eyelid rash, alopecia of the eyebrows and eyelashes, dacryocystitis, signs of conjunctivitis, episcleritis, scleritis, iris papules, lens dislocation, interstitial keratitis, intermediate uveitis, posterior uveitis, panuveitis, cystoid macular edema, and sign of retinitis (including retinal necrosis).14 figure 12. pigmentary retinopathy in acquired syphilis13 full-field ergs are usually subnormal, unlike the undetectable ergs fromretinitis pigmentosa (figure 13).15 diagnosis of ocular syphilis can be made by serologic testing. the venereal disease research laboratories (vdrl) and rapid plasma reagin (rpr) antibody tests can indicate active disease but may be negative in tertiary disease. the fluorescent treponemal antibody absorption (fta-abs) test is the most specific test of infection. 13 figure 13. full-field erg in ocular syphilis15 40 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 vdrl or rpr and fta-abs were not performed in our patient. nevertheless, based on anamnesis, ophthalmological examination, and multifocal electrophysiology exam, we can still rule out ocular syphilis as the etiology of unilateral pigmentary retinal degeneration in this patient. the patient did not complain about eye redness that can be found in uveitis and ophthalmological examination revealed a normal anterior segment. there were no signs of papulosquamous eyelid rash, alopecia of the eyebrows and eyelashes, interstitial keratitis, signs of conjunctivitis, episcleritis, scleritis, iris papules, lens dislocation, and signs of uveitis. based on erg examination, ocular syphilis revealed relatively good responses than recorded in our patient. retinopathy is the most common finding in congenital rubella syndrome (crs). it may be unilateral or bilateral. fine, granular, symmetric mottling of the pigment epithelium is seen in the posterior fundus. occasionally, pigment spicules and changes in the choroidal vasculature may be seen.13-16 however, pigment spicules in our patient were unlikely caused by crs. based on anamnesis, the onset of the symptom was one year before admission, whereas the onset of crs should be presented since birth. there was no cardiac malformation, cataract, corneal clouding, microphalmia, strabismus, or deafness which can be found in crs.16 most often today, the diagnosis of rubella is attempted by the use of a single serum test for identifying rubella igm antibody.17 from the laboratory test, we found a non-reactive anti rubella igm in our patient. based on anamnesis, ophthalmological exam, and laboratory test, rubella was then excluded. the most common form of unilateral pigmentary retinopathy referred to as unilateral rp is diffused unilateral subacute neuroretinitis (dusn). dusn is the term used for the disorder previously called “unilateral wipe-out syndrome,” and “unilateral rp.” true unilateral inherited rp does not exist, except as an example of extreme lyonization of retinal involvement in a carrier of xlinked rp. this disease is believed to result from the panretinal degeneration that have been infected by any of several possible worms.6 the pathogenesis of dusn appears resulting from a local toxic reaction by the products of the worm. this toxic reaction affects both the inner and outer retinal tissues. this later reaction is manifested initially by rapid loss of visual function and alterations of the ergs, suggesting inner retinal abnormalities. 18 another features of late stage dusn are pigment epithelial disruption, and pigment migration into the retina (bone spicule). 19 one of the important examination that excludes dusn as the etiology of unilateral pigmentary retinal degeneration in our patient is erg examination. the rod and cone components of the full-field ergs in dusn were moderately reduced, whereas the rod and cone components in the unilateral rp were extremely depressed or nearly undetectable. 10,18 (figure 14) figure 14. mferg in diffused unilateral subacute euroretinitis (left picture)18.mferg in patient’s left eye. with clinical examination and some ancillary tests, we can make a clinical diagnosis of rp. nowadays, there is genetic test for to confirm clinical diagnosis of rp and provide additional information about familial risk. genetic information can be informative for prognosis, and providing risk information to family members. from a perspective research, genetic testing improves the understanding of the pathophysiology of the disease and provides information for gene-based therapies.2 unfortunately we did not perform this examination because it is still not available in indonesia. our patient was included in primary rp, because the disease only involved the eyes, without any other systemic manifestations. 1 based on clinical examination and some ancillary test we could diagnose unilateral rp in our patient. nevertheless, to make a diagnosis of true unilateral rp, we must follow the patient for at least five years to rule out bilateral but highly asymmetric disease.1 unilateral rp can occur in two mechanisms. the first is the carrier state for xlinked rp. lyonization, or x-chromosomal inactivation, occurs close in time to lateralization during embryogenesis. thus, if the number of cells undergoing inactivation of the xchromosomes that contain the normal gene for rp is uneven at the time of lateralization and, by chance occurrence, a greater number of those cells are directed to one side of the developing embryo, the carrier will express an extremely asymmetrical phenotype with asymmetrical field loss and pigmentary changes. the second mechanism can occur as a genetic trait is through somatic mosaicism of a dominant gene for rp. this mechanism has been reported as the cause of unilateral rp in a patient with somatic mosaicism of rp1. 6 because these diseases are rare, most ophthalmologists have limited experience working with retinal dystrophy patients. management of rp includes regular ophthalmic evaluation at intervals of 12 years. although the death of photoreceptor cells in rp cannot be reversed, routine follow up allows the clinician to monitor progression with visual field and erg evaluation.1 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2019; 02; 01;1 41 it is important to support the patient to become adjusted to rp by supplying useful information of rp, by giving appropriate correction of refractive error and access to low-vision aids, cataract extraction or treatment of macular edema when it indicated.6 various nutritional supplements have been investigated as therapy for rp such as vitamin a, docosahexaenoic acid (dha), and lutein supplements.1-6 nowadays, gene therapy is one of the future management of rp. 6,20 as a target for genetic manipulation, the retina has some advantages. target cells (usually photoreceptors) are more directly accessible than in most tissues, and the effects of manipulations can be directly observed.6 the visual prognosis of patient with rp is poor.21 most patients with rp are anxious about the possibility of blindness. however, total blindness is an infrequent endpoint, and prognosis of each patient varies depending on the clinical findings.1 the visual prognosis of our patient is poor, as the visual field was severely depressed and the erg function was extremely depressed with reduction of foveal responses. conclusion making the diagnosis of unilateral rp has becomes one of the most challenging case. clinicians must be able to rule out the secondary causes that show unilateral pigmentary retinal degeneration such as a previous vascular occlusion, trauma, uveitis, infection, or retained metallic intraocular foreign body. based on clinical examination and some ancillary tests, the patient was diagnosed with unilateral rp. nevertheless, to make a diagnosis of true unilateral rp, we must do a routine follow-up of the patient for at least five years to rule out bilateral, yet highly asymmetric disease. acknowledgments address for reprints and sources of support that require acknowledgement is none. references 1. american academy of ophthalmology: hereditary retinal and choroidal dystrophies. in: retina and vitreus, basic and clinical science course. san fransisco: american academy of ophthalmology; 2003. p: 228-236 2. cukras catherine, zein wadih. progressive and ‘stationary’ inherited retinal degenerations. in: ophthalmology 4th edition. elsevier. 2014. 480-490 3. nettleship e. in: retinitis pigmentosa and allied diseases. r lond ophthalmol hosp rep 1907. p:1–56. 4. boughman ja, conneally pm, nance we. population genetic studies of retinitis pigmentosa. am j hum genet 1980. p: 223–35. 5. daiger sp, bowne sj, sullivan ls. perspective on genes and mutations causing retinitis pigmentosa. arch ophthalmol 2007. p:151–8. 6. evans kevin, pennesi mark. retinitis pigmentosa and allied disorders. in: retina 5th edition. elsevier. 2013. p: 761-835. 7. moster mark, kay matthew. glaucoma: the neuroophthalmologic differential diagnosis. jaypee journals. jaypee brothers medical publishers. 2013. 8. american academy of ophthalmology: clinical evaluation. in: glaucoma, basic and clinical science course. san fransisco: american academy of ophthalmology; 2003. p: 51-54. 9. falardeau julie, oregon portland. compressive optic neuropathies. in: roy and fraunfelder’s current ocular therapy 6th edition. elsevier. 2008. p: 575-6. 10. miyake y. hereditary retinal and allied disease. in: electrodiagnosis of retinal diseases. springer. tokyo: 2006. p: 4550. 11. burton m, gregor z. retinal arterial occlusion. in: retinal vascular disease. springer: berlin. 2007. p: 510-1. 12. miyake y. central retinal artery occlusion. in: electrodiagnosis of retinal diseases. springer. tokyo: 2006. p: 180-2. 13. lew julie, friedman alan. infectious causes of posterior uveitis. in: albert & jakobiec’s principles & practice of ophthalmology 3rd edition. elsevier. 2008. p: 1173-93. 14. shalaby ismail. acquired and congenital syphilis. in: roy and fraunfelder’s current ocular therapy 6th edition. elsevier. 2008. p: 2-4. 15. miyake y. luetic chorioretinitis. in: electrodiagnosis of retinal diseases. springer. tokyo: 2006. p: 196. 16. american academy of ophthalmology: infectious ocular inflamatory. in: intraocular inflamation and uveitis, basic and clinical science course. san fransisco: american academy of ophthalmology; 2003. p: 209-11 17. cherry james, adaci kristina. rubella virus. feigin and cherry’s textbook of pediatric infection diseases 7th edition. saunders. 2014. p: 2218. 18. miyake y. diffuse unilateral subacute neuroretinitis. in: electrodiagnosis of retinal diseases. springer. tokyo: 2006. p: 1912. 19. jumper michael, mcdonald richard. diffuse unilateral subacute neuroretinitis. in: albert & jakobiec’s principles & practice of ophthalmology 3rd edition. elsevier. 2008. p: 2135-40. 20. berson eliot. retinitis pigmentosa and allied diseases. in: albert & jakobiec’s principles & practice of ophthalmology 3rd edition. elsevier. 2008. p: 2225-52. 21. kansky j. fundus dystrophies. in: clinical ophthalmology: a synopsis. 2009. elsevier. p:354-5. this work licensed under creative commons attribution published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 51 international journal of retina (ijretina) 2018, volume 1, number 2. p-issn. 2614-8684, e-issn.2614-8536 correlation between systemic risk factors and diabetic retinopathy in patients with diabetes mellitus at cicendo national eye hospital rizki rahma nauli1, rova virgana2, iwan sovani2, arief sjamsulaksan kartasasmita2, erwin iskandar2, grimaldi ihsan2 1 ophthalmology department universitas padjadjaran, cicendo national eye hospital 2 vitreoretina unit, ophthalmology department universitas padjadjaran, cicendo national eye hospital abstract introduction: diabetic retinopathy (dr) is a highly specific microvascular complication of both type 1 and type 2 diabetes mellitus (dm) that can cause significant visual impairment in adult populations worldwide. the risk of having and/or developing dr is influenced by many systemic features. identification and management of particular systemic risk factors as early as possible during the course of dm might lower incidence of further progression and severity of dr. the aim of this study is to describe the correlation between systemic risk factors and dr in patients with dm in cicendo national eye hospital on december 1st 2017 – january 31st 2018. methods: an analytical cross-sectional study. the subjects were all patients diagnosed with dr based on ophthalmology examination at outpatient clinic of vitreoretinal division in cicendo national eye hospital. the data were analyzed using chi-square (x2) with significances of p < 0.05. result: seventy-one eyes were included in this study, among of which has been classified as mild npdr (n= 1), moderate npdr (n= 9), severe npdr (n= 27), and pdr (n= 34). severe npdr group had older age distribution at range 51-60 years old (n= 18, 66.7%, p = 0.001). stage 1 hypertension was found to be dominant in pdr group (n= 18, 66.7%, p = 0.043). both high total serum cholesterol group (n= 27, 76.5%, p = 0.048) and high fasting blood glucose (n= 27, 79.4%, p = 0.01) were significantly present in patients with pdr. positive (+1) urine glucose was statistically significant in pdr group. conclusion: there were several systemic risk factors from laboratory findings correlated in patient with dr in this study, however further study is needed to determine their role for predicting progression and severity of dr. keywords: diabetic retinopathy, diabetes mellitus, systemic risk factors cite this article: nauli, rizki rahma et al. correlation between systemic risk factors and diabetic retinopathy in patients with diabetes mellitus at cicendo national eye hospital. international journal of retina, [s.l.], v. 2, n. 1, aug. 2018. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/40>. introduction *correspondence to: rizki rahma nauili, department of ophthalmology, universtias padjadjaran kikinauli@gmail.com diabetes mellitus (dm) is a global epidemic with significant morbidity. the global prevalence of dm is predicted to increase dramatically from an estimated 422 million in 2014 to 592 million by 2035. according to international diabetes federation (idf), indonesia has 10.5 million people with dm in 2017 and about 7.7 million of them have not been diagnosed and are at a higher risk of developing harmful complications. world health organization (who) estimates the prevalence of dm in indonesia itself will increase to 21.3 million in 2030. diabetic retinopathy (dr) is a highly specific complication of dm. it remains the leading cause of acquired vision loss in adult populations worldwide and with the increasing number of people with dm, the number of dr and vision-threatening dr (vtdr) has been estimated to rise to 191.0 million and 56.3 million, respectively by 2030.1-6 52 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; the risk factors for development and progression of dr can be broadly divided into modifiable factors; hyperglycaemia, hypertension, hyperlipidemia and obesity, and non-modifiable factors such as; duration of dm, puberty and pregnancy. although there are an increasing number of therapeutic strategies for dr, the best method of minimizing its impact is prevention of ocular complications. insulin resistance, which often precedes type 2 dm (t2dm), is a component of the metabolic syndrome. those with dm are more likely to have other components of the metabolic syndrome including abdominal obesity, dyslipidemia, hypertension, prothrombotic state, and a proinflammatory state. having one or more of these components of the metabolic syndrome has been associated with a higher risk of diabetic complications, including dr itself. 6-9 the diabetes control and complications trial (dcct) and united kingdom prospective diabetes study (ukpds) were the two landmark clinical trials that showed intensive glycaemic control could reduce the risk of dr development and progression in diabetic patients. the ukpds stated that for every 1% decrease in hba1c, there was a reduction in 40% of dr development, 25% progression to vtdr, 25% need for laser therapy and 15% blindness in people with diabetes. the ukpds was the first rct that showed the importance of tight blood pressure (bp) control in reducing retinopathy. it has been shown that every 10mmhg increase in systolic blood pressure was associated with 10% increased risk of early dr and 15% risk of pdr. on the other hand, various studies have reported inconsistent results on the effect of lipid on the development and progression of dr. dcct showed that the severity of dr correlated positively with increasing triglycerides (tg) and inversely with high-density lipoprotein (hdl) in type 1 dm (t1dm). however, there was no association between total cholesterol and dr shown in the multi-ethnic study of atherosclerosis (mesa), but of the subset in the lipid panel, tg were shown to be related to the presence of dr. the subgroup of action to control cardiovascular risk in diabetes eye (accord) study has also demonstrated that fenofibrate, a tg-lowering agent, reduced the dr progression at 4 years in t2dm patients, compared to placebo group (6.5% vs 10.2%). 2,8,10,11 meanwhile, the influence of bmi on dr had shown conflicting results, more recent reports showed positive correlation of increased bmi with increased risk of dr, although in wisconsin epidemiologic study of diabetic retinopathy (wesdr) the association between obesity (bmi >31 for men and >32 for women) versus dr severity and progression (2+ etdrs steps) was not statistically significant (p > 0.05). also in wesdr, there was a 30% excess risk of dr development in post pubertal period an pregnancy could increased the risk of dr progression by 2.3 times. taken together, optimization of systemic risk factors is clearly important.11-14 thus, the purpose of this study is to describe the correlation between systemic risk factors and dr in patients with dm. methods this is an analytical cross-sectional study on subjects diagnosed with dr based on eye examination had been done by consultants, fellows and residents in vitreoretinal division outpatient clinic in cicendo national eye hospital between december 1st 2017 – january 31st 2018. eyes with any severity of dr and no other retinal diseases were included, and patients with incomplete laboratory results were excluded. eye examination has done with indirect ophthalmoscope, classification of dr stage was determined using international classification of dr scale. blood pressure, body weight and height were previously measured by calibrated device provided in the clinic, then the day after all patients underwent laboratory examination for hematology, urine, renal and liver function, lipid profile, fasting blood glucose, glycosylated hemoglobin, and hemostasis profile. all data were analyzed using spss statistical software version 21, chi-square test was used to compare categorical variables. a p value < 0.05 was considered to be statistically significant. results seventy one eyes of 36 patients were enrolled in this study, 1 eye was excluded because of an anophthalmic status, among of which has been classified as mild npdr (1 eye), moderate npdr (9 eyes), severe npdr (27 eyes), and pdr (34 eyes). patients’ demographic characteristics and baseline bp measurement at the time of first visit are reported in table 1. table 1 showed that age distribution and baseline blood pressure have significant differences among all groups of dr with p value 0.043 and 0.001 repectively. age distribution in range 51-60 years old was mainly found in severe npdr group otherwise younger age group at 41-50 years old was found in pdr. stage 1 hypertesion was dominantly present in both severe npdr and pdr group. from all 36 patients included in this study there were 10 patients with stage 1 hypertension at baseline measurement and 8 of them already had previous history of antihypertensive medication. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 53 table 1. demographic patients data table 2. systemic risk factors parameters in diabetic retinopathy diabetic retinopathy p-value mild npdr moderate npdr severe npdr pdr n= 1 n= 9 n= 27 n= 34 n % n % n % n % triglyceride 0.355 < 150 1 100.0 3 33.3 16 59.3 14 44.1 ≥ 150 0 0.0 6 66.7 11 40.7 20 55.9 total cholesterol 0.048 < 200 1 100.0 3 33.3 11 40.7 7 23.5 ≥ 200 0 0.0 6 66.7 16 59.3 27 76.5 ldl 0.421 < 100 0 0.0 4 44.4 10 37.0 8 26.5 ≥ 100 1 100.0 5 55.6 17 63.0 26 73.5 hdl female 0.375 < 50 0 0.0 2 22.2 12 44.4 10 29.4 ≥ 50 male 0 0.0 0 0.0 2 7.4 6 17.6 < 40 0 0.0 5 55.6 6 22.2 11 32.4 ≥ 40 1 100.0 2 22.2 7 25.9 7 20.6 pp blood glucose 0.46 < 200 1 100.0 5 55.6 9 33.3 13 38.2 ≥ 200 0 0.0 4 44.4 18 66.7 21 61.8 fasting blood glucose 0.01 < 126 1 100.0 7 77.8 9 33.3 7 20.6 ≥ 126 0 0.0 2 22.2 18 66.7 27 79.4 hba1c new onset dm 0.095 diabetic retinopathy pvalue mild npdr moderate npdr severe npdr pdr n= 1 n= 9 n= 27 n= 34 n % n % n % n % age 0,001 ≤ 40 y.o 0 0,0 2 22,2 1 3,7 1 3,0 41 50 y.o 0 0,0 0 0,0 1 3,7 18 51,5 51 60 y.o 0 0,0 7 77,8 18 66,7 13 39,4 61 70 y.o 1 100,0 0 0,0 5 18,5 2 6,1 > 70 y.o 0 0,0 0 0,0 2 7,4 0 0,0 gender 0,351 male 1 100,0 7 77,8 13 48,1 18 52,9 female 0 0,0 2 22,2 14 51,9 16 47,1 region 0,042 west java 1 100,0 7 77,8 26 96,3 28 82,4 outside west java 0 0,0 2 22,2 1 3,7 6 17,6 dm type 0,001 t1dm 0 0,0 2 22,2 0 0,0 0 0,0 t2dm 0 0,0 5 55,6 24 88,9 30 88,2 dm duration 0,442 ≤ 5 years 2 200,0 10 111,1 8 29,6 21 63,6 5-10 years 4 400,0 4 44,4 6 22,2 14 42,4 > 10 years 1 100,0 8 88,9 11 40,7 20 60,6 no answer 0 0,0 2 22,2 4 14,8 6 18,2 dm therapy 0,052 regular 0 0,0 7 77,8 15 55,6 16 47,1 irregular 0 0,0 0 0,0 7 25,9 10 29,4 no therapy 0 0,0 0 0,0 2 7,4 4 11,8 blood pressure 0,043 normal 0 0,0 1 11,1 8 29,6 4 11,8 prehypertension 0 0,0 4 44,4 3 11,1 3 8,8 stage 1 0 0,0 0 0,0 9 33,3 11 32,4 stage 2 0 0,0 2 22,2 4 14,8 10 29,4 urgency/emergency 0 0,0 0 0,0 0 0,0 2 5,9 54 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; < 6.5 1 100.0 2 22.2 2 7.4 1 2.9 ≥ 6.5 already on therapy 0 0.0 0 0.0 3 11.1 7 20.6 < 7 0 0.0 2 22.2 6 22.2 4 11.8 ≥ 7 0 0.0 5 55.6 16 59.3 22 64.7 ureum 0.283 < 10 0 0.0 2 22.2 0 0.0 2 5.9 10-50 1 100.0 4 44.4 19 70.4 17 50.0 > 50 0 0.0 3 33.3 8 29.6 15 44.1 creatinin 0.332 0.5-0.9 0 0.0 0 0.0 7 25.9 7 21.2 > 0.9 0 0.0 2 22.2 7 25.9 9 27.3 < 0.6 0 0.0 2 22.2 2 7.4 0 0.0 0.6-1.1 1 100.0 2 22.2 2 7.4 7 21.2 > 1.1 0 0.0 3 33.3 9 33.3 11 30.3 ast 0.665 < 32 0 0.0 2 22.2 13 48.1 13 38.2 ≥ 32 0 0.0 0 0.0 1 3.7 4 8.8 < 38 1 100.0 7 77.8 11 40.7 17 52.9 ≥ 38 0 0.0 0 0.0 2 7.4 0 0.0 alt 0.948 < 31 0 0.0 2 22.2 11 40.7 13 38.2 ≥ 31 0 0.0 0 0.0 3 11.1 3 8.8 < 41 1 100.0 7 77.8 12 44.4 17 50.0 ≥ 41 0 0.0 0 0.0 1 3.7 1 2.9 hb 0.275 <12 0 0.0 2 22.2 6 22.2 4 12.1 12-16 0 0.0 0 0.0 8 29.6 12 36.4 <13 0 0.0 3 33.3 9 33.3 12 36.4 13-18 1 100.0 4 44.4 4 14.8 6 15.2 wbc 0.934 4000-10600 1 100.0 9 100.0 25 92.6 31 94.1 >10600 0 0.0 0 0.0 2 7.4 3 5.9 diabetic retinopathy p-value mild npdr moderate npdr severe npdr pdr n= 1 n= 9 n= 27 n= 34 n % n % n % n % thrombocyte 0.468 150000-440000 1 100.0 9 100.0 26 96.3 29 85.3 > 440000 0 0.0 0 0.0 1 3.7 5 14.7 urine protein 0 (-) 0 0.0 5 55.6 1 3.7 0 0.0 (+) 1 100.0 2 22.2 11 40.7 10 29.4 (++) 0 0.0 0 0.0 6 22.2 14 35.3 (+++) 0 0.0 2 22.2 8 29.6 5 17.6 (++++) 0 0.0 0 0.0 1 3.7 5 17.6 urine glucose 0.042 (-) 1 100.0 6 66.7 5 18.5 5 15.2 (+) 0 0.0 3 33.3 7 25.9 13 36.4 (++) 0 0.0 0 0.0 4 14.8 6 18.2 (+++) 0 0.0 0 0.0 10 37.0 10 30.3 from laboratory examination listed in table 2 we found that total serum cholesterol above 200 mg/dl was significantly found in pdr group with p value 0.048, but abnormal value of serum lipid such as triglyceride (tg), ldl, and hdl was not differ significantly among these groups with p = 0.355, p = 0.421, p = 0.375. fasting blood glucose exceeded 126 mg/dl had occured significantly in patients with pdr in this study (p = 0.01). it might equivalent with positive elevated glucose urine level happened in the same group (p = 0.042). this result might explain high glycosylated hemoglobin result found in pdr group although that was not statistically significant. similiar findings also found in serum urea and creatinin, both of these renal function marker were higher in pdr patients but not statistically significant. discussion diabetes is a chronic condition and managing the disease can be a substantial burden to patients. diagnosing dr itself can be a pivotal moment in the patients’ lives. a threat of vision loss can be a critical wakeup call for patients to invest in habits that will maintain their overall health and the health of their eyes. the risk factors from hematologic and biochemical aspect proposed to be correlated with development and severity of dr are; increase platelet adhesiveness and erythrocyte aggregation, upregluation of vegf, abnormality of serum lipids, growth hormone and whole-blood viscocity, and local and systemic inflammation, but the precise role of these findings is not well defined. 8, 15 in this study we have found that stage 1 hypertesion was dominantly present in both severe npdr and pdr group. from 36 patients included in this study there were 10 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 55 patients with stage 1 hypertension at baseline measurement and 8 of them already had previous history of antihypertensive medication. diabetic’s patients are particularly susceptible to the effects of hypertension with respect to their risk for developing cardiovascular disease. hypertension is the most common modifiable risk factor for cardiovascular disease. one mechanism implicates interactions between hormonal control of blood sugar levels in diabetic patients and the renin-angiotensin-aldosterone system (raas) at multiple levels and in both directions; those with diabetes have elevation of the raas leading to hypertension. the combination of diabetes and hypertension is associated with an increased mortality rate due to cardiovascular disease also increases a patient’s risk of retinal complication. 16-18 one study by zheng et al in 2012 found that for every 10 mmhg increase in systolic blood pressure, there was a 1.23 times increased risk of dr and 1.19 times increased risk of vtdr. including raum et al and jin et al in 2015, effective treatment of hypertension with bp less than 150/85, has been shown to reduce the rate of worsening of diabetic retinopathy by 34 % over 7.5 years also lowered the risk of vision loss of three lines or more by 47 %. these matched several earlier studies. the ukpds showed that the incidence of retinopathy was associated with systolic blood pressure. of the 1919 patients with older onset t2dm from that study with retinal photographs taken at diagnosis and 6 years later, systolic blood pressure was significantly associated with retinopathy incidence. those in the top tertile range at baseline (systolic bp ≥140 mm hg) were 2.8 times as likely to develop retinopathy as people in the lowest tertile range (systolic bp <125 mm hg). there was no relation of systolic bp at baseline with retinopathy progression. in the wesdr, diastolic blood pressure was a significant predictor of progression of diabetic retinopathy to proliferative diabetic retinopathy over 14 years of follow up in patients with t1dm. however, neither systolic or diastolic bp nor hypertensions at baseline were associated with the incidence and progression of retinopathy in people with t2dm. in the wesdr, patients with t2dm with high bp and retinopathy were at a higher risk of death than people with high bp without retinopathy, and the inability to find a relation between progression of retinopathy and blood pressure may have been due to this selective mortality-at least in part. the action to control cardiovascular risk in diabetes (accord) trial did not find a significant difference in the rates of dr progression between those undergoing intensive blood pressure control (goal systolic blood pressure ≤120 mmhg) and standard management (goal ≤ 140 mmhg), although control of bp to a level of ≤ 140/90 is recommended under the joint national committee (jnc) 8 regulations. 19-23 elevated serum cholesterol and lipid levels are a known component of the metabolic syndrome. in this study we found that high total serum cholesterol was significantly present in pdr group. abnormal value of other serum lipids was found in this study in the same group of patients but not statistically significant among all groups. these findings similar to one study by chew et al has been found that elevated cholesterol and lipid levels have also been linked to higher rates of hard retinal exudates. compared to those with a cholesterol level ≤200 mg/dl, those with a cholesterol level ≥200 mg/dl were twice as likely to have hard retinal exudates; the effects of hdl and tg in this study were modest and not statistically significant either. however monitoring serum lipids level according to the national cholesterol education program adult treatment panel iii (ncep atp iii) guidelines of cut off ldl ≤100 mg/dl is a reasonable goal. controlling serum cholesterol and lipids is associated with a lower rate of complications from diabetic eye disease, according to a study by sen et al in 2002 and nielsen et al in 2014, statins and fibrate are a common treatment for high cholesterol, and their use prior to diabetes diagnosis has been associated with a significantly decreased rate of development of dr and has been linked to better average visual acuity improvement in dr. in this study body mass index (bmi) of each patients could not be collected properly because some desirable variables are incompletely measured in some patients, so that we can’t conclude subjects with high total serum cholesterol to ones with metabolic syndrome for further data analysis related to this study. the diabetes incidence study in sweden reported significant association between baseline high bmi and severe npdr and pdr (p = 0.001) after 10 years of follow up. even though the evidence is still equivocal between bmi and dr in other studies, however it is still critical for people with diabetes to maintain an optimal bmi to prevent development and progression of dr and other diabetes-related complications. 9, 24-26 elevated fasting blood glucose level exceeded 126 mg/dl occurs significantly in patients with pdr in this study (p = 0.01), comparable to another significant result in this study that was positive (+) glucose urine level happened in pdr group also. hyperglycemia is one of the most important risk factors for dr. glucosuria only begins to occur at higher than normal plasma glucose levels. glucosuria in diabetic patients is the result of increased glucose reabsorbtion from glomerular filtrate in people with dm. 27 wong et al had meta-analysis of three large populationbased studies that found a graded relationship between the level of glycemia and frequency of retinopathy signs. the dcct showed that intensive glycemic control reduced the incidence of retinopathy by 76 % and progression from early to advanced retinopathy by 54 %. this 56 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; highlights that strict glycemic control is much more effective in preventing or delaying the onset of dr in patients with dm without dr, rather than limiting the severity of dr after it has occurred. poor glycemic control should correlate with glycated hemoglobin (hba1c) level. multiple studies have consistently shown hba1c to be an independent risk factor for diabetic retinopathy. the ukpds stated that for every 1% decrease in hba1c, there was a reduction in 40% of dr development, 25% progression to vtdr, 25% need for laser therapy and 15% blindness in people with diabetes. however in this study, the pdr group achieved the highest portion of hba1c ≥ 7 but that was not significant statistically. a1c-derived average glucose (adag) study formulated the relationship between blood glucose and hba1c. in this study, the cut-off point for hba1c was 6.5% and 7% which is equivalent to 140 mg/dl and 154 mg/dl if converted to adag formula respectively. 7, 28 this study has several limitations due to the nature of its study design. research subjects are small, many data had not been collected properly at the time of subject recruitment started, and we difficult to analyze the correlation between those systemic factors with progressivity of dr because of relatively short sample collection time. we recommend to make a cut-off point of hba1c to ≤6.5% to all recruited subjects in order to compare the result with fasting blood glucose value equipotentially. conclusion our study demonstrates that particular systemic factors value such as uncontrolled systemic blood pressure, high fasting blood glucose and glucosuria state significantly correlates with severity of dr. although we still have to unify all parameters needed regarding to this study to prevent any missing data thus many more related variables can be further analyzed. references 1. world health organization: global report on diabetes. switzerland ; 2016; p.4–84. 
 2. duh ej, sun jk, stitt aw. diabetic retinopathy: current understanding, mechanisms, and treatment strategies. jci insight. 2017;2(14):1-13 3. international diabetes federation. idf diabetic atlas 8th edition [internet]. internatoional diabetes federation. 2017. download from : http://diabetesatlas.org/ 4. world health organization. global report on diabetes. [internet]. download from: apps.who.int/iris/bitstream/10665/204871/1/9789 241565257_eng.pdf 5. perkumpulan endokrinologi indonesia. konsensus pengelolaan dan pencegahan diabetes melitus tipe 2 di indonesia. [internet]. perkeni. 2015. download from : pbperkeni.or.id/doc/konsensus.pdf 6. ting ds, cheung gc, wong ty. diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. clinical & experimental ophthalmology. 2017;44: 260–277. 7. lee r, wong ty, sabanayagam c. epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. eye and vision. 2015:2(17);1-25 8. atchinson e, barkmeier a. the role of systemic risk factors in diabetic retinopathy. curr ophthalmol rep. 2016:4;84-9 9. third report of the national cholesterol education program. (ncep) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii) final report. circulation. 2002;106(25):3143–421. 
 10. shah ar, gardner tw. diabetic retinopathy: research to clinical practice. clinical diabetes and endocrinology. 2017:3(9);1-7 11. chatziralli ip. the role of dyslipidemia control in progression of diabetic retinopathy in patients with diabetes mellitus. diabetes ther. 2017:8;20912. 12. klein r, klein be, moss se. is obesity related to microvascular and macrovascular complications in diabetes? the wisconsin epidemiologic study of diabetic retinopathy. archives of internal medicine 1997; 157: 650–6. 13. klein be, moss se, klein r. is menarche associated with diabetic retinopathy? diabetes care 1990; 13: 1034–8 14. diabetes c. complications trial research g. effect of pregnancy on microvascular complications in the diabetes control and complications trial. the diabetes control and complications trial research group. diabetes care 2000; 23: 1084–91. 15. american academy of ophthalmmology. retina and vitreous. section 12. san fransisco; 20152016. p. 20-25, 89-111.
 16. klein r, klein bek, moss se, et al. is blood pressure a predictor of the incidence or progression of diabetic retinopathy?. arch intern med. 1989;149:2427–32. 17. mauer m, zinman b, gardiner r, et al. ace-i and arbs in early diabetic nephropathy. journal of the renin–angiotensin–aldosterone system: jraas 2002; 3: 262–9. 18. wang b, wang f, zhang y, et al. effects of ras inhibitors on diabetic retinopathy: a systematic review and meta-analysis. lancet diabetes endocrinol. 2015;3(4):263–74. 19. zheng y, lamoureux el, lavanya r. prevalence and risk factors of diabetic retinopathy in migrant published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 2; 57 indians in an urbanized society in asia: the singapore indian eye study. ophthalmology. 2012:119(10);2119-24. 19. raum p, lamparter j, ponto ka, et al. prevalence and cardiovascular associations of diabetic retinopathy and maculopathy: results from the gutenberg health study. plos one. 2015; 10(6):e0127188. 20. jin p, peng j, zou h, et al. a five-year prospective study of diabetic retinopathy progression in chinese type 2 diabetes patients with ‘‘wellcontrolled’’ blood glucose. plos one. 2015;10(4):e0123449 21. the action to control cardiovascular risk in diabetes (accord) study group. effects of intensive blood-pressure control in type 2 diabetes mellitus. n engl j med.2010;362:1575-85. 22. doe dv, wang x, vedula ss, et al. blood pressure control for diabetic retinopathy. cochrane database syst rev. 2015; 1:cd006127. 23. armstrong c. jnc8 guidelines for the management of hypertension in adults. am fam physician. 2014;90(7):503–4. 24. chew ey, klein ml, ferris fl 3rd, et al. association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. early treatment diabetic retinopathy study (etdrs) report 22. arch ophthalmol. 1996;114(9):1079–84. 25. sen k, misra a, kumar a, pandey rm. simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. diabetes res clin pract. 2002;56(1):1–11. 26. nielsen sf, nordestgaard bg. statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study. lancet diabetes endocrinol. 2014;2(11):894–900. 27. gerich je. role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. diabet med. 2012:27(2); 136-42. 28. ghazanfari z, haghdoost aa, alizadeh sm. a comparison of hba1c and fasting blood sugar test in general population. int j prev med. 2010:1(3); 187-94. this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 17 international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 clinical characteristics of proliferative diabetic retinopathy (pdr) patients with vitreous hemorrhage at cipto mangunkusumo hospital reyno satria ali1, andi arus victor2, ari djatikusumo2, gitalisa andayani2, anggun rama yudanta2, mario marbungaran hutapea2 1 faculty of medicine, universitas bengkulu, bengkulu tengah district hospital, indonesia 2department of ophthalmology, faculty of medicine universitas indonesia cipto mangunkusumo national general hospital, jakarta abstract introduction: proliferative diabetic retinopathy is the most common cause of blindness in adults. in the management of vitreous hemorrhage, vitrectomy is the main choice and also laser photocoagulation with or without anti-vegf administration as additional therapy. this study aims to determine the number of patients, demographic characteristics, clinics, risk factors, distribution of treatment, and treatment outcomes for pdr patients with vitreous hemorrhage at cipto mangunkusumo hospital. methods: this study was retrospective descriptive study conducted from january 2020 to october 2022 who met the inclusion criteria. population in this study were patients at cipto mangunkusumo hospital with pdr accompanied by vitreous hemorrhage. data shown in the table were mean (standard deviation) and number (percentage) based on the type of the data. result: a total of 146 patients with the diagnosis of proliferative diabetic retinopathy (pdr) with vitreous hemorrhage. majority of subjects were men (60,9%), diagnosed with dm more than 10 years (63,0%) with another systemic risk factor. the most common clinical characteristics found visual acuity at the initial visit <3/60 (80,8%), diagnosed phakia (78,9%), retinal detachment (85,3%), grade 2 vitreous hemorrhage (80,8%). the majority of eyes underwent vitrectomy (90,44%), anti-vegf injections (22,92%), laser prp (11,46 %), phacoemulsification pre and post vitrectomy as adjuvant treatment. the condition of the vitreous was clear after vitrectomy (99,1%). mean visual acuity before vitrectomy is 2.10 (1.80 – 2.50), while mean visual acuity after vitctomy was 1.00 (1.30 – 2.40), with a difference in initial and final visual acuity of -0.10 (-0.50 – 0.60). conclusion: majority of study subjects were men with an age range of 25-77 years. vitrectomy as the main treatment combined with intravitreal injection of anti-vegf, laser prp as adjuvant treatment. in nearly all cases, vitreous hemorrhage was clear after vitrectomy treatment. visual acuity after vitrectomy shows progress even though in some cases there was no improvement. keywords: diabetic retinopathy, proliferative diabetic retinopathy, vitreous hemorrhage, vitrectomy. cite this article: ali, reyno satria et al. clinical characteristics of proliferative diabetic retinopathy (pdr) patients with vitreous hemorrhage at cipto mangunkusumo hospital in january 2020-october 2022. international journal of retina, [s.l.], v. 6, n. 1, p. 17, feb. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/227>. date accessed: 28 feb. 2023. doi: https://doi.org/10.35479/ijretina.2023.vol006.iss001.227.. 18 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; correspondence to: andi arus victor, universitas indonesia, cipto mangunkusumo national general hospital, jakarta, arvimadao@yahoo.com introduction the vitreous is a transparent gel-like structure inside the eyeball. this structure has a composition of 98% water, 2% structural protein, extracellular matrix and other components.1 vitreous hemorrhage is a condition where there is blood in the vitreous cavity which occurs as a result of extravasation of blood on the posterior side of the eyeball namely the internal limiting membrane (ilm), the anterior side, namely the posterior lens capsule, and the lateral side of the ciliary body. . with a significant amount of lod this condition can interfere with vitreous transparency and result in impaired vision.2, 3 one of the most common causes of vitreous hemorrhage is proliferative diabetic retinopathy (pdr). diabetic retinopathy is the most common cause of blindness in the age range of 25-74 years, with 3 out of 4 patients suffering from diabetic retinopathy within 15 years of being diagnosed with diabetes mellitus. chronic hyperglycemia is a major factor in the occurrence of diabetic retinopathy. the classic sign of diabetic retinopathy are microaneurysms, venous beading, hard exudate, cotton-wool spots, intraretinal microvascular abnormality (irma) and neovascularization. diabetic retinopathy is divided into non-proliferative diabetic retinopathy (npdr) and proliferative diabetic retinopathy (pdr) phases. patients with vitreous hemorrhage experience decreased visual acuity and the condition of the blood in the vitreous can last for days to months, until the bleeding is absorbed or disappears. however, permanent decreased visual acuity can occur in some cases.4 diagnosis is based on anamnesis and physical examination of ophthalmological status. investigations for the posterior segment, such as ultrasonography (usg), can be performed if visualization is obstructed by the density of vitreous hemorrhage. in conditions of vitreous hemorrhage, minimal turbidity can be found due to red blood cell particles or vitreous opacity. if there is detachment of the posterior hyaloid membrane, vitreous strands may be found, which may also develop into tears or traction on the retina.5 in the management vitreous hemorrhage, vitrectomy is the main choice and also laser photocoagulation with or without anti-vegf administration as additional therapy. pars plana vitrectomy is the main choice in conditions of nonclearing vitreous hemorrhage and other conditions such as retinal tears. pdr patients with vitreous hemorrhage with visual acuity less than 5/200 mostly do not experience spontaneous resolution even after 1 year of observation. with the development of surgical techniques with better surgical outcomes and minimal complications, operations can be carried out more quickly with an observation clinical period of less than 3 months.6 this study aims to determine the number of patients, demographic characteristics, clinics, risk factors, distribution of treatment, and treatment outcomes for pdr patients with vitreous hemorrhage at cipto mangunkusumo hospital in the period january 2020 october 2022. methods this study is a retrospective descriptive study based on medical records. this study was conducted at cipto mangunkusumo hospital, jakarta. the data were collected between november 2022december 2022. the population in this study were patients at cipto mangunkusumo hospital with pdr accompanied by vitreous hemorrhage in the period january 2020 – october 2022. the subjects of this study were accessible populations that met the inclusion and exclusion criteria. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 19 subject with incomplete data, untreated patients, patient with no return visit after the initial visit, didn’t come for post-treatment evaluation or the duration of follow-up less than 1 month after treatment, vitreous hemorrhage caused other than pdr were not included in this study. we recorded and searched for medical records that met the inclusion criteria, based on data from the clinic , operating room, and procedure room register books. age, gender, chief complaint, duration, hba1c data, antiplatelet drugs, visual acuity, refractive status, eyeball pressure, lens status, diagnosis, treatment. performed, treatment time, and follow-up visual acuity, eye pressure, and post-treatment ophthalmological examination each subjects were recorded ethics statement this study was conducted following the declaration of helsinki and approved by the health research ethics committee faculty of medicine universitas indonesia (no. ket1396/un2.f1/etik/ppm.00.02/2022). written informed consent was obtained for all subjects before study enrollment. statistical analysis data presented in this paper were analyzed using spss ver. 25.0 (spss inc., chicago, il, usa). data shown in the table were mean (standard deviation) and number (percentage) based on the type of the data. results a total of 169 medical records of patients with the diagnosis of proliferative diabetic retinopathy (pdr) with vitreous hemorrhage. however, after conducting a search based on predetermined inclusion and exclusion criteria, a total of 146 medical records were included in the analysis. the record tracing flow can be seen in the following diagram figure 1. flow chart of research subjects 20 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; table 1. demographic data variable frequency (n=146 patient) percentage (%) sex male 89 60,9 female 57 39,1 age 55 (22-77) years laterality unilateral 135 89,7 bilateral 11 10,3 vitreous hemorrhage were found more in males than females with an age range of 25 – 77 years. in this study, it was found that the majority of patients experienced vitreous hemorrhage in one eye only. the demographic characteristics of the groups were presented in table 1. table 2. systemic risk factors of research subjects variable frequency (n=146 patient) percentage (%) systemic risk factorshypertension 95 65,0 chronic kidney failure 1 0,2 strokes 3 2,7 coronary heart disease 4 2,7 dyslipidemia 43 29,4 long suffered from dm < 5 years 18 12,4 5-10 years 36 24,6 >10 years 92 63,0 hba1c ≤ 7,0 % 46 31,5 > 7,0% 95 65,0 no data 5 3,4 antiplatelet drugs yes 8 5,4 no 138 94,6 consulted to internal medicine yes 31 21,2 no 115 78,8 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 21 in this study, the other systemic risk factor beside pdr such as hypertension and dyslipidemia. in the study subjects, data were collected on the history of used anticoagulants, and found 8 patients using blood-thinning drugs, due to coronary heart disease, if was variable frequency (n=157 patient) percentage (%) initial complaint blur 141 90,4 floaters 5 3,1 blur and floaters 7 4,4 blur, floaters, photopsia 4 2,1 complaint duration ≤ 6 months 24 15,3 > 6 months 133 84,7 early vision ≥ 6/12 (logmar ≥ 0.30) 0 0 < 6/12 s.d. ≥ 6/18 (logmar < 0.30 to ≥ 0.48) 2 1,3 < 6/18 to ≥ 6/60 (log mar < 0.48 to ≥1.00) 7 4,5 < 6/60 to ≥ 3/60 (logmar < 1.00 to ≥1.30) 21 13,4 < 3/60 (log mar < 1.30) 127 80,8 diagnostic tool funduscopy 72 45,9 ultrasound 85 54,1 initial lens status phakia 124 78,9 pseudophakia 31 19,7 aphakia 2 1,4 initial retinal condition no retinal detachment 134 85,3 retinal detachment 23 14,7 grading vitreous hemorrhage grade 0 0 0 grade 1 13 8,2 grade 2 127 80,8 grade 3 17 11,0 table 3. clinical characteristics of study subjects 22 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; that stroke and chronic kidney failure undergoing hemodialysis therapy. however, no information was obtained regarding the type and amount of these drugs. in patients suspected of having systemic disorders who have not received adequate treatment, consult to internal medicine specialist for evaluation and management of to systemic disorders was done. the duration of from dm in the subjects of this study was grouped into 3 groups, less than 5 years, 5 to 10 years and more than 10 years, most subjects were in the group have suffered from dm between >10 years suffering from dm. data on the hba1c values of the study subjects were also shown and the majority were research subjects with an hba1c value of more than 7.0%. systemic risk factors in research subjects are described in table 2. the main complaint of the subjects of this study was blurring that occurred slowly or suddenly with the most onset being more than 6 months. blur of vision is also sometimes followed by other complaints such as floaters and photopsia. initial visual acuity assessment, method of diagnosis of vitreous hemorrhage, initial lens status, and initial retinal condition were carried out in patients. visual acuity at the initial visit was the most in the blindness group with the best visual acuity with correction at <3/60. the diagnosis of vitreous haemorrhage was made by fundoscopy or ultrasound, with the number of diagnostic methods being similar between groups, which were and respectively 45.9% and 54.1%. the most common lens status found is phakia and the most common initial retinal condition is non-retinal detachment. the grading of vitreous hemorrhage was based on the grading of the diabetic retinopathy vitrectomy study (drvs) and the majority subjects were with grade 2 vitreous hemorrhage. the clinical characteristics of the subjects are described in table 3. the treatment depends on the condition of vitreous turbidity due to accumulation of blood in the vitreous cavity. the initial treatment obtained from this study included intravitreal injection, prp laser, vitrectomy surgery, and other operations, such as cataract surgery or hyphema irrigation/aspiration in cases of bleeding in the anterior chamber. initial management was carried out when the patient first came and was diagnosed as a vitreous hemorrhage. table 4 describes the types of initial management of research subjects based on the grading of vitreous hemorrhage. table 4. initial management based on the grade of vitreous hemorrhage etiology eyes n (%) observation n (%) intravitreal injection prp laser vitrectomy other operations grade 1 13 0 3 (23) 10 (77) 0 0 grade 2 127 0 23 (18,1) 0 91 (71,6) 13 (10,3) grade 3 17 0 2 (11,8) 0 (0) 12 (76,4) 3 (1,9) published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 23 from table 3.5, a total of 157 eyes diagnosed with vitreous hemorrhage underwent different initial management and then continued with secondary treatment during the follow-up period. initial management can be the main action or supporting action for visualization of the surgeon for the next action plan, which is vitrectomy. the majority of subjects underwent vitrectomy surgery as initial management. in a total of 28 eyes treated initially with intravitreal anti-vefg injections, 3 eyes were grade 1 and 25 eyes were grade 2 and 3 which were treated with the aim of reducing vitreous turbidity. at follow-up there were 3 patients who responded so they continued for further intravitreal injections. meanwhile, 20 patients did not show any improvement in vitreous opacities, so the vitrectomy was continued. in grade 2 and grade 3 patients who were treated with phacoemulsification + iol, the procedure was aimed at improving operator visualization before vitrectomy was performed. in one case, during the follow-up period, postvitrectomy rebleeding occurred, so the follow-up treatment was re--vitrectomy. other advanced treatments were prp laser as a top up from the previous laser, continued intravitreal laser injection, ndyag capsulotomy after phacoemulsification, hyphema irrigation in cases of anterior chamber bleeding due to neovascular, complicated cataract phacoemulsification surgery after vitrectomy and filtration surgery with vgi implants as a treatment for secondary glaucoma as a complication the care of. silicon oil or neovascular glaucoma table 5. table 5. distribution of types of treatment of research subjects distribution of types of treatment of research subjects variable frequency (n) percentage (%) initial treatment (n=157) anti-vegf injection 28 17,8 laser prp 10 6,3 vitrectomy 103 65,8 phacoemulsification + iol 16 10,1 follow up-treatment anti-vegf injection 8 10,5 laser prp 8 10,5 nd yag laser capsulotomy 3 2,6 vitrectomy after phacoemulsification 16 21,1 vitrectomy after intravitareal injection 22 28,9 re-vitrectomy for current bleeding 1 1,3 another operation irigation/ hyphema aspiration 1 1,3 phacoemulsification + iol 16 21,1 vgi (virna glaucoma implant) 2 2,6 24 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; vitrectomy performed on patients with vitreous hemorrhage can be done as a primary treatment or as a secondary treatment. the total eyes of the study subjects who underwent vitrectomy were 142 eyes. primary vitrectomy was performed in all eyes with hemorrhages grades 2 and 3. secondary vitrectomy was performed in patients after other medical procedures, such as intravitreal injection, photocoagulation and phacoemulsification. all vitrectomy procedures were accompanied by endolaser procedures and the most common use of tamponade was with silicone oil. in the secondary vitrectomy procedure, an endolaser procedure was also carried out and in all cases a silicon oil tamponade was inserted. the distribution of the types of primary and secondary vitrectomy procedures is described in table 6 . table 6. distribution of the types of primary and secondary vitrectomy procedures variable frequency (n) percentage (%) primary vitrectomy (n=103) intraoperative tamponade gas 101 1,9 silicone oil 2 98,1 laser intraoperative with endolaser 103 100 without endolaser 0 0 secondary vitrectomy (n=39) intraoperative tamponade 3 2,6 gas 0 0 silicone oil 39 100 laser intraoperative with endolaser 39 100 without endolaser 0 0 table 7. vitreous anatomical condition follow-up after the last treatment vitreus final condition management n (157 eyes) clearing (%) non clearing n(%) re-bleeding (%) vitrectomy 120 119(99,1) 0(0) 1(0,8) anti-vegf injection 8 6 (75) 2 (25) 0 (0) prp laser 7 4(57,1) 3(42,9) 0 (0) ndyag laser 3 2(100) 0 (0) 0 (0) phacoemulsification + iol 16 16(100) 0 (0) 0 (0) vgi 2 2 (100) 0 (0) 0 (0) hyphema irigation 1 0(0) 1 (100) 0 (0) published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 25 there were two outcomes assessed in this study at the end of the set follow-up period, which are the final condition of the vitreous, and changes in visual acuity with correction. table 7 shows the final condition of the vitreous after follow-up treatment at the end of the follow-up period. all patients who underwent vitrectomy had a clear vitreous end condition, with silicone oil tamponade. at the last follow-up, the majority of vitreous clearing was found in almost all treatment groups, vitreous clearing were found in 100% in vitrectomy treatments. while in the case of intravitreal injection and prp laser residual vitreous hemorrhage nonclearing conditions were still found in study subjects who grade 1 vitreous hemorrhage which. there was one case of rebleeding that underwent revitrectomy, but postoperatively the patient was seen again. in patient eyes that underwent phacoemulsification procedure, vgi insertion and hyphema irrigatio who had previously been treated with vitrectomy. cataract, glaucoma and hyphema are complications of vitrectomy and insertion of silicone oil tamponade visual acuity with correction in the logmar was obtained from the initial visit and post-treatment follow-up. in general, mean visual acuity before treatment is 2.10 (1.80 – 2.50), while mean visual acuity after treatment was 1.00 (1.30 – 2.40), with a difference in initial and final visual acuity of -0.10 (0.50 – 0.60). this data, the majority of subjects experienced improvement in visual acuity, except for the group which underwent vgi and hyphema treatments. the mean or median of best visual acuity with correction in logmar changes based on management can be seen in table 8. discussion based on demographic characteristics, the number of subjects with vitreous hemorrhage was male (60.9%) compared to female. research on diabetes based on gender conducted by willer stated that men are more susceptible to diabetes because of the obesity factor which tends to occur more quickly in men than women of the same age. it is also said that the lower limit of the body mass index (bmi) for men to get dm is also lower than women.7 research on vitreous hemorrhage in general was carried out by fitri et al6, wang et al8, show that subjects with vitreous hemorrhage were found more in men, with a percentage of around 52.18 64.1%.3, 6, 8 the age range in this study was 55 years with an age range of 25-77 years. this is similar to the study by ansari et al., diabetic retinopathy is recorded as the main cause of blindness in the working age group, namely 20-65 years. table 8. changes in visual acuity with correction based on the last treatment at the end of follow-up treatment n (157 eyes) early visual acuity final visual acuity ∆logmar vitrectomy 120 2.10 (1.80– 2.50) 1.00 (1.30 – 2.40) -0.10 (-0.50– 0.60) anti-vegf injection 8 1.30 (1.00 – 1.80) 1.20(0.70 – 1.80) -0.10 (-1.18 – 0.32) prp laser 7 0.70(0.30 – 1.20) 0.60 (0.30-1.20) -0.10 (0.30-0.32) ndyag laser 3 2.20 ±0.20 2.20 ±0.20 0.0 phacoemulsification + iol 16 2.10 (1.80-2.40) 2.00(1.50 – 2.40) -0.10 (-0.301.50) vgi 2 2.40 2.40 0.0 hyphema irigation 1 2.40 2.40 0.0 26 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; progression of complications of diabetes is higher when compared to older age9. study by zou et al. showed that subject with diabetes in the age range of 31-45 years, the risk of developing complications from diabetes is higher when compared to older age.10 based on clinical characteristics, in the study subjects, the majority of vitreous hemorrhages occurred unilaterally (89.7%). this is similar to the study by metita et al regarding vitreous hemorrhage with most patients being the result of pdr, it was stated that unilateral cases occurred in 89.6% of cases.4 this study shows that most common systemic risk factors were hypertension and dyslipidemia. bek t,et al, dm patients who are accompanied by increased pressure diastolic over 80, is more at risk for the progression of pdr, while an increase in systolic > 160 mm hg, is at risk for diabetic macular edema (dme).11 the grouping of duration of dm in the study was divided into 3 groups, with the highest number of patients in the duration > 10 years. this is in accordance with research by piyush et al who examined the duration of dm which was associated with the incidence of npdr and pdr where duration <5 years of suffering from dm had a risk of 9.04% and increased to 76.47% after >20 years of suffering from dm.12 the highest hba1c in the subjects of this study was in the group of subjects with an hba1c value > 7%. in a study by lind et al, it wasconcluded that the risk of diabetic retinopathy and nephropathy was not significant at hba1c values <6.5% and began to increase at hba1c values >7% and the risk of severe complications was higher at hba1c values > 8.6%.13the use of anticoagulants was also noted in this study, especially in patients with a history of chd, stroke and chronic kidney failure. a study by jeng et al, states that the use of antiplatelet/anticoagulant (apac) significantly protects against the emergence of npdr. it was not significant to the emergence of pdr and dme.14 the study subjects complained of increasingly severe blurred vision and sometimes accompanied by floaters and photopsia because of vitreous hemorrhage. in npdr that does not involve the macula, the patient's vision is not impaired. as the retinopathy process progresses, macular involvement can be a major factor in decreased visual acuity. in pdr neovascularization is at high risk for rupture and blood extravasation occurs into the intraretinal, pre retinal and vitreous. a significant amount of blood can cause decreased vision. examination of the posterior segment in conditions of accumulation of blood in the vitreous cavity is difficult to do, as the number of subjects who underwent ultrasound examination was quite large. the majority of the lens status in the our study were phakia,. in patients planned for vitrectomy, phacoemulsification + iol surgery was performed to assist in visualization of the posterior segment during surgery. retinal detachment occurred in 23 patients. the most common type of retinal detachment is the tractional type as a complication of proliferation of the retinal and vitreous fibrovascular membranes. in an article by stewart et al, it was stated that the presence of tractional retinal detachment is a predictor of poor prognosis in pdr patients. retinal detachment can also be a combination of tractional and rhegmatogenous detachment.15 other studies also state that 17-35% of pdr cases that undergo vitrectomy are with tractional or rhegmatogenous detachment. the classification of vitreous hemorrhage in this study was the drvs classification where most patients were grade 2 where the fundus reflex was still visible but the details of the posterior segment were difficult to identify. a study conducted by petrovic et al to assess the effectiveness of intravitreal triamcinolone against vitreous hemorrhage due to pdr also used the drvs classification.5 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 27 initial management of grade and grade 3 patients is vitrectomy. however, in 25 patients administration intravitreal injection was performed prior to vitrectomy. in a study by chatziralli et al, anti-vegf injections 3-7 days before vitrectomy could reduce the risk of intraoperative bleeding, lower the duration of surgery and reduce the risk of rebleeding.15 a study by lim et al mentioned that proactive and periodic intravitreal injections every 34 months in patients pdr can prevent the formation of nvd and reduce the risk of vitreous hemorrhage. in ten patients with grade 1, laser prp was performed. the ischemic condition of the retina triggers the formation of neovascularization. the laser is applied to non-perfused areas to improve oxygenation and prevent neovascularization. based on the etdrs, the laser is given in the phase between severe npdr and early pdr.16 the majority of follow-up treatments for the subjects of this study were vitrectomy after the initial treatment of phacoemulsification, post-intravitreal injection and one case was rebleeding. follow-up anti-vegf and prp injections are given to patients who respond well to the initial treatment. phacoemulsification surgery is performed on complicated cataracts after vitrectomy. cheng et al reported that cataracts occurred in 80% of cases after vitrectomy within 6 months of follow-up. cataracts occur due to oxidation of the lens due to high air pressure during a vitrectomy, or due to the use of gas or silicone tamponade or also due to iatrogenic effects due to contact with the vitrector. in two study subjects, vgi implants were performed for indications of secondary glaucoma. studies by nicolai et al. mention that increased intraocular pressure (iop) occurs in 3-40% of cases. the onset of increased iop was <2 weeks postoperatively and decreased by follow-up. increased iop after silicon tamponade is caused by inflammatory reaction that causes trabecular damage, microbubbles from so that migrate to the trabeculum and increased levels of peroxide and free radicals that cause trabecular damage.21 management of vitreous hemorrhage is observation or vitrectomy. observation is carried out if the vitreous opacities are not sight threatening. indications for vitrectomy in cases of vitreous hemorrhage are conditions where the vitreous hemorrhage is permanent and does not experience resolution. vitrectomy aims to overcome media turbidity and stabilize the proliferative process and increase retinal vascularization.4, 15, 17 in this study the majority of treatments were vitrectomy performed in 142 eyes. all cases that underwent vitrectomy were grade 2 and 3 vitreous hemorrhage. the final condition of the vitreous after vitrectomy treatment using silicone oil tamponade at the end of follow-up found that 99% of patients had clear vitreous.4, 17, 18 this is due to good management of vitreous cleansing and intraoperative endolaser action to overcome neovascularization causes of bleeding. the majority of patients who underwent vitrectomy experienced an improvement in visual acuity when compared before and after the procedure. however, visual acuity is greatly affected by other conditions such as the macula and optic nerve. in patients with secondary glaucoma, vgi procedure does not show changes in visual acuity after the procedure which may be caused by the atrophic condition of the optic disc. conclusion the subjects of this study were 157 eyes of 146 patients diagnosed with pdr with vitreous hemorrhage. majority of study subjects were men with an age range of 25-77 years and most vitreous hemorrhage occurred unilaterally. the choice of treatment for the majority of patients is vitrectomy as the main treatment or by intravitreal injection of anti-vegf as adjuvant treatment. 28 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; anatomical assessment showed good results, as the condition of the vitreous that was clear after vitrectomy treatment, and there was no deterioration in treatment with anti-vegf injections and prp laser. visual acuity before treatment compared to after treatment shows progress even though in some cases there was no improvement. acknowledgments: none potential conflicts of interest: the authors declare no conflicts of interest. funding: none data sharing statement: the datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. references 1. mccannel ca ba, holder ge, kim sj, leonardo bc, rosen rb. retina and vitreous. 20222023 basic and clinical science course. 2020th– 2021st ed. san fransisco;2022. p. 331-50. 2. jena s, tripathy k. vitreous hemorrhage. statpearls. treasure island (fl): statpearls publishing copyright © 2022, statpearls publishing llc.; 2022. 3. darajati it, wardhana fs, sasongko mb, supanji s, widayanti tw, agni an. vitreous hemorrhage in dr.sardjito general hospital. ophthalmologica indonesiana. 2017;42(3). 4. metita m, sovani i, kartasasmita a, iskandar e, virgana r. surgical approach in vitreous hemorrhage. international journal of retina. 2017(1):12-6%v 1. 5. petrovic n, todorovic d, sreckovic s, sarenac-vulovic t, petrovic janicijevic m, paunović s, et al. the influence of intravitreally applied triamcinolone acetonide on vitreal hemorrhage resorption and visual acuity in patients with proliferative diabetic retinopathy. srpski arhiv za celokupno lekarstvo. 2017;146:131-. 6. razief fitri ma, yudantha ar. pars plana vitrectomy for vitreous hemorrhage in ciptomangunkusumo hospital. international journal of retina. 2021(2):99%v 4. 7. kautzky-willer a, harreiter j, pacini g. sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. endocr rev. 2016;37(3):278-316. 8. wang cy, cheang wm, hwang dk, lin ch. vitreous haemorrhage: a population-based study of the incidence and risk factors in taiwan. int j ophthalmol. 2017;10(3):461-6. 9. ansari p, tabasumma n, snigdha nn, siam nh, panduru rvnrs, azam s, et al. diabetic retinopathy: an overview on mechanisms, pathophysiology and pharmacotherapy. diabetology. 2022;3(1):159-75. 10. zou w, ni l, lu q, zou c, zhao m, xu x, et al. diabetes onset at 31-45 years of age is associated with an increased risk of diabetic retinopathy in type 2 diabetes. sci rep. 2016;6:38113. 11. bek t. systemic risk factors contribute differently to the development of proliferative diabetic retinopathy and clinically significant macular oedema. diabetologia. 2020;63(11):246270. 12. bansal p, gupta r, kotecha m. frequency of diabetic retinopathy in patients with diabetes mellitus and its correlation with duration of diabetes mellitus. medical journal of dr dy patil university. 2013;6(4):366-9. 13. lind m, pivodic a, svensson am, ólafsdóttir af, wedel h, ludvigsson j. hba(1c) level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: swedish population based cohort study. bmj. 2019;366:l4894. 14. jeng c-j, hsieh y-t, lin c-l, wang ij. effect of anticoagulant/antiplatelet therapy on the development and progression of diabetic retinopathy. bmc ophthalmology. 2022;22(1):127. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 29 15. stewart mw, browning dj, landers mb. current management of diabetic tractional retinal detachments. indian journal of ophthalmology. 2018;66(12):1751-62. 16. chatziralli i, loewenstein a. intravitreal antivascular endothelial growth factor agents for the treatment of diabetic retinopathy: a review of the literature. pharmaceutics. 2021;13(8). 17. zong y, gao qy, hui yn. vitreous function and intervention of it with vitrectomy and other modalities. int j ophthalmol. 2022;15(6):857-67. 18. liao m, wang x, yu j, meng x, liu y, dong x, et al. characteristics and outcomes of vitrectomy for proliferative diabetic retinopathy in young versus senior patients. bmc ophthalmology. 2020;20(1):416. this work licensed under creative commons attribution abstract introduction methods ethics statement results discussion conclusion 78 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; international journal of retina (ijretina) 2021, volume 4, number 1. p-issn. 2614-8684, e-issn.2614-8536 ipsilateral ophthalmic artery stenosis in amaurosis fugax: a case report referano agustiawan1, ferdy iskandar2, muhammad ikhsan mokoagow3,4, firman hendrik5, kanovnegara6 1ophthalmologist, jakarta eye center hospitals and clinics, jakarta, indonesia 2general practitioner, pondok indah – puri indah hospital, jakarta, indonesia 3internist, pondok indah – puri indah hospital, jakarta, indonesia 4internist, jakarta eye center hospitals and clinics, jakarta, indonesia 5neurologist, pondok indah – puri indah hospital, jakarta, indonesia 6radiologist, pondok indah – puri indah hospital, jakarta, indonesia abstract introduction: amaurosis fugax is caused by an abrupt reduction of blood flow to the retina. determining the etiology of amaurosis fugax should ensure proper management. case report: a 47-year-old female patient complaint about the first episode of sudden vision loss in her right eye and was referred to our hospital. the vision loss resolved spontaneously, however, we found a 3 mm long stenosis at her right ophthalmic artery during magnetic resonance angiography. she had clinical histories of untreated hypertension and dyslipidemia. transient ischemic attack (tia) was suspected and unfractionated heparin, aspirin, antihypertensive agent, and statin were given. treatments were maintained, the symptoms had not recurred in the following 6 months after the event. discussion: stenosis of the ophthalmic artery is very rare. it occurs in approximately 2% of patient suffering from amaurosis fugax. in our case, stenosis of the right ophthalmic artery due to thromboembolism might cause retinal ischemia leading to a transient visual loss. conclusion: this case suggests stenosis of ophthalmic artery as the cause of amaurosis fugax. keywords: amaurosis fugax, ipsilateral, ophthalmic artery, stenosis cite this article: agustiawan, referano et al. ipsilateral ophthalmic artery stenosis in amaurosis fugax: a case report. international journal of retina, [s.l.], v. 4, n. 1, p. 78, feb. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/131>. date accessed: 22 feb. 2021. doi: https://doi.org/10.35479/ijretina.2021.vol004.iss001.131. introduction amaurosis fugax describes monocular or binocular loss of vision, typically lasting seconds to minutes.1,2 this symptom is generally caused by a manifestation of thromboembolic event in which atherosclerotic debris originating in the carotid artery or the aortic arch temporarily disrupts blood flow in the branch or central retinal arteriolar network.2,3 immediately treating a patient with amaurosis fugax in whom aortic or carotid atherosclerosis is detected with an anti-platelet agent and a statin are consistent established guidelines.4 migraine, retinal detachment, optic disc drusen or papilledema, glaucoma, emboli from thoracic arteries or external carotid, mitral valve prolapse, hypercoagulable state, giant cell arteritis (gca), vasospasm, postural hypotension, acute sharp pain, nose-blowing, and sensitivity to cold, however, can also be the cause of amaurosis fugax.4-5 therefore, proper management depends on the underlying cause. case report a 47-year-old female patient presented with the first episode of sudden vision loss in her right eye for approximately 30 minutes, prior to reaching the hospital. she experienced no headache. she had clinical histories *correspondence to: ferdy iskandar, pondok indah – puri indah hospital, jakarta, indonesia iskandar.ferdy@gmail.com, published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 79 of hypertension and dyslipidemia, and was not under medical therapy. she was fully alert, and visual acuity of both eyes had returned to 20/20 by the time of initial clinical examination. her blood pressure was 158/77 mmhg. slit-lamp and ophthalmoscopy examination findings were unremarkable (figure 1). intraocular pressure (iop) in the right eye and left eye was 19.7 mmhg and 18.0 mmhg respectively, and was measured with applanation tonometry. laboratory studies demonstrated high levels of total cholesterol (222 mg/dl), low-density lipoprotein/ldl (139 mg/dl), triglycerides (169 mg/dl), and normal level of highdensity lipoprotein/hdl (55 mg/dl). coagulation parameters including d-dimer, fibrinogen, and platelet aggregation studies were within normal limits. other neurological and hematological parameters were within normal ranges. magnetic resonance angiography revealed a 3 mm long stenosis at the right ophthalmic artery (figure 2 and 3). optical coherence tomography (oct) examination was within normal limits (figure 4 and 5). the amaurosis fugax resolved spontaneously. we treated her case as retinal transient ischemic attack (tia), and figure 2. mr angiography, blue arrow demonstrated a 3mm-long stenosis at the right ophthalmic artery (axial image). figure 1. normal color fundus photograph of right eye (a) and left eye (b). 80 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; she received unfractionated heparin during hospitalization. aspirin, candesartan, and rosuvastatin regiments were initiated promptly. discussion braat et al.6 reported a patient with isolated ophthalmic artery stenosis and one episode of amaurosis fugax. during the episode, fundoscopy revealed a cholesterol crystal in the lower temporal branch of the central retinal artery with hemorrhage of the macula. micro-embolism of the ophthalmic artery seemed to cause amaurosis figure 3. mr angiography, blue arrow demonstrated a 3mm-long stenosis at the right ophthalmic artery (sagittal image). figure 4. normal optical coherence tomography (oct) of the right eye (od) published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 81 fugax, and anticoagulation was maintained successfully for preventing attacks. nakajima et al.7 postulated that high frequency of amaurosis fugax attacks in the ophthalmic artery stenosis could be explained by platelet hyperaggregability since aspirin proved effective in preventing attacks. cerebral angiography may show focal stenosis at the origin of the central retinal artery or ophthalmic artery.8 stenosis of the ophthalmic artery is very rare. according to a previous study, the prevalence of ophthalmic artery stenosis is approximately 2% in patients suffering from amaurosis fugax.5 in our case, we did not perform the visual field examination because our hospital did not have the device. the patient’s ophthalmic examination finding was unremarkable, and despite the absence of significant pathologic finding of the right internal carotid on mra, we found stenosis of right ophthalmic artery due to thromboembolism which might cause ischemia of the retina, leading to transient visual loss. amaurosis fugax and tia are clinical conditions with shared etiology that both increase the risk of ischemic stroke, as the patient had several risk factors, notably dyslipidemia and hypertension. the treatment for retinal tia is similar to that of cerebral tia9, therefore unfractionated heparin and aspirin were administered along with candesartan and rosuvastatin to manage the underlying conditions. tia suspected patients should be evaluated as soon as possible after an event. if retinal tia is present within 72 hours, american heart association recommends admission to a hospital setting. for longer presentation, between 3 to 7 days, hospitalization is still recommended if the patient already had a known untreated source of ischemia (carotid stenosis, atrial fibrillation).10 the assessment of vascular risk factors is most important. patient should be assessed for hypertension, dyslipidemia, diabetes mellitus, figure 5. normal optical coherence tomography (oct) of the right eye (os) 82 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; cardiac disease, and tobacco use. laboratory studies, electrocardiogram, and neuroimaging studies should be done.4 treatment first aimed at controlling and treating the underlying vascular risk factors. conclusion amaurosis fugax is caused by an abrupt reduction of blood flow to the retina, with multiple possible etiologies. this case suggests stenosis of ophthalmic artery as the cause of amaurosis fugax. anticoagulant, antiplatelet, angiotensin receptor blocker, and statin were given and treatment for underlying conditions was maintained. the patient remains under treatment for her hypertension and dyslipidemia, and symptoms had not recurred in the following 6 months after the initial (and only) event. references 1. sibel i, guliz y, ubeyt iu. homocysteinemia as a cause for amaurosis fugax in a patient without an apparent embolic source. rom j ophthalmol. 2019;62(2):188-92. 2. parsons mr, stoner mc, doyle a, mix d, cameron sj. lights out: an unusual case of amaurosis fugax. am j med. 2018 feb;131(2):e39-e42. doi: 10.1016/j.amjmed.2017.08.032. 3. shim dh, cha jk, kang mj, choi jh, nah hw. vasospactic amaurosis fugax diagnosed by cerebral angiography. j stroke cerebrovasc dis. 2015 nov;24(11):e323-5. doi:0.1016/j.jstrokecerebrovasdis.2015.07.014. 4. pula jh, kwan k, yuen ca, kattah jc. update on the evaluation of transient vision loss. clinical ophthalmology 2016:10 297–303 5. adams hp, putman sf, corbett jj: amaurosis fugax: the results of arteriography in 59 patients. stroke 1983;14:742–744. 6. braat ae, hoogland ph, de vries ac, van otterloo am. amaurosis fugax and stenosis of the ophthalmic artery. vascular surgery 2001;35:141-3. 7. nakajima m, kimura k, minematsu k, saito k, takada t, tanaka m. a case of frequently recurring amaurosis fugax with atherothrombotic ophthalmic artery occlusion. neurology 2004;62:117-8. 8. park ms, kim jt, lee kr, lee sh, choi sm, kim bc, et al. recurrent transient monocular blindness with ophthalmic artery stenosis. eur neurol 2008;59:2024. 9. jun, bokkwan. diagnostic considerations in patients presenting with transient vision loss. missouri medicine. 2017;113(1):63-7. 10. easton jd, saver jl, albers gw, et al. definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the american heart association/american stroke association stroke council; council on cardiovascular surgery and anesthesia; council on cardiovascular radiology and intervention; council on cardiovascular nursing; and the interdisciplinary council on peripheral vascular disease. stroke. 2009; 40(6) 2276–2293. this work licensed under creative commons attribution 60 published by : inavrshttps://www.inavrs.org/| international journal of retina https://ijretina.com 2020; 03; 02; international journal of retina (ijretina) 2020, volume 03, number 02. p-issn. 2614-8684, e-issn.2614-8536 comparison of wave amplitude, implicit time and comfort level using dawson-trick-litzkow, jet and dencott electrodes in electroretinography in normal adults theresia yinski pg1, m. sidik1, syntia nusanti1, aria kekalih2 1ophthalmology department medicine faculty universitas indonesia 2community medicine department medicine faculty universitas indonesia abstract introduction: several electrodes can be used in standard full-field electroretinography (erg). however, there are no standard values for indonesians yet. therefore, this research aims to establish normal values, to compare them and to compare comfort levels using dtl, dencott and jet electrodes in indonesian adults. methods: this was a correlative analytical study as well as a population descriptive study which took place in ciptomangunkusumo hospital over the course of april-august 2016. through convenient sampling, 58 normal indonesian subjects, age 19-49 years old were selected. erg amplitudes and implicit time values were measured according to recommendations by the international society for clinical electrophysiology of vision (iscev). evaluations consisted of scotopic 0.01, 3.0, op and photopic 3.0 flicker. after examination, all subjects filled in a questionnaire about comfort levels, adopted from the visual analog scale of a 10 centimetre line. the score was later measured by ruler in centimetres. result: pearson/spearman correlation shows moderate to strong correlation between all parameters in the 3 electrodes (r≥0.3). the paired t-test analysis showed a statistically significant difference in erg normal values between electrodes with higher wave amplitudes and longer implicit times in dencott and jet electrodes, compared to dtl electrodes (p<0.05). jet and dtl electrodes are more comfortable than dencott electrodes for indonesian adults in standard full-field electroretinography with scores of 5.21 (dencott), 6.93 (jet) and 7.64 (dtl). conclusion: dtl electrodes give the lowest wave amplitudes and the shortest implicit times and are the most comfortable electrode compared to dencott and erg jet electrodes, in standard full-field electroretinography in indonesian adults. keywords: electroretinography, dencott, dtl, jet, electrode cite this article: gondosari, theresia yinski pistari. comparison of wave amplitude, implicit time and comfort level using dawson-trick-litzkow, jet and dencott electrodes in electroretinography in normal adults. international journal of retina, [s.l.], v. 3, n. 2, sep. 2020. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/123 introduction *correspondence to: theresia yinski pg, department of ophthalmology universitas indonesia, cyinski@hotmail.com electroretinography is a very important type of examination since it can be used to evaluate the retina function objectively and can calculate the results in numbers. electroretinography may serve as baseline data and follow up measurement for therapy, as well as a means to predict the prognosis of patients if surgery is considered.1,2 the international society for clinical electrophysiology of vision (iscev) recommends that every centre should have its own normal set of data because the characteristics of patient vary widely.3,4 nowadays, there is quite a wide variety of electrode types published by : inavrshttps://www.inavrs.org/| international journal of retina https://ijretina.com 2020; 03; 02; 61 which can be used for the electroretinography examination, such as scleral electrodes, corneal electrodes and eyelid electrodes. good electrodes are important in order to produce a good electroretinography wave result. however, we should not forget to also consider the patient’s comfortability in wearing the electrodes during the examination. despite a lot of types of electrodes, the standard depends on the parameter used in the electroretinography examination and therefore there is no methods difference per electrodes usage. there are three main groups of electrodes which are scleral, corneal and eyelid electrodes. in this research we limited the comparison to dencott electrodes as the example of scleral electrodes, jet electrodes as the example of corneal electrodes and dawson-tricklitzkow (dtl) electrodes as the example of eyelid electrodes. this research aims not only to establish the normal values of standard full-field electroretinography at our hospital for the indonesian population, but also to compare the values and comfort levels of using the 3 types of electrode in indonesian adults. methods this study is a correlative analytical study which compares the normal results of standard full-field electroretinography as well as the comfort level of the electrodes usage in normal indonesian adults. however, this study also serves as population descriptive study as it gives normal standard values for electroretinography examination in indonesia. all 58 subjects, ages between 19-49 years old, were selected through convenient sampling and their normal status of both eyes were established through a series of examinations of visual acuity, intraocular pressure, humphrey visual field, anterior segment evaluation, fundus photography, ishihara colour blind test and pelli-robson contrast sensitivity test, over the course of april-august 2016. subjects were excluded if they had high myopia (≥ 6 dioptres), a history of intraocular surgery or laser treatment (photocoagulation), eye trauma, long-term drug usage or difficulty in pupil dilation. the electroretinography examination was performed based on iscev recommendations. the order of electrode usage was randomised per subject, but all of the examinations was done on the same day for each subject by the same operator. iscev recommendations are as following: 1. pupil dilation is done with tropicamide 1% prior to the examination 2. a drop of tetracaine 0.5% is used as topical anesthetics in both eyes 3. 20 minutes of dark adaptation is done prior to the placement of the electrodes (based on the randomisation order) and subjects are instructed to look straight forward to the fixation point in the machine dome for the scotopic 0.01 and 3.0 erg and 3.0 op 4. afterwards, 10 minutes of light adaptation is done prior to the photopic fast flicker 30 hz erg the questionnaire about comfort levels, adopting the visual analog scale of a 10 centimetre line, was given to the subjects after they had completed all examinations. the score was later measured by ruler in centimetres. all procedures performed in this study involve human participants and therefore the procedures were in accordance with the ethical standards of the institutional research committee and with the 1964 helsinki declaration and its later amendments or comparable ethical standards. this research has been approved by the ethical committee of the medicine faculty of universitas indonesia based on the helsinki declaration and ethic permission has been obtained. informed consent was obtained from all individual participants included in the study. results the image below can further clarify the results of the standard full-field electroretinography examination. from the 58 subjects recruited, 43 were female, totaling 116 eyes. pearson/spearman correlation showed moderate to strong correlation between the three electrodes in all of the parameters measured, as given in table 1. 62 published by : inavrshttps://www.inavrs.org/| international journal of retina https://ijretina.com 2020; 03; 02; table 1. correlation between electrodes parameter correlation (r) dencott vs jet dencott vs dtl jet vs dtl implicit time of b wave scotopic 0.01 0.626 0.609 0.650 amplitude of b wave scotopic 0.01 0.604 0.436 0.572 implicit time of a wave scotopic 3.0 0.737 0.476 0.487 amplitude of a wave scotopic 3.0 0.564 0.358 0.388 implicit time of b wave scotopic 3.0 0.615 0.582 0.641 amplitude of b wave scotopic 3.0 0.826 0.668 0.649 implicit time of op wave 0.382 0.300 0.392 sum amplitude of op wave 0.787 0.584 0.688 implicit time of b wave photopic flicker 0.623 0.565 0.636 amplitude of b wave photopic flicker 0.640 0.467 0.584 normal values of standard full-field electroretinography in indonesian adults, using dencott electrodes, jet electrodes and dtl electrodes, are shown in table 2. the p-values were obtained from the paired t-test analysis. table 2. normal values of standard full-field electroretinography in indonesian adults parameter dencott jet dtl imp.time b wave scotopic 0.01 77+7 76+6 74+7*^ amp. b wave scotopic 0.01 293 (133-544) 332 (109-576)* 283 (146-496)^ imp.time a wave scotopic 3.0 25+1 25+1 24±1*^ amp. a wave scotopic 3.0 -258 (-445;-138) -281 (-459;-132)* -220 (-358;-100)*^ imp.time b wave scotopic 3.0 45+3 46+4 46+5 amp. b wave scotopic 3.0 482 (315-737) 509 (261-771)* 417 (202-724)*^ imp.time op wave 21+1 21+1 21+1 sum amp. op wave 345 (106-589) 338 (149-797) 281 (107-717)*^ imp.time b wave photoflicker 29+2 29+2 29+2 amp. b wave photoflicker 105 (44-236) 108 (44-264) 88 (37-186) * *) p value < 0.05 compared with dencott ^) p value < 0.05 compared with jet the mean comfort level scores from the questionnaire using each electrode are shown in table 3. table 3. mean comfort level score of electrode electrodes mean comfort level score dencott 5.21+2.5 erg jet 6.93+2.3 dtl 7.64+1.8 the paired t-test comparison between the electrodes are shown in table 4. table 4. comparison of comfort level between electrodes electrode comparison p value dencott – erg jet 0.001 dencott – dtl 0.001 erg jet – dtl 0.064 there were no side effects or complications, such as eye infection or corneal abrasion, in any of the subjects during this research. published by : inavrshttps://www.inavrs.org/| international journal of retina https://ijretina.com 2020; 03; 02; 63 discussion standard full-field electroretinography is an important clinical tool that provides an objective quantitative measure of retinal function. decreased a and b wave amplitudes and prolonged implicit time correlate to reductions in retinal function.1 because of the wide variety of patient characteristics, iscev recommends that every laboratory should have its own normal data using iscev protocols so that it becomes comparable all over the world.1,3,4 however, until this time, there has been no research done in indonesia regarding this matter. correlation analysis shows moderate to strong correlation between all parameters in the 3 electrodes. this explains that the higher the values are collected with dencott electrodes, the higher the values will be collected with the two other electrodes. this result is similar to the research conducted in japan by kuze, et al. 5 the electrode order was randomised to eliminate the possibility of bias of eye fatigue or electrode type. the recording conditions also specify 20 minutes of dark adaptation before recording dark-adapted electroretinography (scotopic), and 10 minutes of light adaptation before recording light-adapted electroretinography (photopic) according to iscev standards.6 this research shows that erg jet electrodes give a higher amplitude than the other electrodes, with dtl giving the lowest. this happens because the dtl is quite far located from the centre of the cornea if compared with dencott or jet electrodes.5 however, the implicit times are not significantly different between electrodes, even though the material of each electrode is different. silver, the material of dtl electrodes, has the highest conductivity of 6.8 x 107 (ωm)-1, while gold, the material of jet electrodes, has conductivity of 4.3 x 107 (ωm)-1.7 in malaysia and iran adults the normal values of scotopic a and b wave amplitude is lower than in the indonesian population when the recording is done by using dtl electrodes.8,9 similar results are shown in research from korea using jet electrodes, which show lower results of wave amplitudes compared to the indonesian population.10 however, it proved difficult to compare this research’s results with other research, because the differences of electroretinography machines, as well as the electrodes, may contribute to a variety in results. race is known to be another factor that contributes to the difference of results. one research, comparing the caucasian and asian populations, showed that caucasians tend to have a higher wave amplitude than asians. the hypothesis of what cause this is said to be the ocular pigmentation of iris, in which melanine serves as a resistant barrier for the electroretinography wave signal.11 the results from the questionnaires given to the subjects reveal that dtl electrodes give the most comfort of the three electrodes used. this is because of the position of the electrode, which is buried deep in the lower fornix, thus barely being in contact with the cornea. the electrode’s position is stable as well, as the position is not necessarily affected by blinking of the eye. however, statistical analysis shows that there is no significant difference between dtl and jet electrodes, which are shaped as contact lens touching the cornea. the most ideal electrode is the one that give the highest amplitude, has low variability, and is welltolerated by the patients (most comfortable). the study by mohidin n, et al shows that corneal electrodes such as jet electrode may give a high variability because it tends to easily slide during blinking.12 this makes the dtl as a non-corneal electrode a more favourable choice, as its variability is low due to its stable position.13 dencott electrodes are the least favourable electrode due to their discomfort, caused by their bulky shape. however, its long legs make it stable, because once it is positioned well on the eye surface, it will not move even with rapid eye blinking. in the future we hope to be able to conduct the examination with more varieties of electrodes on children as well as the geriatric subjects so that more complete normal standard values erg can be obtained for all age population groups and more types of electrodes. conclusion there is a statistically significant difference in the wave amplitudes between dencott, jet and dtl electrodes. dtl and erg jet electrodes are the most comfortable electrodes in standard full-field electroretinography for normal indonesian adults. due to the presence of many 64 published by: inavrshttps://www.inavrs.org/| international journal of retina https://ijretina.com 2020; 03; 02; parameters in the examination, the normal values of wave amplitude, implicit time and comfort levels of the three electrodes are given in the result section. references 1. karanjia r, tenhove mw, coupland sg. electroretinograms and normative data. in: belusic g (ed). electroretinograms. rijeka: intech; 2011. p.1-238. 2. miyake y, shinoda k. clinical electrophysiology. in: sadda sr, ryan sj (eds). retina. 5th ed. philadelphia: elsevier; 2013. p. 202-26. 3. marmor mf, zrenner e. introduction to the iscev standards. in: heckenlively jr, arden gb (eds). principles and practice of clinical electrophysiology of vision. 2nd ed. london: the mit press; 2006. p. 287-8. 4. marmor mf, holder ge, seeliger mw, yamamoto s. standard for clinical electroretinography (2004 update). doc ophthalmol. 2004; 108: 107-14. 5. kuze m, uji y. comparison between dawson, trick, and litzkow electrode and contact lens electrodes used in clinical electroretinography. jpn j ophthalmol. 2000; 44: 374-80. 6. mcculloch dl, marmor mf, brigell mg, hamilton r, holder ge, tzekov r, et al. iscev standard for full-field clinical electroretinography (2015 update). doc ophthalmol. 2015; 130: 1-12. 7. callister wd. materials science and engineering: an introduction. 7th ed. new york: john wiley & sons, inc; 2007. p. 674. 8. parvaresh mm, ghiasian l, falavarjani kg, sanjari ms, sadighi n. normal values of standard full field electroretinography in an iranian population. j ophthalmic vis res. 2009; 4(2): 97-101. 9. saiful ar, chen ah, muhamad smr. scotopic adapted full-field electroretinogram effect in young malay adults. ijerste. 2013; 2(6): 47-9. 10. seong gm, young hl, sun yj. result of visualevokedpotential, electroretinography and electrooculography in normal subjects using monpack system. j korean ophthalmol soc. 2014; 55(11): 16937. 11. abdlseaed a, mctaggart y, ramage t, hamilton r, mcculloch dl, meigen t, et al. light-and dark-adapted electroretinogram and ocular pigmentation: comparison of brownand blue-eyed cohorts. doc ophthalmol. 2010; 121: 135-46. 12. mohidin n, yap mkh, jacobs rj. electrodes for multifocal electroretinography: a comparison of four electrodes types. sains malays. 2014; 43(7): 1089-94. 13. hébert m, vaegan, lachapelle p. reproducibility of erg responses obtained with the dtl electrode. vision res. 1999; 39: 1069-70. this work licensed under creative commons attribution published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 17 international journal of retina (ijretina) 2018, volume 1, number 1. p-issn. 2614-8684, e-issn.2614-8536 the outcome of vitrectomy in acute postoperative endophthalmitis: an eight-year experience sindy boru sembiring,1 yulia aziza,2 gitalisa adriono2 1 sumatera eye hospital, medan, indonesia 2 cipto mangunkusumo hospital, jakarta, indonesia abstract introduction: twenty years ago, the results of endophthalmitis vitrectomy study (evs) were adapted worldwide as the standard management of endophthalmitis. the study suggested that there was no benefit of performing vitrectomy for acute postoperative endophthalmitis, unless for patients who presents with visual acuity of light perception. however, vitrectomy with advanced technology and technique has been changed rapidly in the last decades; therefore, we need to reconsider its role. we conducted a study and the purpose of our study was to describe the indications for vitrectomy and the outcomes in acute postoperative endophthalmitis at cipto mangunkusumo hospital, jakarta, indonesia. methods: our study was a descriptive-retrospective case series. we reviewed clinical and microbiological records of all patients with clinical diagnosis of acute postoperative endophthalmitis who underwent vitrectomy in cipto mangunkusumo hospital between 2007 and september 2015. presenting visual acuity, visual outcome and complications were described. result: our study was a descriptive-retrospective case series. we reviewed clinical and microbiological records of all patients with clinical diagnosis of acute postoperative endophthalmitis who underwent vitrectomy in cipto mangunkusumo hospital between 2007 and september 2015. presenting visual acuity, visual outcome and complications were described. conclusion: an eight-year experience has taught us that vitrectomy offers better treatment outcome in the group with visual acuity of hand movement than those who only had visual acuity of light perception. keywords: endophthalmitis, vitrectomy cite this article: sembiring, sindy boru; aziza, yulia; adriono, gitalisa andayani. the outcome of vitrectomy in acute postoperative endophthalmitis. international journal of retina, [s.l.], v. 1, n. 1, july 2018. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/12 introduction *correspondence to: sindy boru sembiring, sumatera eye hospital dr.sindyboru@yahoo.com endophthalmitis is an intraocular fluid accumulation of purulent inflammation. it is the most terrifying condition developed following intraocular surgery. without judicious and timely management, it may lead to the loss of vision and even loss of the eye. endophthalmitis is basically an abscess; therefore, the principles of treatment are similar to therapy for abscess, i.e. eliminating the microorganism and draining fluid accumulation to cease the ongoing inflammatory process. vitrectomy ensures that both principles are applied. however, the endophthalmitis vitrectomy study (evs) in 1995, which has been known as the bestdesigned research on the management of acute post operative endophthalmitis, found that there was no benefit of performing vitrectomy, unless for patients with visual acuity of light perception. kuhn suggested that since the era of evs, the role of vitrectomy has become less prioritized, except for those who have visual acuity of light perception. twenty years after the evs, advanced vitrectomy techniques, improved intraoperative visualization technology and new antibiotics have been developed; therefore, the role of vitrectomy in the treatment of acute postoperative endophthalmitis should be reconsidered. 18 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; in the study by kuhn, which included 47 eyes, early vitrectomy was performed as the first-line treatment for acute postoperative endophthalmitis. the study shows that 91% eyes achieve better treatment outcome (final visual acuity of ≥ 20/40) as opposed to only 53% in evs.3 although the evs has suggested the appropriate condition for vitrectomy in acute postoperative endophthalmitis, but twenty years later, there are still controversies worldwide on the indication for vitrectomy. as a national referral hospital in indonesia and one of the few having vitreoretina surgeon and machine available, cipto mangunkusumo hospital enables vitrectomy as a standard approach in managing acute postoperative endophthalmitis. the hospital is no longer use the evs recommendation. therefore, we conduct a study to evaluate the outcome of vitrectomy in the hospital. clinical characteristics including presenting visual acuity, visual outcome and complications will be described. the purpose of our study was to identify the treatment outcome of vitrectomy in acute postoperative endophthalmitis. method the study was a descriptive-retrospective case series. we reviewed clinical and microbiological records of all patients with clinical diagnosis of acute postoperative endophthalmitis who underwent vitrectomy in cipto mangunkusumo hospital between 2007 and september 2015. the clinicaldiagnosis of acute endophthalmitis was made, which was defined as a marked intraocular inflammation occurring after intraocular procedure characterized by increased pain, redness and decreased vision in the presence of hypopion and cellular infiltration in the anterior chamber and vitreus within 6 weeks following intraocular surgery. subjects were excluded if there were other retinal pathologies diagnosed before the preceding intraocular surgeries. cipto mangunkusumo hospital is a teaching hospital; hence, multiple surgeons performed the vitrectomy. all patients with acute endophthalmitis who sought treatment at cipto mangunkusumo hospital or other hospitals and subsequently being referred to cipto mangunkusumo hospital were included in our study. collected data included age, gender, interval between the preceding intraocular surgery and the symptoms, presenting visual acuity, final visual acuity, microbial profiles, complications and time to follow up. categorical variables were described as frequency or proportion, while numeric variables were described as mean, median or range. data was computed using spss version 21 for mac. visual acuity (va) was determined as the bestcorrected snellen va found at the time of diagnosis and the last known va. for the purpose of data analysis, patients were categorized into three groups based on presenting visual acuity; better than hand movement, hand movement and light perception. visual outcome was categorized into two; good visual outcome defined as visual acuity better than 6/12 and poor visual outcome defined as visual acuity hand movement or worse. results over the 8-year period, there were 98 eyes of 98 acute endophthalmitis patients (51 right eyes and 47 left eyes) that underwent vitrectomy. the mean age was 61.2 years (age range: 12-88 years) and there were 59.2% male patients. the characteristics of the subjects are described in table 1. table 1. subject characteristic as (n=98 eyes) total percentage demographics age (years) (mean) 61.2 gender male 58 59.2 % female 40 40.8 % surgical characteristics operated eye right 51 52 % left 47 48 % procedure type phacoemulsification 67 68.4 % ecce 19 19.4 % vitrectomy 4 4 % others 8 8.2 % interval between the preceding intraocular surgery and symptoms (days) (mean) 13.1 ecce : extra capsular catar act extraction published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 19 acute endophthalmitis in our study mostly occurred following phacoemulsification (68,4%) and extra capsular cataract extraction (19%). the mean interval between the preceding intraocular surgery and symptoms was 13.1 days (range, 1-42 days). the mean of follow up was 24.5 weeks (range, 1-228 weeks). the microbiological profiles were based on the culture results of 67 patients, which 33 (49.25%) of them showed positive results. the most common causative microorganism was pseudomonas sp (30%) followed by acinetobacter (18%). seventy percent of the microorganisms were gram-negative, 18% were grampositive and 12% were fungi. the microbiological profile is described in table 2. table 2. the microbiological profiles causative microorganisms total % pseudomonas 10 30 acinetobacter 6 18 streptococcus 3 9 klebsiella 3 9 pseudomonas and acinetobacter 2 6 aspergillus 2 6 bacillus 2 6 others 5 15 presenting visual acuity of hand-movement was found in most subjects, i.e. in 57 eyes (58.2%) followed by visual acuity of light perception in 36 eyes (36.7%); while visual acuity of better than hand movement was found in 5 patients (5.1%). twenty four percent cases achieved good visual outcome, while 25 % achieved poor visual outcome. the comparison of final visual outcome following the vitrectomy based on presenting visual acuity can be found in figure 1. proportion of subject achieving good visual outcome was highest in hand movement group presenting visual acuity (22 of 57, 38.6%). proportion of subject having poor visual outcome was highest in light perception presenting visual acuity (15 of 36, 41.7%). in 34 cases vitrectomy procedure was carried out one day after the diagnosis. in 93.5% cases, was performed within 7 days after the diagnosis of endophthalmitis was made. figure 1. comparison of visual outcome based on the presenting visual acuity 20 38,6 17,5 2,8 41,7 0 5 10 15 20 25 30 35 40 45 good poor p e rc e n ta g e visual outcome better than hm hm lp 0 20 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; complications following vitrectomy in acute endophthalmitis were found in 20 cases (20.4%) listed in table 3. the most common complication was retinal detachment, which was found in 10 cases (10.2%). table 3. complications following vitrectomy complications total percentage retinal detachment 10 50% persistent vitreus haziness 2 10% secondary glaucoma 2 10% choroidal detachment 2 10 % iol dislocation 1 5 % iatrogenic hole 1 5 % preretinal hemorrhage 1 5 % recurrent inflammation 1 5 % 20 100 % iol : intraocular lens discussion our study showed that endophthalmitis occurred in older age, which is similar to the results shown by previous studies.4,5 there are two possible causes that may explain this finding. first, in cataract surgery, complications are more prevalent in elderly than young patients since the lens is harder and the zonules are weaker. second, elderly patients have more conjunctival bacteria.4 in our study, endophthalmitis was found mostly following the phacoemulsification procedure. the findings is different from another study that found equal or higher rate of endophthalmitis in patients underwent extra capsular cataract extraction (ecce).4 however, our result is similar with the result of wong ty study6 and it is also consistent with previous study reported by aziza.5 wong ty found that phacoemulsification was associated with a higher risk of acute endophthalmitis compared to ecce.6 clear corneal incision surgery such as phacoemulsification is getting more popular nowadays. the surgical rate was raising from 5% in 1993 to 72% in 2003.7 based on ex vivo study conducted by may et al,8 it has been known that wound construction in a singleplane clear corneal incision enables micro particles to enter the eye. twenty-four percent cases in our study achieved visual outcome of better than 6/12. the result was lower than those in other studies. choi et al9 found 58.8% cases achieved visual outcome of better than 6/12; while kuhn et al3 found that in 91% cases. we learned that our microbiological profile was different from choi et al study. gram-negative bacteria, the most pathogenic causative micro-organism that commonly associated with poorer prognosis,10 were predominant in our study. in our study, most patients had presenting visual acuity of hand movement; 38.6% of them results in good visual outcome. in the other hand, only 2.8% of lp presenting visual acuity subjects that achieved good visual outcome. poor visual outcome was higher in the lp presenting visual acuity (41.7%) as opposed to that of hm (17.5%). from this data we concluded that vitrectomy in the hm group provided better visual outcome. moreover, poor visual outcome was found more frequent in those with lp presenting visual acuity. we assumed that this finding results from the advantages of vitrectomy; improved identification on microbiological profile, removal of infectious microorganism and reducing inflammatory cells and mediators.11 the earlier vitrectomy performed, the greater advantages it could provide in managing the disease. although our data is contradictory with evs recommendation, we strongly advised that clinical diagnosis and principal of therapy should be the most important consideration in deciding when to perform vitrectomy in endophthalmitis. in our hospital, vitrectomy was performed within 7 days after the diagnosis was made in 93.5% patients. moreover, the procedure was performed one day after diagnosis in 34 cases. immediate vitrectomy became possible since the national health insurance had been implemented. in gower et al study,12 76% percent of cases with initial acuity of lp underwent immediate vitrectomy, and 9% underwent vitrectomy in 2 days or more after initial presentation. among cases with initial acuity better than lp, 28% underwent immediate vitrectomy and 13% underwent vitrectomy 2 days or more later.7 the most common complication found in our study was retinal detachment (10.2%). the rate was similar with evs report.2 however, unlike the evs, kuhn1,3 reported 0% of retinal detachment in his series. we believed that his excellent visual outcome could be achieved since the study included only a single expert surgeon to perform the procedure. we believe that a champion data belongs only to the champion. therefore, it could not be generalized to a population. the limitations of this study originated from its retrospective study design. important variables that may confound the outcome were not well documented the medical record, i.e. intraoperative retinal condition, the exact time interval between symptoms and surgery. published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2018; 1; 1; 21 vitrectomy performed by multiple surgeon so that wide variability of surgeon factor is inevitable. in conclusion, an eight-year experience has taught us that vitrectomy in the group of patients with presenting visual acuity of hand movement provides a better visual outcome compared to those with visual acuity of light perception. however, these advantages should be weighed further against the risk of postoperative complications. conflicts of interest: the authors affirm there is no conflict of interest in this study acknowledgment: thank you to all people who has contributed in organizing this study references 1. kuhn f, gini g. ten years after. are findings of the endophthalmitis vitrectomy study still relevant today? graefes arch clin exp ophthalmol. 2005 dec;243(12):1197-9. 2. endopthalmitis vitrectomy study group. results of the endophtalmitis vitrectomy study. a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. arch ophthalmol. 1995 dec;113(12):1479-96 3. kuhn f, gini g. complete and early vitrectomy for endophthalmitis as today’s alternative to the endophthalmitis vitrectomy study. in vitreoretinal surgery pp53-68. springer-verlag berlin heidelberg 4. jabbarvand m, hashemian h, khodaparast m, et al. endophthalmitis occuring after cataract surgery. ophthalmology 2016; 123:295-301 5. aziza y, susianti m. insiden dan faktor-faktor yang mempengaruhi keberhasilan penatalaksanaan endoftalmitis pasca operasi intra okuler di rsup dr. cipto mangunkusumo periode januari 2007 – juli 2010. presented in the 37th ioa meeting in surabaya. 6. wong ty. chee s. the epidemiology of acute endophthalmitis after cataract surgery in an asian population. opthalmology 2004; 111:699705. 7. leaming dv. practice styles and preferences of ascrs members-2003 survey. j cataract refract surg 2004; 28:892-900. 8. may w, castro-combs j, camacho w, wittmann p, behrens a. analysis of clear corneal incision integrity in an ex vivo model. j cataract refract surg 2008; 34:1013-8. 9. choi sc, cho hj, kim hs, et al. analysis of referred 113 patients with endophthalmitis after cataract surgery and associated prognostic factors, j korean ophthalmol soc 2016;57(3):420-8. 10. pinna a, usai d, sechi la, et al. an outbreak of post-cataract surgery endophthalmitis caused by pseudomonas aeruginosa. ophthalmology. 2009 dec;116(12):2321-6. 11. barry p, cordoves l, gardner s. escrs guidelines for prevention and treatment of endophthalmitis following cataract surgery. the european society of cataract and refractive surgeons, temple house, temple road, blackrock, co dublin, ireland 12. gower ew, keay lj, stae de, et al. characteristics of endophthalmitis after cataract surgery in the united states medicare population. opthalmology 2015 aug;122(8)1625-32. this work licensed under creative commons attribution 4. central macular thickness after combined therapy of bevacizumab intravitreal injection and topical diclofenac compared with bevacizumab intravitreal injection in diabetic macular edema.docx 106 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 central macular thickness after combined therapy of bevacizumab intravitreal injection and topical diclofenac compared with bevacizumab intravitreal injection in diabetic macular edema melvina nidya sandra1, yumni shabrina1, tri wahyu widayanti1, retno ekantini1, agus supartoto1, muhammad bayu sasongko1, supanji1 1 department of ophthalmology universitas gadjah mada – sardjito hospital abstract introduction: to evaluate whether the combination of diclofenac eye drops and bevacizumab intravitreal injection would provide additional benefits over bevacizumab only in the treatment of naïve diabetic macular edema (dme). methods: a total of 43 patients were randomized into two groups to receive combination treatment with bevacizumab intravitreal injection and topical diclofenac (group 1) or bevacizumab intravitreal injection only (group 2). group 1 patients received single bevacizumab intravitreal injection and got self-administered diclofenac eye drop four times daily for one month. group 2 patients received single bevacizumab intravitreal injection alone. outcome data were achieved from patient visits at primary visit and at 1 month after bevacizumab intravitreal injection. all patients underwent measurement of best corrected visual acuity (bcva), a complete eye examination, and measurement of central macular thickness (cmt). result: the mean reduction in cmt in the group 1 was 130.42±32.57 µm (p<0.01), while in the group 2 the reduction was 141.38±45.27 µm (p<0.01), there is no significant difference between the two groups (p=0.866). the mean improvement of bcva was 0.32±0.10 log mar in the combination group and 0.26±0.12 in group 2, there is no significant difference between the two groups (p=0.691). there was no adverse ocular event in the two groups. conclusion: in patients with naïve dme, adding diclofenac eye drop as adjuvant of bevacizumab intravitreal injection are less likely to have a meaningful effect on reducing the central macular thickness. keywords: diabetic macular edema, nsaid, diclofenac, anti-vegf, bevacizumab, central macular thickness cite this article: haryanto, supanji; sandra, melvina nidya. central macular thickness after combined therapy of bevacizumab intravitreal injection and topical diclofenac compared with bevacizumab intravitreal injection alone in diabetic macular edema. international journal of retina, [s.l.], v. 4, n. 2, p. 106, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/164>.doi: https://doi.org/10.35479/ijretina.2021.v ol004.iss002.164. correspondence to: supanji, ophthalmology department universitas gadjah mada , supanji@ugm.ac.id introduction diabetic macular edema (dme) can appear at various stages of diabetic retinopathy. dme has a prevalence of 6.8% of patients with diabetes mellitus. (1) dme is the most common cause of permanent visual loss in patients with diabetes. intravitreal anti-vegf has been widely used as therapy in dme but 30% of patients are resistant to this therapy.(2) it can be thought that there are other mechanisms involved in the pathogenesis of dme, one of which is inflammation. (3) low-grade subclinical inflammation are responsible for the https://www.ijretina.com/index.php/ijretina/article/view/164 https://doi.org/10.35479/ijretina.2021.vol004.iss002.164 https://doi.org/10.35479/ijretina.2021.vol004.iss002.164 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 107 development of dme. the expression of interleukin-6 (il-6) and cyclooxygenase-2 are upregulated, therefore vascular permeability deteriorates. corticosteroids are an effective therapy because of their ability to fight inflammatory factors that contribute to dme but have many unwanted side effects such as cataracts and increased intraocular pressure. (4) in order to overcome this issue, alternative nsaids can be used as a strategy to get an anti-inflammatory effect without promoting side effects. topical nsaids are widely used in the prevention and therapy in the case of cystoid macular edema after cataract extraction. (5) the use of topical nsaids combined with anti-vegf has been shown to reduce retinal thickness in pseudophakic cystoid macular edema. (6) however, the effectiveness of the combination of topical nsaids and anti-vegf in dme is not well known. in this study, we prospectively evaluated whether the combination of diclofenac eye drops four times a day and intravitreal bevacizumab injections would provide additional benefits over bevacizumab only in patients with naïve dme. methods data for this study were collected using a doubleblind randomized controlled trial. the study included 43 patients with naïve dme. all patients were enrolled consecutively and randomized to receive combination treatment with bevacizumab intravitreal injection and topical diclofenac (group 1) or bevacizumab intravitreal injection (group 2).(7) all patients received single bevacizumab intravitreal injection. patients were self-administered with topical diclofenac four times a day for one month and the participants were evaluated. subjects were qualified if the following criteria were met: (1) patients diagnosed with dme by a retinal specialist; (2) age > 18 years; (3) never had corticosteroid/nsaids or prostaglandin analog therapy, anti-vegf, and pan-retinal photocoagulation laser. exclusion criteria were as follows: (1) patients with significant media opacity; (2) underwent intraocular surgery during the study period; (3) having anterior segment infection or inflammation. the following assessments were performed by a blinded examiner at every visit: (1) measurement of bcva; (2) assessment of adverse ocular event (e.g, infection, inflammation, endophthalmitis); (3) fully dilated ophthalmic examination; (4) cmt measurement by oct. statistics were performed using the wilcoxon test for changes in bcva and cmt within the group. between subgroups, mannwhitney analysis was used. statistical analyses were performed using spss software. results a total of 43 patients met the study criteria and randomly assigned to either group 1 or group 2. one patient in group 1 drops out because the patient passed away. the table below illustrates the baseline characteristics of the participant group (group 1, bevacizumab and diclofenac; group 2, bevacizumab). table 1. baseline characteristics 108 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; as can be seen from the table below (table 2), the baseline means bcva were 1.16±0.15 log mar in group 1 and 0.94±0.16 log mar in group 2. at 1 month follow up the mean bcva group 1 were improved significantly to 0.83±0.12 (p=0.005) while in group 2 the improvement was not statistically significant (p=0.052). there was no statistically significant difference between the two treatment arms (p=0.691). table 2. bcva and cmt between two groups. (infection, inflammation, and endophthalmitis) during the study period. from this data, it can be seen that cmt was significantly reduced in group 1 and group 2. in group 1 the mean reduction from baseline was 130.42±32.57 µm (p=0.000) while in group 2 was 141.38±45.27 µm (p=0.002). there was no statistically significant difference between the two treatment arms (p=0.866). there was no ocular adverse effect in both groups. discussion the result of this study suggests that there is likely no benefit in the addition of topical diclofenac in naïve dme. however, this outcome does not support the previous research where the combination of bevacizumab intravitreal injection and diclofenac intravitreal injection reduced cmt more than bevacizumab intravitreal injection only in patient with naïve diabetic macular edema.(8) a possible explanation for this might be because the nsaids used were delivered directly to vitreous. another study conducted by warren showed greater retinal thickness reduction in patients who received combination of bevacizumab and intravitreal dexamethasone intravitreal injection with topical nsaid (nepafenac or bromfenac or ketorolac) compared to bevacizumab and dexamethasone intravitreal injection in patients with refractory diabetic macular edema. the bromfenac and nepafenac group required fewest number of additional intravitreal injection.(9) the differences between this study and the study conducted by warren are the naïve/refractory status of the diabetic macular edema and the nsaid used of this study were different. compared with diclofenac, amfenac, and ketorolac, bromfenac is reported to be a 3 to 18 times more potent inhibitor of cox-2. (10) cox-2 is thought to be primarily responsible for inflammation, and therefore the anti-inflammatory actions of nsaids are assumed to relate to their ability to inhibit this isoform.(5) in a study comparing the efficacy of bromfenac, nepafenac, and diclofenac founded that bromfenac was more effective in preventing cystoid macular edema after cataract surgery than nepafenac. however, nepafenac is more effective in reducing inflammation than bromfenac. nepafenac and bromfenac were more effective at reducing macular thickness in post-cataract macular edema compared to diclofenac.(11) a study conducted by friedman et al founded that administration of topical nepafenac two times a day have no beneficial effect on retinal thickening and visual acuity outcome.(12) this is contrary to reports showing a beneficial effect of nepafenac on macular edema in patients with diabetes. the difference might be caused by the different mechanism of macular edema, especially macular edema in the setting of cataract surgery.(13) as with any study with topical eye drop treatment, patients’ compliance can affect the outcome. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 109 vegf is a potent vasopermeability factor that has been targeted extensively in dme. compared with non-diabetic eyes, the vegf levels are significantly increased in vitreous of dme patients.(14) vegf induced leukostasis in the retina, enhancing vascular permeability and capillary non-perfusion. despite of being mostly a vasogenic factor, vegf also trigger inflammation. vegf induced icam-1 expression, leukocyte adhesion, and monocyte migration.(15) the inflammatory process is also initiated by microglial cells, together with muller cells and astrocytes, escalate this response and low-grade inflammation is preserved by the production of interleukin 6 (il-6) and interleukin 8 (il-8). il-6 changes the function of astrocytes, thus breaking the inner blood-retinal barrier.(16) currently, the first line treatment in centerinvolving dme were anti-vegf agents. however, despite the treatment, 40% of dme eyes endured persistent macular edema (pme) after 6 monthly injections, and 32% of dme eyes had concomitant visual loss based on the results from protocol i and protocol t.(17, 18) several factors influence the prognosis of successful therapy in dme including the presence of wrinkled epiretinal membrane (erm), presence of serous retinal detachment, disruption of external limiting membrane, hyper-reflective retinal spots, disruption of ellipsoid zone and the disorganization of inner retinal layers. increased cmt after treatment also considered predictor of poor response to treatment.(19, 20) the limitation of this study were short follow up and the diagnostic criteria for macular edema were only based on the cmt despite the presence of hard exudate and macular ischemia, both of which could affect the results of this study. conclusions the results of this study suggest that there is likely no benefit of adding diclofenac eye drop as an adjuvant of bevacizumab intravitreal injection in reducing cmt in patients with naïve dme. further longer studies, which take presence of hard exudate and macular ischemia into account are necessary to establish whether or not adding diclofenac as an adjuvant may be of long-term benefit in the treatment of naïve dme. references 1. yau jw, rogers sl, kawasaki r, lamoureux el, kowalski jw, bek t, et al. global prevalence and major risk factors of diabetic retinopathy. diabetes care. 2012;35(3):55664. 2. wells ja, glassman ar, ayala ar, jampol lm, aiello lp, antoszyk an, et al. aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. the new england journal of medicine. 2015;372(13):1193-203. 3. funatsu h, yamashita h, ikeda t, mimura t, eguchi s, hori s. vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. ophthalmology. 2003;110(9):1690-6. 4. ohira a, hara k, jóhannesson g, tanito m, ásgrímsdóttir gm, lund sh, et al. topical dexamethasone γ‐cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema. acta ophthalmol (copenh). 2015;93(7):610-5. 5. kim sj, flach aj, jampol lm. nonsteroidal anti-inflammatory drugs in ophthalmology. surv ophthalmol. 2010;55(2):108-33. 6. warren ka, bahrani h, fox je. nsaids in combination therapy for the treatment of chronic pseudophakic cystoid macular edema. retina. 2010;30(2):260-6. 7. sandra mn, widayanti tw, ekantini r, supartoto a, sasongko mb, haryanto s. changes in central macular thickness after combined therapy of bevacizumab intravitreal injection and topical diclofenac compared with bevacizumab intravitreal injection in diabetic macular edema. thesis. 2021. 110 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 8. ghanbari h, kianersi f, sonbolestan sa, abtahi m-a, akbari m, abtahi z-a, et al. intravitreal diclofenac plus bevacizumab versus bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial. int ophthalmol. 2017;37(4):867-74. 9. warren ka. combination therapy for diffuse macular edema (dme). paper presented at the retina society and the societa italiana della retina meeting. 2011. 10. ahuja m, dhake as, sharma sk, majumdar dkjtaj. topical ocular delivery of nsaids. 2008;10(2):229-41. 11. capote amc, soto ml, ruiz fr, peláez ec, vazquez ag, oftacosta g, et al. comparative study of the efficacy and safety of bromfenac, nepafenac and diclofenac sodium for the prevention of cystoid macular edema after phacoemulsification. 2018;11(7):1210. 12. friedman sm, almukhtar th, baker cw, glassman ar, elman mj, bressler nm, et al. topical nepafenec in eyes with non-central diabetic macular edema. 2015;35(5):944. 13. almeida dr, khan z, xing l, bakar sn, rahim k, urton t, et al. prophylactic nepafenac and ketorolac versus placebo in preventing postoperative macular edema after uneventful phacoemulsification. 2012;38(9):1537-43. 14. funatsu h, noma h, mimura t, eguchi s, hori sjo. association of vitreous inflammatory factors with diabetic macular edema. 2009;116(1):73-9. 15. zur d, iglicki m, loewenstein ajor. the role of steroids in the management of diabetic macular edema. 2019;62(4):231-6. 16. romero-aroca p, baget-bernaldiz m, parejarios a, lopez-galvez m, navarro-gil r, verges rjjodr. diabetic macular edema pathophysiology: vasogenic versus inflammatory. 2016;2016. 17. elman mj, aiello lp, beck rw, bressler nm, bressler sb, edwards ar, et al. randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. 2010;117(6):1064-77. e35. 18. wells ja, glassman ar, ayala ar, jampol lm, bressler nm, bressler sb, et al. aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. 2016;123(6):1351-9. 19. ashraf m, souka a, adelman rjbjoo. predicting outcomes to anti-vascular endothelial growth factor (vegf) therapy in diabetic macular oedema: a review of the literature. 2016;100(12):1596-604. 20. parravano m, costanzo e, querques gjad. profile of non-responder and late responder patients treated for diabetic macular edema: systemic and ocular factors. 2020:1-11. this work licensed under creative commons attribution melvina nidya sandra1, yumni shabrina1, tri wahyu widayanti1, retno ekantini1, agus supartoto1, muhammad bayu sasongko1, supanji1 1 department of ophthalmology universitas gadjah mada – sardjito hospital abstract methods results conclusions 30 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; international journal of retina (ijretina) 2023, volume 6, number 1. p-issn. 2614-8684, e-issn.2614-8536 neurodevelopmental outcomes after anti-vegf treatment for retinopathy of prematurity: a systematic review and meta-analysis nizma permaisuari, julie dewi barliana department of ophthalmology, faculty of medicine universitas indonesia cipto mangunkusumo hospital, jakarta abstract introduction: the objective of this study was to assess the neurodevelopmental outcomes in preterm infants who have undergone intravitreal anti-vascular endothelial growth factor (anti-vegf), either as monotherapy or in combination with laser therapy, for treatment of retinopathy of prematurity (rop). secondary, efficacy of anti-vegf was also evaluated. methods: literature search was conducted using 7 online databases (central, pubmed, sciencedirect, scopus, ebsco, proquest, and jstor). studies were selected based on the established inclusion and exclusion criteria. primary outcomes were neurodevelopmental impairment (ndi), severe ndi (sndi), neurodevelopmental scores, and cerebral palsy (cp) incidence. secondary outcomes included impairment and severe impairment of each domain (motor, cognitive, and language) and retreatment of rop. result: seventeen studies were included. random-effects model meta-analysis showed no differences were observed between anti-vegf compared to control group in ndi (unadjusted odds ratio (uor) 1.28; 95% confidence interval (ci) 0.85 to 1.94), sndi (uor 1.33; 95% ci 0.92 to 1.93), and cp outcomes . meta-analysis showed insignificant result with lower overall scores, motor, cognitive, and language domains associated with anti-vegf treatment. secondary outcomes showed inferior cognitive impairment (or 1.41; 95% ci: 1.03 to 1.92) and higher retreatment rate (or 47.55; 95% ci: 12.35 to 183.09) in anti-vegf group. conclusion: there were no differences in neurodevelopmental outcomes between anti-vegf and control group. despite not causing any adverse neurodevelopmental effect, clinicians should carefully weigh the benefits and risks of anti-vegf injection for treating infants with rop, since it has higher retreatment rate. keywords: anti–vascular endothelial growth factor, neurodevelopmental outcome, retinopathy of prematurity cite this article: permaisuari, nizma; barliana, julie dewi. neurodevelopmental outcomes after anti-vegf treatment for retinopathy of prematurity: a systematic review and meta-analysis. international journal of retina, [s.l.], v. 6, n. 1, p. 30, mar. 2023. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/205>. date accessed: 01 mar. 2023. doi: https://doi.org/10.35479/ijretina.2023.vol006.iss001.205.. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 31 correspondence to: nizma permaisuari, universitas indonesia cipto mangunkusumo hospital, jakarta permaisuari@gmail.com introduction retinopathy of prematurity (rop) is a vasoproliferative retinal disorder affecting premature infants that can lead to poor visual acuity and blindness in children.1–3 rop is a biphasic disease related to excessive supplemental oxygen administered during early postnatal period.4 phase 1 is characterized by relative hyperoxia and downregulation of vascular endothelial growth factor (vegf), resulting in cessation of retinal vascular development that leads to hypoxic ischemia. this condition induces the release of vegf, . with small pupil or presence of media opacities, and cause less refractive errors.8,11 however, there is the uncertainty of long-term systemic side effects of anti-vegf administration in premature population, especially its effects in neurodevelopment. vegf plays an important role, not only for angiogenesis in the eye, but also in other vital organs such as the lungs, kidneys, and brain.6,12 the possibility of systemic absorption after intravitreal anti-vegf, may further decrease serum vegf levels and have longterm effects on development of central nervous system and other systems.13,14 morin et al15 reported increased odds of neurodevelopmental impairment (ndi) in preterm infants treated with ivb compared to laser treatment. contrarily, lien et al14 reported no differences. hence, a focused systematic review was conducted to evaluate the neurodevelopmental outcomes of preterm infants with rop treated with intravitreal anti-vegf. methods eligibility criteria in this review, we included level 2-3 studies according to oxford centre for evidence-based medicine.16 we considered studies that enrolled preterm infants (< 37 weeks’ gestation at birth) with rop at enrolment for inclusion. intervention group consisted of preterm infants with rop treated with administration of vegf inhibitors by intravitreal route. intravitreal anti-vegf is administered either as monotherapy or in combination with laser therapy in either eye. anti-vegf given is either bevacizumab, ranibizumab, aflibercept pegaptanib sodium, or conbercept. control group is those with any stage of rop who did not receive anti-vegf therapy. it can receive laser therapy or who did not receive any form of treatment. studies were included if they provide at least one of the primary outcomes. primary outcomes included ndi; severe ndi (sndi); neurodevelopmental scores including overall scores, motor, cognitive, and language scores; and cerebral palsy (cp) incidence. secondary outcomes were also evaluated if available, such as impairment and severe impairment of each domain (motor, cognitive, and language), also efficacy of anti-vegf (retreatment of rop). the operational definitions of the terms used in this review are presented in table 1. the exclusion criteria were studies in non-human subjects, articles that could not be fully accessed, articles with only published abstracts, editorial publications, and articles published not in english. duplications were also excluded. literature search we conducted a literature search in 7 electronic databases including cochrane central register of controlled trials (central) in the cochrane library, medline via pubmed, sciencedirect, scopus, ebsco, proquest, and jstor. the detailed search strategies are presented in table 2. the search was not time-limited in order to obtain all studies related to the objective of this literature review. 32 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; we also searched the reference lists of all studies identified for potential relevant sources. table 1. operational definitions terms definition cerebral palsy (cp) cp is a spectrum of neurological deficits resulting from damage to the developing nervous system that affect a person’s ability to move and maintain balance and posture.19 cp can be determined based on gross motor functional classification system (gmfcs)11,20,21 or the general movement assessment (gma).12 definition of cp in present study is based on operational definition in each included studies. cognitive impairment defined as presence any of the following:7,15,20,22–24 • bsid-iii cognitive score <85, • bsid-ii mdi score <70, • any comparable score with validated tools. cognitive score cognitive score is measured by using cognitive domain in bsid-iii or any comparable validated tools.11,20–23 language impairment defined as presence any of the following:7,15,22–24 • bsid-iii language score <85, • bsid-ii mdi score <70, • any comparable score with validated tools. language score language score is measured by using language domain in bsid-iii or any comparable validated tools.11,20–23 motor impairment defined as presence any of the following:7,15,20,22–24 • bsid-iii motor score <85, • bsid-ii pdi score <70, • any comparable score with validated tools. motor score motor score is measured by using motor domain in bsid-iii or any comparable validated tools.11,20–23 neurodevelopmental impairment (ndi) definition of ndi in present study is based on operational definition in each included studies. it can be measured by using any neurodevelopmental tools or defined as presence of cp, visual impairment, or hearing impairment.12,20–23,25,26 overall scores overall scores is measured by using any neurodevelopmental tools. intelligence quotient (iq) or developmental quotient (dq) is derived from the tools. • iq is a total score derived from a set of standardized tests or subtests designed to assess human intelligence.27 • dq is a score which describes the normal developmental proportion with child at that age.28 retreatment defined as rop recurrences requiring additional treatment after receiving anti-vegf, laser, or cryotherapy.29,30 severe cognitive impairment defined as presence any of the following:20,22,25 • bsid-iii cognitive score <70, • any comparable score with validated tools. severe language impairment defined as presence any of the following:20,22,25 • bsid-iii language score <70, • any comparable score with validated tools. severe motor impairment defined as presence any of the following:20,22,25 • bsid-iii motor score <70, • any comparable score with validated tools. severe neurodevelopmental impairment (sndi) definition of sndi in present study is based on operational definition in each included studies. it can be measured by using any neurodevelopmental tools or defined as presence of cp, visual impairment, or hearing impairment.7,15,20,22,23 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 33 study selection based on the search results above, articles were considered eligible based on the following characteristics: study population (preterm infants with rop), study intervention (administration of intravitreal anti-vegf drugs with or without laser therapy), study control (not receiving anti-vegf therapy), study outcome (ndi), and study design (randomised controlled trials, cohort). we reviewed the titles and abstracts of all identified studies. we retrieved and reviewed the full text of the article if we could not ascertain relevance by screening the title and the abstract. the full texts of all potentially eligible articles were then evaluated to ensure that the studies met the eligibility criteria the trial author was contacted by email correspondence for additional information or for clarification as necessary. data collection and extraction we performed data extraction regarding study setting (year and country), study design, patient characteristics, study intervention and control, screening tools for neurodevelopmental evaluation, length of follow-up, risk of biases, and outcomes of interest were independently extracted for further analysis. for dichotomous outcomes, we extracted the total number of participants for each group and the number of participants experiencing an event. for continuous outcomes, we extracted mean, standard deviation (or data required to calculate this), and the total number of participants for each group. risk of bias assessment author assessed the risk of bias of articles included in this review using different tools according to the types of study. a revised cochrane risk-of-bias tool for randomized trials (rob 2) is the tool used to assess the risk of bias in randomized trials.17 meanwhile, to assess the risk of bias in nonrandomized studies, we use risk of bias in nonrandomized studies of interventions (robins-i) tool.18 table 1. search strategies in each database database search strategy central #1 mesh descriptor : [retinopathy of prematurity] explode all trees #2 mesh descriptor : [bevacizumab] explode all trees) #3 mesh descriptor : [ranibizumab] explode all trees) #4 aflibercept # 5 pegaptanib #6 conbercept #7 #2 or #3 or #4 or #5 or #6 #8 #1 and #2 pubmed (retinopathy of prematurity[mesh terms]) and (((((bevacizumab[mesh terms]) or ranibizumab[mesh terms]) or aflibercept) or pegaptanib) or conbercept) proquest ab(retinopathy of prematurity) and ab(bevacizumab or ranibizumab or aflibercept or pegaptanib or conbercept) and ft(neuro*) scopus ( abs ( retinopathy and of and prematurity ) and abs ( bevacizumab or ranibizumab or aflibercept or pegaptanib or conbercept) and titleabs-key ( neuro* ) ) sciencedirect ( abs ( retinopathy and of and prematurity ) and abs ( bevacizumab or ranibizumab or aflibercept or pegaptanib or conbercept) and titleabs-key ( neuro* ) ) ebsco ab retinopathy of prematurity and ab ((bevacizumab) or (ranibizumab) or (aflibercept) or (pegaptanib) or (conbercept)) and neuro* jstor ((retinopathy of prematurity) and (bevacizumab or ranibizumab or aflibercept or pegaptanib or conbercept)) data synthesis and analysis for dichotomous outcomes, comparative effect sizes were calculated as odds ratios (ors), with 95% confidence intervals (ci), using the mantel–haenszel method. for continuous outcomes, mean difference (md) was reported with 95% ci based on an inversevariance, weighted meta-analysis. 34 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; if the study provided median, range, interquartile range, and standard error, these were converted into mean and standard deviation. estimated mean was calculated based on the study from luo et al31 and hozo et al,32 meanwhile estimated standard deviation was acquired based on study by wan et al.33 revman calculator assisted in data entry of dichotomous, continuous and generic inverse variance outcome types if the outcomes expressed as a ratio, the analysis required use of the generic inverse-variance method in revman.34 if available, the comparative effect sizes were also calculated using adjusted analysis. a random effect model was performed for all outcomes. the meta-analysis for randomized controlled trials (rcts) and non-randomized studies was performed separately. publication bias assessed by funnel plot asymmetry when there are at least 10 studies included in the meta-analysis. we evaluated forest plots qualitatively and used p for chi-square and i2 values (derived from the chi-squared qstatistic) for assessing heterogeneity. we considered significant statistical heterogeneity if p for chi-square <0.10 or i2 values 75-100%.34 all statistical analyses were performed using review manager 5.4.1 (cochrane collaboration, nordic cochrane center, copenhagen, denmark). results by using the search in 7 electronic databases, we retrieved a total of 345 studies, of which 17 fulfilled the eligibility criteria and were included in the review. one study by kang et al30 was excluded in metaanalysis because no events found in both intervention and control group. figure 1 is the flowchart of the selection process based on prisma flow diagram.35 study characteristics table 3 presents the study characteristics which published between 2014 and 2021. all studies used anti-vegf monotherapy for the treatment group, except for 4 studies that used laser combined with anti-vegf for the treatment group. cohort was the study design in all studies except one from kennedy et al20 which was an rct. intravitreal bevacizumab (ivb) was used in all studies, except for kang et al,30 which used ranibizumab. the bevacizumab dosage was 0.625 mg/0.025 ml in 11 of the included studies; the remaining studies did not specify the dosage. the dosage injected in ranibizumab administration was 0.25 mg/0.025 ml. regarding the control groups, most studies used laser monotherapy as the control. meanwhile, natarajan et al20 employed laser and/or cryotherapy, chang et al24 and fan et al7 enrolled rop patients with rop but requiring no treatment. risk of bias assessment kennedy et al11 was assessed “low risk of bias” using rob 2 tool. other 16 studies were assessed by robins-i tool and summarized in figure 2. nine studies were at serious risk of bias and 2 studies were at critical risk of bias. the detailed risk of bias assessment is provided in table 4. effects of intervention neurodevelopmental impairment eight studies reported ndi incidence in their original reports. the result for this analysis was presented in the forest plot in figure 3. ndi incidence did not differ significantly between the anti-vegf and control groups, with an overall or for ndi of 1.28 (95% ci: 0.85 to 1.94; test for overall effect: z = 1.17, p = 0.24) with no heterogeneity (i2 = 0%). the or was the same under fixed-effect model. adjusted analysis of ndi incidences was not significantly different (table 5). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 35 severe neurodevelopmental impairment of the 9 studies included in the analysis of sndi outcomes, the result was shown in figure 4. the risk was similar in anti-vegf and control groups with or 1.33 (95% ci: 0.92 to 1.93; test for overall effect: z = 1.53, p = 0.13). mild heterogeneity was detected in this analysis (i2 = 21%). adjusted analysis of sndi incidences was not significantly different as shown in table 5. neurodevelopmental scores there are 14 included studies reporting the scores of neurodevelopmental tests. the meta-analysis showed lower scores for overall scores, motor, cognitive, and language domains associated with anti-vegf treatment. overall scores (md = −1.74; 95% ci: −16.53 to 13.05; test for overall effect: z = 0.23, p = 0.82; figure 5a), motor scores (md = −2.05; 95% ci: −5.09 to 0.98; test for overall effect: z = 1.32, p = 0.19; figure 5b), cognitive scores (md −2.00; 95% ci −4.35 to 0.36; test for overall effect: z = 1.66, p = 0.10; figure 5c), and language scores (md −1.87; 95% ci −4.61 to 0.87; test for overall effect: z = 1.34, p = 0.18; figure 5d) did not differ significantly between anti-vegf and control groups. after performing subgroup analysis, the metaanalysis result of motor, cognitive, and language scores in non-randomised studies were still insignificant. stratified analyses based on the risk of bias and sensitivity analysis with fixed-effect model application were done with insignificant result. when we restricted the analysis by eliminating study with critical risk of bias by zayek et al,23 the motor scores (md = −3.32; 95% ci: −6.19 to -0.44; test for overall effect: z = 2.26, p = 0.02) showed significant result. adjusted analysis of cognitive, language, and motor scores were not significantly different as shown in table 5. funnel plots for cognitive, language, and motor scores are shown in figure 6ac. the 3 plots were both relatively symmetrical, which indicated no evidence of publication bias. cerebral palsy cp risk was similar in anti-vegf and control groups (or = 1.32; 95% ci: 0.93 to 1.86; figure 7). no heterogeneity was detected (i2 = 0%; chi2 = 4.77, p = 0.57). in study by morin et al,15 the number of infants with cp in the anti-vegf group was reported as “<5”. we inserted “0 to 4” for the sensitivity analysis and found no difference. the results also remained the same during the sensitivity analysis when fixed-effect model was applied. meta-analysis of 3 studies providing adjusted odds ratio also did not find significant differences between the groups (table 5). motor, language, and cognitive impairment the meta-analysis showed significant increased odds of cognitive impairment associated with antivegf treatment with or 1.41 (95% ci: 1.03 to 1.92; z = 2.14, p = 0.03; i2 = 0%). no statistically significant differences were noted on unadjusted and adjusted analyses of impairment and severe impairment in motor and language domain (table 5). a trend favoring the control group was observed in all analysis. efficacy of anti-vegf the present study showed that the retreatment rate was higher following anti-vegf treatment compared to control with or 47.55 (95% ci: 12.35 to 183.09; z = 5.61, p = <0.001; i2 = 0%) (table 5). 36 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; figure 1. study flow diagram published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 37 figure 1. summary plots of robins-i figure 2. odds ratio for neurodevelopmental impairment in rop infants treated with anti-vegf compared with control figure 3. odds ratio for severe neurodevelopmental impairment in rop infants treated with anti-vegf compared with control 38 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; figure 4. mean differences of neurodevelopmental scores between rop infants treated with anti-vegf compared with control in multiple domains published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 39 figure 5. funnel plot of twelve studies reporting mean differences of neurodevelopmental scores in multiple domain 40 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; figure 6. odds ratio for cerebral palsy in rop infants treated with anti-vegf compared with control published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 41 table 3. summary of study characteristics of all included studies author(s) year country study design study population intervention group control group screening tool(s) age at evaluation (months) sample (n) intervention(s) dose (mg) sample (n) control(s) celik et al22 2021 turkey cohort retrospective preterm infants treated for rop 22 ivb ± laser na 32 laser bsid-iii gmfcs 12 42 murakami et al29 2021 japan cohort retrospective preterm infants treated for type 1 rop 12 ivb 0.625 14 laser wisc iv/kspd 60 ahmed et al26 2020 usa cohort retrospective preterm infants treated for type 1 rop 18 ivb + laser na 48 laser bsid-iii 24 arima et al36 2020 japan cohort retrospective preterm infants (ga < 32 weeks or bw < 1500 gr) treated for type 1 rop 14 ivb 0.625 39 laser kspd 18 zayek et al23 2020 usa cohort retrospective preterm infants (ga ≤ 26 weeks and bw < 1000 gr) treated for type 1 rop or high-risk pre-threshold rop 50 ivb 0.625 64 laser bsid-iii gmfcs 18 24 chang et al24 2019 taiwan cohort retrospective screened preterm infants with rop 18 ivb 0.625 86 no treatment bsid-ii or bsid-iii 24 fan et al7 2019 taiwan cohort prospective screened preterm infants (ga <37 weeks) with rop 38 ivb 0.625 31 no treatment bsid-iii 12 36 kennedy et al11 2019 usa rct participants of beat-rop trial in a single center (ga < 27 weeks) 7 ivb 0.625 9 laser bsid-iii gmfcs >18 natarajan et al20 2019 usa cohort retrospective extremely preterm infants (ga < 27 weeks) with severe rop 181 ivb na 224 laser and/or cryotherapy bsid-iii gmfcs 18 26 raghuram et al21 2019 canada cohort retrospective preterm infants treated for rop 34 ivb 0.625 30 laser bsid-iii/asq gmfcs 18 24 rodriguez et al12 2019 usa cohort retrospective preterm infants (ga < 31 weeks and bw < 1500 gr) treated for rop 13 ivb na 9 laser bsid-iii gma 24 chen et al37 2018 usa cohort retrospective preterm infants treated for tw-rop 15 ivb 0.625 10 laser bsid-iii capute scales 20.4 kang et al30 2018 korea cohort retrospective preterm infants (ga < 32 weeks and bw < 1500 gr) treated for type 1 rop 153 ivr 0.25 161 laser denver 36.3 ± 31.9 lien et al14 2016 taiwan cohort retrospective elbw infants (bw < 1000 gr) treated for type 1 rop 28 ivb ± laser 0.625 33 laser bsid-ii 24 morin et al15 2016 canada cohort retrospective preterm infants (ga < 29 weeks) treated for type 1 rop 27 ivb na 98 laser bsid-iii gmfcs 18 kong et al38 2015 usa cohort retrospective preterm infants treated for type 1 rop or severe zone 3 rop 10 ivb 0.625 9 laser rgds capute scales 6 12 araz-ersan et al25 2014 turkey cohort retrospective type 1 rop infants treated with ivb and matched controls 13 ivb + laser 0.625 13 laser bsid-iii 24 abbreviations: rop — retinopathy of prematurity, ga—gestational age (weeks), bw—birth weight (grams), beat-rop — bevacizumab eliminates the angiogenic threat of rop, elbw— extremely low birth weight, ivb — intravitreal bevacizumab, ivr — intravitreal ranibizumab, na — not available, bsid — bayley scales of infant development, gmfcs — gross motor functional classification system, wisc — wechsler intelligence scale for children, kpsd — kyoto scale of psychological development, asq — ages and stages questionnaires, gma — general movement assessment 42 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; table 4. risk of bias summary for each included study author(s) year co nf ou nd in g se le ct io n of p ar ti ci pa nt s/ ra nd om iz at io n cl as si fic at io n of in te rv en ti on s d ev ia ti on s of in te nd ed in te rv en ti on m is si ng d at a m ea su re m en t o f o ut co m es se le ct io n of re po rt ed r es ul t o ve ra ll rcta kennedy et al11 2019 non-randomised studiesb celik et al22 2021 murakami et al29 2021 ahmed et al26 2020 arima et al36 2020 ? zayek et al23 2020 chang et al24 2019 fan et al7 2019 natarajan et al20 2019 raghuram et al21 2019 rodriguez et al12 2019 chen et al37 2018 kang et al30 2018 lien et al14 2016 morin et al15 2016 kong et al38 2015 araz-ersan et al25 2014 a : risk of bias assessment using revised cochrane risk-of-bias tool for randomized trials (rob 2) b : risk of bias assessment using risk of bias in non-randomized studies of interventions (robins-i) : low risk of bias : moderate risk of bias : serious risk of bias : critical risk of bias ? : insufficient information provided to determine risk of bias published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 43 table 5. meta-analysis of primary and secondary outcomes outcomes unadjusted analysis adjusted analysis ndi uor 1.28; 95% ci: 0.85 to 1.94; z = 1.17, p = 0.24; i2 = 0% eight studies; 562 participants aor 1.42; 95% ci: 0.87 to 2.33; z = 1.39, p = 0.16; i2 = 0% five studies; 458 participants sndi uor 1.33; 95% ci: 0.92 to 1.93; z = 1.53, p = 0.13; i2 = 21% nine studies; 883 participants aor 1.42; 95% ci: 0.79 to 2.57; z = 1.17, p = 0.24; i2 = 54% six studies; 744 participants neurodevelopmental scores overall scores md -1.74; 95% ci: −16.53 to 13.05; z = 0.23, p = 0.82; i2 = 69% two studies; 79 participants na motor scores md −2.05; 95% ci: −5.09 to 0.98; z = 1.32, p = 0.19; i2 = 14% twelve studies; 952 participants md −1.91; 95% ci: −5.58 to 1.76; z = 1.02, p = 0.31 i2 = na one study; 354 participants cognitive scores md −2.00; 95% ci: −4.35 to 0.36; z = 1.66, p = 0.10; i2 = 0% twelve studies; 964 participants md −3.07; 95% ci: −6.46 to 0.33; z = 1.77, p = 0.08; i2 = na one study; 357 participants language scores md −1.87; 95% ci: −4.61 to 0.87; z = 1.34, p = 0.18; i2 = 0% twelve studies; 954 participants md −5.77; 95% ci: −17.82 to 6.29; z = 0.94, p = 0.35; i2 = 74% two studies; 406 participants cerebral palsy uor 1.32; 95% ci: 0.93 to 1.86; z = 1.57, p = 0.12; i2 = 0% eight studies; 868 participants uor 1.32; 95% ci: 0.72 to 2.43; z = 0.90, p = 0.37; i2 = 31% three studies; 528 participants motor impairment uor 1.14; 95% ci: 0.67 to 1.94; z = 0.48, p = 0.63; i2 = 57% six studies; 793 participants aor 1.31; 95% ci: 0.55 to 3.10; z = 0.62, p = 0.54; i2 = 77% five studies; >635 participants severe motor impairment uor 1.06; 95% ci: 0.71 to 1.60; z = 0.30, p = 0.76; i2 = 0% three studies; 434 participants aor 1.05; 95% ci: 0.65 to 1.70; z = 0.20, p = 0.84; i2 = na one study; 354 participants cognitive impairment uor 1.41; 95% ci: 1.03 to 1.92; z = 2.14, p = 0.03; i2 = 0% six studies; 800 participants aor 1.72; 95% ci: 0.95 to 3.08; z = 1.81, p = 0.07; i2 = 57% six studies; >696 participants severe cognitive impairment uor 1.40; 95% ci: 0.91 to 2.16; z = 1.54, p = 0.12; i2 = 0% three studies; 437 participants aor 1.53; 95% ci: 0.80 to 2.91; z = 1.83, p = 0.07; i2 = 0% two studies; 437 participants language impairment uor 1.23; 95% ci: 0.72 to 2.13; z = 0.76, p = 0.45; i2 = 27% five studies; 438 participants aor 1.72; 95% ci: 0.63 to 4.70; z = 1.06, p = 0.29; i2 = 61% four studies; >280 participants severe language impairment uor 1.01; 95% ci: 0.66 to 1.52; z = 0.03, p = 0.98; i2 = 0% three studies; 433 participants aor 1.03; 95% ci: 0.60 to 1.76; z = 0.10, p = 0.92; i2 = na one study; 353 participants retreatment uor 47.55; 95% ci: 12.35 to 183.09; z = 5.61, p = <0.001; i2 = 0% two studies; 171 eyes na the details of the outcome definitions are provided in methods; the analyses highlighted in bold represent significant statistical differences between the groups. abbreviations: ndi — neurodevelopmental impairment, sndi — severe neurodevelopmental impairment, uor — unadjusted odds ratio, ci — confidence interval, aor — adjusted odds ratio, md — mean difference, na — not available 44 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; discussion anti-vegf have been used as an attractive therapeutic agent for rop treatment. it has ability to block vegf locally, thus inhibiting pathologic neovascularization and slowing the progression of the disease. currently, available drugs for rop treatment include bevacizumab, ranibizumab, aflibercept, pegaptanib, and conbercept.39 in this review, bevacizumab is the most frequently used anti-vegf for rop treatment. it might be caused by its widespread availability, low cost, and effectivity.8 unfortunately, systemic absorption and potential side effects of anti-vegf agents raised some concerns. increasing odds in cognitive impairment as shown in our study might support the hypothesis. several studies have shown vegf suppression following anti-vegf administration in preterm infants. kong et al40 reported that serum bevacizumab was detected 2 days following ivb injection, peaked at 14 days, and persisted in the blood as long as 60 days with a half-life of 21 days. wu et al41 demonstrated that serum vegf level was 379 pg/ml at baseline and decreased to 72 pg/ml 6 weeks following ivb treatment. wu et al42 also found that serum vegf levels were less affected after intravitreal ranibizumab (ivr) treatment, compared with those who received ivb treatment. huang et al43 have sown further that vegf levels in type 1 rop infants were suppressed for 12 weeks after either ivb or intravitreal aflibercept (iva) injection, but the suppression was more pronounced in ivb compared with iva treatment. vegf plays an important role in neurogenesis in embryos and preterm newborns. bagnard et al44 found that vegf can modulate migration, survival, and proliferation of neural progenitor cell line. malik et al45 showed that preterm delivery and room air exposure reduced vegf expression in rabbit pups. however, significant neurogenesis continued in human preterm infants until 28 gestational weeks. this study might explain effects of vegf deprivation in preterm infants on neurodevelopmental delay condition. blocking vegf-a expression has been shown to impair brain vascularization. it may have long-term effects on the development of the central nervous system and other systems. another possible reason for the inferior cognitive function reported by morin et al15 and natarajan et al20might be the imbalance of baseline conditions between intervention and control group. preterm infants treated with antivegf in the study had severe systemic illnesses and more severe rop statuses compared with control. more patients were also excluded from the control group in study by morin et al15 because of inability to undergo neurodevelopmental assessment and might have been associated with poorer outcomes. neurologic outcome may be related with to the choice of intervention. intravitreal anti-vegf can be performed with lighter anesthesia than laser teraphy. thus, in critical infants, anti-vegf injection may be perceived as safer than rop surgery, with the accompanying general anesthesia and intubation risks. the variation in patient populations among included studies might lead to difference baseline. seven studies11,12,15,20,23,30,36 only included infants with small ga (sga). blencowe et al46 reported that incidence of ndi increased from 5% among infants born at 32-36 weeks ga to 24.5% among those born at 28-31 weeks ga, and further to 52% among those born before 28 weeks. sga infants were more likely to develop severe rop. these extremely preterm infants were also at higher risk of developing aggressive posterior retinopathy of prematurity (aprop), a severe and rare form of rop which is more likely treated with anti-vegf treatment. it is supported by kang et al30 where 100% preterm infants with ap-rop were treated with ivr. in addition, 3 large neonatal networks published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 45 (the national institute of child health and development neonatal research network,47 the vermont oxford network,48 and the canadian neonatal network)49 showed that elbw infants were at a higher risk for ndi. for elbw infants, every 100gram decrease in birth weight increased the risk of severe disability by 31%.48 therefore, ga and bw should be evaluated as potential confounders as we assess neurodevelopmental outcomes. some included studies tried to adjust some confounders, however the adjustments were not consistent among those studies. clinical trial can be done in the future by stratifying the treatment based on the severity of rop. according to glass et al,50 severe rop is associated with abnormal white matter maturation and adverse neurodevelopmental outcome. supplemental use of high concentration oxygen for a prolonged duration may play a more significant role in older and heavier babies.51 murakami et al29 stated that protracted mechanical ventilation increased risk of neurodevelopmental disability. however, altendahl et al52 stated that poorer neurodevelopmental outcomes in preterm infants are not related with severity of rop. chang et al24 and fan et al7 minimized the selection bias by choosing any rop except type 1 rop as controls, instead of laser therapy. they reported no difference in neurodevelopmental outcomes between rop infants with and without treatment. anti-vegf administration in this present study was showing a higher retreatment rate compared to control group. meta-analysis performed by li et al53 also stated that retreatment incidence was significantly increased for anti-vegf compared to the laser treatment with or 2.52 (95% ci 1.37 to 4.66; p = 0.003). changes of vegf level might explain this phenomenon. reduction of vegf level in vitreous is noted following anti-vegf administration. when the level of anti-vegf in the vitreous reduced gradually and eventually was not in effective concentration anymore, increased levels of vegf caused development of neovascularization and rop progression. xiang et al54 demonstrated a compensatory mechanism. other vascular growth factors of rop including basic fibroblast growth factor (bfgf) and angiopoietin 1 (ang1) were upregulated when vegf was expressed at a low level. kang et al30 stated that greater proportion of zone 1 rop cases in ranibizumab-treated-group required more time to achieve full vascularisation after initial treatment. during an extended period of vascular growth, an elevation in vegf levels may cause rop reactivation requiring additional ranibizumab injections. also concluded in the american academy of ophthalmology report,6 eyes treated with antivegf, mostly with rop in zone i, may never completely vascularize and still need retreatment after 55 weeks of postmenstrual age. meanwhile, retreatment or recurrences in laser therapy is caused by inadequate treatment. decrease of retreatment rate over the years indicates a better quality of therapy by the clinician. the weakness of our review was that the data mainly from nonrandomized studies. the choice of intervention in each participants was mostly based on clinician’s preference. in some studies,14,21,23,38 the chosen treatment was made by the agreement of the ophthalmologist and the parents after the off-label status, benefits, and risk of using anti-vegf had been thoroughly explained. chen et al37 stated that they typically chose anti-vegf over laser therapy in sicker infants. this selection bias might affect the result of neurodevelopmental outcomes. second, some studies did not report their dosage usage. remaining studies with intravitreal bevacizumab used a dosage of 6.25 mg, half of the adult dosage, as recommended by the beat-rop study. kong et al40 reported that systemic exposure of vegf was variable among the participants and was dose dependent. 46 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; according to the calculation based on the volume of neonates’ vitreous, the size-adjusted dosage of should be 0.4 mg.55 wallace et al56 demonstrated that dose of bevacizumab as low as 0.031 mg was effective for premature infants with type 1 rop and might reduce the risk for neurodevelopmental disability or detrimental effects on other organs. however, after after low-dose bevacizumab injection, many eyes received additional treatment. the effect of anti-vegf on ndi might differ if using a lower dosage. in the other side, raghuram et al21 stated that systemic absorption of bevacizumab is too low to exert any significant clinical effects. we recommend a trial with varying concentrations of anti-vegf to provide more evidence regarding dosedependent effect of anti-vegf on ndi. other limitation included the differences in definitions of each outcomes among the analyzed studies. this difference is caused by different ways of measuring the outcomes. most included studies used bsid-iii for outcome evaluations. bsid-iii is considered to be the gold standard for the early detection of developmental delays in children.25 it separates of the original mental development index (mdi) and psychomotor development index (pdi) from bsid-ii into distinct cognitive, receptive language, expressive language, fine motor, and gross motor scales. these scales were converted further into 3 composite scores including cognitive, language, and motor composite scores.7 there are a conversion formula to conver bsid-ii scores to bsidiii scores to make it comparable. in addition, bayleyiii cognitive and language scores <85 had 99% agreement with mdi <70.57 however, the results of the kspd and bsid-ii were comparable with only moderate correlation (r = 0.61-0.63).58,59 conclusion nevertheless, the review is important as it summarizes the current and updated literature with some limitations. the search was broad across 7 databases and contained additional search methods. anticipating the heterogeneity, we used the random-effects model, an appropriate method in the presence of heterogeneity. the results of the current meta-analysis which analyzed more than 700 infants, concluded that there was no difference in neurodevelopmental outcomes between anti-vegf and control group. increased odds of retreatment rate in preterm infants treated with anti-vegf was also noted. we suggest that until high-quality evidence has been established, clinicians should carefully weigh the benefits and risks of anti-vegf injection for treating infants with rop. references 1. hered rw, lee ka, archer sm, lueder gt, braverman rs, o’hara ma, et al. disorders of the retina and vitreous. in: rapuano cj, stout jt, mccannel ca, editors. 2020-2021 basic and clinical science course: pediatric ophthalmology and strabismus. san fransisco: american academy of ophthalmology; 2020. p. 325–35. 2. kaushal m, razak a, patel w, pullattayil ak, kaushal a. neurodevelopmental outcomes following bevacizumab treatment for retinopathy of prematurity: a systematic review and meta-analysis. j perinatol. 2021;41(6):1225– 35. 3. subramanian ks, kern md, deegan wf. retinopathy of prematurity [internet]. medscape. 2021 [cited 2021 dec 23]. 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quotient to estimate intelligence in autism spectrum disorder. pediatr int. 2016;58(10):963–6. 28. wangke l, victory w, rampengan nh, lestari h. external risk factors associated with language disorders in children. paediatr indones. 2021;61(3):133–40. 29. murakami t, sugiura y, okamoto f, okamoto y, kato a, hoshi s, et al. comparison of 5-year safety and efficacy of laser photocoagulation and intravitreal bevacizumab injection in retinopathy of prematurity. graefe’s arch clin exp ophthalmol. 2021;259(9):2849–55. 30. kang hg, choi ey, byeon sh, kim ss, koh hj, lee sc, et al. intravitreal ranibizumab versus laser photocoagulation for retinopathy of prematurity: efficacy, anatomical outcomes and safety. br j ophthalmol. 2018;0:1–5. 31. luo d, wan x, liu j, tong t. optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. stat methods med res. 2018;27(6):1785–805. 32. hozo sp, djulbegovic b, hozo i. estimating the mean and variance from the median, range, and the size of a sample. bmc med res methodol. 2005;5(1):1–10. 33. wan x, wang w, liu j, tong t. estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. bmc med res methodol 2014 141. 2014;14(1):1–13. 34. jpt h, j t, j c, m c, t l, mj p, et al. cochrane handbook for systematic reviews of interventions. 2nd ed. jpt h, j t, j c, m c, t l, mj p, et al., editors. chichester: john wiley & sons; 2019. 35. page mj, moher d, bossuyt pm, boutron i, hoffmann tc, mulrow cd, et al. prisma 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. bmj. 2021;372:n71. 36. arima m, akiyama m, fujiwara k, mori y, inoue h, seki e, et al. neurodevelopmental outcomes following intravitreal bevacizumab injection in japanese preterm infants with type 1 retinopathy of prematurity. plos one. 2020;15(3):1–7. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 49 37. chen ta, schachar ih, moshfeghi dm. outcomes of intravitreal bevacizumab and diode laser photocoagulation for treatmentwarranted retinopathy of prematurity. ophthalmic surg lasers imaging retin. 2018;49(2):126–31. 38. kong l, dinh k, schechet s, coats d, voigt r, demny a, et al. comparison of ocular and developmental outcomes in laser-and bevacizumab-treated infants with retinopathy of prematurity. ophthalmol res an int j. 2015;3(1):13–22. 39. eldweik l, mantagos is. role of vegf inhibition in the treatment of retinopathy of prematurity. semin ophthalmol. 2016;31(1–2):163–8. 40. kong l, bhatt ar, demny ab, coats dk, li a, rahman ez, et al. pharmacokinetics of bevacizumab and its effects on serum vegf and igf-1 in infants with retinopathy of prematurity. invest ophthalmol vis sci. 2015;56(2):956–61. 41. wu wc, lien r, liao pj, wang nk, chen yp, chao an, et al. serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity. jama ophthalmol. 2015 apr 1;133(4):391–7. 42. wu wc, shih cp, lien r, wang nk, chen yp, chao an, et al. serum vacular endothelial growth factor after bevacizumab or ranibizumab treatment for retinopathy of prematurity. retina. 2017;37(4):694–701. 43. huang cy, lien r, wang nk, chao an, chen kj, chen tl, et al. changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity. graefes arch clin exp ophthalmol. 2018;256(3):479–87. 44. bagnard d, vaillant c, khuth st, dufay n, lohrum m, püschel aw, et al. semaphorin 3avascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor. j neurosci. 2001;21(10):3332–41. 45. malik s, vinukonda g, vose lr, diamond d, bhimavarapu bbr, hu f, et al. neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. j neurosci. 2013;33(2):411–23. 46. blencowe h, lawn je, vazquez t, fielder a, gilbert c. preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. pediatr res. 2013;74(suppl 1):49. 47. kono y. neurodevelopmental outcomes of very low birth weight infants in the neonatal research network of japan: importance of neonatal intensive care unit graduate followup. clin exp pediatr. 2021;64(7):313–21. 48. mercier ce, dunn ms, ferrelli kr, howard db, soll rf. neurodevelopmental outcome of extremely low birth weight infants from the vermont oxford network: 1998–2003. neonatology. 2010;97(4):329. 49. vohr br, wright ll, dusick am, mele l, verter j, steichen jj, et al. neurodevelopmental and functional outcomes of extremely low birth weight infants in the national institute of child health and human development neonatal research network, 1993–1994. pediatrics. 2000;105(6):1216–26. 50. glass tja, chau v, gardiner j, foong j, vinall j, zwicker jg, et al. severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment. arch dis child fetal neonatal ed. 2017 nov 1;102(6):f532–7. 51. kumawat d, sachan a, shah p, chawla r, chandra p. aggressive posterior retinopathy of prematurity: a review on current understanding. eye (lond). 2021 apr 1;35(4):1140–58. 50 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2023; 6; 1; 52. altendahl m, sim ms, kokhanov a, gundlach b, tsui i, chu a. severe retinopathy of prematurity is not independently associated with worse neurodevelopmental outcomes in preterm neonates. front pediatr. 2021 jun 10;9. 53. li z, zhang y, liao y, zeng r, zeng p, lan y. comparison of efficacy between anti-vascular endothelial growth factor (vegf) and laser treatment in type-1 and threshold retinopathy of prematurity (rop). bmc ophthalmol. 2018;18(1):1–10. 54. xiang n, zhao mj, li xy, zheng hh, li gg, li b. redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro. ophthalmic res. 2011 jan;45(2):92–101. 55. spandau u. what is the optimal dosage for intravitreal bevacizumab for retinopathy of prematurity? acta ophthalmol. 2013; 56. wallace dk, kraker rt, freedman sf, crouch er, hutchinson ak, bhatt ar, et al. assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study. jama ophthalmol. 2017 jun 1;135(6):654–6. 57. johnson s, moore t, marlow n. using the bayley-ii to assess neurodevelopmental delay: which cut-off should be used? pediatr res. 2014;75(5):670–4. 58. tatsuta n, suzuki k, sugawara t, nakai k, hosokawa t, satoh h. comparison of kyoto scale of psychological development and bayley scales of infant development second edition among japanese infants. j spec educ res. 2013;2(1):17–24. 59. janzen d, delaney ka, shapiro eg. cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types i, ii, and iii: a review of the literature. mol genet metab. 2017;121(2):57–69. this work licensed under creative commons attribution nizma permaisuari, julie dewi barliana abstract introduction figure 3. odds ratio for severe neurodevelopmental impairment in rop infants treated with anti-vegf compared with control abbreviations: rop — retinopathy of prematurity, ga—gestational age (weeks), bw—birth weight (grams), beat-rop — bevacizumab eliminates the angiogenic threat of rop, elbw—extremely low birth weight, ivb — intravitreal bevacizumab, ivr — intravitreal ... discussion conclusion published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 75 international journal of retina (ijretina) 20xx, volume 03, number 02. p-issn. 2614-8684, e-issn.2614-8536 clinical features and factors affecting the success of retinal vasculitis therapy lia meuthia zaini1, arief sjamsulaksan kartasasmita2 1 zainoel abidin hospital / medicine faculty univ of syiah kuala, banda aceh 2cicendo eye hospital / medicine faculty univ of padjajaran, bandung abstract introduction: retinal vasculitis is an inflammatory eye condition that threatens vision. inflammation occurs in the branches of retinal arteries, cause by primary ocular diseases or associated with other diseases. this study aims to describe clinical features and factors affecting therapeutic success in 52 patients with retinal vasculitis. methods: this study was conducted using retrospective cohort in retina clinic of cicendo eye hospital in vasculitis patients from january 1stdecember 31st 2017. data were collected retrospectively from the ophthalmic records of 52 patients (74 affected eyes). descriptive analysis was performed on all data, chisquare and eksak fisher test were used to analyze risk factor and factors affecting the success of therapy. result: out of 529 vasculitis and vitreous hemorrhage cases, retinal vasculitis was found in 52 patients (9.8%). mean age of retinal vasculitis patients were 42.3 years (range: 13-74 years). 35 patients (62.3%) were men and 22 patients (42.3%) had bilateral retinal vasculitis. we also found 44,2% patients had a history of toxoplasma infections, and 23.76 % had a history of tuberculosis infections. at initial presentation, almost all patients (93.2%) came with chief complaint of blurry vision, 42 patients (56.8%) came with baseline visual acuity 20/200. vitreous hemorrhage was identified from retinal examination in 43 patients (58.1%). therapeutic success was found better in patients with underlying disease (74,1%). conclusion: most of the patients came with already bad condition. the main complaint was blurred vision (<20/200) which may be related to vitreous hemorrhage. most of the causes are tuberculosis and toxoplasmosis. good management of course includes anti-inflammatory accompanied by therapy of the underlying disease. in this study, corticosteroid administration accompanied by antimicrobials (cotrimoxazole for toxoplasmosis and four drug regimens (rhze) for ocular tuberculosis) seems to have a good respond to retinal vasculitis associated with toxoplasmosis and tuberculosis keywords: retinal vasculitis, vitreous hemorrhage, vitreous opacity cite this article: zaini, lia meuthia. clinical features and factors affecting the success of retinal vasculitis therapy in cicendo eye hospital, bandung. januari-december 2017. international journal of retina, [s.l.], v. 3, n. 2, sep. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/118 introduction *correspondence to: lia meuthia zaini, department of ophthalmology, zainoel abidin hospital/ medicine faculty, univ of syiah kuala lia_mzaini@unsyiah.ac.id retinal vasculitis is a group of diseases characterized by inflammation of the retinal arteries.1 based on the consensus of the standardization of uveitis nomenclature working group in november 2004, retinal vasculitis is a term used to describe inflammation and changes in retinal blood vessels, including perivascular sheathing, vascular leakage, and occlusion.2 incidence of retinal vasculitis is 1-2 per 10.000.3 in a study conducted in north america, retinal vasculitis was found in 15% of uveitis patients, of which 17% of the cases were isolated retinal vasculitis.4 76 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; another study conducted by sarief l, et al found that retinal vasculitis was found in 6-15% of uveitis patients.5 the findings seen on funduscopic examination are usually from venous sheathing to vascular damage that affects the permeability of blood vessel walls. this results in leakage of blood into the retinal extracellular space and cystoid macular edema. non-perfused area of the retina can cause permanent visual loss, especially when ischemia occurs in the macula. in addition, neovascularization can cause recurrent vitreous hemorrhage and ultimately results in retinal detachment, rubeosis iridis, and neovaskular glaucoma, which can cause vision loss.5 the prognosis of patients with retinal vasculitis varies greatly, and is determined by the underlying disease, degree of inflammation, and location of the affected retinal blood vessels.1 complication that can occur in patients with retinal vasculitis are quite severe. ischemic retinal vasculitis has a very poor visual outcome compared to retinal vasculitis that is not accompanied by ischemic condition. other events that can worsen the disease are retinal detachment, macular edema, vascular occlusion, neovascularization, and the formation of epiretinal membrane that greatly affect vision.1 one thing to note in retinal vasculitis is the heterogeneity of this disease. the cause is numerous and patient’s characteristics also vary.2 the limitation of supporting examinations experience in most hospitals in indonesia is the reason for the need to find this characteristic of disease. therefore, this study was conducted to determine the clinical characteristic of retinal vasculitis patients at the national eye referral center, and assess the factors that influence the success of therapy. method this study was a retrospective cohort study of retinal vasculitis patients who came to the retinal clinic at cicendo eye hospital, bandung from 1 january to 31 december, 2017. diagnosis of retinal vasculitis was made by retinal doctors who served in retinal clinic when patients came for treatment. data collection data collection was performed by evaluating the medical record. medical record data was collected by hospital information and technology (it) personnel by tracking patients who seek treatment throughout 2017 with the icd 10 for retinal vasculitis (h.35.06), vitreous hemorrhage (h.43.1), and other vitreous opacities (h.43.39). data was provided to two hospital medical record officers to collect medical records. through the collected medical records, patient’s data such as personal data, diagnosis, treatment, visual acuity during the first visit, 1 month after treatment, and 3 months after treatment are recorded. positive laboratory results were also taken. all figures, tables, or informative illustrations are prepared as image file. data management and statistical analysis all medical records that meet the icd 10 code above are collected and recorded. medical records with a diagnosis of retinal vasculitis will be analyzed directly, while cases with a diagnosis of vitreous hemorrhage or vitreous opacification, we first determined its etiology. only medical records with cases of retinal vasculitis were further analyzed. demographic and clinical characteristics data in the medical records are recorded. to find out whether age and sex are risk factors or not, a chi-square analysis was performed. data on all vasculitis patients (52 patients), compared with 52 other patients such as non-vasculitis vitreous hemorrhage. sampling of non-vasculitis patients was taken randomly. then an assessment of the factors affecting the success of therapy is carried out. the factors assessed are the presence or absence of underlying diseases, initial visual acuity, and type of therapy. therapy is considered good/successful if there were reduction or loss of vitreous opacification, reduction or loss of infiltrates, and / or increases vision. therapy is considered not good or fails if vitreous opacification increases, exudate or infiltrates increase, regressions occur such as exudative retinal detachment, or traction retinal detachment. systemic disease and underlying disease were seen from the diagnosis of other doctors (internist) who are consulted by retinal specialist at the retinal clinic. assessment of factors affecting the success of therapy was only done in patients who returned for control at month 1 and / or month 3. whereas patients who only came once were not include in the analysis. the chi square and fisher exact statistical tests were performed to assess the relationship. results total medical records found by hospital medical records staff using the specified icd 10 code are 853 medical records. however, 324 of them had to be excluded because they were not cases of vasculitis or vitreous opacities. of the 529 medical records obtained, 52 cases of vasculitis (9,8%) were found, and it was the second most common disease after diabetic retinopathy published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 77 (300 cases). other cases found were vitreous hemorrhage caused by age related macular degenerations (37 cases), retinal vein occlusions (34 cases), trauma (20 cases), posterior vitreous detachment (19 cases), retinal detachment (17 cases), and polypoidal choroidal vasculopathy (1 cases). there were also 49 cases of unknown vitreous bleeding. the demographic characteristics of the patients such as age, sex, bilaterality, and history of systemic disease shown in table 1. in follow up period shown that 10 peoples did not come for control in the first and /or third moths, which might be due to an improve eye condition, or because they wanted control to another hospital. this caused that the ten patients could not be analyzed to determine the success factors of management. table 1. demographic characteristics the clinical characteristics of vasculitis patients shown in table 2. data were taken at the time the patient first came to the hospital. data presentation is based on complaints and symptoms felt in each eye. of all the analyzed medical records, there were 22 patients affected by vasculitis in both eyes, so there were total of 74 eyes analyzed. each patient can have one or more symptoms at a time. risk factor analysis is shown in table 3. age and sex appear to have a significant relationship with the incidence of retinal vasculitis. age 30-39 years has the greatest risk for vasculitis, which is 9.21 times compared with age  50 years; men have a risk of vasculitis 3.04 times greater than women. table 4 shows the factors affecting the success of vasculitis therapy. in this table, assessments are also carried out in each eye. a total of 74 eyes will be analyzed. as mention before, because there were 10 peoples (17 eyes) that did not come for control in the first and third months, so these 17 eyes had to be excluded. therefore, there were 57 eyes analyzed to assess the success of therapy. for the type of therapy given, we classify it as a drug, surgery, corticosteroid, and also a combination of these therapies. drugs are therapies administered to manage the underlying disease, while surgery is pars plana vitrectomy performed because of severe vitreous opacity or hemorrhage. table 2. clinical characteristics no characteristics amount (n=74 eyes) percentage 1 ucva  20/50 20/50-20/160  20/200 18 14 42 24.3 18.9 56.8 2 symptoms blurred floaters photopsia pain visual field defect headache eyelid edema redness halos around light dazzled no symptoms 69 29 18 7 6 2 2 2 1 1 4 93.2 39.2 24.3 9.5 8.1 2.7 2.7 2.7 1.4 1.4 5.4 no characteristics amount (n=52) percentage 1 age mean  sd median range 42.3  14.6 42 13 74 2 sex male female 35 17 67.3 32.7 3 history of systemic diseases and possible related diseases tuberculosis diabetes mellitus hypertension autoimmune disease toxoplasmosis cytomegalovirus rubela herpes symplex type 1 12 2 13 2 23 19 21 30 23.0 3.8 25.0 3.8 44.2 36.5 40.4 57.7 4 bilaterality bilateral unilateral 22 30 42.3 57.7 5 follow up period no follow up 1 month  3 months 10 11 31 19.23 21.53 59.61 78 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 3 fundus vitreous hemorrhage vitreous fibrosis exudate sheathing ghost vessels pre-retinal hemorrhage vitreous cells retinal hemorrhage sclerotic vessel exudative rd scar fibrovascular membrane retinal ischemia shunt vessel tortuous vessel 43 25 30 39 16 7 7 3 2 2 2 2 1 1 1 58.1 33.8 40.5 52.7 21.6 9.5 9.5 4.1 2.7 2.7 2.7 2.7 1.4 1.4 1.4 4 anterior segment cataract keratic precipitate ciliary injection cells/flare synechiae pseudophakic no abnormalities 17 9 4 3 1 1 39 23.0 12.2 5.4 4.1 1.4 1.4 52.7 in table 4 it appears that factor affecting the success of therapy is the presence of underlying disease. patients who had underlying disease were more successful in the treatment than those without underlying disease (74.1% vs 46.7%) and this difference was statistically significant (p<0.05). details of the underlying disease and treatment provided can be seen in table 5. out of a total of 57 eyes, only 27 eyes found with underlying disease. those diseases were toxoplasmosis, tuberculosis, and cytomegalovirus. table 3. risk factor no risk factor retinal vasculitis p value or (95% ci) yes (n=52) no (n=52) 1 age < 30 years 30 – 39 years 40 – 49 years  50 years mean  sd median range 10 13 13 16 42.3  14.6 42 13 74 5 3 10 34 50.4  12.5 52 12 78 0.002 4.25 (1.25 – 14.5) 9.21 (2.30 – 36.93) 2.76 (1.00 – 7.63) 1.0 2 sex male female 35 17 21 31 0.005 3.04 (1.27 – 7.36) note: *) based on the chi-square test; or (95% ci) = odds ratio and confidence interval 95% table 4. factor affecting the success of therapy no factor affecting therapy details therapeutic results p value improve no improvement/ worse 1 underlying diseases yes no 20 (74.1 %) 14 (46.7%) 7 (25.9%) 16 (53.3%) 0.037 2 initial visual acuity < 20/200  20/200 13 (54.2%) 21 (63.6%) 11 (45.8%) 12 (36.4%) 0.472 3 therapy drugs drugs + steroid drugs + steroid + surgery surgery observation 1 (50.0%) 22 (55.0 %) 8 (88.9%) 2 (100%) 1 (25.0%) 1 (50.0%) 18 (45.0%) 1 (11.1%) 0 (0.0%) 3 (75.0%) 0.137 note: *) based on the chi-square test except for the therapy using fisher exact test published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 79 table 5. underlying disease and its management *tb drugs in these patients were given by internists, namely the four-drug regimen (rifampicin, isoniazid, pyrazinamide, and ethambutol) ** arv were anti-viral drugs given by internists in other hospital discussion from all the medical records traced, we found that the most frequent cause of vitreous bleeding was diabetic retinopathy. retinal vasculitis was the second most with a prevalence of 9.8%. chi-square test found that the age of 30-39 years statistically proven to have the greatest risk of suffering from retinal vasculitis, and men had the possibility of suffering from vasculitis 3.04 greater that women. previous studies of the causes of vitreous hemorrhage and the age range of vasculitis sufferers mostly have the similar results with this study. 1,6-8 research explaining that there is no significant difference between sexes, one of which is a study conducted by shulman et al, in israel that did not find any gender predisposition in patients with noninfectious retinal vasculitis.9 a characteristics of retinal vasculitis is that the diagnosis made clinically based on funduscopic examination and from supporting investigation such as fluorescence angiography. biopsy examination for histological confirmation is not carried out because of the risk. this is what distinguishes retinal vasculitis from systemic vasculitis.4,10 fluorescence angiography is a very important examination in this case. this procedure is actually quite safe in healthy people, but with a history of any systemic disease.11 this examination is currently not possible at our hospital, and almost all hospital in indonesia. therefore, it is unfortunate that we could not get the results of fluorescein angiography. so, in this study we can only got clinical findings on the retina by ophthalmoscopy examination. ischemic area which is one of the most important factors in the management of retinal vasculitis could not be evaluated. it is surprising that out of a total of 74 eyes evaluated, 68 of them came with vitreous opacity. forty-eight of them came with initial visual acuity less then 20/200. this means that most patients came for treatment after severe eye complications. another thing about retinal vasculitis is their relationship with infection. systemic vasculitis is rarely caused by an infection process, whereas retinal vasculitis is often associated with the infection (tuberculosis, torch, syphilis and other viral infection). other diseases that can be associated with retinal vasculitis are bechet’s, sarcoidosis, multiple sclerosis, collagen-vascular disease, sympathetic ophthalmia, and others.2,5,12,13 retinal vasculitis can also be a part of posterior uveitis, where this disease is found in 6-15% of patients with posterior uveitis. our study found that the history of torch infection was the most frequent systemic disease compare to other diseases. if we look at the number of cases, our finding was somewhat different from vasculitis or uveitis cases in other developing countries, where tuberculosis is the most common cause.14,15 we didn’t carry out further statistical analysis for this finding. limited laboratory facilities and public financial problems have caused a number of cases not to undergo a complete laboratory examination, no underlying disease therapy dose route total 1 toxoplasmosis cotrimoxazole methylprednisolone 2x960 mg 1 mg/bw oral oral 12 3 toxoplasmosis cotrimoxazole methylprednisolone surgery 2x960 mg 1 mg/bw oral oral parsplana vitrectomy 2 4 tuberculosis methylprednisolone surgery tb drugs* 1 mg/bw oral parsplana vitrectomy 2 5 tuberculosis methylprednisolone tb drugs* 1 mg/bw oral oral 8 6 cytomegalovirus ganciclovir arv** 2 mg intravitreal 3 total 27 80 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; so we only carried out examinations that are considered the most important. the initial visual acuity, signs, and symptoms experience by most patients were in line with other theory and study that has been done before.2,15-17 management of retinal vasculitis depends on the underlying disease. non-infectious retinal vasculitis is treated with corticosteroids and / or immunosuppressive agents, whereas infectious retinal vasculitis is given antimicrobials.1 however, the success of therapy is determined by many factors. in this study, we analyzed the factor affecting the success of therapy. it was found that patients with systemic disease had better therapeutic success compared to those who did not have any systemic disease. this finding was statistically significant, perhaps because the cause of the disease has been detected, so treatment for the underlying disease can also be done. while patients who did not have an underlying disease may be because they did not have it or it was not detected. so, procedure for the underlying disease could not be performed. other indicators such as initial visual acuity and type of treatment did not affect the success of therapy. this study confirms previous studies by jennifer h. ku et al, who found that patients with systemic infections and poor initial vision had better visual outcome.2 this study has several limitations such as a retrospective design, so some of the required data was not stated in incomplete medical records. the evaluation period was quite short causing a limited number of subjects. a very important angiographic examination could not be performed, making it difficult to evaluate the ischemic area. fundus description can only be seen from sketch drawings, there were no picture of fundus photograph. the limited laboratory facilities that occur in almost all hospitals in indonesia caused many underlying diseases could not be evaluated. conclusion retinal vasculitis is a quite common disease found in retinal clinics. although mostly idiopathic, associations with systemic conditions are also frequently reported. financial problem and limitations of diagnostic facilities (mainly laboratories) occur in almost all hospital in indonesia. so, the ophthalmologist must be able to choose examinations that are really needed to confirm the diagnosis and treatment. this study and several studies of retinal vasculitis in developing countries conclude that the tuberculosis, torch, and autoimmune test are important examination in the management of retinal vasculitis. the presence of the underlying diseases is one of the success factors, this is probably because the therapy is not only steroids, but also drugs that were directly targeted to the underlying disease, such as addition of cotrimoxazole for toxoplasmosis or tuberculosis drugs for vasculitis in ocular tuberculosis. references 1. mir ta, reddy ak, burkholder bm, walsh j, shifera as, khan ir, et al. clinical feautures and incidence rates of ocular complications in patients with retinal vasculitis. am j ophthalmol. 2017;179:171-8 2. ku jh, ali a, suhler eb, choi d, rosenbaum jt. characteristics and visual outcome of patients with retinal vasculitis. arch ophthalmol. 2012;vol.130(10) 1261-64 3. hughes eh, dick ad. the pathology and pathogenesis of retinal vasculitis. neuropath appl neuro. 2003; 114(5):593-599 4. pelegrín l, hernández-rodríguez j, espinosa g, llorenç v, sainz-de-la-maza m, fontenla jr, et al. characterization of isolated retinal vasculitis. analysis of a cohort from a single center and literature review. 5. sharief l, lightman sue, blum-hareuveni t, bar a, tomkins-netzer o. clinical outcome of retinal vasculitis and predictors for prognosis of ischemic retinal vasculitis. am j ophthalmol 2017;177:206–12. 6. rishi p, rishi e, gupta a, swaminathan m, chhablani j. vitreous hemorrhage in children and adolescents in india. j aapos. 2013; vol.17(1)64-9 7. sudhalkar a, chhablani j, rani pk, jalali s, balakrishnan d, tyagi m. bilateral vitreous hemorrhage in children: clinical features and outcomes. j ophthalmic vis res. 2015;vol.10(2)139–43. 8. agrawal r, gonzalez-lopez jj, cardoso j, gupta b. peripheral retinal vasculitis. retina. 2017;37:112–7. 9. shulman s, kramer m, schaap-fogler m, habot-wilner z. characteristics and long-term outcome of patients with noninfectious retinal vasculitis. retina 2015; 35: 2633–40. 10. mesquida m, llorens v, adán a. new imaging techniques in retinal vasculitis. med clin (barc) 2017;149(6)261–6. 11. yang yi, mai j, wang j. risk factors for adverse reactions of fundus fluorescein angiography. eye sci. 2016;vol.31(2)86-91. 12. rosenbaum jt, ku j, ali a, choi d, suhler eb. patients with retinal vasculitis rarely suffer from systemic vasculitis. semin arthritis rheum. 2012; vol.41(6) 859– 65. 13. do bk, giovinazzo j. retinal vasculitis. adv ophthalmol optom. 2016;vol.1(1) 69–84. 14. apinyawasisuk s, rothova a, kunavisarut p, pathanapitoon k. clinical features and etiology of retinal vasculitis in northern thailand. indian j published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; 81 ophthalmol. 2013;(dec)739-42 15. walton rc, ashmore ed. retinal vasculitis. curr opin ophthalmol 2003;14: 413–9. 16. milston r, madigan mc, sebag j. vitreous floaters: etiology, diagnostics, and management. surv ophthalmol 2016;vol.61(2)211–27. 17. ali a, ku jh, suhler eb, choi d, rosenbaum jt. the course of retinal vasculitis. br j ophthalmol. 2014; 98: 785–9. this work licensed under creative commons attribution 2 differences of apolipoprotein a1 and apolipoprotein b levels in type 2 diabetes mellitus (t2dm) patients with diabetic retinopathy and without diabetic retinopathy.docx published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 93 international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 differences of apolipoprotein a1 and apolipoprotein b levels in type 2 diabetes mellitus (t2dm) patients with diabetic retinopathy and without diabetic retinopathy shabrina hanifah1, indra tri mahayana1*, suhardjo1, angela nurini agni1, teguh triyono2 1department of ophthalmology, faculty of medicine, public health, and nursing, universitas gadjah mada dr. sardjito general hospital, yogyakarta, indonesia 2department of clinical pathology, faculty of medicine, public health, and nursing, universitas gadjah mada dr. sardjito generalhospital, yogyakarta, indonesia abstract introduction: apolipoprotein a1 is antiatherogenic in blood serum and has an anti-inflammatory effect in blood serum while apolipoprotein b is potentially atherogenic. diabetic retinopathy occurs due to the inflammation process. apolipoprotein a1 plays a role as a protector in the case of diabetic retinoplathy.this study aimed to determine whether there were differences in the levels of apolipoprotein a1 and b in diabetic retinopathy patients and without diabetic retinopathy. methods: this study used a cross-sectional design. this study's subjects were t2dm patients with diabetic retinopathy and without diabetic retinopathy at dr. sardjito general hospital (yogyakarta, indonesia) from july to september 2020. subjects consisted of 32 patients with diabetic retinopathy and 31 patients without diabetic retinopathy. the levels of apolipoprotein a1 and apolipoprotein b were analyzed using an independent t-test. the factors affecting apolipoprotein a1 and apolipoprotein b were examined using multiple regression tests. result: there were no significant differences (p> 0.05) in age, gender, duration of diabetes, hdl, triglycerides, hba1c, bmi, physical activity, and smoking history. the mean apolipoprotein a1 level in the diabetic retinopathy group was 1.46 ± 0.177 mg/dl higher than the non-diabetic retinopathy group, which was 1.44 ± 0.27 mg/dl (p = 0.699). the mean level of apolipoprotein b in the diabetic retinopathy group was 1.26 ± 0.289 mg/dl higher than the non-diabetic retinopathy group of 1.01 ± 0.26 mg/dl (p = 0.001). the mean ldl levels were 162.5 ± 48.38 mmol/l in the diabetic retinopathy group and 127 ± 38.45 mmol/l in the group without diabetic retinopathy (p = 0.012) conclusion: apolipoprotein b levels were found to be higher in t2dm patients with diabetic retinopathy than in those without diabetic retinopathy. there was a significant difference between the two assumed due to an atherogenic process in the diabetic retinopathy group. further research is needed to assess the causal relationship between elevated levels of apolipoprotein b and the incidence of diabetic retinopathy by calculating the ratio of apolipoprotein b to apolipoprotein a1. keywords: intravitreal, macular edema, pharmacotherapy, vein occlusion, vitreous detachment cite this article: hanifah, shabrina. differences in levels of apolipoprotein a1 and apolipoprotein b in patients diabetes mellitus type 2 with diabetic retinopathy and without diabetic retinopathy. international journal of retina, [s.l.], v. 4, n. 2, p. 93, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/153>.doi: https://doi.org/10.35479/ijretina.2021.v ol004.iss002.153. correspondence to: shabrina hanifah, dr. sardjito general hospital, yogyakarta, indonesia, shab.hanifah@gmail.com introduction diabetic retinopathy is the most common microvascular disease. it can cause blindness and vision problems in the world. https://www.ijretina.com/index.php/ijretina/article/view/153 https://doi.org/10.35479/ijretina.2021.vol004.iss002.153 https://doi.org/10.35479/ijretina.2021.vol004.iss002.153 94 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; the likelihood of retinal disease increases with the duration of diabetes and will become one of the causes of blindness for more than 10,000 people with diabetes mellitus per year. (1) in patients with diabetes mellitus, hyperglycemia occurs and causes microangiopathy. microangiopathy may result in vascular leakage, which leads to diabetic macular edema and capillary occlusion. capillary occlusion causes retinal ischemia and increased levels of vascular endothelial growth factor (vegf), which is responsible for the development of neovascularization and the proliferative stage of diabetic retinopathy.(2) developing countries such as australia and new zealand have a lower prevalence of t2dm than other developing countries. also, another study stated that asian patients had higher postprandial blood sugar than caucasians. almost all asian countries have different nutritional transitions with increased carbohydrates, animal fats and meat, and less fiber and vegetables. diets in south asia are characterized by a high intake of carbohydrates, trans fats, and saturated fats, so that there is a risk of t2dm.(3)from several studies, it is stated that apolipoproteins are more influential in diabetic retinopathy's appearance compared to traditional fatty serum such as hdl, ldl, and vldl.(4–6)from wesdr xiii reported that cholesterol levels were not related to the severity of either ocular condition in older-onset patients. hdlc was unrelated to the severity of either lesion. totalto-hdl cholesterol ratio and ldl-c could predict the development of csme and hard exudate. higher serum lipids were associated with an increased risk of csme and retinal hard exudate.(7)although apolipoprotein a1 is associated with hdl and apolipoprotein b is associated with ldl, it does not mean that hdl and ldl have the same relationship with diabetic retinopathy. there are several reasons to explain this. first, apolipoproteins reflect protein binding with structure, enzymes, and function as receptors, while hdl cholesterol and ldl cholesterol only reflect hdl and ldl cholesterol's fat content. hdl contains several apolipoprotein a1 molecules while ldl, vldl, idl only contains one apolipoprotein b molecule. second, patients with dm induce several changes, such as glycation, oxidation, and modification of the advanced glycation end products of lipoproteins. in contrast, apolipoprotein a1 and apolipoprotein b levels are more stable than traditional serum fat because they are not affected by prandial status.(4,6) the retina has a protective mechanism through apoa1 to fight lipid and lipotoxin deposits that induce inflammation resulting in diabetic retinopathy. apoa1 has antiinflammatory and antioxidant effects and is key to intraretinallipid transport. if the level of apoa1 is low, it will accelerate the occurrence of diabetic retinopathy.(8)this study aims to determine whether there were differences in the levels of apolipoprotein a1 and b in diabetic retinopathy patients and without diabetic retinopathy. methods the research employed a cross-sectional study and conducted at dr. sardjito general hospital in july to september 2020. the research subjects were t2dm sufferers with diabetic retinopathy and without diabetic retinopathy. patients who were included in the study criteria were carried out anamnesis regarding the length of suffering from t2dm, history of smoking, history of dyslipidemia treatment, history of aerobic physical activity, physical and ophthalmological examinations. the clinical laboratory took blood for the examination of hdl, ldl, triglycerides, hba1c, apolipoprotein a1, and apolipoprotein b. physical activity is defined as any bodily movement by skeletal muscle that requires energy expenditure. still, in this study we didn’t count the intensity. the inclusion criteria were t2dm patients with diabetic retinopathy and without diabetic retinopathy, willing to attend the study, published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 95 not currently pregnant, not being treated for dyslipidemia, and no history of hereditary lipid disorders. the exclusion criteria were samples that did not meet the requirements such as lysis. the collected data were then processed using spss. all data were tested for normality with the kolmogorov test to determine whether the data distribution was normal or not. normally distributed data such as body mass index (bmi), apolipoprotein a1, and apolipoprotein b were then analyzed using unpaired t-test while not-normally distributed data were analyzed using mann whitney. multiple linear regression tests were used to analyzed the factors that influence apolipoprotein a1 and apolipoprotein b. results the mean age in the diabetic retinopathy group was not significantly different from the non-diabetic retinopathy group (54.5 ± 6.72 vs 57.35 ± 7.48, p = 0.134). this study found demographic and clinical characteristic subjects as follows(table 1). table 2. mean levels of apolipoprotein a1 and apolipoprotein b according to severity of diabetic retinopathy npdr severe (n=6 eyes) pdr early (n=9 eyes) pdr high risk (n= 20 eyes) pdr advan ced (n=11 eyes) p apo a1 (mg/dl) 1,4 ± 0,18 1,48±0, 23 1,42±0, 17 1,49± 0,20 0,31 9 apo b (mg/dl) 0,90±0,22 1,23±0, 17 1,29±0, 275 1,10± 0,307 0,05 8 apo b/apo a1 0,66±0,98 0,84±0, 168 0,92±0, 22 0,76± 0,26 0,08 7 table 3. correlation betweenapolipoprotein a1 with some variables in diabetic retinopathy variables correlation coefficient p bmi -0,176 0,168 age -0,155 0,198 smoking 0,489 0,002 physical activity -0,022 0,43 hdl cholesterol 0,559 <0,001 ldl cholesterol 0,029 0,437 trigliseride -0,159 0,192 table 1. demographic and clinical characteristic subjects variable diabetic retinopathy (n=32) non diabetic retinopathy (n=31) p age (years) 54,5 ± 6,72 57,35 ± 7,48 0,134 gender(%) male female 16 (50%) 16 (50%) 19 (61,3%) 12 (38,7%) 0,367 visual acuity od (logmar) 0,89 ± 0,59 0,68 ± 0,54 0,00 visual acuity os (logmar) 0,86 ± 0,55 0,79 ± 0,65 0,297 dme (eyes) yes no 11 (23,4%) 36 (76,6%) 0% 31 (100%) 0,004 physical activity yes no 16 (50%) 16 (50%) 11 (35,5%) 20 (64,5%) 0,241 bmi (m/kg2) 23,97±3,1 24,28±3,47 0,710 smoking yes no 7 (21,9%) 24 (78,1%) 12 (38,7%) 19 (61,3%) 0,146 duration of dm (years) 9,75 ± 5,68 8,06 ± 5,507 0,167 hdlcholesterol (mmol/l) 46,25 ± 9,84 49,06 ± 16,47 0,512 ldlcholesterol (mmol/l) 162,5 ± 48,38 127 ± 38,45 0,012 trigliserida (mmol/l) 239,46 ± 181,54 255 ± 227,09 0,929 hba1c (%) 8,94 ± 2,50 8,70 ± 2,2 0,690 apo a1 (mg/dl) 1,46 ± 0,177 1,44 ± 0,27 0,699 apo b (mg/dl) 1,26 ± 0,289 1,01 ± 0,26 0,001 96 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; table 4. correlation between apolipoprotein b with some variables in diabetic retinopathy variables correlation coeffiecients p bmi 0,103 0,287 age -0.179 0,164 smoking -0.143 0,218 physical activity 0.109 0,277 hdl cholesterol -0,280 0,060 ldl cholesterol 0,732 <0,001 trigliseride 0,393 0,013 tables 3 and 4 describe the correlation between apolipoprotein a1 and apolipoprotein b with several variables in diabetic retinopathy patients. ldl cholesterol had a strong correlation with apolipoprotein b, while triglycerides had a weak correlation with apolipoprotein b. in this study, triglycerides were not significantly different between the two groups, while ldl cholesterol levels were significantly different. the results of the study were not influenced by triglycerides but by ldl levels. in this case, these variables do not affect the levels of apolipoprotein a1 and apolipoprotein b. discussion this study reveals that the levels of apolipoprotein a1 between the two groups were not significantly different, but significantly different in apolipoprotein b. it can be concluded that there is already an atherogenesis process in the diabetic retinopathy group. this result was similar to the study conducted by namitha et al., according to which the levels of apolipoprotein a1 and apolipoprotein b were not significanty different between the groups with diabetic retinopathy and without diabetic retinopathy. however, the differenceis significant if the group of healthy patients (not suffering from dm) both with the diabetic retinopathy group and without diabetic retinopathy.(9)previous studies demonstrated that the highest significant results were apolipoprotein a1 in healthy patients without t2dm followed by t2dm patients without diabetic retinopathy, npdr, and the lowest result in the pdr group. similar results were obtained in a study by sasongko et al, where apolipoprotein a1 levels decreased significantly in patients with diabetic retinopathy and with increasing severity of diabetic retinopathy (p = 0.001).(4,10)another study stated that apolipoprotein b had a positive correlation with the severity of diabetic retinopathy (p≤ 0.001) while apolipoprotein a negatively correlated with the severity of diabetic retinopathy (p≤ 0.001).(6) this study concluded that ldl and triglycerides affect apolipoprotein b levels in both patients with or without diabetic retinopathy. the levels of apolipoprotein a1 in the two groups did not differ significantly possibly because hdl levels were not statistically significant. apolipoprotein a1 is the major structural protein in hdl. high levels of apolipoprotein a1 suggest a protective mechanism in the retina via apolipoprotein a1 against lipid deposits inflammation-inducing lipotoxicity that causes diabetic retinopathy. increased levels of apolipoprotein b are associated with worsening of diabetic retinopathy according to severity. moreover, high levels of apolipoprotein b lead to the production of the lipoproteins related totoxins that can damage retinal vascular cells.(11) in this study, age and sex did not differ significantly between the two groups. this result was not much different from the study by namitha et al. the mean age of the control group, the t2dm group without diabetic retinopathy, and the t2dm group with diabetic retinopathy were 50.43 ± 11.74, 52.97 ± 12.46, and 56.16. ± 7.93, and each was not statistically significant. in addition, the distribution of men and women in each group was not statistically significant.(9)). similarly, sharma et al. explained that there was no significant difference in the age and sex of the patient group with t2dm and the group of patients without t2dm(10). the duration of sharma et al.’s study was slightly longer in the diabetic retinopathy group, but still, both groups were not significantly different. this result is contrast to the study by sharma et al., which stated that the duration published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 97 of dm was significant with a mean of 7.5 ± 4.7 years in the group without diabetic retinopathy, 10 ± 5.2 years in the npdr group, and 14.1 ± 6.9 years in the pdr group (p <0.001).(10) other studies also mention a significant relationship between the duration of t2dm and diabetic retinopathy, namely the prevalence of diabetic retinopathy 5 to 25% after 14 years of suffering from diabetes and 3.5% if it is less than 14 years.(12) in this study, the bmi was not significantly different. in other studies, it is stated that bmi negatively correlates with retinopathy, while several studies have reported that bmi is a risk factor for retinopathy. however, several studies also found that bmi was not significant towards the occurrence of diabetic retinopathy.(13) in addition, diabetic macular edema (dme) in this study did not differ significantly between the two groups. however, another study stated that the estimated prevalence of pdr was 41% in each patient, and 23.8% had macular edema. the estimated incidence of pdr was 1.21% annually, and 0.77% had macular edema. in addition, total serum cholesterol was associated with an increased risk of developing pdr (hr per 20 mg/dl 1.13, 95% ci 1.06-1.21), and serum hdl cholesterol reduced the risk of macular edema (hr per 10 mg/dl). 0.83, 0.71-0.96).(14) in this study, both groups' smoking history was not significant for the occurrence of diabetic retinopathy (1.78 ± 0.42 vs. 1.78 ± 0.42, p = 0.357). in another study, it was stated that the incidence of diabetic retinopathy was 66.6% in patients with a history of smoking and 47% in patients who did not smoke. the risk of developing diabetic retinopathy was 1.47 times in patients with a history of smoking (p> 0.05).(13) the mean physical activity in the diabetic retinopathy group was slightly lower than the non-diabetic retinopathy group, but this difference was not statistically significant (1.46 ± 0.507 vs 1.61 ± 0.49, p = 0.255). another study mentioned that apolipoprotein a1 levels would increase after aerobic activity and was significant (p <0.05). likewise, the levels of apolipoprotein b also increased after aerobic activity (p <0.05).(15) in this study, hdl and triglyceride levels were not significantly different between the two groups, but the results were significantly different for ldl. this is in contrast to amoorthy's study, which states that hdl levels are opposite to the severity of diabetic retinopathy, triglycerides are associated with an increased incidence and severity of diabetic retinopathy, but there was no significant difference in ldl and total cholesterol levels.(5,11) research by namitha et al also states that there is a significant increase in total cholesterol, triglycerides, vldl, and ldl in the group without diabetic retinopathy and a greater increase in the group with diabetic retinopathy compared to the healthy patient group.(9) in that study, there was no relationship between serum lipids and the incidence and worsening of the severity of diabetic retinopathy.(16) hba1c levels were also not significantly different in the two groups. these results differ from the results of the study by garg et al., where the severity of diabetic retinopathy is associated with hba1c levels and is significant. in another study, it was explained that severe diabetic retinopathy (including severe npdr, pdr, and cme) was more common in patients with hba1c more than 10%.(17) the study of leske et al. stated that every increase in hba1c levels 1% from the baseline is associated with more than two times the risk of diabetic retinopathy. (18) conclusions apolipoprotein b levels were higher in the group with diabetic retinopathy than in the group without diabetic retinopathy and there were significant differences between the two. the limitations of this study are the small number of dme samples,so we cannot analyze the specifics. this study also did not include blood pressure as the variable studied so that the correlation between blood pressure and levels of apolipoprotein a1 and apolipoprotein b. in this study, we did not count the intensity of physical 98 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; activity. further research is needed with other research methods such as case-control studies or cohort studies to assess the causal relationship between elevated levels of apo b and the incidence of diabetic retinopathy by calculating the ratio of apolipoprotein b to apolipoprotein a1. references 1. amoorthy rkk, kaliaperumal r, achalam r, poovitha r, rajagopalan g. apolipoproteins an early and better diagnostic marker for diabetic retinopathy. j clin diagnostic res. 2017; 2. nentwich mm. diabetic retinopathy ocular complications of diabetes mellitus. world j diabetes [internet]. 2015;6(3):489. 3. ramachandran a, snehalatha c, chan jcn, chia ks, shaw je, zimmet pz. diabetes in asia and the pacific : implications for the global epidemic. diabetes care. 2016;39(march):472–85. 4. sasongko mb, wong ty, nguyen tt, kawasaki r, jenkins a, shaw j, et al. serum apolipoprotein ai and b are stronger biomarkers of diabetic retinopathy than traditional lipids. diabetes care. 2011; 5. prakash g, agrawal r, satsangi sk, prakash s. comparison of serum apolipoproteins and traditional lipids in eyes with diabetic retinopathy in indian population : a case series. middle east afr j ophtalmol. 2016;23(2):212–4. 6. ankit b, mathur g, agrawal r, mathur k. stronger relationship of serum apolipoprotein a-1 and b with diabetic retinopathy than traditional lipids. indian j endocr metab [internet]. 2017;21(1):102. 7. chang yc, wu wc. dyslipidemia and diabetic retinopathy. rev diabet stud. 2013;10(2– 3):121–32. 8. sasongko mb, wong ty, nguyen tt, kawasaki r, jenkins a, shaw j, et al. serum apolipoprotein ai and b are stronger biomarkers of diabetic retinopathy than traditional lipids. diabetes care. 2011;34(2):474–9. 9. namitha d, shilpashree, a n, a r, na r. apolipoprotein a-i and apolipoprotein b : better indicators of dyslipidemia in diabetic retinopathy patients ? indian j med biochem. 2017;21(2):142–6. 10. sharma y, saxena s, mishra a, saxena a, natu sm. apolipoprotein a-i and b and subjective global assessment relationship can reflect lipid defects in diabetic retinopathy. nutrition [internet]. 2017;33:70–5. 11. amoorthy rkk, kaliaperumal r, achalam r, poovitha r, rajagopalan g. apolipoproteins an early and better diagnostic marker for diabetic retinopathy. j clin diagn res. 2017;11(10):nc01–5. 12. rasoulinejad sa, hajian-tilaki k, mehdipour e. associated factors of diabetic retinopathy in patients that referred to teaching hospitals in babol. casp j intern med. 2015;4(july):224–8. 13. manaviat mr, rashidi m. four years incidence of diabetic retinopathy and effective factors on its progression in type ii diabetes. eur jophtalmol. 2008;18(4):572–7. 14. klein r, klein bek, myers ce, howard kp. serum lipids and proliferative diabetic retinopathy and macular edema in persons with long term type 1 diabetes: the wisconsin epidemiologic study of diabetic retinopathy. jama ophthalmol. 2016;133(5):503–10. 15. yazdani r, marefati h. effect of aerobic exercises on serum levels of apolipoprotein a1 and apolipoprotein b , and their ratio in patients with chronic obstructive pulmonary disease. tanaffos. 2018;17(2):82–9. 16. idiculla j, nithyanandam s, joseph m, vk am, vasu u, sadiq m. serum lipids and diabetic retinopathy : a cross-sectional study. indian j endocr metab. 2012;16:492–5. 17. lokesh s, shivaswamy s. study of hba1c levels in patients with type 2 diabetes mellitus in relation to diabetic retinopathy in indian population. int j adv med. 2018;5(6):1397– 401. 18. leske mc, wu sy, hennis a, hyman l. hyperglycemia , blood pressure , and the 9year incidence of diabetic retinopathy. ophtalmology. 2005;799–805. this work licensed under creative commons attribution shabrina hanifah1, indra tri mahayana1*, suhardjo1, angela nurini agni1, teguh triyono2 abstract methods results discussion conclusions published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 137 international journal of retina (ijretina) 2022, volume 5, number 2. p-issn. 2614-8684, e-issn.2614-8536 choroidal neovascularization in a case of chorioretinal coloboma treated with intravitreal anti-vegf injectons: a case report dicky budiman simanjuntak1, andi arus victor2, gitalisa andayani2 1department of ophthalmology, faculty of medicine university of indonesia, cipto mangunkusumo hospital, jakarta 2staff of vitreoretina division, department of ophthalmology, faculty of
medicine, university of indonesia, cipto mangunkusumo hospital, jakarta abstract introduction: chorioretinal coloboma (crc) results from abnormal closure of the embryonic fissure. choroidal neovascularization (cnv) is a rare complication that associated with coloboma of the choroid. vegf is an important factor in the development of cnv. case report: a 52-year-old woman with gradual blurred vision of the left eye since 4 months ago. right eye was already blurred since she was a child with uncorrected visual acuity (ucva) was 0.5/60. her right iris showed coloboma in inferior and chorioretinal coloboma. ucva of the left eye was 6/20. her left iris showed inferior coloboma, chorioretinal coloboma and macular edema with soft drusen. macular optical coherence tomography (oct) confirmed macular subretinal fluid, and indicated a cnv lesion of the left eye. she underwent a loading dose of three monthly intravitreal anti-vascular endothelial growth factor (anti-vegf) injections (bevacizumab) for the left eye. one month after completion of treatment, ucva of the left eye improved to 6/12. discussion: cnv is a complication associated with crc. intravitreal anti-vegf treatment using loading dose regimen is shown to be effective in treating cnv. one month after completion of treatment, ucva of the left eye improved. conclusion: chorioretinal coloboma is a rare posterior segment congenital anomaly. classical, bilateral coloboma of the choroid and iris indicates a deformation of the choroidal fissure closure. coloboma of the choroid can have a complication such as choroidal neovascularization. treatment with a loading dose of three monthly intravitreal anti-vegf injections showed good anatomical and functional results. keywords: chorioretinal coloboma, iris coloboma, choroidal neovascularization, intravitreal anti-vegf injections cite this article: simanjuntak, dicky budiman; victor, andi arus; andayani, gitalisa. choroidal neovascularization in a case of chorioretinal coloboma treated with intravitreal anti-vegf injectons: a case report. international journal of retina, [s.l.], v. 5, n. 2, sep. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/124>. date accessed: 27 sep. 2022. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss002.124. https://www.ijretina.com/index.php/ijretina/article/view/124 https://doi.org/10.35479/ijretina.2022.vol005.iss002.124 138 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; introduction chorioretinal coloboma (crc) is characterized by absence of part of the choroid and retinal pigment epithelium (rpe). colobomas can present in various parts of ocular tissue, such as eyelid, iris, uvea, lens or optic nerve. 1-3 crc results from abnormal closure of the embryonic fissure. this leads to the absence of choriocapillaris and formation of a defective bruch membrane and postulated to be an entry site for the growth of abnormal blood vessels.4-6 ocular coloboma is a rare condition that occurr in only 0.5 until 2.4 infants per 10.000 live births. crc can present out of the whole colobomas for 60 to 70%.7-9,10-13 clinically, crc presents as a prominent depigmented white zone most commonly located in the inferonasal quadrant. because of incomplete closure of the embryonic fissure, so the inner layer grows faster than the outer layer. the defective development of rpe can cause absence of choroid in the area of coloboma since normal choroidal development is influenced by rpe. 2,8,9,14,15 choroidal neovascularization (cnv) is a complication that associated with choroid’s coloboma. cnv development can be found at the edge of the coloboma. signs of cnv include: hemorrhagic detachment of the retina, rpe with subsequent fibrous tissue, subretinal membrane, rpe proliferation and disciform scarring, subretinal or intraretinal or exudates in the absence of retinal vascular disease, serous detachment of the rpe and subretinal pigment epithelial ring lesions. 4,16-18 fluorescein angiography is important tools to detect and evaluate cnv in clinical practice. oct also can be performed, cnv usually presented as thickening of the choriocapillaris or well-defined cnv and fusiform disruption, suggesting breaks in the rpe makes penetration of new vessels. the coloboma-related cnv can be seen with fundus fluorescein angiography, or with macular oct; both located at the edge of coloboma, if it is located in macula/fovea area can cause the blindness.19-20 progressive worsening to spontaneous resolution of visual acuity (va) can be be achieved by the untreated of coloboma-associated cnv. the primary treatment of cnv are photodynamic therapy (pdt), focal laser photocoagulation and intravitreal injections of anti-vascular endothelial growth factor (anti-vegf).21-24 the development of cnv is influenced by vegf. the hypoxic rpe cells produces vegf and induces retinal vascular permeability and endothelial cell proliferation. vegf is as a major mediator of retinal ischaemia-associated neovascularisation. the antivegfs has improved treatment outcomes in cnv patients, beside conventional treatments such as pdt and laser photocoagulation. anti-vegfs can maintain or improve vision of patients when vision loss can occur even with conventional treatments.25 clinical response of anti-vegfs cannot be estimated by the duration of action and it needs to be individually assessed. ranibizumab can inhibit all subtypes of vegf-a, it is a humanised monoclonal antibody that has a rapid onset of action. after ranibizumab injection, optical coherence tomography (oct) changes can be assessed from 12 hours to 24 hours. in 2006, ranibizumab has fda approval for the treatment of neovascular amd. bevacizumab also binds all vegf subtypes, it is also a humanised monoclonal antibody that has onset 34 days with visual improvements reported within a week, it has a longer onset of action than ranibizumab. intravitreal bevacizumab has off-label in amd and it is practiced worldwide. in 2004, intravenous bevacizumab was approved for use in metastatic colorectal cancer.26,27 correspondence to: dicky budiman simanjuntak, department of ophthalmology, faculty of medicine universitas indonesia dickybudimansimanjuntak@gmail.com published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 139 the following case demonstrates a case of chorioretinal coloboma with the complication of macular edema and soft drusen in the good eye, successfully managed with intravitreal anti-vegf (bevacizumab). case report female, 52 years old came to our clinic at kirana ciptomangunkusumo hospital with chief complaint gradual blurred vision of the left eye since 4 months ago. there was no history of redness, floaters, recurrent red eye, headache, and trauma. her family history was also noncontributory. she had history of hypertension controlled by amlodipine, and diabetes mellitus type 2 controlled by metformin. based on the eye examination (four months after the chief complaint), her ucva of the right eye was 0.5/60 with an intraocular pressure was 20.5 mmhg. the right eyelids and bulbar conjunctiva were quiet. cornea was clear. the anterior chamber was deep with no cells and flare. there was an iris inferior coloboma (figure 1). the lens showed grade 2 cataract. fundus examination of the right eye showed chorioretinal coloboma, which extends past the macular area. the ucva of the left eye was 6/20, with an intraocular pressure of 17.9 mmhg. the left eyelids and bulbar conjunctiva were quiet. cornea was clear. the anterior chamber was deep with no cells and flare. there was iris inferior coloboma (figure 1). the lens showed grade 1 cataract. fundus examination of the left eye showed chorioretinal coloboma and macular edema with soft drusen. figure 1. slitlamp examination of the right eye (left) and the left eye (right) showed iris coloboma. macular oct of the left eye was performed, which revealed subretinal fluid (srf) and rpe disturbance (figure 2). there was also thickening of the neurosensory retina and a hyperreflective area at the edge of coloboma, indicating cnv lesion. treatment with a loading dose of three monthly intravitreal anti-vegf injections (bevacizumab) was administered to the left eye. figure 2. macular oct of the left eye before loading dose of three monthly intravitreal anti-vegf injections showed hyperreflective area at the edge of coloboma (black arrow), subretinal fluid (srf) involving the fovea (red arrow) and rpe disturbance with central macular thickness (cmt) 347 µm. 140 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; the patient underwent a loading dose of three monthly intravitreal anti-vegf injections (bevacizumab). one month after completion of treatment, ucva of the left eye improved to 6/12. left eye macular oct showed absorbed srf and cmt decreased from 347 µm to 201 µm (figure 3). fundus photography was also performed (figure 4&5). figure 3. macular oct of the left eye after loading dose of three monthly intravitreal anti-vegf injections showed srf absorbed with cmt 201 µm. figure 4. fundus photography of the left eye after loading dose of three monthly intravitreal anti-vegf injections showed chorioretinal coloboma with macular edema and soft drusen. figure 5. fundus photography of the right eye showed chorioretinal coloboma. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; 141 discussion our patient was an adult female who came with gradual blurred vision of the left eye since 4 months ago with no history of previous systemic illness. her right eye already blurred since she was child. at presentation, we found that initial ucva of the right eye was 0.5/60 with grade 2 cataract and ucva of the left eye was 6/20 with grade 1 cataract. in this case, the left eye is the functional eye. variable dependent of the severity visual disability is dependent on size of coloboma, cataract, extend of optic nerve or macular involvement. visual disability is also associated with anomalies of the eye such as nystagmus, microphthalmos, retrobulbar cysts and microcornea.2,28,9 vincent et al.29 reported that in the 87% eyes with colobomas had a va <20/200. uhumwangho and jalali2 observed that bilateral chorioretinal coloboma patient is 69.7% and patient with unilateral involvement is 29.8%. asymmetrical involvement in bilateral colobomas because of its histopathological nature in both eyes, it presented with different va level. iris defects in coloboma are related to d trisomy, but coloboma of the choroid are rare. dysplasia of the retina in trisomies is opposed to inhibiton of morphogenesis of choroid and retina through deletions. furthermore, coloboma of the choroid can be observed with various other anomalies of chromosomes sporadically and with the oculoanalsyndrome regularly.30 ophthalmological examination in our patient revealed iris coloboma in inferior and cataract on both eye. fundus examination of the right eye showed chorioretinal coloboma and left eye showed chorioretinal coloboma and choroidal neovascularization. the presence of iris coloboma and chorioretinal coloboma of both eye were strong indicator of ocular coloboma. coloboma of iris and choroid on both sides indicates a deformation of the choroidal fissure closure but it is not specific for an aberration of chromosomes. there is no reliable comparison with other described cases since the chromosome of group d involved and the extent of the deletion was in individual cases.31,32 macular oct of the left eye indicated cnv the presence of srf and rpe disturbance, with cmt 347 µm. cnv is best viewed with fundus fluorescein angiography (figure 6). however, due the unavailability, this diagnostic modality cannot be performed in this case. we believe it was a cnv because of its positive response with anti-vegf treatment. previous studies have reported various treatment modalities for cnv associated with crc. management options of coloboma-related cnv are photocoagulation therapy, pdt alone, and anti-vegf intravitreal monotherapy and in combination.19,33-35 figure 6. example of patient with an active cnv showing the leak of the cnv surrounded by blocked fluorescence of the subretinal haemorrhage in the late-phase angiogram.36 treatment of the left eye was warranted immediately, because it is the functional eye, and also there is a risk of blindness due to the potential complications of cnv to the macula. the patient underwent a loading dose of three monthly intravitreal anti-vegf injections (bevacizumab). one month after completion of treatment, macular oct was performed and showed srf absorbed and cmt decreased from 347 µm to 201 µm. fundus photography was also performed. ucva of the left eye after a loading dose of three monthly intravitreal anti-vegf injections was 6/12. all these findings showed that the left eye of the patient responded well with intravitreal anti-vegf treatment. in this case, our patient had positive response with anti-vegf treatment. anti-vegf was preferred than pdt due to the unavailability, but in clinical practice, verteporfin pdt is usually performed in subfoveal cnv but it can cause severe damage to the rpe. anti-vegf was preferred than laser photocoagulation due to this patient had a cnv with srf and 142 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 2; located in fovea, meanwhile laser photocoagulation can treat extrafoveal and juxtafoveal cnv at distance of >200 µm and 1–199 µm from the center of the foveal avascular zone.37,38,39 bhende et al16 reported three cases treatment of pdt for coloboma with cnv. in cases 1 and 2, intravitreal bevacizumab combined with reduced fluence pdt had good results, and anti-vegf monotherapy was also taken into consideration. case 3 was treated with standard fluence pdt monotherapy and had regression with rpe atrophy. cases 1 and 3 were closely monitored compared to case 2, however all cases were stable within five months post treatment. anti-vegf type that was given to the patient in this case was bevacizumab. the reason of choosing bevacizumab, beside it is not an expensive antivegf, it also was widely used, the structure is also very close to ranibizumab. the indication of antivegf intravitreal injections agents was rapidly indicated to other diseases complicated by cnv.40,41,42 bevacizumab is composed of structural region of human antibody (93%) and complementaritydetermining region of murine monoclonal antibody (7%). it is also a full-length humanized anti-vegf monoclonal antibody. it binds to all the vegf isoforms, mainly vegf-a. so, it can inhibit the biological activities of vegf.43,44,45 the usage of intravitreal anti-vegf injections with or without pdt in treating coloboma with cnv have been reported by several authors. there was a successful treatment of intravitreal bevacizumab in 67-year-old patient coloboma associated cnv with subfoveal hemorrhage and cnv. after two months follow up, she had successful hemorrhage resolution and improvement of bcva from finger counting to 20/200. after one month, the patient who did not get an intervention had cnv spontaneous regression and 12 months later, fluorescein angiography did not show evidence of leakage.46-48 a recent study determined that qualitative oct and clinical examination combination can be used for guiding anti-vegf treatment if monthly antivegf injections are not administered, it worked by maintaining ‘normal’ retinal anatomy to maximize the benefit to risk ratio (va gains to number of injections required ration). patients should be assessed monthly to know whether the patient should get intravitreal anti-vegf injections.49,50 future plan management in this case if there is a recurrency of the cnv we can do anti-vegf injections pro re nata and plan macular oct to examine macula condition. the treatment depending on oct findings and va. if the cnv remained perfused, some authors suggested deciding additional treatments or performing one initial injection. a single initial intravitreal injection, if necessary followed by other injections may be a wise option in an unproven therapy and avoid unnecessary injections although it is not yet possible to define the best approach.51 conclusion chorioretinal coloboma (crc) is an rare congenital anomaly of the posterior segment. classical, bilateral coloboma of chorioretina and iris, indicates a deformation of the choroidal fissure closure. cnv is a complication associated with crc. intravitreal antivegf treatment using loading dose regimen is shown to be effective effective in treating cnv associated with crc. references 1. gan ny, lam wc. retinal detachments in the pediatric population. taiwan j ophthalmol. 2018;8:222-36. 
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5; 2; 145 47. naithani p, vashisht n, mandal s, sankaran p, garg s. intravitreal bevacizumab in choroidal neovascularization associated with congenital choroidal and optic nerve coloboma in children: long-term improvement in visual acuity. j aapos. 2010;14:288-90. 48. bhende m, suganeswari g, gopal l, bhende ps, gopal l, rao c. choroidal neovascularization associated with coloboma of the choroid: a series of three cases. indian j ophthalmol. 2011;59:148-51. 49. brown da, regillo cd. anti-vegf agents in the treatment of neovascular age-related macular degeneration: applying clinical trial result to the treatment of everyday patients. am j opthalmol. 2007;144:627-37. 50. lalwani ga, rosenfeld pj, fung ae. a variabledosing regimen with intravitreal ranibizumab for neovascular agerelated macular degeneration: year 2 of the pronto study. am j ophthalmol. 2009;148:43-58. 51. fung ae, lalwani ga, rosenfeld pj. an optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (lucentis) for neovascular age-related macular degeneration. am j ophthalmol. 2007;143:566 -83. this work licensed under creative commons attribution dicky budiman simanjuntak1, andi arus victor2, gitalisa andayani2 1department of ophthalmology, faculty of medicine university of indonesia, cipto mangunkusumo hospital, jakarta abstract case report figure 1. slitlamp examination of the right eye (left) and the left eye (right) showed iris coloboma. figure 2. macular oct of the left eye before loading dose of three monthly intravitreal anti-vegf injections showed hyperreflective area at the edge of coloboma (black arrow), subretinal fluid (srf) involving the fovea (red arrow) and rpe disturbance ... figure 5. fundus photography of the right eye showed chorioretinal coloboma. discussion conclusion 50 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; international journal of retina (ijretina) 2021, volume 4, number 1. p-issn. 2614-8684, e-issn.2614-8536 the outcome of vitrectomy in macular hole at cipto mangunkusumo national general hospital eko hadi waluyojati1, ari djatikusumo2, elvioza2, gitalisa andayani2, anggun rama yudantha2, mario marbungaran hutapea2, andi arus victor2 1fatmawati general hospital, jakarta 2department of ophthalmology, faculty of medicine universitas indonesia cipto mangunkusumo national general hospital, jakarta abstract introduction: this study aims to determine the anatomical and functional outcomes in patients with macular hole (mh) underwent vitrectomy with internal limiting membrane (ilm) peeling. method: a descriptive retrospective study at vitreoretinal division of ophthalmology department, faculty of medicine: universitas indonesia – cipto mangunkusumo national general hospital (fkui-rscm). secondary data obtained from medical records of patient with mh within january – december 2017. the anatomical outcome was observed from the closure of mh. functional outcome was observed from post-operative visual acuity at day-1, month-1, month-3, and month-6. result: 16 patients who met the criteria were included in this study. mh closure was observed in 43.8% of cases and failed closure in 56.2%. improvement of visual acuity was observed on closure cases in 3 months and 6 months, occurred in 71.43% and 100% of cases, respectively. conclusion: mh closure rate was 43.8%. satisfying result of improvement in visual acuity achieved after vitrectomy with ilm peeling.. keywords: macular hole, ilm peeling, membrane peeling cite this article: victor, andi arus et al. the outcome of vitrectomy in macular hole at cipto mangunkusumo national general hospital. international journal of retina, [s.l.], v. 4, n. 1, p. 50, feb. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/150>. date accessed: 22 feb. 2021. doi: https://doi.org/10.35479/ijretina.2021.vol004.iss001.150. introduction macular hole (mh) is one of the causes of visual impairment and quite often found as a cause of blindness. the visual impairment can be found as a distortion of image (metamorphopsia), decrease of visual acuity, and loss of some visual fields that can cause disturbances in daily activities, especially in reading and driving.1 the eye disease case-control study group study shows that 72% of primary (idiopathic) mh is found mainly in women and more than 50% in people aged 65-74 years.2 the beijing eye study in crosssectional populations with 4346 subjects reported a prevalence of mh 0,09  3,04%.3 in the population in rural india, mh prevalence is 0.20 ± 0.05% .4 studies in the united states with a sample of 90% of caucasian races have an incidence of mh of 7.8 people and 8.7 eyes per 100,000 people per year.5,6 mh is also related to cystoid macular edema due to inflammation, diabetic retinopathy, vascular occlusion, hypertensive retinopathy, high myopia, macular pucker, retinal detachment, and trauma.7 early detection of mh is associated with the increased success rate of mh closure and improvement in visual acuity after vitrectomy *correspondence to: andi arus victor, cipto mangunkusumo national general hospital jakarta, indonesia arvimadao@yahoo.com published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 51 surgery, especially in the smaller size of mh. the diagnosis of mh as early as possible is very important, especially in the other eye. oct can provide detailed anatomy and size of mh and the presence of vitreous traction, which will aid in the diagnosis, staging, and follow-up, as well as for patient education.5 in the early stages of 1a or 1b, the mh can close completely spontaneously but 50% will continue to become full-thickness mh (ftmh). this occurs because the vitreous adhesions are separated from the fovea in the other 50%, and the fovea becomes normal again or looks like a reddish spot. an improvement in visual acuity will occur if there is a spontaneous posterior vitreous detachment from attachment in the macula.8 if the mh continues beyond stage 2, the decrease in visual acuity will continue and nearly 75% of mh stage 2 will continue to stage 3 or 4. epiretinal membrane can occur as the complication of the expansion of mh which can reduce the anatomical success rate after vitrectomy. patients with ftmh are at risk of experiencing ftmh in the other eye about 10-15%. the fellow eye that has undergone complete posterior vitreous detachment has a lower risk of developing ftmh.5 in mh stage 2, vitrectomy is performed not only to improve visual acuity but to prevent a decrease in visual acuity and prevent progression to stage 3 or 4.5 there have been a variety of results of the anatomical and functional success rate of mh surgery. therefore, this study aims to determine the anatomical and functional success of mh surgery performed from january to december 2017. method this research is a retrospective descriptive study conducted in the vitreoretinal division of the department of ophthalmology, cipto mangunkusumo general hospital jakarta. subjects were patients who had undergone vitrectomy surgery on the macula in the january-december 2017. the inclusion criteria were patients with macular hole with at least stage 3 and stage 4 mh in the vitreoretinal division, cipto mangunkusumo general hospital jakarta in the period january 2017 december 2017 who had performed vitrectomy with internal limiting membrane (ilm) peeling. data were obtained from medical records and recapitulation records of patient that had undergone vitrectomy operations with ilm peeling in the period january december 2017 at cipto mangunkusumo general hospital jakarta. data taken were age, sex, the onset of disease, preoperative visual acuity, lens status, diagnosis, oct examination, type of anesthesia, operative measures, and postoperative visual acuity. if there is a mismatch of data between the medical and the recapitulation record, the patient's medical record will be excluded. anatomical success is defined as closure of the hole in the retinal macula after vitrectomy based on funduscopic and oct examination results. functional success is defined as visual acuity after vitrectomy surgery. result 16 patients underwent vitrectomy surgery with ilm peeling in the january-december 2107 period that met the study criteria. 52 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; table 1. characteristics of patient variable frequency percentage gender (n=16) male 6 37.5% female 10 62.5% age (n=16) 41-50 3 18.7% >50 13 81.3% history of diabetes mellitus (n=13) yes 6 37.5% no 10 62.5% history of hypertension (n=13) yes 8 50% no 8 50% lens status (n=16) pseudophakic 3 18.7% phakic 13 81.2% type of anesthesia (n=16) local 14 87.5% general 2 12.5% the most frequent type of anesthesia used was retrobulbar local anesthesia (87.5%). table 2. time (onset) from complaint to the surgery variable frequency (n=16) percentage  6 months > 6 months 11 5 68.8% 31.2% the time (onset) from complaints to surgery in most cases was  6 months (68.8%), while 31.2% of cases had an onset of > 6 months. table 3. status of preoperative va and the outcomes of macular hole surgery number anatomical closure rate (%) postoperative va of 6/12 snellen or better preoperative va 6/36 snellen or better 5 4 (80) 0 less than 6/36 snellen 11 3 (27.2) 1 (9) table 3 showed the status of preoperative va which categorizes the 6/36 snellen or better (5 patients), followed by less than 6/36 snellen (11 patients) and the final outcome of closure and postoperative va of 6/12 snellen or better published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 53 table 4. surgical treatment of macular hole variable frequency (n=16) percentage vitrectomy + ilm peeling + sf6 vitrectomy + ilm peeling + c3f8 vitrectomy + ilm peeling + so 8 5 3 50% 31.2% 18.8% table 4 showed that the most frequent procedure was vitrectomy with ilm peeling using sf6 gas tamponade (8 patients), followed by vitrectomy with ilm peeling using c3f8 gas tamponade (5 patients). table 5. anatomical changes after vitrectomy table 5 showed anatomical success rate achieved as high as 43.8%, whereas 56.2% of failed closure cases after vitrectomy with ilm peeling. figure 1. percentage of best corrected visual acuity in all closure cases following 1 – 6 months follow up period the decrease in visual acuity occurred 1 day after the vitrectomy with ilm peeling in the all of closure cases (100%). improvement of visual acuity seen at the 3rd and 6th months in 71.43% and 100% of cases, respectively. in addition, based from the preoperative oct, the finding of mean macular hole index (mhi) of the entire 16 patients were 0.43 0,00% 10,00% 20,00% 30,00% 40,00% 50,00% 60,00% 70,00% 80,00% 90,00% 100,00% 1 day 1 month 3 month 6 month constant decrease improve variable frequency percentage closure failed closure 7 9 43.8% 56.2% 54 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; discussion in this study, the number of female patients more than men. these results are consistent with several studies that there are more women than men.2, 7-8 and even the ratio of women to men can reach 2 to 1.8 it is still unclear what causes this gender difference. most age groups were found at age 61-70 years (46%) with a median age of 60,43 years in this study. this corresponds to many studies that mh is more common in elderly, estimated as the age of occurrence of posterior vitreous detachment.2, 6-12 secondary mh can be associated with other eye disorders, such as abnormal vitreous adhesions and inflammation in certain areas, retinal bleeding, retinal artery occlusion, retinopathy, which all of mentioned before can be related to hypertension or diabetes.8-9,13 in this study only 3 (18.75%) of the total of 16 patients who had cataract surgery with a pseudophakic lens, while the other patients had never been operated on. several studies reported a history of eye surgery can also be associated with secondary mh.8-9,13 there is a pattern of visual acuity in most cases of mh. a drastic decreased in visual acuity occurred initially on day 1 after the surgery followed by an increased in visual acuity in month 1, month 3, and it increased until finally stabilized in month 6. it turned out that the highest group of visual acuity at 6 months postoperatively was not different from the preoperative visual acuity. this pattern corresponds to existing research that the surface architecture of the macula improves significantly in the majority of patients, although a decrease in visual acuity occurs in the short term after the surgery is often encountered.11 several studies in the last 5 years reported successful closure of mh with surgery ranging from 91-98% 25-28 with a median postoperative va (on successful closure of mh) was around 20/40 or 6/12.25-31 a lower success rate is documented in this study at 43.8% however there was an increased in va in all of cases at 6-months postoperatively with closure result. post-operative anatomical success is followed by better visual acuity.14-20 meanwhile, unsuccessful closure of mh were recorded at 56.2% in this study. there are several factors that might be of influence of this result, according to jaycock et al, the latency between hole onset until surgery, the anatomical hole and stage of the mh, and preoperative va are an important factor to unsuccessful closure. surgical intervention at stage 3 and 4 mh also had its effect on the outcome of the vitrectomy, jaycock et al, reported anatomical closure rates for holes of up to 4 months preoperative latency of 82.5% and found closure rates of 77.8% and 63.6% respectively. in addition, for the functional success, holes that present for 4-6 months and 6-12 months they found that the percentage of patiens with a postoperative va of 6/12 or better in these three groups were 33.3%, 29.6% and 18.2%. jaycock et al also reports that the closure rate for macular holes of less than 6 months duration was 95.2%, and for those from 6 – 12 months duration and greater than 1 year was 91.7% and 47.4% respectively. this shows that patient’s waiting time from diagnosis to surgical intervention is an important factor for the anatomical success of mh closure. this trend is also consistent with tsipursky et al in which their findings are preoperative mh duration which had < 3-month duration had better closure rates than the ≥ 3-month group. this findings are in line with the result of this study which found that those who waits ≤ 6 months had better outcome than ≥6 months at 68.8% and 31.2% respectively. furthermore, according to venkatesh et al32, they stated that the macular hole index (mhi) are also an important factor that can predict the anatomical closure of mh. we found that the mean mhi of these 16 patients were 0.43 which predicts poor anatomical closure outcome even after vitrectomy. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 55 preoperative va is also an important factor which can influence the anatomical and functional success of mh intervention, this is supported by jaycock et al which reports patients with preoperative va of 6/36 or better the closure rate was 91.2%, meanwhile those with preoperative va of less than 6/36 snellen had a closure rate of 57.1%, and they reported successful functional achievement of 6/12 snellen or better were 61.8% and 14.3% respectively. sustained postoperative face-down positioning effectiveness as a successive mh closing factor is still unclear, as mittra et al conclude that sustained face-down position for postoperative position may not be necessary since 93% of eyes achieved hole closure with prone positioning for only 1 day, however the study did had 4 eyes that had unsuccessful closure in which 3 of the failure claimed that they did not position at all postoperatively. the duration of onset under 6 months is one of the functional success factors, namely a better improvement in va after the closure of mh.5, 21, 22 in mh that has occurred for more than 2-3 years, the reported success rate is lower (63%) and visual acuity is worse than early mh.21, 23-27 the statistical analysis of the relationship between visual acuity and duration of onset until the patient is operated is not possible to be done because of the small size of data. in addition to that there are several confounding factors that might affect the outcome, such as patient’s compliance on face down posture after vitrectomy, and the operator’s experience on the vitrectomy on mh might also add to the reasons why the low success rate on anatomical closure on this study. from existing research, decreased metamorphopsia complaints are known to occur in 85% of patients and this can improve quality of life even though there is no increase in visual acuity.9 retinal tamponade with air (for several days), sf6 gas (2-4 weeks), c3f8 (1-3 months) or silicone oil (for the long term) can be used at the end of mh surgery to help achieve anatomical closure on mh with not much different result.24 in general, there is no consensus about the best selection for this tamponade.5 conclusion the success rate of closure of mh was 43.8%. there is a quite high increased in visual acuity after vitrectomy with ilm peeling in mh cases. references 1. lee r, wong ty, sabanayagam c. epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. eye vis (lond). 2015;2(1):17. pubmed pmid: 26605370. pmcid: pmc4657234. epub 2015/11/26. 2. group tedc-cs. risk factors for idiopathic macular holes. american journal of ophthalmology. 1994;118(6):754-61. 3. wang s, xu l, jonas jb. prevalence of fullthickness macular holes in urban and rural adult chinese: the beijing eye study. am j ophthalmol. 2006 mar;141(3):589-91. pubmed pmid: 16490523. epub 2006/02/24. 4. nangia v, jonas jb, kulkarni m, matin a. prevalence of age-related macular degeneration in rural central india: the central india eye and medical study. retina. 2011 jun;31(6):1179-85. pubmed pmid: 21293316. epub 2011/02/05. 5. panel aaoorv. preferred practice pattern guidelines. idiopathic macular hole. san francisco: american academy ophthalmology; 2014. 6. mccannel ca, ensminger jl, diehl nn, hodge dn. population-based incidence of macular holes. ophthalmology. 2009;116(7):1366-9. 7. corcostegui b, pimentel lp. macular hole. in: quiroz-mercado h, kerrison jb, iii dva, mieler wf, liggett pe, editors. macular surgery. 2nd ed. philadelphia: lippincott williams & wilkins; 2001. p. 247-54. 8. cantor lb, rapuano cj, cioffi ga. disease of the vitreous and vitreoretinal interface. retina and vitreous basic and clinical science course. basic and clinical science course. 12. san francisco: american academy of ophthalmology; 2016. p. 235-9. 56 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 9. lin rc, mieler wf, wirostko wj. epiretinal membrane. in: quiroz-mercado h, kerrison jb, iii dva, mieler wf, liggett pe, editors. macular surgery. 2nd ed.philadelphia: lippincott williams & wilkins; 2001. p. 233-44. 10. gottlieb jl. idiopathic macular hole. in: albert dm, miller jw, azar dt, blodi ba, cohan je, perkins t, editors. alberts principles and practice of ophthalmology. vol. ii. 3rd ed. philadelphia: saunders elsevier; 2008. p. 2029-37. 11. haivala dr, parke dw. macular epiretinal membrane. in: albert dm, miller jw, azar dt, blodi ba, cohan je, perkins t, editors. alberts principles and practice of ophthalmology. vol. ii. 3rd ed. philadelphia: saunders elsevier; 2008. p. 2073-81. 12. kim jw, freeman wr, azen sp, el-haig w, klein dj, bailey il. prospective randomized trial of vitrectomy or observation for stage 2 macular holes. american journal of ophthalmology. 1996;121(6):60514. 13. xiao w, chen x, yan w, zhu z, he m. prevalence and risk factors of epiretinal membranes: a systematic review and meta-analysis of population-based studies. bmj open. 2017 sep 25;7(9):e014644. pubmed pmid: 28951399. pmcid: pmc5623383. epub 2017/09/28. 14. almeida dr, wong j, belliveau m, rayat j, gale j. anatomical and visual outcomes of macular hole surgery with short-duration 3-day face-down positioning. retina. 2012 mar;32(3):506-10. pubmed pmid: 22392092. epub 2012/03/07. 15. tsipursky ms, heller ma, de souza sa, gordon aj, bryan js, ziemianski mc, et al. comparative evaluation of no dye assistance, indocyanine green and triamcinolone acetonide for internal limiting membrane peeling during macular hole surgery. retina. 2013 jun;33(6):1123-31. pubmed pmid: 23514800. epub 2013/03/22. 16. mittra ra, kim je, han dp, pollack js. sustained postoperative face-down positioning is unnecessary for successful macular hole surgery. british journal of ophthalmology. 2009;93(5):664-6. 17. tadayoni r, vicaut e, devin f, creuzot-garcher c, berrod jp, le mer y, et al. a randomized controlled trial of alleviated positioning after small macular hole surgery. ophthalmology. 2011 jan;118(1):150-5. pubmed pmid: 21035869. epub 2010/11/03. 18. da mata ap, burk se, riemann cd, rosa rh, jr., snyder me, petersen mr, et al. indocyanine greenassisted peeling of the retinal internal limiting membrane during vitrectomy surgery for macular hole repair. ophthalmology. 2001 jul;108(7):1187-92. pubmed pmid: 11425673. epub 2001/06/27. eng. 19. jaycock pd, bunce c, xing w, thomas d, poon w, gazzard g, et al. outcomes of macular hole surgery: implications for surgical management and clinical governance. eye (lond). 2005 aug;19(8):879-84. pubmed pmid: 15389276. epub 2004/09/25. 20. hirneiss c, neubauer as, gass ca, reiniger iw, priglinger sg, kampik a, et al. visual quality of life after macular hole surgery: outcome and predictive factors. br j ophthalmol. 2007 apr;91(4):481-4. pubmed pmid: 17077117. pmcid: pmc1994732. epub 2006/11/02. 21. thompson jt, sjaarda rn, lansing mb. the results of vitreous surgery for chronic macular holes. retina. 1997;17(6):493-501. pubmed pmid: 9428011. epub 1997/01/01. eng. 22. wendel rt, patel ac, kelly ne, salzano tc, wells jw, novack gd. vitreous surgery for macular holes. ophthalmology. 1993;100(11):1671-6. 23. brooks hl. macular hole surgery with and without internal limiting membrane peeling. ophthalmology. 2000;107(10):1939-48. 24. scott ra, ezra e, west jf, gregor zj. visual and anatomical results of surgery for long standing macular holes. br j ophthalmol. 2000 feb;84(2):150-3. pubmed pmid: 10655189. pmcid: pmc1723387. epub 2000/02/03. 25. cheng l, azen sp, el-bradey mh, toyoguchi m, chaidhawangul s, rivero me, et al. effects of preoperative and postoperative epiretinal membranes on macular hole closure and visual restoration. ophthalmology. 2002 aug;109(8):1514-20. pubmed pmid: 12153804. epub 2002/08/03. eng. 26. ullrich s, haritoglou c, gass c, schaumberger m, ulbig mw, kampik a. macular hole size as a prognostic factor in macular hole surgery. british journal of ophthalmology. 2002;86(4):390-3. 27. ip ms. anatomical outcomes of surgery for idiopathic macular hole as determined by 28. optical coherence tomography. archives of ophthalmology. 2002;120(1). 28. tadayoni r, vicaut e, devin f, creuzot-garcher c, berrod jp, le mer y, et al. a randomized controlled trial of alleviated positioning after small macular hole surgery. ophthalmology. 2011 jan;118(1):150-5. pubmed pmid: 21035869. epub 2010/11/03. 29. da mata ap, burk se, riemann cd, rosa rh, jr., snyder me, petersen mr, et al. indocyanine greenassisted peeling of the retinal internal limiting membrane during vitrectomy surgery for macular hole repair. ophthalmology. 2001 jul;108(7):1187-92. pubmed pmid: 11425673. epub 2001/06/27. eng. 30. jaycock pd, bunce c, xing w, thomas d, poon w, gazzard g, et al. outcomes of macular hole surgery: implications for surgical management and published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 57 clinical governance. eye (lond). 2005 aug;19(8):879-84. pubmed pmid: 15389276. epub 2004/09/25. 31. hirneiss c, neubauer as, gass ca, reiniger iw, priglinger sg, kampik a, et al. visual quality of life after macular hole surgery: outcome and predictive factors. br j ophthalmol. 2007 apr;91(4):481-4. pubmed pmid: 17077117. pmcid: pmc1994732. epub 2006/11/02. 32. venkatesh r, mohan a, sinha s et al. newer indices for predicting macular hole closure in idiopathic macular holes: a retrospective, comparative study.ijo.2019;nov;67(11):18571862.doi:10.4103/ijo.ijo_364_19. this work licensed under creative commons attribution published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 19 international journal of retina (ijretina) 2022, volume 5, number 1. p-issn. 2614-8684, e-issn.2614-8536 vitreoretinal diseases in outpatient department of bali mandara eye hospital in 2019 tyas dwi1, diah pantjawati1, semara budiyasa1, cindy hartono1 1 department of ophthalmology, vitreo retinal division, bali mandara eye hospital, indonesia abstract introduction: the purpose of this study is to identify pattern and distribution of vitreo-retinal (vr) diseases in bali mandara eye hospital methods: a retrospective descriptive study was conducted for this study. we reviewed all medical records of new patient diagnosed with vr diseases, from 1 january to 31 december 2019. we recorded and measured demography, history of systemic and eye disease, symptoms and onset, ophthalmic examinations, diagnostic investigations, final diagnoses, therapies, and the completion of the visit. result: out of 2118 total visits, we found 1191 new cases with vr diagnosis. male to female ratio was 1.3:1. we found group of 46-65 years are represented in 678 cases (56.9%). type 2 diabetes mellitus was the most commonly found as a systemic disease (15.5%), followed by the combination of diabetes and hypertension (14%) and hypertension alone (12.9%). history of previous cataract surgery was found in 174 cases (14.6%). out of 1191 patients, 553 patients (46.4%) were blind. the most common diagnosis was diabetic retinopathy (24.3%), followed by rhegmatogenous retinal detachment (14.2%), and pathological myopia (8.9%). diabetic retinopathy and pathological myopia affected both eyes in 257 cases (88.6%) and 96 cases (90.6%), respectively, while rhegmatogenous retinal detachment affected one eye in 164 cases (97%). proliferative diabetic retinopathy was found in 173 cases (59.7%). conclusion: diabetic retinopathy and rhegmatogenous retinal detachment were the most two common diagnoses. proliferative type was slightly common than non proliferative diabetic retinopathy. as diabetes and hypertension were the most systemic conditions we found, a collaboration with another department is needed to create a strategic screening system and an early detection. an evaluation related to rhegmatogenous retinal detachment is needed to decrease the number of cases. keywords: retinal diseases, diabetic retinopathy, blindness, bali, indonesia cite this article: tyas dwi arshanti, ni made et al. vitreoretinal diseases in outpatient department of bali mandara eye hospital in 2019. international journal of retina, [s.l.], v. 5, n. 1, p. 19, feb. 2022. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/148>. doi: https://doi.org/10.35479/ijretina.2022.vol005.iss001.148. correspondence to: cindy hartono, bali mandara eye hospital, indonesia cindyhartonoo@gmail.com introduction vr diseases has become one of the causes of global visual impairment and blindness both in children and adults.1 age macular degeneration is the third most common cause of irreversible blindness worldwide that is mostly found in the elderly. in the meantime, diabetic retinopathy is the fifth most common cause of blindness which tends to increase among working age population.2,3,4 20 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; diabetes mellitus and hypertension are often mentioned as the underlying diseases for the emergence of retinal abnormalities.4 in asia alone, problems in vr are estimated to increase as there is an increase in the number of people with diabetes mellitus in 2030.5 parallel with these, riskesdas data show an increase in the prevalence of diabetes mellitus by 1.6% between 2013 and 2018 in indonesia. the prevalence of hypertension was also increased by 8.3% compared to the previous five years.6,7,8 in indonesia, epidemiology data of vr diseases is still limited. based on data from bali mandara eye hospital in january 2020, vr diseases are the most common cases found in the outpatient department (36%) compared to other eye diseases. the majority of these vr diseases are retinal detachment with retinal break (10%), followed by vitreous opacity (8%), tractional retinal detachment (6%), diabetic retinopathy (6%), and others (6%).9 however, this study only used small sample size and unmeasured study method therefore it’s not truly representative. this study is our initial attempt to determine the description and pattern of vr diseases in the outpatient department of bali mandara eye hospital, as a referral center for vr diseases in eastern indonesia. methods this study was conducted at bali mandara eye hospital. bali mandara eye hospital is a tertiary eye hospital, owned by the local government of bali province, located in denpasar. this hospital accepts referrals for eye diseases from all hospitals in bali and eastern indonesia. ophthalmic services are provided by subspecialists in their respective fields. this study was a retrospective descriptive study with consecutive sampling methods. thus, we enrolled 1191 patients from 2118 patients who visited during a year. data were taken from medical records of all new vr cases during the period of 1 january 2019-31 december 2019. there is no age limit in this study. the exclusion criteria were all medical records stating that someone had come and received therapy from the vr department before 1 january 2019 and after 31 december 2019 the study enrollment started on 1 july 2020, immediately after ethics approval obtained from ethics commitee of bali mandara eye hospital. the study was recorded in research instruments while maintaining the confidentiality of patient medical record data. the variables that were measured included: demographics, history of systemic disease, history of eye disease, history of systemic medication, onset of symptoms, best corrected visual acuity (bcva) on first visit at the vr department, intraocular pressure, type and frequency of laboratory and diagnostic tests, diagnosis of vr diseases, vr interventions that were done, and completion of visit. the demographic variables were recorded based on the identity card on the medical record. age grouping in this study used a modified international classification of disease for general purpose.10 occupation variables were categorized into groups of unemployed, employees, self-employed, farmers, laborers, and others. employees are defined as civil servants and private employees. the definition of unemployed was namely housewives, children who are still in school, and also retirees. laterality of blindness was classified into unilateral or bilateral. bcva was classified based on the icd 10 classification for visual impairment as mentioned below: ● mild visual impairment: ≥ 6/18 ● moderate visual impairment: 6/24 to 6/60 ● severe visual impairment: <6/60 to 3/60 ● blindness: <3/60 to no perception of light. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 21 vr diseases with bilateral impact on vision were assessed as visual impairment in the better eye using icd 10 visual classification as mentioned above. in this study, we differentiated diabetic retinopathy into non-proliferative diabetic retinopathy (npdr) and proliferative diabetic retinopathy (pdr). we processed the initial data using excel spreadsheet software and analyzed the data with the spss software (version 25, ibm, new york, ny). results from a total of 2118 patients who visited the vr department throughout 2019, 1191 new cases met the inclusion criteria. there were 667 (56%) males and 524 (44%) females giving a male: female ratio of 1.3: 1. the youngest patient was 5 years old, and the oldest was 92 years old. between the age groups, the group of 46-65 years old (678 cases, 56.9%) accounted for majority visits to vr department. the majority of patients came from bali (1104 cases, 92.7%) and mostly came from denpasar (355 cases, 32.2%) compared to eight other regions in bali. most of the patients were employees (35.4%), and senior high school graduates were the most common educational level (36.5%). type 2 diabetes mellitus (dm) was found in 185 cases (15.5%), a combination of dm and hypertension in 167 cases (14%), and hypertension in 154 cases (12.9%). other systemic conditions such as heart, kidney, stroke, tuberculosis, thyroid disorders, rubella, vitiligo, bone tumors, and systemic lupus erythematous (sle) are present in only a small amount of patients. meanwhile, type 1 dm was obtained as much as 0.1% of the total cases. a total of 637 cases (53.5%) had no recorded systemic conditions. there was 174 cases with history of cataract surgery (14.6%) accompanied vr diseases. this was followed by refractive error in 158 cases (13.3%), trauma in 22 cases (1.8%), glaucoma in 18 cases (1.5%), history of previous retinal laser from other hospital in 16 cases (1.3%), history of vitrectomy from other hospital in 6 cases (0.5%), history of lasik in 3 cases (0.3%), table 1. demographic characteristics 22 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; history of previous anti vegf injection from other hospital in 2 cases (0.2%), history of previous scleral buckle in other hospital 2 cases (0.2%) and other conditions which are a combination of above conditions. a total of 754 cases (63.3%) had no history of eye diseases. the use of insulin was recorded in 67 patients (5.5%), 41 patients with oral antidiabetic drugs (3.4%), 19 patients (1.59%) were on antihypertensive therapy and blood vessel disorders, and one patient with levothyroxine (0.01%). from a total of 1191 patients, 880 (73.9%) patients had blurred vision and 80 (6.7%) patients complained of having floaters. other presenting symptoms include black spots in the visual field, seeing flashes of light, sudden loss of vision, distorted vision, and night blindness which can arise alone or coexist with other symptoms. most patients came to the hospital after 2 weeks-6 months since the onset of the symptoms (450 cases; 37.8%). shorter periods (less than 2 weeks) were found in 15.9% of cases. according to table 2, nearly half of the patients were blind with the ratio of unilateral: bilateral blindness = 2.72:1. the mean intraocular pressure was 12.5 mmhg for the right eye, and 12.8 mmhg for the left eye. the most frequent laboratory and diagnostic tests requested by the vr department were blood sugar checks, followed by macular oct, ultrasound b scan, fundus photography, and onh oct respectively. in this study, we found different types of vr diseases over 1 year (table 3), in which diabetic retinopathy was the most common diagnosis (24.3%), followed by rhegmatogenous retinal detachment (14.2%), and pathological myopia (8.1%). as it was shown on the table 3 that diabetic retinopathy affected both eyes of 257 patients (88.6%), while rhegmatogenous retinal detachment most commonly affected one eye (164 patients, 95%). amount of 106 patients (8.1%) of vitreous opacity cases appeared bilaterally. from 290 cases of diabetic retinopathy, 173 (59.7%) cases were proliferative diabetic retinopathy and 117 (40.3%) cases were non-proliferative diabetic retinopathy. out of 290 diabetic retinopathy cases, there are 111 (38.3%) cases of diabetic macular edema with 67 (60.4%) cases affected both eyes and 34 (30,6%) cases affected only one eye. the result of this study also showed 38.2% of patients with vr diseases had concomitant cataract either in one or both eyes. table 2. baseline data of visual acuity based on icd 10 visual acuity n (total = 1191) percent (%) mild moderate severe blindness 242 278 118 553 20.3% 23.3% 118% 46.4% published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 23 table 3. vr diagnosis and affected eye 24 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; among 1191 cases, vitrectomy was the most frequent intervention done by vr department, which was done in 258 cases (21.7%), followed by injection of anti-vascular endothelial growth factor which was done in 189 cases (15,9%), barrage laser in 144 cases (12.1%), pan retinal photocoagulation in 97 cases (8.1%), silicon oil evacuation in 62 cases (5.2%), pneumatic in 16 cases (1.3%), macular grid laser in 4 cases (0.3%) and the least was hyaloidotomy which was done in only 2 cases (0.2%). cases that still needed follow-up to vr department bali mandara eye hospital were 1.4 times higher (59.1%) than cases who had completed the treatment (40.9%). discussion the increase of vr diseases cases, as the most frequent disease in bali mandara eye hospital in january 2020, intrigued us to conduct this study as we are eager to know the pattern and distribution of vr diseases in a larger number of participants.10 global estimate and report from riskesdas 2018 about the increase of diabetic patients is in concordance with our study result which showed that diabetes mellitus was the most common systemic factor found in patients with vr diseases.2,6,7,8 more than a half of total patients visited vr department were new patients. our study classified 36 types of vr diseases in 2019. male patients were higher than female patients, some similar studies conducted in subsaharan, africa and nigeria also reported the same result. these studies mentioned that the underlying reason may be contributed by social norms which restricted women to access health facilities.11,12 patients aged between 45 and 65 years old was the most common age group found in this group. the result was similar to other studies in karachi and nigeria. it was reported that vr diseases were mostly observed in this age group.12,13 in this study, we found that 94% of study participants received formal education, in which most participants were senior high school graduates. from a total of 1191 subjects, over 826 patients (69.4%) were still actively working. majority of subjects were employees, either civil servants or general employees (422 patients; 35.4%), while 365 (30.6%) subjects did not work, including housewives, students and pensionary. systemic comorbids were found in 554 participants (46.5%). the most commonly found systemic disease was type 2 dm in 185 cases (15.5%), combination of dm and hypertension in 167 cases (14%) and hypertension in 154 cases (12.9%). the same pattern was observed in sub-saharan and karachi studies.11,13 however, another study in tehran reported that hypertension was the systemic comorbid most commonly found (21.14%), followed by diabetes mellitus (15.99%).14 most of the cases (37.8%) had symptoms for approximately 2 weeks – 6 months before visiting the hospital, this may be due to distance from health care facilities, referral system, slow symptoms progression and also patient’s own rejection to seek treatment.16 majority of patients in our study came with blindness (46.4%), which most commonly affected one eye (42.4%). however, this result might be affected by cataract that accompanied in 38.2% of cases, other than the retinal disease itself. diabetic retinopathy was the diagnosis with the highest incidence found in this study this study (24.3%), this finding is parallel to the increase of diabetic cases nationally. table 4. diabetic retinopathy types dr type n (total = 290) percent (%) pdr npdr 173 117 59.7 40.3 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 25 diabetic retinopathy was also the most commonly reported vr diseases of hospital based studies as in karachi studies.13 however, the result of this study was different from a study in nepal, in which age macular degeneration (amd) was mostly diagnosed followed by diabetic retinopathy.15 according to table 3, bilateral diabetic retinopathy cases were higher that unilateral involvement, similar to study reported in karachi.13 among all 290 cases of new diabetic retinopathy patients, proliferative diabetic retinopathy was the type that most commonly found (59.7%). in the study done in nepal, the non-proliferative type was mostly diagnosed in new patients with equal distribution in the left and right eye.16 in our study, amd contributed around 95 cases (8.0%) and was the fifth most commonly found from other 36 types of vr diseases. our study also reported that in patients who came with initial presentation, amd commonly affected one eye (61.6%). a study from rai bb in nepal found that unilateral involvement of amd in the initial stage would slowly progress to bilateral cases. unilateral involvement was more common than bilateral amd in early presentation.16 aside from diabetic retinopathy, another vascular disease that was commonly found was crvo (2.0%), followed by hypertensive retinopathy (1.8%), brvo (1.3%), crao (0.3%) and brao (0.2%). this pattern is similar to study in germany and nepal, crvo incidence was found higher that brvo and crao was more common than brao.17,18,19 rhegmatogenous retinal detachment diagnosed in 169 patients (14.2%) from a total of 1191 cases with vr diseases. it was the second most common diagnosis reported in this study. we found 164 (97.0%) cases had unilateral involvement. this result is in accordance with a study conducted in india and pakistan, in which bilateral involvement was lower with percentage of 13.5% (51 cases) and 2.8% (3 cases) respectively.20,21 our study result was also similar to the theory stated that rhegmatogenous retinal detachment was more commonly found than tractional retinal detachment (4.3%) and exudative retinal detachment (0.4%). several studies mentioned that the increase of the incidence of rhegmatogenous retinal detachment is correlated with higher incidence of high myopia, peripheral degeneration, cataract surgery, trauma and rhegmatogenous disease in contralateral eye.22 in east asia, pathological myopia cases in college students contributed around 80 – 90% of rhegmatogenous retinal detachment.16,23 the research method of this study was retrospective descriptive study, thus the data was obtained from medical records. multicenter analytic prospective cohort study is considered the more appropriate research method to generalize study result in population and analyze the correlation between variables. however, this study can still provide insight regarding the characteristic of vr diseases in bali mandara eye hospital. the classification of diabetic retinopathy according to wesdr and etdrs was not presented in this study because the diagnosis was not evenly distributed. data of bcva may be influenced by disease other than retinal origin, including cataract thus, to minimize bias the proportion of cataract was presented in this study. conclusion diabetic retinopathy and rhegmatogenous retinal detachment were the most common diagnosis found in this study. strategic management must be implemented to lower the incidence including screening programs and early detection by identifying risk factors. due to higher incidence of blindness in patients with vr diseases, reducing the number of these cases may have an impact to reduce blindness. high incidence of hypertension and diabetes mellitus found in this study is in accordance with an increase of hypertension and diabetes cases according to a report from riskesdas. joint care with other departments like internal medicine and clinical pathology may be needed to formulate proper screening and management strategy. 26 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 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27(3). 14. hatef e, fotouhi a, hashemi h, mohammad k, jalali hj. prevalence of retinal diseases and their pattern in tehran: the tehran eye study. retina. 2008;28:755–762. 15. thapa et all. prevalence and pattern of vitreoretinal diseases in nepal: the bhaktapur glaucoma study. bmc ophthalmology 2013: 13:9. 16. rai et all. pattern and presentation of vitreoretinal diseases: an analysis of retrospective data at a tertiary eye care center in nepal. asia pac j ophthalmol (phila). 2019;8:481– 488. 17. thapa et al. prevalence, pattern and risk factors of retinal vein occlusion in an elderly population in nepal: the bhaktapur retina study. bmc ophthalmology. 2017; 17:162 18. ponto et all. prevalence and risk factors of retinal vein occlusion: the gutenberg health study. journal of thrombosis and haemostasis. 2015;13(7): 1254–1263. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 27 19. rajhi et all. retinal and ophthalmic artery occlusions preferred practice pattern. san fransisco; elsevier inc; 2019 [cited 2020]. available from https://www.aaojournal.org/article/s01616420(19)32095-0. 20. takkar b, azad s, bhatia i, azad r. clinical patterns and risk factors for rhegmatogenous retinal detachment at a tertiary eye care centre of northern india. nepal j ophthalmol 2017; 9(18): 60-65. 21. jamil mh, farooq n, khan mt, jamil az. characteristics and pattern of rhegmatogenous retinal detachment in pakistan. j coll physicians surg pak. 2012;22 (8): 501-504. 22. rajhi, ali. posterior vitreous detachment, retinal breaks, and lattice degeneration preferred practice pattern. san fransisco; elsevier inc; 2019 [cited 2020]. available from https://www.aaojournal.org/article/s01616420(19)32094-9/ 23. morgan ig, ohno-matsui k, saw sm. the lancet: myopia. new york: elsevier ltd 2012;379:1739–1748. this work licensed under creative commons attribution abstract introduction methods results from 290 cases of diabetic retinopathy, 173 (59.7%) cases were proliferative diabetic retinopathy and 117 (40.3%) cases were non-proliferative diabetic retinopathy. out of 290 diabetic retinopathy cases, there are 111 (38.3%) cases of diabetic macula... among 1191 cases, vitrectomy was the most frequent intervention done by vr department, which was done in 258 cases (21.7%), followed by injection of anti-vascular endothelial growth factor which was done in 189 cases (15,9%), barrage laser in 144 case... discussion conclusion 5. ocular changes in patients on long term treatment.docx published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 111 international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 ocular changes in patients on long term treatment with hydroxychloroquine anuradha singh1, sagarika patyal2, vivek vasudev3, vijay sharma4, hemant singh trehan5 1167 military hospital, pathankot, punjab, india 2 centre for sight, new delhi, india 3 military hospital bhopal, madhya pradesh, india 4 command hospital (eastern command), kolkata, west bengal, india 5command hospital (air force), bangalore, karnataka, india abstract introduction: to study the ocular changes in patients on long term treatment with hydroxychloroquine (hcq); and detect means for early detection of toxicity. methods: we conducted a cross-sectional observational study at a tertiary care hospital, in which 100 patients, male and female, aged 35 years or more, taking hcq for 5 years or more were included. patients with any known ocular or systemic diseases were not included. indication, dosage, duration and cumulative dose of hcq intake were recorded. history of ocular symptoms, visual acuity, colour vision, complete ophthalmic examination, visual field using amsler grid and 10-2 humphrey’s automated fields (hvf), spectral domain optical coherence tomography (sd-oct), colour fundus photography, fundus fluorescein angiography (ffa) and fundus autofluorescence (faf) were recorded. the data was analyzed using descriptive and inferential analysis. result: 15% of the study population showed signs of hcq related ocular toxicity. 17%, 21% and 10% patients had abnormal sd-oct, hvf and faf findings respectively. conclusion: hcq related ocular toxicity has been found in patients in the absence of symptoms. objective tests like hvf, sdoct and faf were more useful in early detection of toxicity than subjective tests such as amsler grid, colour vision and ffa. keywords: hydroxychloroquine, bull’s eye maculopathy, spectral domain optical coherence tomography, fundus autofluorescence cite this article: singh, anuradha et al. ocular changes in patients on long treatment with hydroxychloroquine. international journal of retina, [s.l.], v. 4, n. 2, p. 111, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/170>. doi:https://doi.org/10.35479/ijretina.2021.vol004.iss002.170. correspondence to: anuradha singh, 167 military hospital , pathankot, punjab, india anuradha9000@gmail.com introduction the eyes are target organs for damage from many systemic drugs such as chloroquine, hydroxychloroquine, vigabatrin, isotretinoin, topiramate, ethambutol, amiodarone, herbal medication like gingko biloba.[1] hydroxychloroquine (hcq), a drug initially developed as an antimalarial, was soon found to be effective in the treatment of a variety of systemic diseases, like rheumatoid arthritis, ankylosing spondylosis, systemic lupus erythematosus, discoid lupus, sarcoidosis, sjogren’s syndrome, photosensitivity disorders.[2,3] https://www.ijretina.com/index.php/ijretina/article/view/170 https://doi.org/10.35479/ijretina.2021.vol004.iss002.170 112 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; it initially replaced chloroquine due to irreversible adverse effects of the latter. however, subsequently, hcq was also found to have irreversible ocular side effects, especially retinal toxicity. it has been estimated that the prevalence of ocular toxicity due to hcq is about 7.5% in patients taking the drug for over 5 years.[4] the mechanism of toxicity with hcq is not fully elucidated. the earliest changes appear to occur in the cytoplasm of photoreceptors and ganglion cells. later, the retinal pigment epithelium (rpe) is involved, where the drug binds with melanin. it may have an adverse effect on retinal cell metabolism leading to slow and long-term toxicity.[5] hcq, like chloroquine (cq) is a lysomotropic drug, and is an enhancer of lipofuscinogenesis. [6] numerous studies have been conducted across the world to elucidate the prevalence, mechanism, progression, methods of detection and outcome of hcq induced retinal toxicity. most studies have been aimed at comparing two or more investigative modalities to determine their relative efficacy for early detection of toxicity. this study included multiple testing methods including visual acuity, colour vision, amsler grid testing, 10-2 humphrey’s visual fields (hvf), spectral domain optical coherence tomography (sd-oct), slit lamp examination, dilated fundus examination, colour fundus photography, fundus autofluorescence (faf) and fundus fluorescein angiography (ffa) to maximize the detection of toxicity. multifocal electroretinogram (mf erg), however, could not be done due to non-availability of the test at our hospital. this study is different from previous studies because it exhaustively incorporates multiple methods of detection of hcq induced retinal toxicity. it aims at studying the ocular changes in patients on long term treatment with hcq, with the objective of determining the methods for early detection of toxicity, by eliciting a detailed history about indication, dose, duration and cumulative dose of hcq, ocular symptoms; a detailed ocular examination with visual acuity and colour vision testing, amsler grid testing, anterior and posterior segment examination over the slit lamp and indirect ophthalmoscopy. investigations carried out for every patient were humphrey’s 10-2 hvf, sd-oct, ffa, faf. methods our study was a cross sectional observational study of 100 patients over a duration of one and a half years, carried out in the department of ophthalmology at a tertiary care hospital in new delhi, india. 100 patients who were undergoing long term treatment with hcq were referred from the department of rheumatology of the hospital. male and female patients, aged 35 years or more, who were on treatment with hcq for any rheumatological or inflammatory condition for 5 years or more were included in the study. the exclusion criteria included patients on treatment with hcq for less than 5 years; any known diseases or anomalies affecting the optic nerve, viz. optic neuropathy, optic disc drusen, optic disc pit or coloboma; any known retinal diseases like diabetic retinopathy, retinitis pigmentosa, age related macular degeneration, ocular occlusive vascular diseases; other ocular diseases like uveitis, glaucoma or glaucoma suspects, any past history of intraocular or refractive surgery, any media opacity that may preclude a high quality oct examination, history of diabetes mellitus or hypertension, deranged liver or renal function tests. patients were informed about the investigations they would undergo, including the potential risks with ffa. a written informed consent was taken. the study had the ethical approval from the ethics committee of the hospital, and was carried out in published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 113 accordance with the ethical standards stated in 1964 declaration of helsinki. the patients were counselled about the toxic effect of the said drug, the progressive and irreversible nature of the condition and the rationale of screening for drug toxicity. the patients underwent an exhaustive ophthalmic examination which included a history of visual complaints, visual acuity testing with snellen’s chart and near vision including best corrected visual acuity, colour vision assessment using ishihara plates, amsler grid assessment, slit-lamp examination for anterior segment evaluation, indirect ophthalmoscopy with a 20 diopter lens to look for irregularity in macular pigmentation, blunting of foveal reflex (early finding), bull’s eye maculopathy (classic finding), peripheral pigment irregularity and bone spicule formation, vascular attenuation, optic disc pallor (late finding), 10-2 hvf, sd-oct, colour fundus photography, ffa, faf. descriptive and inferential statistical analysis were carried out in the study. results on continuous measurements are presented on mean ± standard deviation (min-max) while results on categorical measurements are presented in number (%). results a total of 125 patients were considered for the study, of which 100 patients fulfilled the eligibility criteria detailed above. the patients were examined and investigated in a single sitting; hence, no cases were lost to follow up. the mean age of our study population was 52.9 ± 10.30 years, with the age group ranging from 36-76 years. the study population was predominated by females (89%). the mean daily intake of hcq was 212 ± 47.73 mg over a mean duration of 8.25 ± 3.58 years (table 1). table 1. variables related to disease and treatment history variable no of patients mean std dev min max age of patient (years) 100 52.9 10.30397 36 76 duration of disease (years) 100 12.65 6.475088 5 40 daily dose of hcq (mg) 100 212 47.73665 200 400 duration of hcq (years) 100 8.36 3.543439 5 20 cumulative dose of hcq (grams) 100 623.23 268.3256 365 1460 114 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; the cumulative dose intake was 623.23 ± 268.32 g, with minimum and maximum cumulative doses of 365g and 1460g respectively. of the 100 patients studied, 37 patients presented with ocular complaints. these were mostly subjective in nature, ranging from difficulty in reading, dimness, discomfort to bright light, and occasionally, a scotoma in the field of vision. a reduction in visual acuity was noticed in 82% patients using snellen’s distant visual acuity chart at 6m and jaeger chart for near vision at 33 cm. however, most patients could be given a satisfactory best corrected visual acuity with spectacles. if not, the diminished vision could be attributed to the presence of senile cataract or posterior sub capsular cataract which may be due to concomitant oral steroid use. 02 out of 100 patients had diminished vision which could be attributed to the presence of hcq related retinal toxicity. presence of corneal deposits was not detected in any of the 100 patients on slit lamp examination. fundus evaluation done with indirect ophthalmoscope with 20 diopter lens and slit lamp biomicroscope with 90 diopter lens revealed the following findings: 92% patients showed no abnormal pigmentary changes at the macula (fig 1). of the 8% patients who had irregular macular pigmentation, 1 patient had unilateral changes while the rest 7 patients had bilateral changes. blunting of foveal reflex as an early feature of retinal toxicity was seen in 9 out of 100 patients (9%). the remaining 91 patients had normal foveal reflex on fundoscopy. bull’s eye maculopathy was noticed bilaterally on clinical examination in one patient (1%), along with vascular attenuation and optic atrophy (fig 2). changes in peripheral retina and bony spicule pigmentation was not detected in any of the study subjects. the subtlety of clinical findings in our patients was found to be in agreement with a study published by mavrikakis et al in 2003.[7] figure 1: pigmentary changes at macula figure 2: bull’s eye maculopathy with vascular attenuation and optic disc atrophy in left eye 17% patients showed abnormality on oct macula, which ranged from early parafoveal and perifoveal thinning to foveal atrophy in advanced case with bull’s eye maculopathy (fig 3). the classical “flying saucer” sign described by eric chen et al was not detected in any of the subjects.[8] 21% patients showed field defects on 10-2 hvf, which ranged from small paracentral defects to paracentral ring and arcuate scotomas as well as central scotomas (fig 4). 10% of the patients gave an abnormal fundus auto fluorescence, in the form of a ring of hyperautofluorescence surrounding a zone of central hypoautofluorescence at the macula (fig 5, 6). no significant abnormality was detected on ffa, amsler grid, colour vision testing using ishihara plates among any of the patients. among any of the patients. 10-2 hvf, published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 115 amsler grid and colour vision assessment could not be done in 01 patient with bull’s eye maculopathy due to low vision. figure 3. sd-oct macula showing severe foveal, perifoveal and parafoveal thinning figure 4. visual field defects in a patient with hcq toxicity figure 5: fundus autofluorescence of right eye showing hyperautofluorescence at macula figure 6: fundus autofluorescence of left eye of a patient with bull’s eye maculopathy based on sd-oct, 10-2 hvf and faf findings, we detected features of hcq toxicity in 15% of the subjects under evaluation. 17%, 21% and 10% patients showed abnormal sd-oct, automated perimetry and faf findings respectively. the results did not have a direct correlation with age, weight, daily dose and cumulative dose of the drug (table 2). 116 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; table 2. cases of hcq toxicity based on investigation findings discussion this was a cross sectional observational study conducted in a tertiary care teaching hospital in new delhi, india. a sample size of 100 patients on long term hcq treatment was clinically examined and screened for retinal toxicity using a battery of investigative modalities after written informed consent. the findings of the study were analyzed using descriptive analysis. the mean age was 52.9 ± 10.30 years. females predominated the study (89%). the mean daily intake of hcq was 212 ± 47.73 mg over a mean duration of 8.25 ± 3.58 years. the cumulative dose intake was 621 ± 261.80 g. majority of the patients were asymptomatic, reduced visual acuity due to hcq related toxicity was found in 02 cases. sd-oct, 10-2 hvf and faf picked up retinal abnormality in 17%, 21% and 10% cases respectively. amsler grid, colour fundus photography, colour vision and ffa failed to detect abnormalities in these patients. s no age/ sex diag bcva duration of treatment (years) daily dose (mg) cumulative dose (g) sdoct 10-2 hvf faf 1 52/f ra 6/6, 6/6 8 200 576 + + + 2 38/f ra 6/6, 6/6 6 200 438 + + + 3 50/f ra 6/6, 6/6 13 200 949 + + + 4 55/f ra 6/9, 6/9 10 200 730 + + 5 44/f ra 6/9, 6/12 10 200 730 + + + 6 50/f ra 6/6, 6/6 13 200 949 + + + 7 66/f ra 6/6, 6/6 10 200 730 + + 8 47/f ra 6/6, 6/6 10 200 730 + + 9 60/f ra 6/6, 6/6 9 200 660 + + 10 73/m ra 2/60, 3/60 11 200, 400 1168 + nr + 11 42/f sle 6/6(p), 6/6(p) 7 200, 400 653 + + + 12 48/f ra 6/6, 6/6 10 200 730 + + + 13 43/f ra 6/6, 6/6 6 200 438 + + + 14 56/f ra 6/6(p), 6/9(p) 9 200 660 + + + 15 62/f ra 6/9(p), 6/18(p) 14 200 1008 + + published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 117 the outcomes of this study conformed to those of some other studies while they varied from some others. the incidence of retinal toxicity with hcq is estimated to be 0.5% after 5 years of therapy.[9] a retrospective cohort study of 234 thai rheumatology patients revealed the incidence of hcq retinopathy to be 3.28% with cumulative doses from 80-130g over a period of 660-828 days.[10] we found an overall incidence of toxicity of 15% in our study group. age and weight of the patient, and daily dosage of the drug were not found to have strong correlation in our study, which was similar to a study conducted by frederick wolfe and michael f. marmor.[11] a study conducted by doo-ri et al over 310 korean patients and published in march 2017, found a much lesser prevalence of toxicity (9 out of 310 patients). however, the demographic profile, cumulative dose and duration of treatment, visual acuity and findings on oct, hvf and faf revealed similar outcomes among those with toxicity.[12] the study population was predominated by females (89%) which was similar to the study published by doo-ri et al (92.3%)[12] and also reflected a greater prevalence of rheumatological disorders among women.[13] majority of our patients were asymptomatic, as also seen in a study by mavrikakis et al.[14] clinical examination revealed absence of corneal deposits as a consistent finding, as also seen in a study published by rynes ri in 1983.[15] irregular macular pigmentation and blunting of foveal reflex were seen in 8% and 9% patients respectively. bull’s eye maculopathy along with vascular attenuation and optic disc pallor was seen in 1% of the cases; while peripheral pigment abnormality and bone spicule formation were not seen in any cases. the subtlety of clinical findings in our patients was found to be in agreement with a study published by mavrikakis et al in 2003.[16] on investigation, although abnormalities on oct macula were seen in 17% patients, the classic ‘flying saucer’ sign described by eric chen et al was not detected in any of the subjects.[17] the results of the above investigative modalities highlighted the usefulness of the newer modalities of detection of hcq related retinal toxicity over the previously practiced methods like amsler grid, colour vision, fundus photography and fundus fluorescein angiography. the study found sd-oct, 10-2 automated perimetry and faf to be superior to the aforementioned techniques in detection of toxicity. this was in agreement with the latest guidelines issued by the american academy of ophthalmology in 2016 for screening of hcq related retinal toxicity.[18] the study was the first of its kind to incorporate a comprehensive battery of evaluation and investigation modalities. in this regard, we were able to clearly delineate the relative importance of these methods for early detection of toxicity, including the novel methods of investigation. we were also able to detect significant retinal toxicity in seemingly asymptomatic patients. the main limitations of the study were a small sample size of the study, nonavailability of a normal distribution of patient population and absence of linear relationship between different variables leading to difficulty in correlation analysis. conclusions long term hcq treatment should always be viewed with concern, as the risk of toxicity may remain despite a lower than maximum daily dose if given over a prolonged period of time. in our study, majority of the patients were on treatment with 200mg/day dose of hcq. even so, features suggestive of retinal toxicity were detected in 15% of the cases. also, this study highlights the greater utility of newer modalities of investigation over the previously used subjective methods of assessment. the latest guidelines issued by the american academy of ophthalmology are of greatest relevance in the present-day scenario till the time 118 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; new research brings into light better ways of earlier detection of this cause of irreversible vision loss. conflicts of interestthe authors have no personal or financial conflicts of interest. acknowledgement: ms kavita, for assisting with statistical analysis of this work references 1. 1. santaella rm, fraunfelder fw, ocular adverse effects associated with systemic medications, drugs, 67(1), 2007, 75-93. 2. n.j. olsen, m.a. schleich and d.r. karp, multifaceted effects of hydroxychloroquine in human diseas, semin arthritis rheum. , 43(2), 2013, 264 72. 3. leslie raphael de moura ferraz et al. clinical, pharmacokinetic and technological aspects of the hydroxychloroquine sulphate. iosr j pharmacol. 4(11), 2014; 53-64. 4. yusuf ih, sharma s, luqmani r, downes sm. hydroxychloroquine retinopathy. eye (lond). 2017;31(6):828-845. 5. geamånu a et al. retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening.review. j med life. 7(3), 2014; 322-326. 6. sundelin s, terman a. different effects of chloroquine and hydroxychloroquine on lysosomal function in cultured retinal pigment epithelial cells. apmis. 110(6), 2002; 481-489. 7. mavrikakis i, sfikakis pp, mavrikakis e, et al. the incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. ophthalmology. 2003; 110(7):13211326. 8. chen e, brown dm, benz ms, et al. spectraldomain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign). clinical ophthalmology. 2010; 4:1151-1158. 9. paulose rm, chhablani j, jhingan m. update on hydroxychloroquine retinopathy. kerala j ophthalmol. 29(1), 2017; 9-13. 10. tangtavorn n et al. incidence of and risk factors for chloroquine and hydroxychloroquine retinopathy in thai rheumatologist patients. clin ophthalmol. 10, 2016; 2179-2185. 11. wolfe f, marmor mf. rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. arthritis care res. 2010; 62:775784. 12. eo d, lee m g, ham don-ii et al. frequency and clinical characteristics of hydroxychloroquine retinopathy in korean patients with rheamatologic diseases. j korean med sci. 2017 march; 32(3): 522-527. 13. malviya a n, kapoor s k, singh r r et al. prevalence of rheumatoid arthritis in the adult indian population. rheumatol int. 1993; 13:131. 14. mavrikakis m, papazoglou s, sfikakis pp, et al. retinal toxicity in long term hydroxychloroquine treatment. ann rheum dis. 1996; 55:187-189. 15. rynes ri. ophthalmologic safety for long-term hydroxychloroquine sulphate treatment. am j med. 1983; 75(1):35-39. 16. mavrikakis i, sfikakis pp, mavrikakis e, et al. the incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. ophthalmology. 2003; 110(7):13211326. 17. chen e, brown dm, benz ms, et al. spectraldomain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign). clinical ophthalmology. 2010; 4:1151-1158. 18. marmor mf, kellner u, lai tyy, et al. recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). ophthalmology. 2016; 123(6):1386-1394. this work licensed under creative commons attribution anuradha singh1, sagarika patyal2, vivek vasudev3, vijay sharma4, hemant singh trehan5 1167 military hospital, pathankot, punjab, india 2 centre for sight, new delhi, india 3 military hospital bhopal, madhya pradesh, india 4 command hospital (eastern command), kolkata, west bengal, india 5command hospital (air force), bangalore, karnataka, india abstract methods conclusions 34 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; international journal of retina (ijretina) 2022, volume 5, number 1. p-issn. 2614-8684, e-issn.2614-8536 prevalence of advanced diabetic eye disease among diabetic patients in a tertiary care hospital in south india ksheeraja y1, ramya m1 1 m s ramaiah medical college, bangalore abstract introduction: to analyze the prevalence of advanced diabetic eye disease(aded) among diabetic patients methods: this was a prospective cross-sectional study in a tertiary care hospital. a total of 1650 patients with a history of type 2 diabetes who visited ophthalmology department were enrolled in study after obtaining informed consent as per the declaration of helsinki. history regarding socioeconomic status, literacy level, duration of diabetes, comorbidities, medications, hba1c levels were analyzed. visual acuity, slit-lamp, fundus examination were done.medical/surgical intervention was done to restore vision. result: a total of 1650 patients with a history of type 2 diabetes were analyzed. among them 327 patients had fundus changes of diabetic retinopathy, hence the prevalence of dr among diabetics was 19.81%. out of 327 patients, 53 patients had advanced diabetic eye disease and the prevalence of aded among diabetics was 3.20%. the mean age of the patients was 50.91+/9.06years.there were 42 (79.24%)males and 11 (20.7%)females.24 (45.28%)patients had vision of 6/6 6/60, 28 (52.83%|) patients had vision 5/60-cfcf.15(28.30%) patients had pdr with vitreous hemorrhage.12 patients (22.64%) had pdr with subhyaloid hemorrhage,11 patients (20.75%) had pdr with fvp sparing macula,13 patients(24.52%) had pdr with fvp involving the macula,2 patients(3.77 %) had pdr with neovascular glaucoma.34 patients (64.15%) underwent prp,19 patients (35.84 %) needed surgical intervention. conclusion: this study shows that the prevalence of diabetic retinopathy among diabetic patients was 19.81%. the prevalence of advanced diabetic eye disease among diabetic patients was 3.2%. hence effective implementation of primary, secondary and tertiary prevention strategies has the potential to significantly reduce blindness due to dr. keywords: adedadvanced diabetic eye disease, dr-diabetic retinopathy, pdrproliferative diabetic retinopathy, vh-vitreous hemorrhage, fvp-fibrovascular proliferation, hba1c-glycated hemoglobin. cite this article: y, ksheeraja; m, ramya. prevalence of advanced diabetic eye disease among diabetic patients in a tertiary care hospital in south india. international journal of retina, [s.l.], v. 5, n. 1, p. 25, feb. 2022. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/178 doi: https://doi.org/10.35479/ijretina.2022.vol005.iss001.178. correspondence to: ramya m, m s ramaiah medical college, bangalore, india. ramya8366@gmail.com introduction diabetic retinopathy (dr) is a vascular disorder affecting the microvasculature of the retina. it has been found that diabetes mellitus affects 4 percent of the world's population, almost half of whom have some changes of dr at any given time.1 . published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 35 in india diabetic retinopathy is an important cause of visual disability. but this can be prevented and treated if detected early. if managed with timely intervention, the quality of life and the vision can be preserved. this study aims at providing an overview of prevalence and visual disability caused by advanced diabetic eye disease in the indian scenario.2 diabetic retinopathy is a progressive microvascular complication of diabetes. on fundoscopy microaneurysms, cotton wool spots (cws), hemorrhages, venous caliber abnormalities, intraretinal microvascular abnormalities (irmas), neovascularization of disc(nvd), neovascularisation elsewhere(nve) are the features of proliferative diabetic retinopathy. uncontrolled glycemic status leads to advanced diabetic retinopathy ( aded) which is characterized by non resolving vitreous hemorrhage, fibro vascular proliferation,tractional retinal detachment, rubeosis iridis and gradually progresses and leads to irreversible blindness.3 the prevalence of dr varies in type 1 and type 2 diabetes. in eurodiab iddm complications study, the prevalence of dr ranged between 25-60 percent.4 in india, there is a paucity of data on the prevalence of dr in type 1 diabetes mellitus, as a registry for the prevalence of type 1 diabetes is only recently being set up in the country. an earlier study done in a clinic-based population reported an overall prevalence of 14 percent. asian young diabetes research (asdiab) study, reported the prevalence of dr in 724 young diabetic subjects of age 12-40 yr with the duration of diabetes < 12 months in 7 centers of four asian countries. they noted that dr prevalence was least among indians (5.3%) as compared to other ethnic groups. 5. lack of symptoms and the insidious onset of type 2 diabetes may result in the development of dr at an early stage.6 dandona et al found that multiple risk factors including duration of diabetes, more age, gender, poor glycemic control, hypertension, hyperlipidemia, anaemia, nephropathy, socioeconomic status, and family history of dm are significantly associated with the development and progression of diabetes retinopathy (dr).7 methods this was a prospective cross-sectional study conducted at a tertiary care hospital. a total of 1650 patients with a history of type 2 diabetes who visited the ophthalmology department were enrolled in the study. the study period was from march 2019 to february 2020 for 12 months. among them, 327 patients had fundus changes of diabetic retinopathy of various grades including non-proliferative and proliferative diabetic retinopathy. out of 327 patients, 53 patients had advanced diabetic eye disease at presentation. the study adhered to the tenets of the declaration of helsinki and written informed consent was obtained from all the patients. patients with type 2 diabetes mellitus with proliferative diabetic retinopathy with nvd, nve, subhyaloid hemorrhage, vitreous hemorrhage, patients with severe vision-threatening proliferative diabetic retinopathy, fibrovascular proliferation with tractional retinal detachments were included in the study as advanced diabetic eye disease. history regarding demographic details including occupation, socioeconomic status, literacy level, duration of diabetes, medications, hba1c levels at presentation was analyzed. visual acuity was recorded using snellen's visual chart. slit-lamp examination of anterior segment, fundus examination was done for all patients using indirect ophthalmoscopy. 36 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; patients with proliferative diabetic retinopathy with nvd, nve, subhyaloid hemorrhage underwent emergency pan retinal photocoagulation to prevent further progression of diabetic retinopathy and preserve vision. patients with severe vision-threatening proliferative diabetic retinopathy were advised urgent referral to a vitreoretinal surgeon for pars plana vitrectomy with endolaser a, membrane peeling, fluid air exchange, and silicon oil implantation. results a total of 1650 patients with a history of type 2 diabetes were analyzed. among them, 327 patients had fundus changes of diabetic retinopathy of various grades including non-proliferative and proliferative diabetic retinopathy. out of 327 patients, 53 patients had advanced diabetic eye disease at presentation. the mean age of the patients was 50.03+/years. there were 42 (79.24%) males and 11 (20.7%) female patients. in our study, we found that 29 patients (54.71%) are of the age group 51-60 years. out of which 42 were males,11were females. twenty-two patients (41.50 %) had a duration of diabetes of more than 10 years.18 patients (33.96 %) were on oral hypoglycemic drugs.35 patients (66.03%) were on insulin. 33 patients had (62.26 %) hba1c level of 8.1 10.60% of the patients had hypertension and 30.18% patients had dyslipidemia,28.30% patients had chronic kidney disease, 11.32% patients had ishemic heart disease 3.77% patients had a stroke. thirty patients (56.60 %) belonged to middleincome socioeconomic status.58.49 percent of patients were hailing from the urban background, 41.50 % were from the rural background. all the above patient demographic details are shown in table 1. table 1. age distribution and demographic details of patients twenty four(45.28%)patients had a vision of 6/6 6/60, 28 (52.83%|)of patients had vision 5/60counting fingers close to face, one patient (1.88%) had perception of light at presentation.36(67.92%)patients had immature cataract,17(32.07%) patients had undergone previous cataract surgery as shown in table 2. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 37 table 2 visual acuity and lens status in our study 15 (28.30%) patients had pdr with vitreous hemorrhage. twelve patients (22.64%) had pdr with subhyaloid hemorrhage,11 patients (20.75%) had pdr with fvp sparing the macula,13 patients had (24.52%) had pdr with fvp involving the macula 2 patients had (3.77 %) had pdr with neovascular glaucoma. regarding the treatment 34 patients (64.15%) underwent pan retinal photocoagulation,19 patients (35.84 %) needed the surgical intervention pars plana vitrectomy.the details of diagnosis and treatment are as shown in table 3 and shown in figure 1. table 3 diagnosis and treatment figure 1 1a: pdr with nvd and subhyaloid hemorrhage 1 b: pdr with nve, nvd 1 c: pdr with extensive fvp, trd involving the macula 1 d: pdr with fvp sparing macula with subhyaloid hemorrhage visual acuity number(n) percentage(%) 6/6-6/60 24 45.28 5/60cfcf 28 52.83 perception of light 1 1.88 lens status phakia 36 67.92 pseudophakia 17 32.07 diagnosis number(n) percentage(%) pdr with vitreous hemorrhage(vh) 15 28.30 pdr with subhyaloid hemorrhage 12 22.64 pdr with fvp sparing the macula 11 20.75 pdr with fvp involving the macula 13 24.52 pdr with neovascular glaucoma(nvg) 2 3.77 treatment panretinal photocoagulation(prp) 34 64.15 pars plana vitrectomy(ppv) 19 35.84 38 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; discussion diabetes mellitus is one of the leading causes of avoidable blindness. diabetes is a multi-factorial disease. awareness of factors affecting the incidence and the severity of diabetic retinopathy is useful for preventing blindness and other micro-vascular complications of diabetes mellitus. screening of diabetic patients and advising on the regular followup to monitor the progression of diabetic retinopathy is of crucial in preventing advanced diabetic eye disease. in this study, we found that 29 patients( 54.71%) are of the age group 51-60 years. out of which 42 were males,11were females. gadkari et al reported that among these, 61.2% were males. about 88.6% of those screened were between 40 and 80 years of age. 8 we found that twenty two patients (41.50 %) had a duration of diabetes of more than 10 years. mehta et al found that when the duration of diabetes exceeded 10 years, the higher number of subjects (66.10%) had pdr. bhutia et al reported the duration of diabetes was seen to be highest in 72 patients (> 20 years)9 in our study, we found that 18 patients (33.96 %) were on oral hypoglycemic drugs.35 patients (66.03%) were on insulin. raman et al reported that use of insulin (or, 3.52; 95% ci, 2.05–6.02); longer duration of diabetes (>15 years; or, 6.43; 95% ci, 3.18–12.90); and subjects with known diabetes mellitus (or, 2.98; 95% ci, 1.72–5.17) had higher prevalence of dr. we found that thirty patients (56.60 %) belonged to middle-income socioeconomic status.58.49 % of patients were hailing from the urban background, 41.50 % were from the rural background. raman et al found that differences in socioeconomic status did not influence the occurrence of diabetic retinopathy.10 we found that 33 patients had (62.26 %) hba1c levels of 8.110. there is higher prevalence of aded in patients with poor glycemic control ( hba1c > 7%). a study done by shahi et al reported that having good glycemic control (hba1c < 7%) had a lower prevalence of diabetic retinopathy (23.4%) as compared to those having poor control (hba1c > 7%) (76.6%). the percentage increased to as high as 93.1% chances of having diabetic retinopathy if the hba1c levels are above 8.5 % indicating a poor control of diabetes and more severe microvascular complications.11 we found that 60% of the patients had hypertension and 30.18 % of patients had dyslipidemia,28.30 % patients had chronic kidney disease, 11.32 % patients had ischemic heart disease, 3.77% patients had a stroke. karishma et al reported that hypertension was the most common comorbidity followed by heart disease, thyroid disease, neuropathy.12 we reported that 12 patients (22.64%) had pdr with sub hyaloid hemorrhage,11 patients (20.75%) had pdr with fvp sparing the macula,13 patients had (24.52%) had pdr with fvp involving the macula 2 patients had (3.77 %) had pdr with neovascular glaucoma. raman et al reported that 12 patients had aded, 7 of them had retinal detachment, 4 of them had severe maculopathy with blindness and 1 had vitreous hemorrhage.10 we found that 24(45.28%)patients had a vision of 6/6 -6/60, 28 (52.83%|) patients had vision of 5/60 cfcf,1(1.88%) of patients had perception of light.15(28.30%) of patients had pdr with vitreous hemorrhage.khan et al reported that out of the 645 (73.5%), 356 (55.1%) had va of 6/12 or better while 199 (30.8%) and 90 (13.9%) eyes had va of worse than 6/12 and better than 6/60 and 6/60 or worse respectively. almost 3/4th (75.8%) eyes in the persistent pdr group had va < 6/12 as against 45% in the stable treated group (p = <0.0001).13 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 39 in a study done by tien yin wong et al, they found the following reasons for the increase in the prevalence of diabetic retinopathy. lack of awareness of dr among patients, treating physicians, lack of compliance with regular eye checkups, lack of communication between primary care physicians and ophthalmologists regarding patients' ocular findings, efficient referral practices, limited access to dr screening14. hence the following solutions were formulated to overcome the challenges in dr. integrating eye care into routine diabetes care/primary care and integrating dr policies, guidelines, and training into all relevant national health policies and guidelines. promote surveillance and research for assessing the burden of dr, population needs, and evaluating the costeffectiveness of interventions, particularly in low and middle-income countries. developing national action plans for addressing dr in consultation with relevant stakeholders across diabetic and eye health care, patients, the private sector, and provincial government, and then integrating these plans into national diabetes strategies. planning for services to be provided at primary/secondary/tertiary-level health care facilities as shown in table 4. conclusion dr is a global epidemic that accounts for visual disability if not treated on time. the prevalence of diabetic retinopathy among diabetic patients was 19.81%. the prevalence of advanced diabetic eye disease among diabetic patients was 3.2%. hence effective implementation of primary, secondary and tertiary prevention strategies has the potential to significantly reduce blindness due to dr. references 1. aiello lp, gardner tw, king gl, blankenship g, cavallerano jd, ferris fl 3rd, et al. diabetic retinopathy. diabetes care 1998; 21 : 143-56.. 2. m. rema & r. pradeepa, diabetic retinopathy: an indian perspective, indian j med res 125, march 2007, pp 297-310 table 4. primary prevention secondary prevention tertiary prevention 1. improve awareness of diabetic retinopathy to the patients and primary physician 2. lifestyle changes to control the body mass index and glycemic status. 3. medications to control risk factors like hypertension, dyslipidemia 4. systematic screeningfor early detection of dr 5.establishing a dr eye unit, training eye care professionals, screening for dr 1. regular screening to monitor for progression of drperiodic fundus examination and appropriate referral from medicine, endocrinology, nephrology, cardiology departments to ophthalmology to monitor diabetic retinopathy progression. 2. to form the guidelines for managing dr and preserve vision by the appropriate timely intervention 3. comprehensive diabetic workup including an endocrinologist,ophthalmologist,cardio logist, nephrologist, vascular surgeons to be made available for the patients to prevent systemic and ocular complications of diabetes. 1. medical management a.retinal lasers-pan retinal photocoagulation(prp) b.intravitreal anti-vegf injections-ranibizumab c.intravitreal steroids triamcinolone acetate, dexamethasone implant 2.surgical intervention pars plana vitrectomy with endolaser and silicon oil implantation 40 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2022; 5; 1; 3. bano s, som v, dubey a, kumar k. risk factors associated with diabetic retinopathy among patients with type 2 diabetes mellitus in central india. indian j clin exp ophthalmol 2019;5(3):335-8. 4. abrahamian h, hörnlein b, gurdet c, willinger c, zaruba e, irsigler k. insulinabhängiger diabetes mellitus: "eurodiab iddm complications study"--ergebnisse des wiener zentrums [insulindependent diabetes mellitus:"eurodiab iddm complications study"--results from the vienna center]. wien klin wochenschr. 1994;106(5):136-40. german. pmid: 8171869. 5. rema m, premkumar s, and anitha b . prevalence of diabetic retinopathy in urban india: the chennai urban rural epidemiology study) cures (eye study. invest ophthalmol vis sci. 2005;46:2328-33. 6. harris mi. undiagnosed niddm: clinical and public health issues. diabetes care 1993; 16 : 642-52 7. dandona l, dandona r, naduvilath tj. population-based assessment of diabetic retinopathy in an urban population in southern india. br j ophthalmol. 1999;83:937-40. 8. gadkari ss, maskati qb, nayak bk. prevalence of diabetic retinopathy in india: theall india ophthalmological society diabetic retinopathy eye screening study 2014. indian j ophthalmol 2016;64:38-44. 9. bhutia kl, lomi n, bhutia sc. prevalence of diabetic retinopathy in type 2 diabetic patients attending tertiary care hospital in sikkim. 10. raman r, rani pk, reddi rachepalle s, gnanamoorthy p, uthra s, kumaramanickavel g, et al. prevalence of diabetic retinopathy in india: sankara nethralaya diabetic retinopathy epidemiology and molecular genetics study report 2. ophthalmology. 2009;116(2):311–8. doi: 10.1016/j.ophtha.2008.09.010. 11. dr. deepasha shahi bagzai, dr. avinash bagzai*, correlation between severity of diabetic retinopathy with hba1c in type ii diabetic patients, journal of medical science and clinical research, issn (e)-2347-176x issn (p) 2455-0450 doi: https://dx.doi.org/10.18535/jmscr/v7i3.53 12. karishma g, rambharos f, gautam lfactors affecting retinal screening among patients with diabetes in india.djo 2021;31:28-31 13. khan, r., chandra, s., rajalakshmi, r. et al. prevalence and incidence of visual impairment in patients with proliferative diabetic retinopathy in india. sci rep 10, 10513 (2020). https://doi.org/10.1038/s41598-020-67350-6 14. tien yin wonga, b charumathi sabanayagama, b, strategies to tackle the global burden of diabetic retinopathy: from epidemiology to artificial intelligence, ophthalmologica 2020;243:9–20 this work licensed under creative commons attribution https://dx.doi.org/10.18535/jmscr/v7i3.53 abstract introduction methods results table 1. age distribution and demographic details of patients in our study 15 (28.30%) patients had pdr with vitreous hemorrhage. twelve patients (22.64%) had pdr with subhyaloid hemorrhage,11 patients (20.75%) had pdr with fvp sparing the macula,13 patients had (24.52%) had pdr with fvp involving the macula 2 ... discussion conclusion 8.the difference of quality of life and cognitive function between patients with and without age-related macula degeneration (amd).docx 142 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 the difference of quality of life and cognitive function between patients with and without age-related macula degeneration (amd) bobby kristianto1, anak agung ayu sukartini djelantik1, ari andayani1, i gusti ayu made juliari1, anak agung mas putrawati t1, ni made ari suryathi1, i gde raka widiana2 1 departement of ophthalmology, faculty of medicine, udayana university/sanglah general hospital, denpasar, bali 2 departement of internal medicine, faculty of medicine, udayana university/sanglah general hospital, denpasar, bali abstract introduction: to determine the difference in the quality of life and cognitive function in patients with and without amd. methods: this research is an observational analytic study, a prospective cross sectional study with independent t-test statistical analysis. result: study samples’s total are 66 people selected by consecutive sampling with 33 people in the group with amd, and 33 people in the group without amd and each sample must filled the national eye institute visual function questionaire (nei-vfq) and mmse questionaire. the results of the study showed the average age of the group with amd 68 years and the group without amd 67 years old. most of the male sex and residence in denpasar in both groups. most amd with the wet type by 60.6 %. on the measurement of quality of life, it showed decreasing in all subscale in the group with amd compared to the group without amd with total average 27.2 % and also decreasing in cognitive function measured by mmse in the group of amd compared to the group of non – amd with 6.8%, even though the mmse score of the groups are within normal limits. all these things stated significant differences (p<0.05) statistically. conclusion: there are decreasing quality of life and cognitive function in amd groupd compared to non-amd group which is needed more treatment and screening in the future. keywords: age-related macula degeneration,amd,armd,vitreo-retina,macula cite this article: kristianto, bobby et al. the difference of quality of life and cognitive function between patients with and without age-related macula degeneration (amd). international journal of retina, [s.l.], v. 4, n. 2, p. 142, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/168>.doi: https://doi.org/10.35479/ijretina.2021.v ol004.iss002.168. correspondence to: bobby kristianto, departement of ophthalmology, faculty of medicine, udayana university/sanglah general hospital, denpasar, bali; bobby.kristianto91@gmail.com introduction age-related macular degeneration (amd) is the macular disease who can affect loss of central vision for older people.(aao, 2020) amd also as one of world blindness causes with 8.7%. there are two types, dry amd and wet amd which is dry ones is the most common of amd. (aao, 2020) the causes of amd is still not yet determined but history of smoking and hypertension gives higher risk to become amd. main symptoms of amd are loss of central vision. (areds, 2020) in world, amd is estimated almost 20-25 million people for suffering and would be 3 times more in the next 30-40 years.(bhutto, 2014) https://www.ijretina.com/index.php/ijretina/article/view/168 https://doi.org/10.35479/ijretina.2021.vol004.iss002.168 https://doi.org/10.35479/ijretina.2021.vol004.iss002.168 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 143 for western countries, amd has become one of main blindness causes. the incidents are also increasing as getting older. (bhutto, 2014) amd itself could make decreasing quality of life in patients. equade study said that decreasing in all subscale of quality of life in amd patients and getting worse with increasing severity. yuzawa et al confirmed that quality of life is decreasing on amd and increasing with ages.(matamaros, 2015) cognitive function are important thing when you do daily activity. amd could make fall out cognitive function. harrabi et al said that cognitive function in amd group is lower than control group. rozzini et al also said difference of cognitive function score betwen amd group and non-amd group. (rozzini, 2014) decreased quality of life and cognitive function itself can create neurological disorders such as stress, anxiety, dementia and depression. this could be aggravating amd and the quality of life itself. in this study, we conducted a study to determine the difference in the quality of life and cognitive function in patients with and without amd with hyopthesis that there is decreasing in quality of life and cognitive function in amd group which we hope with this study, we can confirm the previous study result and with this study, we can educate doctor to treat thoroughly with such as cooperation with another department . method this study is a prospective cross-sectional study that conducted at sanglah general hospital, denpasar, bali. this study also was approved by the institutional review board of udayana university/sanglah general hospital, denpasar bali. informed consent was given upon research doing. the research are made between october 2020 and december 2020 with total subject 66 and divided into 2 groups ( amd group and non-amd group). the inclusion criteria of patients in this study were all patients with ages more than 49, have complete records with macula oct to determine amd diagnose, willing to join research and answer quisioneirre completely. history of cornea disease, optic neuropathy and another retina disease,history of cataract with grading more than 2 (wisconsin grade)/n2c2p1(locs 2 grade) or visual acuity less than 6/18, history of another lens disease, history of cataract operation with complication, history of retina laser and intravitreal injection more than twelve times, history of amblyopia, history of neurologic and physologic were excluded from the study which the list are used,we cited from similar study. data were collected including age, gender, residence, underlying disease, amd type, visual acuity, history of smoking along with national eye institute visual function questionaire (nei-vfq) and mmse questionaire.the quality of life of both groups was assessed using the questionnaire of the national eye institute visual function questionaire (nei-vfq), which has been translated. the questionnaire assesses the twelve subscale i.e. general health, vision, pain ocular, activities near future, the activities of the far, social function, mental health, the difficulty of the role, dependence, color vision, peripheral vision. while cognitive function was also assessed using questionnaire mini mental state exam (mmse) indonesian version. both of them already been validated using validating test with reliability score > 0.7 . the characteristics and demo figure features were analyzed with descriptive statistics. for statistical comparison between amd group and non-amd group, independet t-test was performed. the statistical analyses were performed using spss 16.0 for windows (spss, chicago, il). result characteristic of samples the sample of this study are 66 people selected in a consecutive of the population of all patients who come to the clinic rsup sanglah who met the inclusion criteria and exclution. table. 1 displays the characteristics of the study sample. 144 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; table 1. characteristics of the study samples the difference in the quality of life and cognitive function between patients with and without agerelated macula degeneration the results of this study showed there was a significant difference (p< 0.05) between the two groups in each of the subscales and decreasing in all aspect quality of lifes in amd group. the significant difference (p< 0.05) was also present at the examination of cognitive function with the mmse between the two groups and also decreasing in cognitive function in amd group even in little differences. graphic.1 displays the result. discussion characteristic of samples amd is an eye disease degeneration which became the cause of blindness in the world today. it is also recognized by the who that amd became a cause of blindness no. 4 in the world by 8.7%. in indonesia itself, there is no exact data about the incidence, prevalence and morbidity of amd until now. one of the research of the faculty of medicine, university of indonesia period march 2008 january, 2009 against 1259 responder found the prevalence of amd reached 4.3 %. the prevalence of amd is increased as like as increasing age (national eye institute, 2019; the indonesian ministry of health, 2014; tany, 2016). in this study, the average age of the group with amd 68 years and the group without amd 67 years old. this result is in accordance with the national eye institute that amd occurs at the age of 60 or more years old and also did not much different with the prevalence of deloitte macular degeneration foundation that amd is increased at the age of 65 years. on research in indonesia by tany,et al (2016) gives result that average age on their research between 60-70 years old, same result as akhmad et al. and singare et al research. wong et al also stated the same thing (akhmad, 2015; singare, 2015; wong, 2014). amd non-amd variabel n:33 n:33 mean age (year),mean+sd 67,82+7.63 66.55+7.90 sex, n (%) male 19 (57.6%) 18 (54.5%) female 14 (42.4%) 15 (45.5%) residency, n (%) denpasar 28 (84.8%) 30 (91%) badung 5 (15.2%) 3 (9%) amd type, n (%) wet 20 (60.6%) dry 13 (39.4%) hypertension history, n (%) hypertension 22 (66.7%) 10 (30.3%) normal 11 (33.3%) 23 (69.7%) smoking habit, n (%) smoking 16 (48.5%) 15 ( 45.5%) no. smoking 17 (51.5%) 18 (54.5%) visual acuity (in 6 meter) best 6/9 6/6 worse 1/300 6/12 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 145 some research, likely that done by chungmin et al (2014), xiang li et al (2014) said that more women suffer from amd (chung-min, 2014; xiang li, 2014). research in indonesia by tany,et al also gives result in line with other research by singare et al showed women more than men in incident of amd (tany, 2016; singare, 2015). but also there are several theories as laitinen et al and chakravarthy et al said that gender is not be influenced in the incidence of amd. in this study indicates that prevalence of men more than the women in both groups (with amd and without amd) (laitinen, 2010; chakravarthy, 2010). based on the diagnosis of the type of amd is obtained that patient with wet amd are common, as many as 60,6%. for dry amd only achieved as much as to 39.4 %. the results of this study differ with the opinion of the ilyas and yulianti, as well as the american optometric association, which wrote that amd dry is found in many patients diagnosed with amd as many as 70-90% compared to amd wet that only 10% ( sidarta llyas, 2014). at the level of visual acuity, this research shows that in visual acuity varied from 6/9 to 1/300 and also judging from the degree of severity of amd itself. at some text book such as aao, kanski revealed that the visual acuity worsened along with the worsening degrees of amd itself. falkenstein et al stated that the average patient vision amd is the 6/45 with a range of 6/9 to <3/60 (falkenstein, 2008). the difference in the quality of life and cognitive function between patients with and without age-related macula degeneration worsening of amd and success of a therapy for amd is strongly associated with adherence and psychological state of the patient itself. amd even if caused by the age of a threat occurrence of blindness and has already become one of the causes of blindness in the world. aspects of quality of life and cognitive function for daily life impacted heavily on amd patients (yuzawa, 2013; rozzini, 2014). the questionnaire nei-vqf 25 is a tool that can help to make an assessment on the quality of life of the amd itself (matamoros, 2015). 0 20 40 60 80 100 120 general health ocular pain far activity mental health dependency perifer visual graphic.1 differences in the quality of life and cognitive function between patients with and without age-related macula degeneration amd group non-amd group 146 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; mmse also a tool that gives an overview of cognitive function in patients with amd (larner, 2015). both of those things can help us to early diagnose if there is a loss of quality of life and cognitive function itself. the results of this study showed the difference score of the subscale on the quality of life where there is a reduction in score in the group with amd with the average of 27.2 % compared with the group without amd. it also shows the difference was statistically significant. decreasing scores in the group with amd compared to the group without amd is the score of the subscale general health with 21.5 %, and the sight of the public with 34.5 %, pain ocular where 28,2%, the near activity 31.7 %, far activity with 25%, social function with 29.8 %, mental health 35 %, the difficulty of the role is quite large with 40.5 %, the dependence of the reach 36.9 %, color vision with 18.9 %, peripheral vision with a 24.8 %. it is also in accordance with the equade study (matamaros, 2015) that in the study they showed a decrease in scores on all subscale of the questionnaire nei-vfq 25 for quality of life. it is also in accordance with that described in yuzawa et al where on amd provides the decline of quality of life and as a worsening of amd providing quality of life are more worsening. in general, yuzawa et al and matamaros et al also explained the decreasing presence of the quality of life can cause anxiety and cause a severe mental disorder such as stress and depression. the level of stress and anxiety that excess in patients with amd are also described can increase the degree of amd itself. this is explained on the abokyi et al where on the animal model showed oxidative stress high provides an more severity on amd (abokyi, 2020). besides, it is also influential to measure the success of therapy to everyday life and also help whether or not to use low vision aid. it can also define and give advice to the family as to whether caregiver needs on the patient. on cognitive function, this study stated that there is a decline of cognitive function in a group with amd in the form of 6.8 % with the result’s score of mmse in the group with amd is 27 compared to the group without amd, namely 29 but indegree score, it is still within normal limits. it is mentioned in the study harrabi et al, where a score of cognitive function were lower in amd patients,fuchs dystrophy and glaucoma. meanwhile, according to rozzini et al mentioned a decrease in the scores of cognitive function with mmse i.e. a score of 27 compared to the control 28 however, according to the degree of the score was still within normal limits (rozzini, 2014). the need for measurement of early cognitive function be able to prevent or diagnose disease early dementia in patients. this is necessary because dementia can worsen the quality of life of the patient itself which will create a vicious circle in the progression and treatment of amd. shi rong et al also stated the presence of the association of dementia with deterioration and increased risk occurance of amd (shi-rong, 2019). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 147 conclusion conclusion in this study is the presence of significant differences and a decrease in quality of life in the group with amd by 27.2 % compared to the group without amd. significant differences and a decrease was also seen in the study with the assessment of cognitive function in a group with amd by 6.8 % compared to the group without amd. the need for measurement of early cognitive function and quality of life would be able to prevent or diagnose neurological disease such as strees, anxiety, dementia and depression that would make severity proggresion of amd. limitation the weaknesses of this research are there is a risk occurs recall bias because of the use of the questionnaire and because of the research done in the middle of the pandemic covid, this can affected psychological and mental level of the subject. references 1. abramoff and kay. 2013. image processing. optical imaging technologies. 6(1). 151-176. 2. abokyi, s. et al. 2020. review article: central role of oxidative stress in age related macular degeneration: evidence from a review of the molecular mechanisms and animal models, journal of hindiawi. 3. age-related eye disease study research group.2006. the age-related eye disease study (areds): design implications areds report no. 2. national eye institute. 4. american academy of ophthalmology and staff. 2019. bcsc: vol.2 fundamentals and principal of ophthalmology. american academy of ophthalmology. 5. american academy of ophthalmology and staff. 2019. bcsc: vol.11 retina and vitreous. american academy of ophthalmology. 6. bhutto,i. lutty,g. 2012. understanding agerelated macular degeneration (amd). molecular aspects of medicine. 33. p295-317. 7. chakravarthy,u. wong, y. fletcher,a. et al. 2010. clinical risk factors for age-related macular degeneration: a systematic review and meta analysis.biomedcentral.availablefrom:http:// bmcophthalmol.biomedcentral.c om/articles/10.1186/14712415-10-31 8. chung min, et al. 2014. prevalence, racial variations, and risk factors of age-related macular degeneration in singaporean chinese, indians, and malays. elsevier. available from www.aaojournal.org. 9. cheier,j. jefferys,j.singerman,l. solomon,s. 2012. detection of newonset choroidal neovascularization using optical coherence tomography the amd doc study. ophthalmology: 119(4).p771-77. 10. dougherty,b. et al. 2010. comparison of scoring approaches for the nei vfq-25 in low vision. journal of optometri and vision science: vol. 87(4). p543-548. 11. dougherty,b. et al. 2017. measurement of perceived stress in age-related macular degeneration. journal of optometri and vision science: vol. 94(3). p290-296. 12. elvioza et al.2015. prevalensi dan karakteristik faktor risiko pada kejadian age related macular degeneration di jakarta timur. [cited 2015 september20].available from: http://mru.fk.ui.ac.id/index.php?upage=profi l.profil_detail&smod=profil&sp=public&idp %20enelitian=1498 13. falkenstein,i. et al. 2008. comparison of visual acuity in macular degeneration patients measured with snellen and early treatment diabetic retinopathy study charts. nih journal of ophthalmology. 115(2): p319–323. 14. friedman,d. o’colmain,b. muñoz,b. 2004. prevalence of agerelated macular degeneration in the united states. archives of ophthalmology. 122(4). p564-572. http://bmcophthalmol.biomedcentral.c/ http://bmcophthalmol.biomedcentral.c/ http://www.aaojournal.org/ http://mru.fk.ui.ac.id/index.php?upage=profil.profil_detail&smod=profil&sp=public&idp%20enelitian=1498 http://mru.fk.ui.ac.id/index.php?upage=profil.profil_detail&smod=profil&sp=public&idp%20enelitian=1498 http://mru.fk.ui.ac.id/index.php?upage=profil.profil_detail&smod=profil&sp=public&idp%20enelitian=1498 148 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 15. hanafi, m. hijazi, a. coenen, f. and zheng, y. 2010. retinal image classification for the screening of age-related macular degeneration. in: sgai international conference on artificial intelligence ai-2010. p325-338. 16. harrabi, h. et al. 2014. clinical and epidemiologic research: age-related eye disease and cognitive function. invest ophthalmol vis sci. 56. p1217– 1221. 17. jager,r. mieler,w. miller,j. 2008. age-related macular degeneration. n. engl. j. med. 358(24). p2606–2617. 18. jefferis, j. et al. 2012. the impact of visual impairment on mini-mental state examination scores in the newcastle 85+ study, journal of age and ageing vol. 41. p565–568. 19. kanagasingam,y. bhuiyan,a. et al. 2014. progress on retinal image analysis for age related macular degeneration. prog. retin. eye res. 38. p20–42. 20. kanski, j.j. 2012. a synopsis of clinical ophtalmology. second edition.united kingdom: elsevier. p.304-306 21. khurana, ak. 2007. comprehensive ophthalmology: fourth edition.india : new age international publisher. 22. laitinen,a. laatikainen,l. härkänen,t. koskinen,s. reunanen,a. aromaa,a. 2010. prevalence of major eye diseases and causes of visual impairment in the adult finnish population: a nationwide population-based survey. acta ophthalmol ;88: p463–471. 23. larner,a. 2015. six-item cognitive impairment test: suitable for the visually impaired?. progress in neurology and psychiatry journal. kementrian kesehatan ri. 2014. infodatin pusat data dan informasi kementrian kesehatan ri. kementrian kesehatan ri. jakarta. 24. matamoros,e. et al. 2015. quality of life in patients suffering from active exudative age-related macular degeneration: the equade study. ophthalmologica journal vol. 234. p151–159.. 25. mookiah,m. r. k. acharya,u. r. koh,j. e. et al. 2014. automated diagnosis of age-related macular degeneration using greyscale features from digital fundus images. computers in biology and medicine. 53. p55– 64. 26. morton,r. f. hebel,j. r. mccarter,r. j. 2009. terjemahan bahasa indonesia: panduan studi epidemiologi dan biostatistika. egc. 27. national eye institute. prevalence of adult vision impairment and agerelated eye diseases in america.https://nei,nih.gov/eyedata/adultvis ion_usa, 20 januari 2019. 28. pennington kl, et al. epidemiology of agerelated macular degeneration (amd): associations with cardiovascular disease phenotypes and lipid factors. eye and vision journal 2016 3:34. 29. rong,s.s. et al. 2019. comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a metaanalysis, british journal of ophthalmology: vol. 19(0). p1-7. 30. rozzini,l. 2014. cognitive dysfunction and age-related macular degeneration, american journal of alzheimer’s disease & other dementias vol. 29(3). p256-262. 31. ryan, s. et al. 2017. ryan's retina: 6th edition. elsevier. 32. sidarta ilyas,hs. yulianti,sr. 2014. mata tenang penglihatan turun perlahan. ilmu penyakit mata (5th ed).fkui; p239-40. 33. singare,r. deshmukh,s. ughade,s.n. thakre,s. 2015. age – related macular degeneration: prevalence and risk factors in elderly population (aged > 60 years) in central india. international journal of scientific and research publications;5: p2 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 149 34. sjahrir,h. ritarwan,k. tarigan,s. rambe,a.s. lubis,i.d. bhakti,i. the mini mental state examination in healthy individuals in medan, indonesia by age and education level. neurol j southeast asia.2001;6: p19-22. 35. tany,c.e. et al. 2016. prevalensi age related macular degeneration di poliklinik mata blu rsup prof. dr. r. d. kandou manado periode januari 2013 – oktober 2015. jurnal eclinic(ecl). vol. 4. no.1. 36. wong,w.l su,x. li,x. cheung,c.m. klein,r. cheng,c.y. et al. 2014. global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. lancet glob health;2: pe106–e116. 37. xiangli, et al. 2012. prevalence and risk factors for age-related macular degeneration in indians: a comparative study in singapore and india.elsevier inc. avaliable from ajo.com. 38. yuzawa,m. fujita,k. tanaka,e. wang,e.c. 2013. assesing quality of life in the treatment of patients with age-related macular degeneration: clinical research and recommendations for clinical practice, clinical ophthalmology journal vo.7. p13251332 this work licensed under creative commons attribution abstract 18 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; international journal of retina (ijretina) 2021, volume 4, number 1. p-issn. 2614-8684, e-issn.2614-8536 partial thickness sclerectomy for uveal effusion syndrome in nanophthalmic eyes. simanta khadka1, raghunandan byanju1, sangita pradhan1, saurav piya2, sweta singh2, ritesh shah3, santosh chaudhary4 1 bharatpur eye hospital, department of vitreo-retina, bharatpur, chitwan, nepal 2 lumbini eye institute, department of vitreo-retina, bhairahawa, rupandehi, nepal 3 mechi eye hospital, department of vitreo-retina, birtamod, jhapa, nepal 4 b.p koirala institute of health sciences, department of ophthalmology, dharan, sunsari, nepal abstract introduction: nanophthalmos characterized by short axial length, high lens-to-eye ratio and thick sclera, is more prone to develop uveal effusion syndrome (ues). this rare entity can result in idiopathic exudative detachment of the choroid, ciliary body and retina. abnormality in the scleral thickness with resultant obstruction of the vortex veins and reduced trans-scleral drainage of fluid is responsible for exudative retinal detachment (erd). methods: a retrospective study of ues in nanophthalmic patients treated with partial thickness sclerectomy in tertiary eye care centre from january 2015 to june 2019. five eyes of five patients (four males and one female) with a diagnosis of nanophthalmos suffered from angle closure glaucoma associated with erd. raised intra-ocular pressure (iop) not amenable to conservative medical management were subjected to surgery. lamellar sclerectomy was performed in two or more quadrants without drainage which was judged on the basis of maximum amount of exudative fluid present in the subsequent quadrants. result: the average age at surgery was 39.2 years and the mean follow-up duration was 9.2 months (6 to 18 months). revision sclerectomy was required in 2/5 (60%) eyes. the serous fluid gradually resolved and retina remained reattached at the end of final follow up. the useful vision was preserved and iop was normalized. conclusion: nanophthalmic ues remains a challenging clinical entity. partial thickness sclerectomy may be an effective option in the treatment of nanophthalmic ues, not amenable to the conventional medical management in a low resource setup. keywords: angle closure glaucoma, exudative retinal detachment, nanophthalmos, uveal effusion syndrome, sclerectomy. cite this article: khadka, simanta et al. partial thickness sclerectomy for uveal effusion syndrome in nanophthalmic eyes. international journal of retina, [s.l.], v. 4, n. 1, p. 18, feb. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/141>. date accessed: 22 feb. 2021. doi: https://doi.org/10.35479/ijretina.2021.vol004.iss001.141. introduction nanophthalmos is a rare disorder characterized by small eyes with short axial length (al) and a thickened sclera. the corneal diameter may reduce marginally and the size of the lens is normal or slightly increased. usually, nanophthalmic patients suffer from hypermetropia between +10 to +20 dioptres (d).1 it usually occurs bilaterally and sporadically, but can also occur as an inherited form in either autosomal dominant or recessive pattern.2, 3 the condition is thought to be caused by a developmental arrest of ocular growth. ultrastructural and histochemical studies have demonstrated abnormal scleral collagen fibers and an alteration in the production of glycosaminoglycans in scleral cells.4 *correspondence to: simanta khadka bharatpur eye hospital, bharatpur, chitwan, nepal simantakhadka@gmail.com published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 19 the examination of nanophthalmic eyes frequently demonstrate crowding and shallowing of the anterior chamber structures mainly due to a high lens-to-eye volume ratio. this factor leads to high predilection to angle-closure glaucoma and uveal effusion in these susceptible eyes.5 uveal effusion syndrome (ues) is a rare clinical entity resulting in idiopathic exudative detachments of the choroid, ciliary body and retina. impaired vascular drainage associated with scleral thickening is assumed to be the primary etiology.6 possible obstruction of the vortex veins and reduced transscleral drainage of protein rich fluid from the suprachoroidal space due to the thickened sclera is believed to be the major coverted cause.3, 7 the association between ues and nanophthalmic eyes was first established by brockhurst.1 gass emphasized the possible congenital scleral anomaly in majority of idiopathic ues while abnormal vortex veins might be another plausible explanation. ues could arise due to various ocular pathological states like postoperative hypotony, post scleral buckling surgery or posterior scleritis.6 medical management have been tried with oral acetazolamide and oral/topical prostaglandin analogues but the success is limited, and yet to be fully validated.8 the management of these type of small eye phenotype represents a major surgical challenge to regulate the intraocular pressure (iop) and to preserve the vision. in this series, we describe the technique and results of sclerectomies in the treatment of ues in five patients with nanophthalmos. methods we reviewed the medical records of five patients who were referred to our department of vitreoretina from general ophthalmology clinic and glaucoma clinic for uncontrolled iop despite maximum tolerated anti glaucoma medications from january 2015 to june 2019. informed and written consent was obtained from all the patients. the identity of the patient has been anonymized throughout the text. institutional approval was not required to publish the retrospective series. the study adhered to the tenets of the declaration of helsinki. a detailed medical and ocular history was taken in each case. each patient underwent comprehensive ophthalmic evaluation including measurement of visual acuity (va), slitlamp biomicroscopy examination, dilated fundus evaluation by indirect ophthalmoscopy, applanation tonometry, and ocular biometry. ultrasonographic a-scans for al measurement was obtained in all cases and b-scans were performed whenever indicated. surgical technique all the cases were managed by surgical approach. the surgery was performed under peribulbar anesthesia under strict aseptic technique. after 360⁰ conjunctival peritomy, blunt dissection of the tenon’s capsule was done with tenotomy scissors. muscle hook was used to isolate all the recti and bridle suture was passed underneath those muscle. the margin of sclerectomies were located just behind the insertion of recti anteriorly and at the equator posteriorly. partial thickness approximately 2/3rd (60%) thickness of sclerectomy (6 x 5 mm flap) was excised in two or more quadrants viz: superonasal (sn), inferonasal (in), superotemporal (st) and inferotemporal (it). the site and number of sclerectomy was decided based on maximal convexity of exudative fluid evident upon preoperative examination findings.no attempt was made to drain the subretinal fluid. the excised area was left bare. the subtenon and conjunctiva was closed with vicryl 8-0 suture (figure 1). postoperatively oral anti-microbial agent (tab. ciprofloxacin 500 mg bd), oral steroid 1mg/kg body weight, oral acetazolamide, oral analgesics in as per need basis and oral proton pump inhibitors was initiated and continued for next five days. oral steroid were tapered off in a weekly interval. topical antibiotics, steroid drops in a tapering fashion, cycloplegic drops and 20 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; steroid antibiotic combination ointment were administered following from the day post surgery and after removal of an eye pad. the patients were followed up for more than six months at conclusion. revision surgery was performed as similar to the procedure described earlier. the remaining quadrants where previous sclerectomy was not performed was selected. post-operative management with respect to medications in the revised cases were also similar as described previously. results case 1 a 48-year-old male presented with complains of diminution of vision in both eyes (be) since 4 months. he was previously managed with maximum tolerated antiglaucoma medications (gtt. timolol maleate 0.5%, gtt. brimonidine tartrate 0.2%, gtt. dorzolamide hydrochloride 2%, gtt. bimatoprost 0.01%) and also subsequently managed with neodymium yttrium aluminium garnett laser peripheral iridotomy (lpi) for high iop. his visual acuity (va) in right eye (re) was hand movement (hm) and left eye (le) 1/60 with no further improvement in refraction. there was no significant family history and no known comorbidities. the iop at presentation was re 31 mmhg and le 16 mmhg respectively. anterior segment examination revealed shallow anterior chamber (ac) of van herick (vh) grade ii and patent lpi in be. dilated fundus examination showed erd in re (figure 2). ocular biometric readings was consistent with nanophthalmos with al of 16.7 mm re and 16.5 mm le. similarly be were phakic with lens thickness (lt) of 4.2 mm re and 4.1 mm le. ultrasonographic (usg) b scan for estimation of retina-choroid-sclera (rcs) complex thickness showed 2.5 mm re and 2.35 le. the choroidal and exudative detachment was more prominent in the in and it quadrants. partial thickness sclerectomy in the two quadrants (in, it) without external fluid drainage was performed in the right eye. figure 1 a-i: intraoperative details of partial thickness sclerectomy technique. a: 360⁰ conjunctival peritomy. b: bridle suture underneath the rectus muscle. c: isolation of all the recti. d: cauterization of the area under exposure. e: area marked and lamellar sclerectomy performed with crescent blade in the infero-nasal quadrant. f: lamellar scleral flap. g: similar procedure in subsequent infero-temporal quadrant. h: sclera left bare without drainage of the subretinal fluid. h: conjunctival closure. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 21 first post-operative va was hm but the iop was lower at 21 mmhg, the retina was not completely attached and there was presence of erd but decreased than pre-operative status. one month following the surgery the best corrected visual acuity (bcva) improved to 1/60 and the iop was stable. three months post surgery the bcva was 3/60 and the retina was re-attached completely. at the end of eight months, the iop remained stable at 13 mmhg, the retina attached and the bcva documented was 5/60. the recovery of the patient was uneventful. case 2 a 62-year-old female was referred for progressive diminution of vision in her right eye since 2 months. her va was hm re and she denied perception of light (dpl) le. she was previously diagnosed as nanophthalmos and treated for secondary angle closure glaucoma with maximally tolerated anti glaucoma medications as well as lpi in her be. however, she was referred for persistently high iop despite medications and deteriorating vision. her iop at presentation was 29 mmhg re and 50 mmhg le. anterior segment examination showed shallow ac of vh i in re and neovascularization of the iris and white pupillary reflex in le. the al reading was 14.2 mm re and excluded in le. the lt was 4.3 mm re and 4.2 mm respectively. fundus finding was consistent with erd in re with maximum amount of fluid in the inferior quadrants. figure 2: preoperative findings of exudative retinal detachment with choroidal effusion of patient 1. (a) fundus photo. (b) ultrasonographic b scan of the same eye showing exudative retinal detachment. figure 3: postoperative findings of patient 1. (a) fundus photo of first postoperative day with resolving exudative fluid. (b) echography of the same patient at three months follow-up which shows complete resolution of the fluid and attached retina. (c) corresponding fundus photo at three months following surgery. 22 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; usg b scan revealed thickened rcs complex of 2.4 mm re and closed funnel retinal detachment in le. conservative topical management with antiglaucoma medications, steroids and cycloplegic agent was continued in her left eye. whereas, surgical option with two quadrants (in and it) partial thickness sclerectomy was opted for re. she was in her course of recovery with va 1/60 and iop 19 mmhg at the end of second postoperative month, but the retina re detached and exudative fluid became prominent inferiorly and nasally during the third month post surgery. following a detailed discussion with the patient, she agreed to proceed with the surgery and similar procedure with lamellar sclerectomy was performed in the sn quadrant. there was no complications documented during the intraoperative as well as post-operative period. we had the record of the patient for the next three months where her bcva was 1/60 and iop was 17 mmhg, then he patient was lost for follow-up. case 3 a 46-year-old male with no other family history and systemic co-morbidities was referred for the complaint of diminution of vision in re and uncontrolled iop despite maximum tolerated antiglaucoma medications. the documented va was hm re and dpl le. the recorded iop was 27 mmhg in re. the al and lt measured in re was 18.7 mm and 3.8 mm respectively. the al and lt reading was not obtained in the fellow phthisical eye. the refractive status of the affected eye was +12 d. the surgery was performed in the inferior quadrants (it, in), where the exudative fluid was more prominent. following surgery, the post-operative event was uneventful till six months. then the patient had redetachment and decision to proceed with second surgery was discussed with the patient and his family members. further partial thickness sclerectomy was carried out in the remaining superior two quadrants (st, sn) accounting for a total of four quadrant sclerectomy after the revision surgery. the patient recovered without any complications. the iop was 16 mmhg and the retina remained attached with bcva of 3/60 at the end of his last follow-up. case 4 a 41-year-old male who was previously prescribed and compliant with maximum tolerated anti-glaucoma medications and a patent lpi was referred with gradual diminution of vision and high iop in right. va was hm re and counting fingers at 1 feet le. the al was 15.7 mm and 15.1 mm respectively and lt was 3.5 mm and 3.9 mm. the iop in affected eye was 30 mmhg, similarly, the eye was hyperopic with +14 d on retinoscopy and the va was not improved with refraction. two quadrants (in, it) lamellar sclerectomy was performed. the patient was followed up for a duration of 11 months where the bcva was 4/60 and the retina remained attached (figure 4) and the iop was within a normal range of 12 mmhg. case 5 a 19-year-old male with progressive diminution of vision in both eye for one and half month duration. the va was hm re with no improvement in refraction and 4/60 le which improved upto 6/36 with +16 d. iop was 28 mmhg and 16 with maximum tolerated antiglaucoma medicines. the al readings were 15.8 mm re and 15.9 mm le. the lt was 3.8 mm re and 3.6 mm le. the ac was shallow in be with vh grade i re and vh grade ii le. there was a marked erd with choroidal figure 4: fundus photo of patient no 4 at 9 months follow-up. leopard spot appearance of the fundus is seen and the retina is attached. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 23 detachment in right and surgery was proceeded accordingly in the most dependable portion of in and it quadrants. the exudative fluid resolved gradually over a period of two months. the patient recovered without any complications and he followed up with us for a period of 12 months post surgery. the findings of his last follow-up revealed a bcva of 2/60 re with an iop of 17 mmhg and attached retina. the average age at surgery was 39.2 years (range 19 – 48 years) and there were four males and one female patient in our series. pre-operative findings of the patients revealed profound vision loss and exclusive right eye affection in all the cases. fundus examination revealed erd with smooth convexity and dome shaped configuration. iop were high in all the cases pre-operatively despite maximally tolerated anti glaucoma medications and peripheral iridotomy. al was below 19 mm in all cases, with a mean al of 16.2 mm (14.2 mm to 18.7 mm) and average lt of 3.9 mm (3.5 mm to 4.2 mm) in the affected re. lens to eye volume in our series was 24.1%. refraction showed high hyperopia with an average of +14.1 d (+12 d to +16d) of the affected re and +14 d (+13 to +15.5 d) in the fellow eye. the details of the patient characteristics were depicted in table 1. on table finding showed tortuous episcleral vessels and abnormally dilated vortex veins. the table 1. patient characteristics patie nt age(years)/ gender va at presentation previous management al measurement (mm) lens thickness (mm) preoperative iop refractive status re le re le re le re le re le 1 48/m hm 1/60 antiglaucoma meds + lpi 16.7 16.5 4.2 4.1 31 16 +14 d +13 d 2 42/f hm dpl antiglaucoma meds + lpi 14.2 4.3 4.2 29 50 +14.5 d + 13.5 d 3 46/m hm dpl antiglaucoma meds 18.7 3.8 27 4 +12 d 4 41/m hm fc 1 feet antiglaucoma meds + lpi 15.7 15.1 3.5 3.9 30 17 +14 d + 14 d 5 19/m hm 4/60 antiglaucoma meds 15.8 15.9 3.8 3.6 28 16 +16 d + 15.5 d va: visual acuity, al: axial length, hm: hand movement, iop: intra-ocular pressure, dpl: denies perception of light, fc: finger counting, lpi: yttrium aluminum garnett laser peripheral iridotomy. 24 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; resected flap demonstrated a thickened sclera. unfortunately, the details of histopathological examination of resected lamellar scleral flap could not be incorporated. following from the day of surgery, the erd gradually resolved and the retina remained attached in all the patients. however, revision surgery was required in two patients due to re-detachment and repeat accumulation of exudative fluid at third and sixth postoperative months respectively. revision was carried out at one more quadrant in second patient and remaining two quadrants in third patient. deliberate decision was taken in these two cases owing to their one eyed status and after explanation of all the possible complications. the retina was attached and iop remained stable at the final follow-up. the post-operative recovery of the patient was uneventful. the mean follow-up duration was of 9.2 months (6 to 18 months). the summary of the surgical management and final outcomes is presented in table 2. conclusion the term nanophthalmos indicates that the eye is small and in contrast to ordinary microphthalmos, not associated with other ocular malformations.10 this rare entity of nanophthalmic eyes are prone to develop glaucoma. the reason for increased iop is postulated secondary to disparity in the ocular dimensions.11 the lens-to-eye volume which is approximately 4% in normal population is deranged and increased to 10% 30% in nanophthalmic eyes.12 another possible mechanism suggested for angle closure glaucoma table 2. management of patients and outcomes at the end of final follow-up patient sclerectomy quadrants bcva iop (mmhg) status of retina f/u duration (months) 1 two quadrants in, it 5/60 13 attached 8 2 three quadrants in, it, sn 1/60 17 attached 6 3 four quadrants in, it, st, sn 3/60 16 attached 9 4 two quadrants in, it 4/60 12 attached 11 5 two quadrants in, it 2/60 17 attached 12 it: infero-temporal, st: supero-temporal, in: infero-nasal, sn: supero-nasal, bcva: best corrected visual acuity, f/u: follow up. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 25 is the development of uveal effusion.1 the serous choroidal detachment and secondary retinal detachment cause forward rotation of the ciliary body, relaxation of lenticular zonules, forward movement of the lens increasing the iridolenticular apposition and pupillary block resulting in angle closure glaucoma.13 glaucoma in nanophthalmic eyes has been treated with various modalities like laser iridoplasty, surgical iridectomy, filtration surgery, cataract extractions and vortex vein decompression. unfortunately, these procedures are accompanied by an extremely high complication rate of failure to control the iop and even loss of vision.12 vortex vein decompression for ues in nanophthalmic eyes was initiated by brockhurst. in the original procedure, scleral beds were dissected at the equator, to decompress the vortex veins and relieve the uveal effusion.14 gass used the same procedure to treat a case of uveal effusion successfully, as he believed that the abnormally thick sclera was the cause for the effusion.6 wax et al suggested that the thickened sclera in nanophthalmos, may have mostly an anterior component. the improved transcleral fluid outflow by thinning it resulted in functional decompression of the anterior vascular bed, thus preventing the dreaded postoperative complications.15 in a report for management of familial nanophthalmos, the scleral flap was not extended posteriorly to the equator and no attempt was made to unroof or transect the vortex veins.13 however, we managed our cases surgically by resecting the scleral flap anteriorly at the boundary of spiral of tillaux contributed by the insertion of recti muscles and extending posteriorly upto the equator. we attempted the lamellar sclerectomy in the inferior quadrants as much as possible so that the superior quadrants can be preserved for the purpose of glaucoma surgery in future. no attempt was made to drain the subretinal fluid and vortex vein was not transected in our procedure. similarly two quadrantic vein decompression with subretinal fluid drainage at the same setting also revealed promising result but the cases have short follow up period.16 this condition can be overlooked easily and attempted to be managed with laser peripheral iridotomy for high iop and shallow anterior chamber.17 nonetheless, the sudden drop in iop after a peripheral iridotomy, results in a relative increase in the choroidal venous pressure and an aggravation of the uveal effusion.14 medical therapy might be a safer alternative than surgery, but the results of medical therapy is variable and not validated.8 the effectiveness of an unsutured sclerotomy or sclerectomy in curing or preventing uveal effusion supports the concept that inadequate transscleral outflow contributes to the production of uveal effusion. the benefit of dissection around vortex veins,14 may not result from decompressing the venous drainage, but from opening the channels for transscleral drainage. transscleral channels made remote from vortex veins seem just as effective and with less risk of haemorrhage.18 the failed sclerectomy procedure was repeated by deep sclerostomy and adjunctive application of topical mitomycin.9 however we did not apply antifbrotic agent in the revision surgery for the fear of scleral melting as the long term reports of adverse effects is not yet available. the success rate of these procedures in achieving an anatomic improvement was reported approximately 83% after a single procedure and about 96% after repeat surgery.19 anatomical attachment achieved in our series after single procedure was 60% which improved 100 % at the end of mean follow up of 9.2 months (6 to 12 months). the anatomical achievement did not translate into functional success. we were able to preserve of at least ambulatory vision in three 26 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; patients similarly gradual improvement in va by two lines was achieved in remaining two patients. the retrospective nature and short follow-up duration are the limitations of this series. this precludes us to propose a definitive statement with regards to long term anatomical success and stable va. the management of nanophthalmic ues in our series is not a novel technique. however, nanophthalmic ues are generally rare, we believe that the findings from this study will contribute to the pool of knowledge in the management of this condition especially in the low resource setup. here, we have presented five cases of ues in nanophthalmic eyes who were successfully managed with partial thickness/lamellar sclerectomy. the surgery was well tolerated by the patients and no significant complications were noted at the end of the follow up period respectively. though the management of this type of condition pose a challenge in itself, the method of partial thickness scleral sclerectomy could be a safe surgical modality in nanophthalmic ues. references 1. brockhurst rj. nanophthalmos with uveal effusion: a new clinical entity. archives of ophthalmology. 1975;vol 93(12):1289-99. 2. moradian s, kanani a, esfandiari h. nanophthalmos. journal of ophthalmic & vision research. 2011;vol 6(2):145-6. 3. gass jdm, jallow s. idiopathic serous detachment of the choroid, ciliary body, and retina (uveal effusion syndrome). ophthalmology. 1982;vol 89(9):1018-32. 4. trelstad rl, silbermann nn, brockhurst rj. nanophthalmic sclera: ultrastructural, histochemical, and biochemical observations. archives of ophthalmology. 1982;vol 100(12):1935-8. 5. lesnoni g, rossi t, nistri a, boccassini b. nanophthalmic uveal effusion syndrome after prophylactic laser treatment. european journal of ophthalmology. 1999;vol 9(4):315-8. 6. gass jd. uveal effusion syndrome: a new hypothesis concerning pathogenesis and technique of surgical treatment. transactions of the american ophthalmological society. 1983;vol 81:246. 7. casswell a, gregor z, bird a. the surgical management of uveal effusion syndrome. eye. 1987;vol 1(1):115-9. 8. park jh, lee ek. medical therapy for bilateral uveal effusion syndrome in nanophthalmos. canadian journal of ophthalmology. 2017;vol 52(6):e199-e201. 9. sabrosa na, smith hb, maclaren re. scleral punch method with topical mitomycin c for safe revision of failed deep sclerectomy in nanophthalmic uveal effusion syndrome. graefe's archive for clinical and experimental ophthalmology. 2009;vol 247(7):999-1001. 10. warburg m. genetics of microphthalmos. international ophthalmology. 1981;vol 4(1-2):4565. 11. kimbrough rl, trempe cs, brockhurst rj, simmons rj. angle-closure glaucoma in nanophthalmos. american journal of ophthalmology. 1979;vol 88(3):572-9. 12. nouri-mahdavi k, nilforushan n, razeghinejad m-r, amini h, perera sa. glaucoma in a patient with nanophthalmos. journal of ophthalmic & vision research. 2011;vol 6(3):208. 13. neelakantan a, venkataramakrishnan p, rao bs, krishnan n, vijaya l, john s, et al. familial nanophthalmos: management and complications. indian journal of ophthalmology. 1994;vol 42(3):139. 14. brockhurst rj. vortex vein decompression for nanophthalmic uveal effusion. archives of ophthalmology. 1980;vol 98(11):1987-90. 15. wax mb, kass ma, kolker ae, nordlund jr. anterior lamellar sclerectomy for nanophthalmos. journal of glaucoma. 1992;vol 1(4):222-7. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 1; 27 16. khatri a, singh s, joshi k, kharel m. quadrantic vortex vein decompression with subretinal fluid drainage for manangement of nanophthalmic choroidal effusions-a review of literature and case series. bmc ophthalmology. 2019;vol 19(1):210. 17. krohn j, seland jh. exudative retinal detachment in nanophthalmos. acta ophthalmologica scandinavica. 1998;vol 76(4):499502. 18. jin jc, anderson dr. laser and unsutured sclerotomy in nanophthalmos. american journal of ophthalmology. 1990;vol 109(5):575-80. 19. elagouz m, stanescu-segall d, jackson tl. uveal effusion syndrome. survey of ophthalmology. 2010;vol 55(2):134-45. this work licensed under creative commons attribution 9. multifocal electroretinogram, central macular thickness and visual acuity in diabetic macular edema following intravitreal injection of anti-vegf.docx 150 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 multifocal electroretinogram, central macular thickness and visual acuity in diabetic macular edema following intravitreal injection of anti-vegf syntia nusanti1, kirana sampurna1, ari djatikusumo1, anggun rama yudantha1, joedo prihartono1. 1 universitas indonesia, cipto mangunkusumo national central general hospital 2 ophthalmology department, faculty of medicine, universitas indonesia, jakarta 3community health department, faculty of medicine, universitas indonesia, jakarta, indonesia abstract introduction: diabetic retinopathy (dr) is one of the major cause of visual acuity deterioration in diabetic patients. the loss of central visual acuity in diabetic patients are mainly due to macula edema, which is found in 29% diabetic patients with the over 20 years duration of disease. the purpose of this study is to assess the correlation between mferg (amplitude and implicit time of p wave), with central macular thickness (cmt) and visual acuity in diabetic macular edema (dme) patients following intra vitreal anti vegf injection. methods: single arm clinical trial. thirty-three eyes of 33 dme patients (16 non-proliferative diabetic retinopathy and 17 non-high-risk proliferative diabetic retinopathy), received intravitreal bevacizumab 1,25mg. all patients underwent complete ophthalmic examination including etdrs va testing, sixty-one scaled hexagon mferg and sd-oct scan at baseline, 1-week and 1-month post-injection. components of the first order kernel (n1, n2 and p1) in central 2o were measured. result: mferg showed reduction of p1 amplitude (p<0.05) at 1-week after injection followed by increase of p1 amplitude (p>0.05) at 1-month after treatment as compared to the baseline in all subjects. there was 19% improvement cmt and 0.2logmar va improvement in 1-month postinjection compared to the baseline (p<005). this study showed no serious ocular adverse effects. there was no significant correlation among changes in visual acuity and changes in cmt or other mferg parameters. conclusion: intravitreal injection bevacizumab resulted in improvement of va, reduction in cmt and mild improvement in the mferg responses. although va changes did not correlate with reduced cmt nor with improved responses of mferg, the combined use of sd-oct and mferg may be used to evaluate macular function in dme patient with worsened visual acuity post anti-vegf injection. keywords: diabetic macular edema; multifocal electroretinography; optical coherence tomography; visual acuity cite this article: nusanti, syntia et al. multifocal electroretinogram, central macula thickness and visual acuity in diabetic macular edema following intravitreal injection of anti-vegf. international journal of retina, [s.l.], v. 4, n. 2, p. 150, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/156>.doi: https://doi.org/10.35479/ijretina.2021.v ol004.iss002.156. correspondence to: syntia nusanti, universitas indonesia, cipto mangunkusumo national central general hospital; syntia_nusanti@hotmail.com introduction diabetic retinopathy (dr) is one of the major cause of visual acuity deterioration. macula edema is the main cause of central visual loss in dr patients, which is found in 29% in diabetic patients.1,2 descriptive study from syabaniah et al5, showed that the incidence of dr from november 2010 – october 2011 was 24.5% of all diabetic patients, https://www.ijretina.com/index.php/ijretina/article/view/156 https://doi.org/10.35479/ijretina.2021.vol004.iss002.156 https://doi.org/10.35479/ijretina.2021.vol004.iss002.156 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 151 which consisted of 565 patients with dr, 200 patients (8.7%) with mild non-proliferative diabetic retinopathy and 207 patients (11.37%) with moderate proliferative diabetic retinopathy. bevacizumab (avastin®, greentech, inc, san francisco,ca) is categorized as an off-label drugs for dme treatment, however there were many reports that shown the effectivity and safety of bevacizumab for dme treatment.5 michaelides et al.,6 reported that in a prospective clinical trial study, the comparison between bevazicumab (bvz) injection group with macular-laser photocoagulation group for 2 years which includes in bolt study, had shown that bvz group had a better effectivity and improvement in visual acuity and macular thickness. a meta-analysis study by reigner et al.7 also stated that intravitreal anti-vegf injection was statistically superior compared to macular photocoagulation for visual acuity improvement. the decrease in thickness of central macula should be followed with improvement of visual acuity, however several studies showed inconsistence results. therefore scientists are eager to find another factors outside the anatomical structure of macular, that influence the improvement of visual acuity, such as photo transduction ability, photoreceptor cells function, in which all of them can be measured with electroretinogram (erg). sutter et al, developed a technique of erg to focus in several area of retina, which was mferg a noninvasive but sensitive method to simultaneously record several area in retina specifically in posterior pole.8 m-sequence is a special algorithm to locate and show the damage area in the retina. previous study also reported the importance of mferg as a predictor in diabetic retinopathy.9,10 the amplitude and implicit time of p wave in mferg have a hhigh sensitivity and specificity in diabetic retinopathy.9 study from greenstein et al.11 and farahsvasah et al.12 reported that in patients with diabetic retinopathy, there were a significant decrease of pwave amplitude and shorter implicit time in macular edema group, compared with non macular edema. the purpose of this study is to assess the correlation between mferg (amplitude and implicit time of p wave), with central macular thickness and visual acuity in dme patients following intra vitreal anti vegf injection. method this was single arm clinical trial, conducted in eye clinic, rs cipto mangunkusomo (rscm) kirana, in jakarta, from november 2015 – march 2016. the sample of this study were subjects with type 1 and type 2 dm, ≥ 18 years old with diagnosis of dme in all stages non proliferative diabetic retinopathy (npdr), mild, moderate and severe and non-high risk proliferative diabetic retinopathy (pdr) according to early treatment of diabetic retinopathy study (etdrs), best corrected visual acuity between 1 and 35 according to etdrs chart (equivalet to 1/60 ≥ x ≥ 6/12 in snellen chart), the thickness of central macula measured by sd-oct is more than 250 μm, and agreed to take part in the research and signed the informed consent. the exclusion criteria in this study without, patients who had oxyhemoglobin level (hba1c) >10.0mg/dl for the last 6 months, history of ocular trauma, intraocular surgery for the last 6 months, laser retinal treatment for the last 6 months, abnormality in vitreretinal surface, had an opacity in refractive media which made the examination impossible and unable to visit for evaluation and follow up. the samples were consecutively obtained until a total number of 35 samples were achieved. each subject had a comprehensive examination from anamnesis and complete ophthalmology examination, followed by the next examination to check the central macular thickness using sd-oct (cirrus oct, carl zeiss meditec). this examination was performed in a dilated pupil with tropicamide 1% eye drop. afterwards, full field electroretinography (fferg) and mferg were conducted using metrovision erg system. before erg examination, the pupil dilated using tropicamide 1% and corrected according to bcva. erg was performed according to iscev standard and guidelines by using jet electrode to acquired the signal. first, the dark room adaptation was carried out for 20 minutes, then continued with scotopic 0.01, 3.0 and 3.0 oscillatory potential (op). light room adaptation was performed 152 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; in 10 minutes before mferg started. the stimulus given was consisted of 61 hexagonal spread over a 26 degree horizontal and 20 degree vertical in visual field. it was displayed on a 20 inch black and white screen with frame rate of 120hz and 1024x768 pixel resolution, 40 cm away from patients eyes. the amplitude and implicit time were measured in five retina area. patients were asked to stay focus on the fixation mark (central area), meanwhile patients with decreased visual acuity were asked to focus on monitor. the measured parameter of mferg were first order kernel. the next procedure was bevazicumab intravitreal injection at procedure room. the procedure began by placing a topical anesthetic eye drop tetracaine (pantocain) into the injected eye. the 1.25 mg bevazicumab was injected to supero-temporal region 3.55 mm (pseudophakia) or 4mm (phakia) from limbus using 1cc syringe and 30g needle. after 1 week and 1 month post injection, all patients returned to get a report examination include in best corrected visual acuity, microscopic slit-lamp, funduscopic, central macular thickness with sd-oct and mferg. this study had passed the ethical clearance review from ethical committee, faculty of medicine, universitas indonesia. result thirty-five subjects (35 eyes) were obtained consecutively in this study. two were dropped out of the study. one subjects did not come for follow up at week four after injection and another one required additional therapy of laser grid macular and pan-retinal photocoagulation (prp) at 3 weeks after injections. basic characteristics in our study included age, gender, duration for dm, hba1c level, systolic and diastolic blood pressure and the degree of retinopathy are shown in table 1. table 1. basic characteristics table 2. clinical characteristics of patient (state unit for each variables) table 1 showed that 17 out of 33 patients (51.5%) had diabetic macular edema (dme) on non high-risk pdr. table 2 shows that from 17 pdr patients, there were two extreme values of best corrected visual acuity (bcva); best bcva (1.78) and worst bcva (0.2). central macular thickness (cmt) data was distributed from 252 um minimum to 670 um maximum. fferg examination showed reduction in all parameters (scotopic 3.0 a and b-wave, flicker wave and op wave). minimum value of op wave was obtained from pdr patient, meanwhile maximum value of op wave was shown in mild npdr patient. the same result was found in extreme value of scotopic a and b-wave amplitude. of the total 33 patients, we did not find any signs of electronegative erg variable total (n=33) percentage (%) age (year) 51.67 ± 7.29 gender men women 16 17 48.5 51.5 duration of dm (year) 9 (0.5;21) total cholesterol (mg/dl) 216.64 ± 35.1 systolic (mmhg) 149.33 ± 17.1 diastolic (mmhg) 87 (52;100) hba1c 8.2 (6.9;10) degree of retinopathy mild npdr moderate npdr severe npdr non high-risk pdr 2 8 6 17 6.1 24.2 18.2 51.5 type of macular edema diffuse cystic 30 3 90.9 9.1 variable mean uncorrected visual acuity (logmar) 0.72±1.59 best corrected visual acuity (logmar) 0.51±1.86 cmt (um) 372.9±1.3 flicker wave hz 77.84±23.65 scotopic 3.0 a-wave hz -147±71.2 scotopic 3.0 b-wave hz 266.2±140.1 sum op-wave hz 78.37±67.9 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 153 b-wave/scotopic a-wave ratio of <1. therefore, in this study, none of the patients had extensive retinal ischemia for more than 50%. the normal b/a wave ratio in erg test is >1, so this sentence actually is to describe that all the 33 subjects reveal their b/a wave ratio are >1, in a clinically pdr cases where it’s linked to more severe degree of retina ischemia compared to non-proliferative diabetic retinopathy (npdr). in this study there was no statistically significant difference in pre-injection visual acuity with the type of macular edema (cystic and diffuse type) (p=0.997). the same result was found in type of diabetic retinopathy, there was no difference in visual acuity, cmt and all mferg parameters (amplitude and implicit time p1, n1 and n2) pre-injection between the npdr group compared with the pdr group. table 3. comparation of pre-injection, 1 week post-injection and 1 month post-injection variabel pre 1 week 1 month p bcva (logmar) 0.48(0.2;1.78) 0.39 ± 1.8 0.34 ± 1.98 0.000b* cmt (um) 372.9 ± 1.3 332.39 ± 74.9 299.39± 70.9 0.000a* mferg n1 amplitude (nv/deg2) 380.26±263.92 214.48 ± 2.36 296.9 ± 2.38 0.185a mferg n1 implicit time (ms) 31.65 ± 5.37 33 (16.2;63.7) 31.04 ±7.26 0.498a mferg p1 amplitude (nv/deg2) 563(82.6,1471) 452.48 ± 265.4 582.42 ± 329.7 0.027b* mferg p1 implicit time (ms) 53.66 ±5.47 53.2 (40.6;64.3) 53.5 ±7.5 0.464a mferg n2 amplitude (nv/deg2) 400(103,1350) 333.35 ± 2.09 406.26 ± 2.04 0.471a mferg n2 implicit time (ms) 77.09 ± 9.37 75.54 ± 10.43 76.57 ± 10.42 0.818a aanova test, bfriedman test, *statistically significant. bcva: best corrected visual acuity; cmt: central macula thickness; mferg: multifocal electroretinogram table 3 showed the mean values of each parameter at baseline, one week and one month after intravitreal bevacizumab injection. the data distribution of bcva was non normal distribution, using the friedman test, there was a significant improvement in visual acuity between pre-injection, one week and one month post-injection (p<0.05). furthermore, from non-parametric wilcoxon rank test, we found statistically significant improvement in visual acuity from pre-injection (baseline) compared to 1 week post-injection. anova test was used for cmt data. there was a significant reduction in cmt at one month post-injection (p <0.05). subsequently, a post-hoc analysis was performed using bonferroni correction with a statistically significant reduction in cmt at baseline-one week (p=0.042) and baseline-one month (p = 0.000) but it was not significant at one weekone month (p> 0.05). meanwhile, the results of friedman test on the p1 mferg amplitude showed a significant change in amplitude at pre-injection, one week and one month after injection. furthermore, using the wilcoxon rank test was carried out. there was a significant decrease at one week after injection (p = 0.008) followed by a significant improvement in the p1 amplitude at one month post-injection (p = 0.014). other mferg parameters such as n1 wave amplitude, n2 amplitude, n1 implicit time and n2 implicit time showed statistically significant (p>0.05) both in anova test (normal distribution) and friedman test (non normal distribution), therefore we did not do post-hoc analysis. 154 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; bc va (l og m ar ) a m pp ( nv /d eg ) figure 1. graphics of mean based on examination time. a. mean median value of bcva based on examination time, b. mean median value of cmt based on examination time. c. mean value of p1 amplitude based on examination time; d. mean value of implicit time p1 based on examination time. the four graphs above showed improvement in mean visual acuity after bevacizumab injection accompanied by reduction in central macular thickness (cmt), improvement in p1 amplitude and p1 implicit time shortening. mean visual acuity on improvement during one month follow-up was 2 lines etdrs chart with a reduction in cmt by 19%. from a total of 33 patients, 3 patients had decreased visual acuity and 5 patients had no change in visual acuity. in those three patients with decreased visual acuity, there were 2 patients with reduced cmt who experienced worsening of the mferg parameter (p1 amplitude), whereas in one patient there was an improvement in mferg parameters but cmt was better (410um). in this study, an additional analysis was done to find correlation between the type of diabetic retinopathy and visual acuity, cmt, also mferg parameters in each examination time. there was a significant difference (p=0.307) between the implicit time of preinjection n1 and the type of diabetic retinopathy, but it was not significant at one week and one month post-injection. there was no significant difference for other parameters (p>0.05). 0 0,1 0,2 0,3 0,4 0,5 0,6 baseline 1 week 1 month 200 250 300 350 400 baseline 1 week 1 month cm t( um ) 52,9 53 53,1 53,2 53,3 53,4 53,5 53,6 53,7 baseline 1 week 1 month im pp 1 (m s) 0 100 200 300 400 500 600 700 baseline 1 week 1 month a b c d published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 155 figure 2. a, b, c. scatter plot graphic. correlation of pre-injection central macular thickness (cmt) and best corrected visual acuity (bcva) (a), 1 week after bevacizumab injection (b), 1 month after intravitreal bevacizumab injection (c). d,e.f. scatter plot graphic. correlation of p1 amplitude and baseline bcva (d), 1 week post-injection bcva (e), 1 month post-injection bcva (f). figures 2a, 2b and 2c showed a relationship between visual acuity improvement and cmt reduction but neither of them had a correlation at baseline, one week or one month after intravitreal bevacizumab injection. meanwhile, figures 2d, 2e and 2f indicated relationship between visual acuity improvement with an increase in p1 amplitude at baseline, 1 week and one month post-injection. statistically, neither of them had a significant correlation (r<0.03, p>0.05). in addition, we analyzed the relationship among the diabetic macular edema (dme) type with visual acuity, cmt, and mferg parameters at each examination time. using the mann-whitney test, we found a significant difference between dme type and p1 implicit time at pre-injection (p=0.307), but it was not significant at one week and one month post-injection. there was also significant difference between dme type with cmt and n1 amplitude at one month post-injection. there was no significant difference for other parameters (p>0.05). this study further analyzed the correlation between diabetic retinopathy type and dme type with changes in each parameter (visual acuity improvement, cmt reduction, amplitude improvement and implicit time shortening). using the mann-whitney test, there was no significant correlation between the type of diabetic retinopathy and each parameter. similar results were obtained for dme type and each parameter. further analysis was done to find correlation between changes in visual acuity (dependent variable) with changes in cmt and changes in mferg parameters, respectively, at one week and 156 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; one month post-injection. correlation test between changes in cmt and changes in mferg parameters was done thereafter. tables 4 and 5 displayed no significant correlation between changes in visual acuity with changes in cmt or other mferg parameters. table 4. correlation of parameter changes between baseline with 1 week post-injection eye parameters eye parameters cmt p1 amplitude p1 implicit time bcva spearman’s coefficient p value 0.002 0.991 0.225 0.207 0.056 0.758 cmt spearman’s coefficient p value 0.080 0.658 0.224 0.209 p1 amplitude spearman’s coefficient p value 0.056 0.755 table 5. correlation of parameter changes between baseline with 1 month post-injection eye parameters eye parameters cmt p1 amplitude n1 implicit time visual acuity spearman’s coefficient p value 0,113 0,531 0.073 0,687 0,107 0,553 macular thickness spearman’s coefficient p value 0,051 0,208 0,065 0,721 amplitude score spearman’s coefficient p value 0,170 0,344 data of complication were obtained from all study subjects including drop-out (35 subjects). three patients (8.57%) had mild complications (subconjunctival hemorrhage). two other patients complained of floaters at one week post injection follow-up. the two subjects then underwent observation and did another follow-up examination at 4 weeks postinjection. there were no subjects who had increased eye pressure, severe inflammation of the front chamber or tractional retinal detachment. discussion previous study reported findings of worsening of fferg parameters in patients with diabetic retinopathy, especially in scotopic 3.0, op and flicker 30 hz. in scotopic 3.0 the amplitude of a and b wave were measured. both waves represent to interpret inner and outer retina layer function respectively. flicker 3.0 hz amplitude is the result of photoreceptor cone cells activities scattered throughout the retina, meanwhile op wave amplitude resulted from amacrine, bipolar and muller cells activities. all subjects in this study had undergone fferg examination. the result of this study showed the decrease in every ferg parameter (op amplitude, a and b wave scotopic amplitude and flicker 30hz amplitude) published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 157 until now, there is no study in indonesia that reported the normal value of ferg, however compared to mohamad rafiudin et al13, our study showed a consistence results with previous study that reported the change in parameter of fferg limited in op wave amplitudes, in patients with mild and moderate diabetic retinopathy. in patients with severe npdr and pdr, prolonged implicit time and significant decreased of ops amplitude were noted. the decreased of amplitude in a and b wave scotopic and flicker also reported in severe npdr and pdr.13,14 the decrease of op amplitude can be explained by the pathophysiology of diabetic retinopathy and diabetic macular edema. histopatologically, in diabetic macular edema, the intracytoplasma muller cells and outer plexiform layer are swelling. persistent retinal edema (macular edema) can lead to necrosis of muller and surrounding neural cells, and eventually forming a cystoid cavity.15-17 this research has similarities from previous studies. the primary outcome of our study was the visual acuity improvement, and previous study had reported a transient effect of intravitreal bevazicumab injection in improving visual acuity in dme patients.18-21 the improvement of visual acuity in this study was 0.2 logmar (2 lines etdrs chart) and the central macular thickness decreased in 19% at 1 month follow up. best corrected visual acuity and decreased of central macular thickness at 1 month after injection were statistically significant (p<0.05). similar results also reported by haritoglou et al.22 there was an improvement in visual acuity from 0.9 logmar to 0.8 logmar and 16.9% decreased in central macular thickness, both at 6 weeks after injection. arvalo et al.23,24 also reported the best visual acuity form 0.9 logmar to 0.6 logmar at 2 month after intravitreal injection of bevazicumab. therefore the results of this study were consistent to the previous studies in order to prove the effectivity of bevazicumab intravitreal injection in dme patients. our study showed that in patients with dme, the increased of cmt was related with the worsening of visual acuity although it was not statistically significant. majority of the patients had a decrease in central macular thickness, but some patients did not experience improvement in visual acuity, even in three patients had a worsening visual acuity. similar with the study from lee et al25, which reported a moderate correlation between central macular thickness (oct scan results) and visual acuity. browning et al26, concluded that although it had a moderate correlation, the variation of visual acuity to central macular thickness was quite large. thus, it can be concluded that oct assessment alone was not sufficient enough as a judgement factor for visual acuity in dme.26 we expect that this matters can be explained through electroretinogram examination. in this study there are some factors on the oct examination were considered in determining visual function. not only retinal thickness but disorganization of inner retinal layer (dril), integrity of photoreceptor is/os junction and the regularity of retinal pigment epithelium can also influence the visual function. some studies mention that diabetic subjects with dril have reduced visual acuity and contrast sensitivity more compared to those without dril. 158 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; previous study suggested that to assess the retinal function in dme, mferg could be the alternative option. the implicit time parameter was considered to be more significant than the amplitude.27 the opposite opinion was stated by greenstein et al11,28, who reported that in patients with clinically significant macula edema/csme there was a decrease in amplitude and shorter implicit time. harrison et al29, also stated that both mferg parameters (implicit time and amplitude) had role in identifying retinal abnormalities in diabetic retinopathy. this was also supported by the international society for clinical electrophysiology and vision (iscev), which stated that mferg showed a greater amplitude in the fovea due to the number of photoreceptor cone cells and bipolar cells.30 thus, the parameter of mferg can be used to assess the outer layer of retina and monitor the damage to photoreceptor cells.31 in this study the function of macular was measured using the mferg parameters, including p1, n1, n2 and implicit time of p1, n1, n2 which were located in the first central macular area (2 degree). mferg represents the local electrophysiology respond in retinal areas. firstly, the mferg would start with negative component (n1) then continued with positive component (p1). these components were respectively in line with a and b wave in fferg. our study found that there was a statistically significant decrease in p1 amplitude (p<0.05) at one week post injection, followed with the increase in p1 amplitude but it was not statistically significant (p>0.05) at one month post injection. the result was different with the previous study, which reported that p1 amplitude increased in npdr patients with diabetic macular edema at one week and two months after intravitreal bevazicumab injection. the reduction of p1 amplitude in our study could be related with the majority of study subjects suffering from proliferative diabetic retinopathy in which there was a progressive damage to muller cells, bipolar cells and surrounding neural cells. the damage in muller cells and bipolar cells can be illustrated by the decreased in oscillatory potential (op) wave in fferg obtained from the baseline data of this study. apart from the decreased of p1 amplitude at one week post, there was an improvement in p1 amplitude at one month post injection which when calculated from one week was statistically significant, but when calculated from pre injection, it was not statistically significant (p>0,05). the improvement of amplitude at one month post injection was consistent with the previous study of shetty et al32, reported that the increased p1 amplitude at two-month post injection of intravitreal bevazicumab. in addition, kumar et al33, also stated that the increase in p1 amplitude at one and threemonth after two times injection of intravitreal bevazicumab in dme patients. the difference between our results and the two previous studies could be due to the difference in inclusion criteria, the amount of injection, grading area of mferg and follow up time, therefore led to different pathophysiology. the results of this study reported an improvement in implicit time of p1 found in both measurements, although it was not statistically significant. previous researchers reported that dm patients will show a delay in implicit time due to the local damage of the process in blood glucose mechanism, resulting in delayed neuron transmission. this results were consistent with a study from greenstein et al11, who reported a prolonged implicit time significantly in diabetic retinopathy patients with csme versus the healthy group. abdollah et al34, and yamamoto et al35, reported the implicit time of p1 prolonged in patients with diabetic macular edema, which indicated a functional deterioration of the outer retinal layers and photoreceptors. the improvement of published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 159 implicit time in p1 wave in this study did not show a statistically significant results, this could be associated with the persistent macular edema and local abnormal (hard exudate) lesions in central macula that were found in several patients. nonetheless, our results were in line with previous studies which stated that even though there was an implicit time improvement close to normal values, a decrease in visual acuity and amplitude still occurred.36 thus it can be reported that the decrease in visual acuity was not associated with the changes in implicit time.19,37 this study showed no significant correlation (p>0.05) among the improvement in visual acuity, reduction of cmt, improvement in amplitude and shortening in implicit time of p1 wave. this was indicated by the presence of individual values that deviate from the expected results, in 2 patients who experienced deterioration in visual acuity even though the cmt was close to normal < 300 but mferg parameter had worsened. meanwhile, 2 patients had improvement in visual acuity along with mferg parameters although the cmt still high. dale et al38, argued that there was a fundamental difference between oct and mferg, in which mferg tends to mistakenly detect small local abnormalities that can be detected with oct. therefore, the functional damage can be detected by mferg before structural changes occur, thus it can be concluded that oct and mferg assessments were complementary as predictors of visual acuity in dme patients.38 clinically, oct and mferg examinations were very useful tools to identify the location and the degree of retinal damage. conclusion there was no correlation among the decrease of central macular thickness, improvement of p1 wave amplitude, and shorter implicit time in p1 wave with improvement of visual acuity in patients with dme post anti-vegf intra vitreal injection. anti-vegf intravitreal injection had a significant depletion in p wave amplitude after 1 week of injection, followed with the improvement of p wave amplitude, however it was not statistically significant after one month of injection. anti-vegf intravitreal injection improved the implicit time of p wave at one month after injection, but it was not statistically significant. antivegf intravitreal injection was statistically significant to decrease the central macular thickness onemonth after injection. anti-vegf intravitreal injection statistically significant to improve the visual acuity one-month after injection. the limitation of this study are the variability of the sample size was quite large, therefore the distribution of pre injection subjects was abnormal. inclusion criteria should be more limited by ranging the bcva patients in 1/60 ≤ x ≤6/60 and 6/60 < to ≤ 6/9. future studies with a large number of subjects are needed to obtain a better research result. the sd value on this study was 309 with a difference in amplitude 129.95, therefore the total sample needed for the future study should be around 44 patients. acknowledgment the authors thank all patients who participated in this study, rianti wulandari pratiwi and dhiny lidinillah as research assistant. references 1. pascolini d, mariotti sp. global estimates of visual impairment: 2010. british journal of ophthalmology. 2012;96(5):614-8. 2. klein bek. overview of epidemiologic studies of diabetic retinopathy. ophthalmic epidemiology. 2007;14(4):179-83. 3. klein r, klein bek, moss se. the wisconsin epidemiologic study of diabetic retinopathy. iv. diabetic macular edema. ophthalmology. 1984;91(12):1464-74. 4. group etdrsr. early photocoagulation for diabetic retinopathy etdrs report. ophthalmology. 1991;98(5):766-85. 160 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 5. fong d, strauber s, aiella l, beck r, callanan d, danis r, et al. comparison of the modified early treatment diabetic retinopathy study and mild macular grid laser photocoagulation strategies for diabetic macular edema. arch ophthalmol. 2007;125:469-80. 6. michaelides m, kaines a, hamilton rd, fraser-bell s, rajendram r, quhill f, et al. a prospective rabdomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (bolt study). ophthalmology. 2010;117:107886. 7. regnier s, malcolm w, allen f, wright j, bezylax v. efficacy of anti-vegf and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network meta-analysis. plos one. 2014;9(7):1-10. 8. lai tyy, chan w-m, lai ryk, ngai jws, li h, lam dsc. the clinical applications of multifoca electroretinography: a systematic review. survey of ophthalmology. 2007;52(1):61-96. 9. jr mab, adams aj, han y, schneck me, ng j, bronsoncastain k, et al. a multifocal electroretinogram model predicting the development of diabetic retinopathy. retinal and eye research. 2006;25:425-48. 10. brodie se, naidu em, goncalves j. combined amplitude and phase criteria for evaluation of macular electroretinograms. ophthalmology. 1992;99:522-30. 11. greenstein v, holopigian k, seiple w, carr r, hood d. atypical multifocal erg responses in patients with diseases affecting photoreceptors. vision research. 2004;44:2867-74. 12. farahvash ms. multifocal electroretinogram in clinically significant diabetic macular edema. archives of iranian medicine. 2006;9(3):261-5. 13. tzekov r, arden gb. electroretinogram in diabetic retinopathy. survey of ophthalmology. 1999;44(1):53-60. 14. maturi rk, bleau la, wilson dl. electrophysiologic findings after intravitreal bevaciumab (avastin) treatment. retina. 2006;26:270-4. 21. 15. pezek c lj. diabetic macular edema: review and update ophthalmol clin north am. 2002;15:555-63. 16. das a, mcguire p, rangasamy s. diabetic macular edema: pathophysiology and novel therapeutic targets. ophthalmology. 2015;1:1-20. 17. brownlee m. the pathobiology of diabetic complications: a unifying mechanism. diabetes. 2005;54:1615-25. 18. higashida r, imamura y, ishikawa a, tsutsumi y, ichikawa y, wakakuri t, et al. intravitreal injection of bevacizumab for diabetic macula edema: morphological and functional outcomes at 1 day after injection. investigative ophthalmology & visual science. 2014;55:1764. 19. sivaprasad s, crosby-nwaobi r, esposti s, rajendram tp, michaelides m, hykin p. structural and functional measures of efficacy in response to bevacizumab monotherapy in diabetic maclar oedema: exploratory analyses of the bolt study (report 4). plos one. 2013;8(8):1-7. 20. nourinia r, azarmina m, soheilian m. intravitreal bevacizumab for treatment if diabetic macular oedema. european ophthalmic review. 2013;7(1):4551. 21. scott i, edwards a, beck r, bressler n, chan c, elman m, et al. a phase ii randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.ophthalmology.2007;114:1860-7. 22. haritoglou c, kook d, neubauer a, wolf a, priglinger s, strauss r, et al. intravitreal bevacizumab (avastin) therapy for persistent diffuse diabetic macular edema. retina. 2006;26:999-1005. 23. arevalo j, j jf-g, quiroz-mercado h, jg sanchez jg, wu l, maia m, et al. primary intravitreal bevacizumab (avastin) for diabetic macular edema: results from the pan-american collaborative retina study group at 6month follow-up.. ophthalmology. 2007;114:743-50. 24. arevalo j, lasave a, wu l, diaz-llopis m, gallegopinazo r, alezzandrini a. pan-american collaborative retina study group (pacores).intravitreal bevacizumab plus grid laser photocoagulation or intravitreal bevacizumab or grid laserphotocoagulation for diffuse diabetic macular edema: results of the pan-american collaborative retina study group at 24 months. retina. 2013;33(2):403-13. 25. lee k, chung h, park y, sohn j. efficacy of intravitreal anti-vascular endhotelial growth factor or steroid injection in diabetic macular edema according to fluid turbidity in optical coherence tomography. korean journal of ophthalmology. 2014;28(4):298305. 26. dj db, glassman a, aiello l, beck r, brown d, diabetic retinopathy clinical research network. relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. opthalmology. 2007;114:526-36. 27. fortune b, schneck m, adams a. multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.invest ophthalmol vis sci. 1999;40:2638-51. 28. greenstein v, holopigian k, hood dc, seiple w, carr r. the nature and extent of retinal dysfunction associated with diabetic macular edema. . invest ophthalmol vis sci. 2000;41:3643-54. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 161 29. harrison w, jr mb, schneck m, wolff b, jewell n, barez s. prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy. invest ophthalmol vis sci. 2011;52:6825-31. 30. hood d, bach m, brigell m, keating d, kondo m, lyons j. iscev standard for clinical multifocal electroretinography (mferg) (2011 edition). doc ophthalmol. 2012;124:1-13. 31. hood dc. assessing retinal function with the multifocal technique. prog retin eye res. 2000;19:607-46. 32. shetty r, pai sa, vincent a, shetty n, narayana km, sinha b, et al. electrophysiological and strusctural assessment of central retin following intravitreal injection of bevacizumab for treatment of macular edema doc ophthalmol. 2008;116:129-35. 33. kumar a, sinha s. intravitreal bevacizumab(avastin) treatment of diffuse diabetic macular edema in an indian population. . indian j ophthalmol. 2007;55(6):451-5. 34. abdollahi a, movassa m, ahmadabadi m, abdollahi m, a aab. multifocal electroretinography assisted comparison of macular photocoagulation versus macular photocoagulation and intravitreal bevacizumab injection in diabetic macular edema . iranian journal of ophthalmology 2010;22(3):23-8. 35. yamamoto s, yamamoto t, hayashi m, takeuchi s. morphological and functional analyses of diabetic macular edema by optical coherence tomography and multifocal electroretinograms. graefe's arch clin exp ophthalmol. 2001;239:96-101. 36. ozkiris a. pattern electroretinogram changes after intravitreal bevacizumab injection for diabetic macular edema. doc ophthalmol. 2010;120:243-50. 37. palmowski am, sutter ee, marcus a. bearse j, fung w. mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram. investigative ophthalmology & visual science 1997;38(12):258696. 38. dale e, hood d, greenstein v, odel j. a comparison of multifocal erg and frequency domain oct changes in patients with abnormalities of the retina. doc ophthalmol. 2010;120:175-86. this work licensed under creative commons attribution abstract 92 published by : inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03; 02; international journal of retina (ijretina) 2020, volume 03, number 02. p-issn. 2614-8684, e-issn.2614-8536 current understanding of age-related macular degeneration swathi kanduri1 1department of ophthalmology, new zealand national eye centre, university of auckland, new zealand abstract age-related macular degeneration (amd) is the leading cause of irreversible blindness in the elderly population in the developed countries. this review discusses the traditional clinical and histopathological presentation of amd, epidemiology and genetics component in relation to the current understanding of the vascular nature of the disease. therapeutic approaches to treat the disease are also included in the review. keywords: age related macular degeneration, imaging techniques, current treatment, risk factors, inflammation. cite this article: kanduri, swathi. current understanding of age-related macular degeneration. international journal of retina, [s.l.], v. 3, n. 2, sep. 2020. issn 2614-8536. available at: https://www.ijretina.com/index.php/ijretina/article/view/112 introduction *correspondence to: swathi kanduri, department of ophthalmology new zealand national eye center university of auckland, swathi@aucklandeye.co.nz age-related macular degeneration (amd) is a degenerative disorder involving not only the central retina macular area but the entire retina as drusen and pigmentary abnormalities are also seen in midperiphery and peripheral retinal areas (1).the disease presentation is characterised by the appearance of soft drusen, pigmentary changes in the retinal pigment epithelium (rpe) and geographic atrophy (ga) (2). then further progression leads into advanced amd with growth of leaky new blood vessels causing choroidal neovascularization (cnv), the wet amd form. the new international classification of amd includes early amd where drusen size of 65-125µm are noted with pigmentary abnormalities. late amd (indeterminate form) include rpe changes, sub retinal fluid and intra retinal fluid with serious pigmentary epithelial detachment with no neovascularisation. late dry stage amd includes geographic atrophy stage. late wet inactive form includes fibrous scar, retinal tear leading to and final late amd (wet active form) includes cnv, retinal angiomatous proliferation (rap) and polypoidal choroidal vasculopathy (pcv) results in loss of central vision(3). most of the “risk factors” which cause amd include advanced age, sunlight exposure, smoking, high blood pressure, cholesterol, obesity; demographic factors, with higher incidence in females, caucasian race, and in those with a family history of amd(4). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 93 few of the risk factors are controllable and which reduces progression of the disease. the diagnosis and management of the disease are based on regular eye examination including visual field testing (vft), fluorescein angiography (ffa), indocyanine green angiography (icg) and optical coherence tomography (oct)(2).optical coherence tomography angiography (oct-a) is a new noninvasive retinal imaging technique useful for detection of choroidal vascular and it’s blood flow. this technique is useful in diagnosis of late wet amd(5). currently, there is no treatment available for dry amd or ga but the intake of antioxidants and other dietary supplements has been suggested for the management of dry amd(6). wet amd treatment involves anti–vascular endothelial growth factor(vegf) injections, laser therapy and/or photodynamic therapy but none of these target the underlying cause or halt the progression. new therapeutic approaches are required to target molecular and cellular changes in the disease, preventing deposition of lipofuscin, drusen, reducing oxidative stress, regenerating and protecting rpe cells, inhibiting inflammatory pathways, all of these related to the role of the choroidal vasculature in the disease (7). morphology of normal retina ophthalmoscopic observation of the posterior segment of the eye allows assessment of the retina up to the ora serrata. the retina is a very thin and transparent tissue of 200 µm thickness in a normal healthy eye(8). the posterior pole of the eye has a central macular zone which contributes to central vision and is fundamental to the perception of sharp, clear, focused images. within the macula, the fovea has the highest density of cone photoreceptors diminishing in numbers towards the periphery of the retina; whereas in the periphery of the retina rods are more prominent. nutrients are delivered to the inner retinal layers through the central retinal artery (cra) the endothelial cells of which form the retinal blood barrier. the blood–retinal barrier is also formed by the retinal pigment epithelium (rpe) that lies adjacent to photoreceptor cells. the rpe functions includes phagocytosis of the photoreceptor outer segment, absorption of scattered light, vitamin a storage, involvement in the visual cycle, nutrients and ion transport and secretion of growth factors. posterior to the rpe lies the vascular layered choroid with the anterior layer in contact with rpe being bruch’s membrane, juxtaposed to which there are three layers of different size blood vessels which form the vascular bed of the choroid. the thinner, fenestrated layer of the choroid is the choriocapillaris which directly supplies nutrients via the rpe to the outer layers of the retina, and is especially important to nurture the central retinal artery-free area of the fovea(8). clinical presentation and classification of the disease amd is classically referred to as dry and wet. clinical manifestations define it as non–exudative (dry, atrophic) and exudative (wet or neovascular)(9) (figure 1). although different international classifications exist for amd, there are a few signs common to the classification by stages of the disease. in early and intermediate stages there are: rpe changes, drusen in bruch’s membrane, hypo and hyperpigmentation at the macula. these signs precede the occurrence of ga. in advanced stages of the disease the choroidal blood vessel region is affected; disciform scarring, neovascularisation and haemorrhages are noted(10). changes in the choroid vessel bed may in fact occur much earlier but are difficult to discern clinically in the dry form of the disease(11). published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 94 figure 1: (a)normal fundus image of the posterior pole (b) dry stage of amd showing confluent soft drusen (c) wet stage of amd showing haemorrhage at macula area and surrounding fibrosis. (acknowledgment: clinical fundus images of different stages of amd are provided by dr. david squirrel). amd clinical presentation starts as an accumulation of lipofuscin in the rpe and drusen between the rpe and bruch’s membrane. these are identified as calcified or cholesterol filled round structures, classified as hard and soft drusen. hard drusen are ≤ 63 µm in size and soft drusen are larger and may be ≥ 125 µm in diameter or in clusters around the central macular area. soft drusen are indistinct confluent structures, which increase in number with age, and they occur more frequently than hard drusen(12). ga usually starts in the parafoveal area and progression towards the fovea is noted in late stages of the disease, causing clinically appreciated scotomas. people with ga also tend to develop pigmentary abnormalities, which then further develop into choroidal neovascularization underneath the rpe or entering the sub retinal space by breaching the rpe. a sub retinal haemorrhage is the first clinical sign noted in cnv. a detached rpe and degeneration of photoreceptors leads to disciform scarring, which is formed due to fibroglial reaction stimulated by continuous blood leakage(13). an amsler grid is used for identification of metamorphopsia, with a perceived distortion of lines indicating loss of central vision. in neovascular amd, the deep retinal vasculature is affected; with the development of new vessels outwards into the sensory retina and anastomose of the retinal tissue with the choroidal circulation(14). imaging modalities multi modal imaging techniques allow diagnosis of amd; these include fundus photography/ fundus autofluorescence, optical coherence tomography (oct), fluorescence angiography (faf) and a c b published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 95 indocyanine angiography (icg). these imaging modalities are useful in evaluating the natural course of the disease and for further identifying possible therapeutic treatments. clinically, spectral domain oct, allows us to visualize microstructural alterations in the retina and choroid. oct is a unique technique useful to measure the progression of the disease such as increase in size of drusen and/or ga area. these are confluent areas in histological or oct analysis that show loss of rpe cells and atrophic patches in photoreceptors regions(15). newer imaging technologies used in understanding subcellular changes of the disease in dry and wet stage are faf and icg. advances in imaging the retina have allowed to identify the choroid as contributing tissue to the onset, progression and understanding of disease mechanisms in am. the most advanced non-invasive angiography technique currently available in clinical practice is oct angiography (oct-a) which enables three-dimensional visualization of retina and choroid blood flow. it makes it possible to estimate the size, structure, configuration, and location of the newly formed vessels. oct-a does not require intravenous dye injection, is free of complications and side effects and allows to identify blood flow particularities of both wet and dry amd(15). risk factors various epidemiological studies have evaluated these factors and the risk for the disease progression although more detailed assessment of risk factors could be useful in understanding etiology, pathogenesis of the disease and to evaluate new treatment therapies of the disease at various stages. age and family history are the main risk factors for the progression of amd. other risk factors associated with the disease are smoking, dietary factors, inflammation, vascular and cardiovascular factors. studies have also found relationships between uv-b exposure and amd(16). d em og r aphi c fa c to rs early amd stages show no difference in gender presentation as reported in the beaver dam eye study, the blue mountain eye study and the rotterdam study(17-19). above the age of 75 years, however, prevalence of disease is slightly higher in females; the blue mountain eye study revealed that the prevalence of the advanced cnv stage doubles in females than males. ethnically, the prevalence of amd is higher in whites than in darkly pigmented races. this thought to be owing to more melanin pigment preventing development of cnv. in contrary, studies in the literature found no association between iris colour and amd disease progression. a study done in the general population, supports the fact that the presence of melanin pigment in rpe and the macular pigment which is composed of carotenoids lutein and zeaxanthin in eyes with and without amd has no difference in prognosis of the disease. c a rd io v as cu la r fa ct or s the most important pathogenetic factors associated with the prognosis of amd are vascular factors. histological evidence shows that the vascular walls of the larger choroidal blood vessels are thicker in amd than in normal age matched human tissues. in fact, accumulation of drusen in bruch’s membrane, and atrophy of rpe layer is due to dysfunction of the choriocapillaris. ( 20)vascular model of amd shows that a combination of elevated choriocapillary pressure, breaks in bruch’s membrane, and secretion of vegf causes cnv.furthermore, in amd donor tissues, the density of the choriocapillaris is halved in rpe atrophic areas, when dry and wet forms of amd are compared to normal age matched eyes(21). studies in literature also shows that with aging lipid deposition is seen in the walls of systemic arteries and apolipoprotein-b lipid deposition is seen in the sclera and the bruch’s membrane of the choroid in amd patient. increased choroidal vascular resistance, resulting in elevated choriocapillary pressure and development of sub-retinal drusen deposits, as well as decreased choroidal blood flow is lately noted in amd patients.the lumen diameter of the choriocapillaris underneath the rpe atrophy is not significantly affected. in patients with ga, the presentation of the disease in both eyes may differ, with one eye presenting with ga and the other eye with cnv. in both, however, the choriocapillaris can be reduced in area which leads to hypoxia of the atrophic regions. some epidemiological studies suggest there is an association between systemic hypertension, cardiovascular diseases and risk of developing amd(22). 96 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; angiotensin ii has been shown to be elevated in animal studies of systemic hypertension. this molecule triggers expression of vegf factors. in human donor tissues, the expression of vegf and its isoforms is elevated in amd eyes compared to normal age match control eyes. there are many other studies showing the link between hypertension and risk of amd , suggesting that the vasculature nature of amd has ample support by a diversity of studies. blood vessel changes are associated with pathogenesis and progression of amd. through histological evidence it is noted that in early stages of amd a number of nonfunctional retinal capillaries with thicker vascular walls are detected compared to normal aged retina. formation of drusen and rpe atrophy is due to dysfunction in choriocapillaris. the increased resistance to the blood flow in the choroid may also contribute to lipofuscin deposition and drusen formation. there is also constriction of blood vessels with increased resistance to blood flow noted in cardiovascular diseases and hypertension. population based studies provide evidence that these risk factors are associated with amd . furthermore, a study using human donor tissues showed that in late stage amd there is 50% reduction in choriocapillaris at the rpe atrophic zones compared to normal control eyes. the surviving choriocapillaris are constricted in the areas below rpe atrophy. nitric oxide is a vasodilator molecular present in blood vessels. it is mainly located on endothelial cells and perivascular nitrogenic neurons. low production of no is seen in amd probably contributing to the constriction of choriocapillaris(23). although there is a reduction in choriocapillaris area, the number of choriocapillaris remains the same. angiogenesis factors also play a key role in progression and development of wet stage of amd. in the dry stage of amd, the unaffected rpe area is associated with development of cnv. in ga, hypoxia leads to up regulation of vegf produced by rpe cells despite a reduction of choriocapillaris being noted. a study done on human amd donor tissues shows that vegf isoforms are absent in normal age matched human donor tissues. animal studies also support the fact that up regulation of vegf in the rpe layer leads to cnv and blood vessel leakage(24). s mo k i ng in addition to age and family history, cigarette smoking is considered an important well-known risk factor associated with development of amd(13). various epidemiological studies have shown the association between smoking and the risk of amd(25). the increased risk of amd prognosis is noted in both prior and current smokers and has a direct relationship with prognosis of the disease. the antioxidant protective mechanism is compromised by smoking, which in turn progresses the disease amd. it is also noted that although amd affects females more than males, male smokers are more prone to the risk of developing amd than female smokers. animal studies support the fact that nicotine stimulates neovascularization by increasing production of vegf and endothelial cell proliferation (26). li gh t e xp osu re a variety of studies support the fact that uv exposure and light damage leads to amd(27). although one study done in human suggested that the light damage is limited to only central and superior regions of the retina, the mechanism of photo activation leads to decrease in the flow of ions in rpe before retinal damage(28). animal studies demonstrated that intense continuous exposure to light causes alterations in the retinal metabolic function. photo-oxidative damage causes an elevation of cations in the retina which in turn affects photoreceptor functionality similar to amd. at the cellular level reactivity includes alterations in müller cells gene expression with increased expression of vimentin and glutamine synthetase. study done on relationship between increase in the blood flow at macula with temperature changes induced through light-generated heat in humans suggests that choroidal vasculature changes occurs in retinal diseases which are un-noted (29). d ie t ar y fa c tor s except for the areds study that assessed the intake of antioxidants, multi vitamins, beta carotenes, carotenoids, retinol and minerals, systematic reviews and various epidemiological studies have found no relationship between intake of the dietary supplements such as zinc, antioxidants, lutein and xanthophylls, and progression of amd. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 97 observational human studies and animal studies suggest that there is no relationship between omega 3 fatty acid consumption and progression of amd disease. a few studies have also suggested that there is no relationship between medications such as angiotensin, a converting enzyme or cholesterol lowering medication in progression of amd(30). in contrast another study done in the united kingdom supports the fact that cholesterol lowering medications such as statin, lowers the risk of prognosis of amd as there is an antiinflammatory effect located at bruch’s membrane (13) o xid a ti v e st re s s oxidative stress is caused by the overbalance of free radicals such as reactive oxygen species (ros) or reactive nitrogen species, and is one of the major factors involved in the aging process. ros are generated under physiological conditions, including normal cellular activities such as nadphdependent membrane–bound enzymes, mitochondrial metabolism, and other intercellular oxidases. cells possess antioxidant enzymes such as superoxide dismutase and glutathione peroxidase which are useful in removal of ros from cells(31). exposure to light leads to oxidative stress in the rpe cell layer, leading to the formation of lipofuscin, an age-related pigment found in different age related diseases. increase in vascular endothelial cell dysfunction is caused by oxidative stress which plays a key role the pathophysiology of several vascular diseases and disorders. nitric oxide is another cytotoxic molecule involved in vascular development and associated with pathogenesis of amd . reductions in the antioxidant defence system and increased oxidative stress may play a role in the pathogenesis of amd(32). r ol e o f in fl am ma t ion the first step of the immune defence development in a retinal injury is to activate macrophages, leukocytes and other phagocytes. macrophages and t cells recognise the oxidative modified lipids. in the eye, enhanced activity of retinal glial cells indicates an inflammatory response before damage to retinal structures. animal studies support the fact that astrocytes are enhanced in activity after light damage and there is immunohistochemical evidence for increased staining of glial acidic fibrillary protein (gfap) in the nerve fibre layer which is a noted inflammatory response. in the inflammatory response process, the most important immune cells involved are glial cells and molecularly the complement system. the inflammatory residue composition in drusen provides evidence that complement factor h, are highly involved in this event(33). the accumulation of lipofuscin at bruch’s membrane leads to drusen formation. the undigested residual waste leads to rpe dysfunction and compromises their lysosomal function. histochemical evidence proves that drusen is a mixture or accumulation of proteins, lipids, lipoproteins, complementary factors (such as c1q, c3a and c5a), complementary regulators (such as complement factor h, clusterin, vitronectrin), immunoglobulins (igg), amyloid β, phospholipids, cholesterol and apolipoproteins b & e.this above process of formation of drusen describes only a part of the inflammatory events happening in amd, a multifactorial disease in which progression is based on other events such as stress, the para-inflammatory response, environmental and genetical factors. studies have shown that genetic variations of several complement genes such as complement regulator factor h, central complement component c3, factor b, c2 are the risk factors involved in the progression of the disease amd(34). this process is also noted at the protein level, accumulation of waste metabolites in formation of drusen, in the sub retinal space, and in capillaries of the choroid. every complement pathway forms a membrane attack complex, which contributes to drusen formation found in the rpechoroid interface. complement factor h plays a key role in forming an alternative pathway by binding with c3b. the other gene associated with complement pathway is c1 with the immunohistochemical evidence indicating that in wet amd, these c1 proteins are found. the c3 complement pathway is also found in wet amd, especially in conjunction with choroidal neovascularization. deposition of these membranes, found in c1 and c3 can be removed surgically. elevated plasma levels of these proteins are found in amd patients with c3 and c5 being associated complement factors. the c5 factor is associated with expression of interleukins. these interleukins are responsible for apoptosis and cellular dysfunction of rpe. 98 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; the complement pathway illustrated in figure 2 highlights the different components found in the eye. figure2: summary of the complement pathway in the eye. figure2: summary of the complement pathway in the eye. the complex complement system with several activated pathways are illustrated in the above image. the risk of progression of the amd disease, is associated with the activation of the compelment factor h. the residential glial cells in the retina are microglia and macroglia(35). the retinal macroglia has two main cellular components; müller cells and astrocytes. studies have suggested that microglial cells are involved in an immune defence mechanism in amd and they enlarge and change their shape to an amoeboid form suggestive of a wound healing mechanism. the removal of debris is done by these cells which relocate from the outer retina to the sub retinal space. the recollection of these cells triggers a pro-inflammatory response, which produces cytokines, chemokines, complement receptors and chemokine receptors. cx3cr1 is one example of a chemokine receptor located on microglia in amd; this protein binds with chemokine ligand 1 (cx3cl1) and it is involved in leukocyte adhesion and migration. many cytokines, chemokines, calcium ions, atp, nitric oxide can also increase with microglial activity. some neurotransmitters such as gabaergic decrease microglial activity whereas glutamatergic neurotransmission increases microglial activity(36). the microglia, astrocytes and müller cells play a key role in pathogenies of amd. these residential glial cells provide support and protection of retinal neurons by supplying nutrients, removing waste and playing a role in phagocytotic mechanisms. gfap is an astrocyte marker which labels that cell type in the nerve fiber and ganglion cell layers of the retina. previous studies suggest that an increased labelling of gfap is also noted in müller cells in amd human donor tissues(37). these astrocytes are increased in number in the ganglion cell layer due to oxidative stress and these cells are found as resident cells in the outer retina and vitreous chamber of young donor tissues. the mechanism by which these cells become enlarged is suggestive of phagocytic activity and maintenance of blood retinal barrier. neurotoxic factors such as nitric oxide (no), are released by the activation of these glial cells, which are involved in neurodegenerative diseases. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 99 vascular factors in amd current management of amd amd has a complicated pathophysiology and multiple risk factors associated with its onset and progression makes it a difficult eye condition to manage. through the course of the pathology there are no persistent molecular targets that can be targeted for treatment of the disease. in the dry form of amd, the formation of drusen is considered a hallmark sign, associated with rpe degeneration. the initial management of dry amd is with increase of dietary supplements consisting of leafy vegetables, vitamin a, c, e, zinc and carotenoids(38). in contrast, in the wet stage of the disease, rpe atrophy, haemorrhages, cnv and fibrosis concentrated in the macular area leads to vision loss. in both dry and wet forms photoreceptor layer loss is noted. current therapeutic treatment options available are only for the wet form of amd and the dry form remains untreatable. these include options such as photodynamic therapy (pdt), injecting anti–anigogenic agents (anti vegf therapy) and laser photocoagulation. in addition to these established approaches, potential new investigations suggest replacement of retinal layers and rpe stem cell therapy. in all cases the treatment remains focused on the signs rather than the cause and the late stage of disease(39). an ti – an gi og eni c ag en t s anti angiogenic agents are the primary therapies for the cnv present in the wet form of amd. this therapy targets vascular endothelial growth factor (vegf) and its isoforms. pegaptanib sodium is an agent which interferes with rna molecules and targets releasing vegf, particularly vegf-a(40). other specific agents, which act on vegf-a, are bevacizumab, ranibizumab and aflibercept. these are all effective in reducing leakage in cnv. in addition to these antibodies, corticosteroids used in treatment of cnv include triamcinolone acetonide(41) and the wet amd anti-inflammatory pathway may be reduced using prostaglandins and leukotrienes(42). apart from cortisone, anecortave acetate reduces progression of cnv. many studies however, indicated that anti–vegf treatment may be a better choice than corticosteroids and/or cortisone usage. long-term profile studies have noted variations in the response to the anti–vegf treatment based on age and genetic profile. based on the extent of lesions, clinicians may choose to perform an anti–anigogenic treatment and/ or photodynamic therapy (pdt) to improve vision (43). ph ot od yn am ic t he r ap y pdt was the primary treatment option in the late 1990s but it is for the most part replaced by pharmaclogical treatments. in monotherapy, though, it remains a strong treatment modality for the wet form of amd(44). this method involves verteporfin, an intravenous photosensitive dye, activated by infrared light. verteporfin activates singlet oxygen species which damages endothelium and accumulates on neovascular membranes in wet amd. lesion size with cnv extending into the fovea and/ or leading to visual loss affecting quality of life of an individual are indications for pdt(45). usually, 6mg/m² of verteoprofin is infused for 10minutes. the lesion size and location may change the energy, intensity and dosage of the dye. the results of a study in new zealand suggest that this treatment is very effective and 70% of patients treated with this therapy avoided moderate visual impairment in first one year of the treatment (46). la s er pho to co a gu la t ion laser photocoagulation is an effective argon laser treatment, for treating wet amd. argon laser is useful in closure of newly formed blood vessels in cnv. studies suggested that it prevents severe visual impairment, especially in eyes with extra foveolar and juxta foveolar choroidal neovascularization. the disadvantage of the treatment is that it causes visual field spots(47). future managements stem cell therapy and cell replacement stem cell therapy is an explorative new route for treating blinding retinal conditions including amd, retinitis pigmentosa, and stargadt’s macular dystrophy. stem cell therapy may play a key role in treating ga(48). the principle differences are their cell source, the age of donor, whether they are clinically graded and whether they are useful for multiple recipients. cell reprogramming affects the immune privilege of donors 100 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; and survival of rpe and photoreceptor cells will be based upon long-term survival of grafted cells. several animal studies supports this therapy. but in humans a better understanding of their role in treating this required assisted technology and adaptation of modern imaging technology(49). g en e ti c ap pro a ch es clinical trials have indicated that cnv growth is arrested by intravitreal transfer of pigment-epithelium– derived factor. the coblat clinical trial showed that intravitreal administration of bevasiranib also inhibited cnv growth(50). genetic approaches are useful in treating later stages of the disease but could potentially treat earlier stages once the true underlying causes of amd are fully elucidated. numerous clinical trials and ongoing research has developed interventions which are useful to alleviate later stages of the disease. literature review also reveals that glatiramer acetate may decrease the size of the drusen, retinal transplantation can be successful, fenretidine acts to decrease the size of ga and incidence of cnv, carotenoids and ω-3 fatty acids may decrease the progression of ga. sildenafil increases choroidal thickness and retinal vascular flow. however, these pharmaceutical treatments do not improve vision. a therapy for treating early stages of amd is absent although current molecular targets identified for potential management of amd are useful in better understanding the disease. the literature and recent experiments in animal and donor tissues suggest loss of vasculature homeostasis is a significant triggering cause. future scope of research is to understand how one progresses to the other (or not), the causative factors for the different stages amd, and an ongoing need for therapeutic treatments for both forms of the disease (dry and wet amd). it is increasingly recognised that current mainstream treatments really only provide a five year delay in progression, with most patients then falling back below baseline of visual acuity. conclusion amd is a global disease that leads to substantial vision loss and significantly affects the quality of life in the elderly population. the underlying causes of the disease and its pathophysiology still need to be understood. the current treatment strategies and imaging modalities are useful to track the progression of the disease, but not for treating or curing the permanent visual damage. there is no much proven research for treating the early/dry stages of the disease amd. the current treatment strategies are more useful for stopping the leakage and growth of the new blood vessels in the late/wet stages of amd. new clinical trials are underway for investigating the novel methods for the treatment of the early stages of amd which will reduce the global impact of visual burden. funding sources: freemasons new zealand national eye centre phd scholarship to sk w & b hadden tom cat trust lottery health research grant of nz maurice and phyllis paykel trust grant of nz acknowledgements: thank you to the staff of the new zealand national eye bank, especially helen twohill and louise moffat, and to the donor families who consented to research use of donor eyes. i acknowledge the help professors colin r green, charles nj mcghee, associate professor trevor sherwin (ophthalmology, university of auckland) and dr monica acosta (optometry and vision science, university of auckland). references: 1. domalpally a, clemons te, danis rp, sadda sr, cukras ca, toth ca, et al. peripheral retinal changes associated with age-related macular degeneration in the age-related eye disease study 2: age-related eye disease study 2 report number 12 by the age-related eye disease study 2 optos peripheral retina (opera) study research group. ophthalmology. 2017;124(4):479-87. epub 2017/01/17. 2. holz fg, strauss ec, schmitz-valckenberg s, van lookeren campagne m. geographic atrophy: clinical features and potential therapeutic approaches. ophthalmology. 2014;121(5):107991. epub 2014/01/18. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 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[optical coherence tomography angiography in the diagnosis of neovascular age-related macular degeneration]. vestnik oftalmologii. 2015;131(5):4-12. epub 2016/02/06. 15. klein r, peto t, bird a, vannewkirk mr. the epidemiology of age-related macular degeneration. am j ophthalmol. 2004;137(3):486-95. epub 2004/03/12. 16. wang jj, rochtchina e, lee aj, chia em, smith w, cumming rg, et al. ten-year incidence and progression of age-related maculopathy: the blue mountains eye study. ophthalmology. 2007;114(1):92-8. epub 2007/01/03. 17. klein r, klein be, jensen sc, meuer sm. the fiveyear incidence and progression of age-related maculopathy: the beaver dam eye study. ophthalmology. 1997;104(1):7-21. epub 1997/01/01. 18. mitchell p, smith w, attebo k, wang jj. prevalence of age-related maculopathy in australia. the blue mountains eye study. ophthalmology. 1995;102(10):1450-60. epub 1995/10/01. 19. mcleod ds, grebe r, bhutto i, merges c, baba t, lutty ga. relationship between rpe and choriocapillaris in age-related macular degeneration. invest ophthalmol vis sci. 2009;50(10):4982-9 20. friedman e. update of the vascular model of amd. the british jounal of opthalmology. 2004;88(2):161-3. 102 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 21. klein r, klein be, tomany sc, cruickshanks kj. the association of cardiovascular disease with the long-term incidence of age-related maculopathy: the beaver dam eye study. ophthalmology. 2003;110(4):636-43. epub 2003/04/12. 22. alderton wk, cooper ce, knowles rg. nitric oxide synthases: structure, function and inhibition. biochem j. 2001;357(pt 3):593-615. epub 2001/07/21. 23. spilsbury k, garrett kl, shen wy, constable ij, rakoczy pe. overexpression of vascular endothelial growth factor (vegf) in the retinal pigment epithelium leads to the development of choroidal neovascularization. am j pathol. 2000;157(1):135-44. epub 2000/07/06. 24. klein r, klein be, moss se. relation of smoking to the incidence of age-related maculopathy. the beaver dam eye study. am j epidemiol. 1998;147(2):103-10. epub 1998/02/11. 25. heeschen c, jang jj, weis m, pathak a, kaji s, hu rs, et al. nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. nat med. 2001;7(7):833-9. epub 2001/07/04. 26. darzins p, mitchell p, heller rf. sun exposure and age-related macular degeneration. an australian case-control study. ophthalmology. 1997;104(5):770-6. epub 1997/05/01. 27. yu ty, acosta ml, ready s, cheong yl, kalloniatis m. light exposure causes functional changes in the retina: increased photoreceptor cation channel permeability, photoreceptor apoptosis, and altered retinal metabolic function. j neurochem. 2007;103(2):714-24. epub 2007/07/12. 28. parver lm. temperature modulating action of choroidal blood flow. eye. 1991;5(2):181-5. 29. klein r, klein be, jensen sc, cruickshanks kj, lee ke, danforth lg, et al. medication use and the 5year incidence of early age-related maculopathy: the beaver dam eye study. archives of ophthalmology (chicago, ill : 1960). 2001;119(9):1354-9. epub 2001/09/27. 30. finkel t. signal transduction by reactive oxygen species. j cell biol. 2011;194(1):7-15. epub 2011/07/13. 31. yildirim z, ucgun ni, yildirim f. the role of oxidative stress and antioxidants in the pathogenesis of age-related macular degeneration. clinics. 2011;66(5):743-6. 32. stanton cm, wright af. inflammatory biomarkers for amd. adv exp med biol. 2014;801:251-7. epub 2014/03/26. 33. zipfel pf, lauer n, skerka c. the role of complement in amd. adv exp med biol. 2010;703:9-24. epub 2010/08/17. 34. muther ps, semkova i, schmidt k, abari e, kuebbeler m, beyer m, et al. conditions of retinal glial and inflammatory cell activation after irradiation in a gfp-chimeric mouse model. invest ophthalmol vis sci. 2010;51(9):4831-9. epub 2010/05/04. 35. fontainhas am, wang m, liang kj, chen s, mettu p, damani m, et al. microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and gabaergic neurotransmission. plos one. 2011;6(1):e15973. epub 2011/02/02. 36. wu kh, madigan mc, billson fa, penfold pl. differential expression of gfap in early v late amd: a quantitative analysis. br j ophthalmol. 2003;87(9):1159-66. epub 2003/08/21. 37. seddon jm au, sperduto rd, et al. . dietary carotenoids, vitamins a, c, and e, and advanced age-related macular degeneration. jama. 1994;272(18):1413-20. epub feb 22. 38. john s, natarajan s, parikumar p, shanmugam pm, senthilkumar r, green dw, et al. choice of cell source in cell-based therapies for retinal damage due to age-related macular degeneration: a review. j ophthalmol. 2013;2013:465169. epub 2013/05/28. 39. lu x, sun x. profile of conbercept in the treatment of neovascular age-related macular degeneration. drug des devel ther. 2015;9:2311-20. epub 2015/05/12. 40. kadam rs, tyagi p, edelhauser hf, kompella ub. influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide. int j pharm. 2012;434(1-2):140-7. epub 2012/05/29. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; 03;02; 103 41. maloney sc, godeiro kd, odashiro an, burnier mn, jr. current and emerging concepts in the management of neovascular age-related macular degeneration. cardiovasc hematol agents med chem. 2007;5(2):147-54. epub 2007/04/14. 42. amoaku wm, chakravarthy u, gale r, gavin m, ghanchi f, gibson j, et al. defining response to anti-vegf therapies in neovascular amd. eye (lond). 2015;29(6):721-31. epub 2015/04/18. 43. kawczyk-krupka a, bugaj am, potempa m, wasilewska k, latos w, sieron a. vasculartargeted photodynamic therapy in the treatment of neovascular age-related macular degeneration: clinical perspectives. photodiagnosis photodyn ther. 2015;12(2):16175. epub 2015/04/07. 44. u schmidt-erfurth jmea. photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. arch ophthalmol. 1999;117:1177-87. 45. sharp dm, lai s, markey cm. photodynamic therapy with verteporfin for choroidal neovascularization due to age-related macular degeneration and other causes: a new zealand outcomes study. clin experiment ophthalmol. 2007;35(1):24-31. epub 2007/02/16. 46. virgili g, bini a. laser photocoagulation for neovascular age‐related macular degeneration. cochrane database of systematic reviews. 2007(3). 47. kvanta a, grudzinska mk. stem cell-based treatment in geographic atrophy: promises and pitfalls. acta ophthalmol. 2014;92(1):21-6. epub 2013/07/31. 48. borooah s, phillips mj, bilican b, wright af, wilmut i, chandran s, et al. using human induced pluripotent stem cells to treat retinal disease. progress in retinal and eye research. 2013;37:163-81. epub 2013/10/10. 49. safety & efficacy study evaluating the combination of bevasiranib & lucentis therapy in wet amd (cobalt) [database on the internet]. 2008 [cited may 19]. available from: http://www.clinicaltrials.gov/ct2/show/nct004 99590.). this work licensed under creative commons attribution http://www.clinicaltrials.gov/ct2/show/nct00499590.) http://www.clinicaltrials.gov/ct2/show/nct00499590.) 7. a prospective study of safety profile and efficacy of three doses of intravitreal bevacizumab in diabetic macular edema.docx published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 127 international journal of retina (ijretina) 2021, volume 4, number 2. p-issn. 2614-8684, e-issn.2614-8536 a prospective study of safety profile and efficacy of three doses of intravitreal bevacizumab in diabetic macular edema nasrin y1, sharma ajay2, sharmila yalakala3 1head of conea and general ophthalmology , sankar foundation eye institute, visakhapatnam, andhra pradesh, india 2 department of vitreo retinal services, sankar foundation eye institute, visakhapatnam, andhra pradesh, india 3 dnb student, sankar foundation eye institute, visakhapatnam, andhra pradesh, india abstract introduction: current study aimed to evaluate efficacy of intravitreal bevacizumab in diabetic macular edema, and to identify their ocular and systemic complications if any. methods: all patients with resistant, center involving macular edema due to diabetes, retinal vein occlusion and age related macular degeneration were recruited. complete baseline ocular examination performed at presentation. all patients were treated by 3 injection of intravitreal bevacizumab with 1 month interval. outcome was measured in terms of variation in central macular thickness (cmt) and also best corrected visual acuity (bcva) at 6 months. result: total of 82 eyes of 68 patients completed whole duration of study with mean age of 59 ± 6.72 years. the mean duration of diabetes was 11.68 ± 7.2 years. there was significant difference (p<0.01) observed in the mean bcva (log mar) units at baseline and after 6 months i.e. 0.64 ± 0.28 vs 0.23±0.27 (snellen’s equivalent 6/36). the mean central macular thickness was significantly reduced at 1st, 3rd and 6th month (p < 0.01). spearman's correlation analysis between cmt and log mar units showed the correlation coefficient of 0.54, 0.07, and 0.75 were seen at pre intervention, at 3 months, and at 6 months with significant difference (p<0.01).the subconjunctival haemorrhage post injection day 1 seen in 10.9%-12.1% cases, and raised intraocular pressure (iop) at post injection day 1 in 2.4%-3.6% cases. but, no complications seen at 3rd and 6th month followups. in persistent macular edema, significant resolution (p=0.01) of cmt was seen (545.91± 111.97µm vs. 341.08 ±122.75µm baseline/6month) without significant (p=0.09) improvement in visual acuity (0.85 ± 0.28vs. 0.34 ± 0.23). whereas, in refractory macular edema, no significant resolution (p>0.05) of cmt was seen (482.53 ± 136.98µm vs. 407 ± 169.64 µm baseline/6month) without significant (p>0.05) improvement in visual acuity (0.53 ± 0.24vs. 0.38 ± 0.30). 69.5% cases improved ≥ 2 snellen lines at 3 months and 78% cases improved ≥ 2 snellen lines at 6 months. there were reduced macular edema seen in 69.5% cases, persistent macular edema in 12.1%, refractory macular edema in 7.3% cases, and recurrence of macular edema in 10.9% cases. no other ocular and systemic complications were observed during follow-up. conclusion: intravitreal bevacizumab is effective in treatment of diabetic macular edema but therapeutic effect is temporary and repeat treatment is needed. it does not show any potential drug related ocular and systemic side effects, hence it is safe and economical therapeutic agent. keywords: diabetic macular edema, proliferative diabetic retinopathy, best corrected visual acuity, intravitreal bevacizumab. cite this article: y, nasrin; ajay, sharma; yalakala, sharmila. a prospective study of safety profile and efficacy of three doses of intravitreal bevacizumab in diabetic macular edema. international journal of retina, [s.l.], v. 4, n. 2, p. 127, sep. 2021. issn 2614-8536. available at: <https://www.ijretina.com/index.php/ijretina/article/view/171>.doi: https://doi.org/10.35479/ijretina.2021.v ol004.iss002.171. https://www.ijretina.com/index.php/ijretina/article/view/171 https://doi.org/10.35479/ijretina.2021.vol004.iss002.171 https://doi.org/10.35479/ijretina.2021.vol004.iss002.171 128 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2020; correspondence to: sharma ajay, department of vitreo retinal services, sankar foundation eye institute, visakhapatnam, andhra pradesh, india, research@sankarfoundation.org introduction diabetes mellitus (dm) is a metabolic disease known since ancient times, characterized by hyperglycemia with its severe variations, secondary to the decrease of endogenous insulin secretion, action or both.1 the diabetic population in india is thought to be estimated as 69.9 million by 2025, and 80 million by 2030.2the global prevalence of impaired glucose tolerance is estimated to be 7.5% (374 million) in 2019 and projected to reach 8.0% (454 million) by 2030 and 8.6% (548 million) by 2045.3 the global prevalence of diabetic retinopathy (dr) and diabetic macular edema (dme) were 27.0% for any dr comprising of 25.2% npdr, 1.4% pdr and 4.6% dme during 2015 to 2019.4 based on a study during a period of 10 years the development of dme occurred in 20.1 % of patients with type 1 diabetes.58 diabetic retinopathy studies done in southern india showed that the range of prevalence of dr to be 12.2 % to 18.03 %, in the dm population. the population above 50 years affected by dr was 16.6 % to 20.9 %.9 the wisconsin epidemiologic study of diabetic retinopathy (wesdr) found the 14year incidence of diabetic macular edema (dme) in type i dm to be 26%.5 prevalence of dme is more in npdr and increases with its severity.10 dme can be diagnosed clinically as well as on oct and fundus fluorescein angiography (ffa).11 sustained-release corticosteroids developed to reduce the need for frequent intraocular injections in the treatment of dme. fluocinolone acetonide implant is a non-biodegradable implant containing 0.59 mg of the drug which releases drug for 2 years. a next-generation fluocinolone acetonide insert, iluvien, developed as a non-biodegradable, sustained-release device containing 0.19 mg drug, has been approved by the us fda for the treatment of dme in patients who have not experienced a rise in iop with steroids.12disadvantages of steroids are because of their side effects and occur in a dose dependent pattern.13this increases the need for additional drugs, which controls the iop.14 intravitreal non-steroidal anti-inflammatory drugs (nsaids) have shown to reduce macular edema by inhibiting pg synthesis. intravitreal diclofenac could possibly be as effective as steroid therapy, with added advantage of avoiding the related adverse effects such as iop elevation.15 an intravitreal drug mp0112, a designated ankyrin repeat protein selectively binds vegf-a isoforms. significant reductions in cmt and improvement in bcva were noted, with the effects showing dose dependency. furthermore, aqueous levels of mp0112 remained detectable after 12 weeks, suggesting a relatively long half-life of this drug. more rct’s are required to evaluate the efficacy of this drug.16 another developed drug is pf-04523655 (pf), an sirna that inhibits the rtp801 gene which is responsible for the production of hypoxia-inducible factor which, in turn, regulates vegf production. the dose-ranging evaluation of intravitreal pf 04523655 for diabetic macular edema trail resulted in greater bcva improvements, although cmt reduction was only half as good as that seen with laser. a newly developed local treatment option for dme is subtenon injection of interferon-𝛼𝛼 (ifn𝛼𝛼). it acts as an inhibitor of vegf and other cytokines and enhances the brb.17 more studies are required to evaluate their efficacy. for many years, laser was the only treatment option available for dme, but since 2011, other options started becoming available. studies carried out to compare the effects of intravitreal anti-vegf’s and mlp in dme, which proves better outcome in antivegf arm but with the need of monthly injections at least for first 3 months.18 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2 129 other agents such as intravitreal corticosteroids (cs) like triamcinolone acetonide (ta), sustained-release implants like dexamethasone and fluocinolone acetonide implants. these drugs eliminate the need for monthly injections but at the cost of various adverse effects like raised intraocular pressure (iop) and early cataractous changes. bevacizumab (bcz) is a recombinant humanized monoclonal antibody with a molecular mass of 149 kda that effectively binds and inhibits all the isoforms of vegf.19 although bcz has been approved for the treatment of metastatic malignancies such as colon cancer20 and ovarian cancer by the us fda,21 it is being widely used off-label for the treatment of dme worldwide since 2005. the half-life of bevacuzumab in aqueous humor after intravitreal delivery of 1.5 mg was 9.82 days. bevacizumab concentration peaked on post-injection day 1, with a mean concentration of 33.3 µg/ml and dropped to less than 1 µg/ml at day 51.22 as to treatment for the recurrence of me, previous studies have shown that repeated injections with intravitreal bevacizumab are required to maintain good visual acuity.23,24 however, the best method (i.e. ivb, mlp, or combined therapy), criteria, and timing for retreatment are still unknown. hence, the present study was carried out to identify the safety and efficacy of bevacizumab in diabetic macular edema. efficacy was assessed anatomically by cmt using oct, functionally by bcva. safety was assessed by complication rate (ocular complications like subconjunctival haemorrhage, retinal breaks, retinal detachment, vitreous haemorrhage, glaucoma, cataract and systemic complications) after intravitreal bevacizumab. primary outcome of the study is to assess the mean resolution of central macular thickness by oct after intravitreal bevacizumab, to calculate the improvement of bcva and to evaluate ocular and systemic complications after intravitreal bevacizumab. method a hospital based prospective interventional study conducted at a tertiary eye care institute sankar foundation eye hospital, visakhapatnam. totally, 82 eyes of 68 patients with diabetic macular edema those who are undergoing intravitreal avastin® injections for dme were included during july 2018 to december 2019 (1.5 years). avastin® (bevacizumab)[f.hoffmann-la roche ltd, grenzacherstrasse 124, ch-4070 basel, switzerland]. inclusion criteria: •patients with presence of clinically significant macular edema in both pdr and npdr with no prior treatment. •patients of either gender and with any type, duration, level of control and severity of diabetes mellitus. •central retinal thickness on oct > 250 µ or presence of cystic spaces. •bcva pre-treatment ≤ 6/12. exclusion criteria: •macular edema secondary to causes other than dr. •vision loss secondary to cause other than dme. •dme previously treated with intravitreal triamcinolone and/or other anti vegf. •laser treatment done within previous 3 months. •corneal diseases, inflammatory eye diseases, optic neuropathy and age-related macular degeneration. •any ocular surgery within previous 6 months. •uncontrolled hypertension with thromboembolic events. intravitreal injection of bevacizumab: procedure was performed in operation theatre. topical anesthesia xylocaine was given after cleaning the ocular surface with povidone iodine 5% and using a sterile drape. patients then receive intravitreal injection of 0.05ml volume containing 1.25mg of avastin using a sharp 27or 30-gauge needle at 3.5 mm posterior to limbus in pseudophakic eye and 4 mm posterior to limbus in phakic eyes. after injection antibiotic eye drops was applied 4 times a day for 1 week. all the patients was treated by 3 injections of intravitreal bevacizumab with 1-month interval for each injection. 130 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; all patients were examined on post op day 1 of each injection. the visual acuity was evaluated monthly, macular oedema was evaluated prior to injection, after completion of 3injections and at 6th month follow-up. at the end of third injection the patients ware scheduled for further injections on as needed basis which evaluated by oct parameters. if the patient is a non-responder or partial responder to bevacizumab, then a change of antivegf ranibizumab was offered to the patient. if the patient has non-centre involving macular oedema then focal laser was considered. outcome measurement: all the patients examined by one individual (the investigator) in order to minimize the bias. a detailed medical history, clinical examination which includes visual acuity recording, slit-lamp examination of anterior and posterior segment using 90d lens and posterior segment evaluation by indirect ophthalmoscopy using 20d lens. uncorrected and bcva using snellen’s visual acuity chart for distant vision and near vision. iop recorded using goldman applanation tonometry. •pre and post injections bcva with snellen’s visual acuity chart converted to log mar units. •pre and post injections central macular thickness measurement using sd-oct. •assessment of ocular & systemic complication after iva injection. data collection: data was collected from the patients selected for the study during the period of july 2018 to december 2019 using the standard case sheet for the study. complete eye examination was performed such as uncorrected and bcva, anterior and posterior segment evaluation with slitlamp biomicroscopy using + 90d lens and posterior segment evaluation by indirect ophthalmoscopy using 20d lens. pre and post injection bcva with snellen’s visual acuity chart. pre and post injection retinal thickness measurement using sd-oct. all patients were examined on post op day 1 of each injection. the visual acuity evaluated monthly, macular oedema evaluated prior to injection, after completion of 3 injections and at 6th month followup. statistical analysis: continuous variables are represented as mean and standard deviation where data follows normal distribution, otherwise as median with range. categorical variables are represented as variables between the groups. statistical tests such as fisher exact test, chi square test, t test, were used accordingly. correlation was done using spearman’s correlation coefficient with r value in the range of -1 to +1. association between the variables was considered statistically significant when p value was < 0.05. statistical analysis performed using spss ver 22.0(spss inc, il, us). result the mean age of patients was 59 ± 6.72years (4180 years) and mean duration of dm 11.68 ± 7.2 years. all the selected patients were treated by 3 injections of intravitreal bevacizumab with 1-month interval for each injection. the visual acuity was evaluated monthly, macular oedema was evaluated prior to injection, and up to 6 months follow-up. male to female ratio 2.57:1. regarding duration of diabetes mellitus, 18% patients had history of diabetes mellitus for 610years, 15% had a history of diabetes mellitus for 16-20yr, 9% had 21-25yrs, and 4% had a 26-30yrs. the mean age of diabetes mellitus among study group was 11.68 ± 7.2years. majority of patients have diabetic retinopathy status of severe npdr. ratio between npdr with pdr 3.8:1. among study group mild npdr 1.2%, moderate npdr 31.7%, severe npdr 42.7%, and very severe npdr 3%, pdr 20.7%. out of 82 eyes in the study group 34(41.5%) were left eye and 48(58.5%) were right eye. 37(62.2%) have hypertension. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 131 table 1. comparison of residual cmt at the 1st and 6th month after three bevacizumab injections *paired‘t’ test the table 1 showing the mean cmt was 436.99µm, 315.79µm and 296.04 µm at baseline, 1st month, and 6th month respectively. the mean difference was found to be statistically significant (p<0.01). table 1 showing the mean difference of cmt at pre-intervention and post-intervention of 3rd month was 121.19µm. the mean difference of cmt at pre-intervention and post-intervention of 6th month is 140.95µm. the difference found to be statistically significant. table 2 . the mean comparison of best corrected visual acuity for distance (bcva) at pre intervention and 1st month and 6th month follow-up. bcva number of eyes pre intervention 1st month after 1st injection 1st month after 2nd injection 1st month after 3rd injection 6th month follow-up ≤ 6/60 16 5 3 1 4 6/36 -6/24 19 23 14 11 8 6/186/12 47 38 35 24 15 > 6/12 0 16 30 46 55 total 82 82 82 82 82 p-value# 0.02 0.03 <0.01 <0.01 #fisher exact test by using fisher exact test, p <0.05 suggestive of statistically significant difference i n bcva at all follow-ups compared to baseline. cmt µm p value * duration mean sd pre-intervention 436.99 135.105 <0.01 1st month 315.79 124.603 6th month 296.04 122.978 cmt difference in comparison to pre-intervention pre-intervention to 3rd month 121.195 106.395 <0.01 pre-intervention to 6th month 140.951 133.174 132 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; table 3: the mean comparison of log mar units of bcva at pre intervention and 1st month and 6th month follow-up. bcva log mar units (mean±sd) p value pre intervention mean difference of log mar units when compared to pre-intervention pre-intervention 0.64± 0.28 <0.01 1 month after 1st injection 0.48±0.27 0.16±0.08 1 month after 2nd injection 0.36±0.24 0.28±0.2 1 month after 3rd injection 0.27±0.24 0.37±0.24 <0.01 at 6th month follow-up 0.23±0.27 0.41±0.33 <0.01 based on paired t test analysis, p <0.01, suggestive of statistically significant difference in log mar units at all follow-ups compared to baseline (table 3). correlation between cmt and bcva: spearman's correlation analysis between cmt and log mar units showed the correlation coefficient of 0.54, 0.07, and 0.75 were seen at pre intervention, at 3 months, and at 6 months respectively with significant difference (p<0.01) (figure 1). figure 1. spearman's correlation analysis between cmt and log mar units at 3 months, and at baseline/3 months difference published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 133 figure 2. correlation analysis of cmt and bcva at 6 months correlation of difference in cmt and difference in bcva when compared to baseline and at 6 months, it shows significant positive correlation between cmt and bcva (figure 2). table 4. comparison of bcva for near vision with pre intervention and iop changes during study follow-up bcva for near vision preintervention [no. of eyes] at 1st month after 1st injection[no . of eyes] at 1st month after 2nd injection[n o. of eyes] at 1st month after 3rd injection[n o of eyes] at 6th month after 3rd injection[n o of eyes] n12 5 2 1 1 1 n10 17 6 4 3 3 n8 42 47 33 25 17 n6 18 27 44 53 61 p value# <0.01 <0.01 0.03 <0.01 iop changes mean±sd 14.26±1.64 14.91±2.46 14.56±2.08 15.2±2.52 14.63±2.36 p value* 0.32 0.33 0.71 0.08 #fisher exact test; * paired‘t’ test based on fisher exact test, p<0.01, suggestive of statistically significant difference in bcva for near at all follow-ups compared to baseline. based on paired t-test analysis, it’s not statistically significant in iop changes between pre intervention and upto 6th month follow up. 134 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; complications: the results shows subconjunctival haemorrhage post injection day 1 around 10.9% 12.1% cases and raised intraocular pressure (iop) post injection day 1 around 2.4% 3.6%. no complications at 3rd month and 6th month. bcva analysis from baseline: the results showing 69.5% cases improved ≥ 2 snellen lines at 3 months and 78% cases improved ≥ 2 snellen lines at 6 months. cmt outcomes at 6th month: there were reduced macular edema s e e n in 69.5% cases, persistent macular edema in 12.1%, refractory macular edema in 7.3% cases, and recurrence in 10.9% cases. table 5. central macular thickness (cmt) in recurrence of macular edema(me) cases at 6 months and mean bcva in recurrent me cases at 6 months compared with pre intervention and 3 months. baseline 3 month 6 month p value persistent macular edema cmt 545.91± 111.97 370.52 ±71.43 341.08 ±122.75 0.01* bcva 0.85 ± 0.28 0.45 ± 0.20 0.34 ± 0.23 0.09* refractory macular edema cmt 482.53 ± 136.98 497.76 ± 161.07 407 ± 169.64 >0.05* bcva 0.53 ± 0.24 0.44 ± 0.31 0.38 ± 0.30 >0.05* cmt in recurrence of me cases at 6 months 447.66 ± 91.35 287.33 ± 53.70 453 ± 150.19 <0.01* bcva in recurrence of me cases at 6 months 0.58 ± 0.15 0.26 ± 0.21 0.65 ±0.39 <0.01* table 5 showing cmt in recurrent macular edema cases at baseline was 447.66 ± 91.35, at 3months decreased to 287.33 ± 53.70, and at 6 months again increased to 453 ± 150.19. by using paired ttest p-value <0.05 therefore significant increase in cmt at 6 months. the table showing bcva in recurrent macular edema cases at baseline was 0.58 ± 0.15, at 3 months improved to 0.26 ± 0.21, at 6 months again decreased to 0.65 ± 0.39. by using paired t-test p-value <0.05 therefore significant decrease in bcva at 6 months. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 135 figure 3. optical coherence tomography (oct) images at pre-intervention and post-intervention of (a & b), patient-1, 60 years male and (c &d), patient-2 of 59 years female discussion this prospective interventional non comparative study was undertaken in patients with dme with aim of the safety profile and efficacy of intravitreal bevacizumab. main objectives of the study are mean resolution of central macular thickness, mean improvement in bcva and ocular and systemic complications after iva injections. all the selected patients were treated by 3 monthly injections of iva followed by as and when required based on oct findings till follow up of 3months after 3rd injection. this study was conducted at sankar foundation eye hospital, visakhapatnam and included eighty two eyes of sixty eight patients attending opd from july 2018 to december 2019.all the patients visual acuity evaluated monthly and cmt evaluated prior to injection, 1 month after 3rd injection and at 6th month follow up. in the present study, the majority belonged to the age group 61-70 years (46%) with mean age of of 59± 6.72 years. this is in concordance with arevalo et al.25 study with mean age of 59.7 ±9.3 years. males represented 72% and females represented 28% of the sample with a male to female ratio 2.57:1 in our study. this difference may be because may be more health facilities are availed by men than women. a similar male 136 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; preponderance was documented in arevalo et al.25 , and tareen ih et al.26 duration of diabetes ranged between 1-30 years in the sample of patients with diabetic macular edema included in our study. 29% of patients were having duration of diabetes of 05 years, 18% for 6-10 years, 25 % for 11-15 years, 15 % for 16-20 years, 9% for 21-25 years and 4% for 26-30 years. mean duration of diabetes in this study was 11.68±7.2 years. it is in concordance with shyam vyas and raba tapa et al, asim ateeq et al. which was 11.88 years and 10.15±3.2 years respectively.27,28 the 82 eyes with diabetic macular edema included in the study were staged for diabetic retinopathy according to etdrs classification. in the present study eyes showing npdr were more compared to pdr (79.03% vs 20.7%). more number of eyes with npdr than pdr could be due to early identification of cases with dr due to regular screening and referral of cases from other specialities in the institute. this is in concordance with sham vyas et al (76.92% vs 23.08%). this is not in accordance with ozikiris et al.29 (40% vs 60%), arevalo et al. (43.6% vs 56.4%). this may be due to lack of awareness on dr screening among their study population. in the present study, baseline cmt was 436.99±135.10μ. this is in concordance with tareen et al, sham vyas et al, with mean cmt of 452±143.1μm, 463±173μm. the baseline mean bcva in this study was 0.64±0.28 log mar. this is in concordance with arevalo et al. and haritoglou et al.30 with baseline mean bcva 0.87 ±0.40 log mar and 0.86±0.38 log mar units respectively. in tareen ih et al. study, the baseline means bcva 0.42±0.14 log mar was better compared to the present study. in ozkiris a et al. study the baseline mean bcva1.09±0.23 log mar was worse than the present study. in the present study, the mean cmt changed significantly from 436.99±135.10 μm at baseline to 315.79±124.60 μm(p<0.01) at 1 month after 3rd iva and this significant change followed with subsequent follow-up with mean cmt of 296.04±122.97 μm(p< 0.01) at 6th month. however, the mean change was a bit lower at 6th month when compared to the 1 month after 3rd iva. the resolution of cmt more during injections period compared with follow-up. in arevalo et al. study, the results were very similar to the present study. in this study the mean cmt of 387±182μm at baseline is decreased to 287±102μm, 282±115μm, and 275±118μm at 1 month, 3 months and 6 months follow up, respectively. in tareen ih et al. study the mean cmt of 452.9±143μm at baseline decreased to 279.8±65μ at 3rd month follow up. this study was like the present study in giving 3 consecutive ivb injections each 1 month apart and the results were in concordance in haritoglou et al., study, mean central retinal thickness was 501 ±163μ at baseline. two weeks postoperatively, a significant decrease of mean retinal thickness to 425 ±180 μm was observed. six weeks after the injection, mean macular retinal thickness had further decreased to 416 ±180 μm, a highly significant difference compared with baseline. after 12 weeks, mean retinal thickness further decreased to 377 ± 117 μm. in the present study at baseline, the mean bcva was 0.64±0.28 log mar. this improved significantly to 0.48±0.27 (p< 0.01)), 0.36±0.24 (p<0.01)), and 0.27±0.24( p<0.01),0.23±0.27 log mar (p< 0.01)) at 1month, 2 months , and 3 months,6 months respectively, these changes are statistically significant. this finding correlates with the change in cmt with iva injections. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 137 the improvement of bcva is also more with 1st iva when compared to subsequent ivas. in arevalo et al. by 1 month the mean bcva improved from 0.87 to 0.6 log mar, a difference which was statistically significant. this was maintained throughout 6 months. at 3rd and 6th months follow up the mean bcva did not differ statistically. in tareen ih et al. study the mean bcva at baseline was 0.42 ± 0.14 log mar. at one month after the 1st injection bcva improved to 0.34±0.13 log mar unit, with statistical significant difference. this improvement in bcva was maintained after 2nd and 3rd injections which were 0.25±0.12 log mar and 0.17±0.12 log mar, respectively. these results were in concordance with present study. in haritoglou et al. study, at baseline, mean visual acuity was 0.86 ±0.38 log mar. after 2 weeks, mean visual acuity had improved to 0.80 ± 0.37 log mar on snellen charts (not significant). six weeks after the injection, a significant improvement to 0.75 ± 0.37 log mar was observed. twelve weeks after the injection, some regression of the increase in mean visual acuity to 0.84 ±0.41 log mar was noted. in the present study, we found a positive correlation between reduction in cmt and improvement in bcva at 1 month after 3rd injection. using spearman’s correlation coefficient, which suggests that as cmt reduces, visual acuity improves. the correlation was weakly positive at 3months but strongly positive at 6 months. this may be due to multiple factors like macular ischemia, hard exudates, etc. this finding is consistent with a study carried out by bressler sb et al.31 in which results showing positive correlation of improvement in bcva with reduction in cmt and also a few cases which didn’t keep up with these results due to macular ischemia, lipid exudation, etc in the present study, bcva for near vision changed significantly from baseline. higher baseline cmt may be responsible for poorer near vision. in the present study, mean iop values were 14.2±1.6 mm hg, 14.9±2.4 mmhg,14.5±2.08 mmhg,15.2±2.5mm hg,14.6 ± 2.36 mm hg at baseline,1 month after 1st injection, 1 month after 2nd injection, 1 month after 3rd injection and at 6th month respectively. no statistically significant difference was found at any evaluation. xiaoyun fang et al.32 mean iop values were 14.2 ± 3.1 mmhg, 13.9 ± 3.0 mmhg, 14.4 ± 3.0 mmhg and 14.4 ± 3.4 mmhg at baseline, and 24 weeks, 8 weeks and 12 weeks post-injection, respectively. no significant difference was found at any evaluation. the present study shows subconjunctival haemorrhage post injection day 1 around 10.9% 12.1% cases and raised iop post injection day 1 around 2.4% 3.6%. no other ocular and systemic complications were observed during follow-up. several reports of ocular haemorrhage following the use of intravitreal anti vegf drugs. subconjunctival haemorrhage has been reported to occur in nearly 10% of injections, with higher frequency in patients who were receiving aspirin. acute rise of intraocular pressure (iop) after intravitreal injection is procedure-related and lasts a few hours at most. a study done by fung et al.33 on the international intravitreal bevacizumab safety survey. none of the adverse event rates exceeded 0.21%. intravitreal bevacizumab injections did not show an increased rate of potential drugrelated ocular or systemic events. 138 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; in the present study, 69.5% cases bcva improved ≥ 2 snellen lines at 3 months, 30.5% cases remained stable. in tareen ih et al. study bcva improved ≥ 1 etdrs line in 69.2% cases at 3 months, 26.9% cases remained stable, 3.8% cases decreased ≥ 1 etdrs line. in shyam vyas et al. study bcva improved ≥ 2 etdrs lines in 42.3% cases at 3 months, 46.15% cases remained stable, 11.53% cases decreased ≥ 2 etdrs lines. these results were in concordance in with present study. in the present study 56% cases recovered with 3 injections of intravitreal bevacizumab. 28% cases persistent macular edema and 15.8% cases refractory to treatment. an analysis of the drcr. net protocol t study revealed that the incidence of persistent dme after 3 consecutive monthly injections was 50.8%, 53.2% and 72.9% through week 12, and 31.6%, 41.5% and 65.6% through week 24 in eyes that received aflibercept, ranibizumab and bevacizumab, respectively.34 a study done by gabriel katz et al.,35 50% cases treatment was switched to ranibizumab after 3 to 6 bevacizumab injections due to persistent macular edema. bolt study a prospective randomised trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema. 21.6% patients achieved dry macula at 4 months in bevacizumab group. in the present study 0ut 0f 82 eyes 36 eyes switched from bevacizumab to ranibizumab injections after 3injections of bevacizumab. out of 36 eyes 23 eyes have persistent macular edema and 13 eyes have refractory macular edema. in the present study 78% cases bcva improved ≥ 2 snellen lines at 6 months,20.7% cases remained stable,1.2% cases decreased ≥ 2 snellen lines. in tareen ih et al. study bcva improved ≥ 1 etdrs line in 73% cases at 6 months, 20.5% cases remained stable, 6.4% cases decreased ≥ 1 etdrs line. in shyam vyas et al. study bcva improved ≥ 2 etdrs lines in 42.3% cases at 6 months, 48.07% cases remained stable, 9.61% cases decreased ≥ 2 etdrs lines. in arevalo et al. study bcva improved ≥ 2 etdrs lines in 55.1% cases at 6 months, 41.1% cases remained stable, 3.8% cases decreased ≥ 2 etdrs lines. these results were in concordance with present study. in the present study 69.5% cases recovered with 3 injections of intravitreal bevacizumab. 12.1% cases persistent macular edema and 7.3% cases refractory to treatment, 10.9% cases recurrence of macular edema at 6th month follow-up. bolt study a prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema. 56.7% patients classified as non-responders at 24 months due to persistent macular edema in bevacizumab group.34 in aseem ateeq et al. study, out of the 54 eyes of 54 patients who were given the intravitreal injection of avastin (bevacizumab), 43 eyes (79.6%) showed >10% decrease in macular thickness from pre-injection thickness, 10 eyes (18.5%) showed <10% decrease and 1 eye (1.9%) showed increase in macular thickness post operatively after one month. in persistent macular edema cases mean cmt reduced from 370.52 ± 71.43 µm after the last bevacizumab injection to 341.08 ± 122.75 µm following ranibizumab injections (p≤ 0.01), this was statistically significant. mean bcva improved from 0.45 ± 0.20 after the last bevacizumab injection to 0.34 ± 0.23 (p=0.09), this was not statistically significant. gabriel katz et al.35 study done to evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (dme). the difference in va between any of these fixed timepoints was not statistically significant. published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 4; 2; 139 the mean cmt was significantly lower after the first 3 ranibizumab injections and at the final follow-up (p<0.001).these results were in concordance with present study. in refractory macular edema cases mean cmt reduced from 497.76 ± 161.07µm after the last bevacizumab injection to 407.84 ± 169.64 µm following ranibizumab injections (p= 0.1),mean bcva improved from 0.44 ± 0.31 after the last bevacizumab injection to 0.38 ± 0.30 (p=0.6). in m ashraf et al.36 study switching to ranibizumab in diabetic macular edema refractory to bevacizumab treatment. 34 eyes switched to ranibizumab showed a statistically significant improvement in mean bcva from 0.67 ± 0.39 log mar to a mean of 0.55 ± 0.36 log mar (p < 0.05). in addition, there was a statistically significant decrease in central subfield thickness (cst) from a mean of 475.3 ± 122.8 to a mean of 417.3 ± 109.1 (p < 0.05). in the present study mean cmt, mean bcva after switching to ranibizumab not significant may be due to study done on small no of cases results may vary. in present study recurrence of macular edema at 6 months in 9 cases. out of 9 cases 5 cases completely responded with 3 injections becacizumab at the end of 3 months. remaining 4 cases even with treatment after 3months they showed increase in macular edema with decreased visual acuity. in roh et al.37 study at 6 weeks after the 1st injection of bevacizumab in clinically significant dme, bcva increased significantly, cmt decreased markedly, which returned to near baseline at 12 weeks. so repeated administration of iva may lead to improvement in csme cases. in xiaoyun fang et al. study done on bevacizumab in dme concluded that therapeutic effect is temporary and repeat treatment may be needed. recurrence of macular edema may be due to uncontrolled diabetes mellitus and other risk factors that leads to progression of diabetic retinopathy. limitations of this study includes small sample size included in the present study. the results would have been stronger and power could have been improved if the sample size would have been large. there is no control group in the study as randomization was not possible, so we cannot rule out the possibility that some of the improvement in macular edema might be associated with improvement in systemic health. control of dm and other risk factors that leads to progression of dme are not assessed in the present study. conclusion there was significant reduction in cmt at 3 months and 6 months of follow-up as compared to baseline. there was significant improvement in bcva for distance at follow-up visit as compared to baseline. reduction in cmt was positively correlated with improvement in vision though not very strongly in our study. switching to ranibizumab in persistent diabetic macular edema cases with bevacizumab injections, there was significant reduction of cmt at 6th month follow up. switching to ranibizumab in diabetic macular edema refractory to bevacizumab, there was no significant reduction of cmt and improvement of bcva. intravitreal injection of bevacizumab is effective in the treatment of diabetic macular edema but therapeutic effect is temporary and repeat treatment may be needed. intravitreal bevacizumab injections did not show an increased rate of potential drugrelated ocular or systemic events. it is a safe and economical therapeutic agent. optical coherence tomography is an important tool in monitoring the progression of macular edema. baseline oct testing provides a background for post-interventional comparison. this strategy helps the clinician in early detection of macular edema as well as monitoring postinterventional status and need for future treatment. 140 published by: inavrs https://www.inavrs.org/ | international journal of retina https://ijretina.com 2021; 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* paired‘t’ test complications: the results shows subconjunctival haemorrhage post injection day 1 around 10.9% 12.1% cases and raised intraocular pressure (iop) post injection day 1 around 2.4% 3.6%. no complications at 3rd month and 6th month.