for numbering.pmd 9 original articleoriginal articleoriginal articleoriginal articleoriginal article pattern of ocular tumors in the eastern region of nepal lavaju p1, arya s k1, sinha a2, pandey s2, adhikari s1, shrestha b g1, chetan s1, t agarwal l1 departments of 1ophthalmology and 2pathology b p koirala institute of health sciences (bpkihs), dharan, nepal abstract background: ocular tumors are commonly encountered in ophthalmic practice. objective: to study the clinical pattern of ocular tumors in the eastern region of nepal. materials and methods: the hospital records of patients with ocular tumors treated at b p koirala institute of health sciences in the eastern region of nepal over a period of 5 years (april 2003 march 2008) were studied retrospectively. results: of 115 consecutive patients with ocular tumors, 40 (34.75%) were below the age of 21 years, 41 (35.65%) were in the age group of 21-50 years and 34 (29.56%) of age above 50 years. there were 48 (41.73%) and 67 (58.26%) patients with benign and malignant tumors respectively. the common benign tumors were conjunctival papilloma, dermoid cysts, nevus, cystic lesions and hemangioma. among the malignant tumors, basal cell carcinoma was the commonest (22.38%). retinoblastoma was the most common ocular malignant tumor in the pediatric age group (88.8%). basal cell carcinoma was the commonest eyelid malignancy 53.57%. conclusion: conjunctival papilloma, dermoid cysts, nevus, cystic lesions and hemangioma are common benign ocular tumors, whereas basal cell carcinoma and retinoblastoma are the commonest ocular malignancies in adults and children respectively. key words: ocular malignancy, retinoblastoma, basal cell carcinoma introduction the management of ocular tumors is a great challenge particularly in developing countries because of the fact that most of the ophthalmic surgeons here are engaged in entertaining patients of cataract blindness. those patients with ocular tumors need a referral to higher centers for diagnosis and management. with the purpose of developing an effective strategy on detection and management of ocular malignancies, it is important to first identify the pattern of the tumors referred to a higher center of the region. received: 04.07.2008. accepted: 10.08.2008 correspondence and reprint requests to: dr poonam lavaju assistant professor department of ophthalmology, bpkihs email : ophth_eye@yahoo.com fax : 00977-25-520251 materials and methods a retrospective study of hospital records of the patients with ocular tumors subjected to histopathological analysis over a period of 5 years from april 2003 to march 2008 was carried out at the departments of ophthalmology and pathology of b p koirala institute of health sciences in the eastern region of nepal. a total of 115 consecutive medical records with histopathological confirmation of the type of tumors of the eye and its adnexa were identified. those cases without histopathological confirmation were not included in the study. two cases of clinically and radiologically suspected retinoblastoma were diagnosed as endophthalmitis after histopathological study. they were, therefore, excluded from the study. nep j oph 2009;1(1):9-12 10 results a total of 115 medical records of patients of ocular tumors were studied. of the total, 64 (55.65%) were male and 51 (44.35%) were female. there were 48 (41.73%) and 67 (58.26%) patients with benign and malignant tumors respectively. it was seen that in the early age group of less than 5 years, prevalence of malignant tumor was very high, accounting for 19 malignant tumors out of a total of 22 patients. all these malignant tumors were retinoblastomas. the benign ones included capillary hemangioma and epidermal inclusion cyst. another peak of malignant tumors was seen in the age group 40+ to 50 years. the majority of malignancy was found to be basal cell carcinoma followed by squamous cell carcinoma. table 1 shows the distribution of benign and malignant ocular tumors according to their location. the eyelid was the most common site of ocular tumors accounting for a total of 49 (42.6%) cases, followed by intra-ocular tumors 26 (22.61%) and orbital tumors 18 (15.65%). eyelid tumors mainly consisted of basal cell carcinoma 15 (30.6%) followed by squamous papilloma 4 (8.16%) and squamous cell carcinoma 5 (10.2%). the other eyelid tumors with or without conjunctival involvment are given in table 2. retinoblastoma was the most common intraocular tumor in 24 (92.3%) followed by intraocular melanoma in 2 (7.69%). among the eyelid malignancies (n=28), basal cell carcinoma was found in 53.57%, squamous cell carcinoma in 17.86% and meibomian gland carcinoma in 14.28%. discussion from table 4 we can see that in the present study, retinoblastoma was seen in 24 patients, accounting for 35.8% of the total ocular malignancies, followed by basal cell carcinoma 15 (22.3%), squamous cell carcinoma 5 (7.46%) and melanoma 5 (7.46%). in a similar study conducted in bpkihs, nepal, between 1995-2000, the most common malignancy was retinoblastoma (45.2%) followed by basal cell carcinoma (22.6%), squamous cell carcinoma (17.9%) and melanoma (9.5%) (thakur et al 2003). lavaju p et al nep j oph 2009;1(1):p-p ocular tumors table 1 distribution of tumors according to their location site benign malignant total % n =115 intraocular 0 26 26 22.61 orbital 14 4 18 15.65 eyelid tumors 21 28 49 42.6 with or without conjunctival involvement conjunctiva 13 9 22 19.13 table 2 eyelid tumors with or without conjunctival involvement types of tumors no % n = 49 basal cell carcinoma 15 30.6 squamous cell carcinoma 5 10.2 squamous papilloma 4 8.1 sebaceous/meibomian 4 8.1 gland carcinoma sebaceous cyst 2 4 basosquamous carcinoma 1 2 eosinophilic cystadenoma 4 8.1 capillary hemangioma 2 4 apocrine hygrocystoma 1 2 malignant melanoma 3 6.1 compound naevus 4 8.1 intradermal naevus 2 4 solid dermoid 2 4 table 3 various orbital tumors no % n = 18 schwannoma 2 11.1 cavernous hemangioma 2 11.1 dermoid cyst 6 33.3 leukemia 1 5.5 lymphangioma 2 11.1 pleomorphic adenoma 2 11.1 rhabdomyosarcoma 1 5.5 fibrous hystiocytoma 2 11.1 11 similarly, in a study from singapore, the common malignancies were retinoblastoma (53.6%), melanoma (19.2%) and squamous cell carcinoma (11.2%); (lee et al 2000). in another study from india, retinoblastoma was seen in 32% and squamous cell carcinoma in 25%, (sunderraj, 1991). in nigeria, retinoblastoma accounted for 55% of ocular tumors (ajaiyeoba et al 1992). in the developed countries, the findings were quite different. in a newyork study, melanoma was the commonest malignancy (70.4%), followed by retinoblastoma (9.8%) and squamous cell carcinoma (9.2%), (mahoney et al 1990). in alabama, melanoma was the commonest ocular malignancy (59%), (swanson and cloud, 1991). lavaju p et al nep j oph 2009;1(1):9-12 ocular tumors followed by sebaceous gland carcinoma (10.2%), squamous cell carcinoma (3.4%) and malignant melanoma (1.2%). in a study from taiwan, the most common eyelid malignancy was basal cell carcinoma (65.1%), followed by squamous cell carcinoma (12.6%), and sebaceous cell carcinoma (7.9%), (hsin-yi et al 2006). similarly, in india, basal cell carcinoma was found in 38.8% of eyelid cancers, followed by sebaceous gland carcinoma (27%) and squamous cell carcinoma (22.4%), (abdi et al 1996). table 4 pattern of primary malignant tumors study retinoblastoma bcc scc melanoma % % % % bpkihs 35.8 22.3 7.46 7.46 (2003-2008) bpkihs 45.2 22.6 17.9 9.5 (1995-2000) singapore 53.6 5 11.2 19.2 nigeria 55 10 13.5 10 india 32 18 25 12 newyork 9.8 5.3 9.2 70.4 alabama 7.8 13.2 9.4 59 table 5 shows the distribution of retinoblastoma in various age groups. in the present study, retinoblastoma was seen in 91.66% in the 5 year olds or younger. in the previous study at bpkihs, 88.2% of patients with retinoblastoma were 5 years old or younger (thakur et al 2003). similar reports were obtained from a singapore study (95.5%), (lee et al 2000), an american study (95%), (tamboli et al 1990), and an indonesian study (76%), (nasution and sutjipo, 1991). this shows that retinoblastoma is the most common ocular malignancy in the pediatric age-group worldwide. table 6 shows the distribution of various eyelid malignancies in 3 different studies. in the present study, 15 patients had basal cell carcinoma of the eyelid, accounting for 53.57% of the total eyelid cancers, followed by squamous cell carcinoma (17.86%) meibomian/sebaceous gland carcinoma (14.28%). in a singapore study, (lee et al 1999) reported basal cell carcinoma as the most common eyelid cancer (84%), table 5 distribution of retinoblastoma in various age groups study <5 years >5-10 years % % % bpkihs 2003-2008 91.66 8.33 bpkihs 1995-2000 88.2 11.8 singapore 95.5 4.5 usa 95 5 indonesia 76 24 conclusion basal cell carcinoma is the commonest ocular malignancy in the older population. retinoblastoma is the most common ocular malignant tumor in the pediatric age group. references abdi u, tyagi n, maheswari v, gogi r, tyagi sp(1996). tumors of eyelid: a clinicopathologic study. j indian aled assoc 94: 405-9,416,418. ajaiyeoba ia, pindiga hu, akang ee (1992). tumors table 6 malignant tumors of eyelids various bcc sebaceous squamous studies gland cell cell carcinoma carcinoma % % % bpkihs 53.57 14.28 17.86 2003-2008 singapore 84 10.2 3.4 india 38.8 27 22.4 12 of eye and orbit in ibadan. east afr med j 69: 4879 hsin-yi lin, ching-yu cheng, wen-ming hsu, linda kao w.h. (2006). incidence of eyelid cancers in taiwan: a 21-year review. ophthalmology 113:2101-2107. lee sb, eong kga, saw sm et al (2000). eye cancer incidence in singapore. br j ophthalmol 84: 767-770. lee sb, saw sm, eong kga et al (1999). incidence of eyelid cancers in singapore from 1968 to 1995. br j ophthalmol 83: 595-97. mahoney mc, burnett ws, majerovics a et al (1990). the epidemiology of ophthalmic malignancies in new york states. ophthalmology 97: 1143-7. nasution r, sutjipo a (1991). childhood retinoblastoma. pediatr indones 31: 17-22 sunderraj p (1990). malignant tumors of the eye and adnexa. indian j ophthalmol 97:1143-7. swanson sw, cloud g (1991). a retrospective analysis of primary eye cancer at the university of lavaju p et al nep j oph 2009;1(1):9-12 ocular tumors alabama at birmingham 1958-88. part i. eye and orbital cancer. j am optom asso 62: 815-19 tamboli a, podger mj, horn jw (1990). the incidence of retinoblastoma in the united states:1974 through 1985. arch ophthalmol 50: 5773-7 thakur skd, sah sp, lakhey m, badhu bp (2003). primary malignant tumors of eye and adnexa in eastern nepal. clinical and experimental ophthalmology 31: 415-417. 186 isolated bilateral complete cryptophthalmos javed hussain farooqui1, thanh huy thiên hà2, ahmed gomaa3,4 1dr. shroff’s charity eye hospital 2department of ophthalmic trauma vietnam national institute of ophthalmology 3moorfields eye hospital, london, uk 4department of ophthalmology, cairo university, cairo, egypt abstract cryptophthalmos is a rare congenital anomaly, characterized by extension of the skin continuously from forehead onto the cheeks and covering eyeballs. although cryptophthalmos, as a part of fraser syndrome, has been reported many times, isolated cryptophthalmos without systemic associations is very rare. we present a 6-monthold child with isolated bilateral complete cryptophthalmos, which to the best of our knowledge, is the first case of cryptophthalmos being reported from vietnam. keywords: cryptophalmos, congenital, eyeball case report farooqui et al isolated bl crytophthalmos nepal j ophthalmol 2016; 8(16): 186-188 received: 28/05/16 accepted: 26/06/16 address for correspondence dr javed hussain farooqui, medical officer comprehensive ophthalmology dr. shroff’s charity eye hospital 5027, kedarnath marg, daryaganj new delhi110002 phone: +91-9599444445 email: jhfarooqui@gmail.com introduction cryptophthalmos (co) is a rare congenital condition in which eyelids are unable to divide in the embryo and the skin extends continuously from forehead onto the cheeks covering eyeballs. (coulon et al 1994, seal et al 992, kanhere et al 1999) it is described only one and a half century ago, and appears with a frequency of 20 for every 100,000 newborns (gonzález-treviño et al 2008). co is classified into three types: complete, incomplete and abortive (kanhere et al 1999). both autosomal recessive and autosomal dominant inheritance have been described, but most cases are autosomal recessive, with consanguinity being reported in 15% to 24.8% cases (stevens et al 1994, ramsing et al 1990, schauer et al 1990, berg et al 2001, slavotinek et al 2002). co is usually accompanied by urogenital anomalies, syndactyly, and cognitive disorders, and is termed as fraser syndrome(stevens et al 1994, ramsing et al 1990, schauer et al 1990, berg et al 2001, slavotinek et al 2002). very rarely, it’s isolated without any syndromic associations (kanhere et al 1999). we are reporting a case of isolated bilateral complete case of co, which to the best of our knowledge is the first case of cryptophthalmos from vietnam and only the 8th case of isolated bilateral complete cryptophthalmos (without any systemic associations) ever reported (chaudhary et al 2010). case report a 6 months old male child from vietnam presented to orbis flying eye hospital program with bilateral complete cryptophthalmos. he was the first child born to 25 years old mother. there is no history of consanguinity. the child was delivered by cesarean section at term. mailto:jhfarooqui@gmail.com 187 farooqui et al isolated bl crytophthalmos nepal j ophthalmol 2016; 8(16): 186-188 there were no postnatal complications. birth weight was 3kgs, with an apgar score of 9 and no respiratory distress. the child had normal head circumference. on examination, his eyes were completely covered by skin with absence of brows, eye lids, lashes and palpebral aperture in both sides. (figure 1) spontaneous globe movements could be detected under the skin, with soft eyeball palpable bilaterally. the left globe appeared to be smaller in size compared to the right. the child had hypertelorism with depressed hypoplastic nasal bridge. there was no umbilical hernia or genitourinary defects. there were no other congenital defects of fingers, ears (figure 2), nose or larynx. mri (magnetic rsonance imaging) showed two eye balls with intact outer wall, with no lens seen in both globes. (figure 3a) b scan confirmed absence of the crystalline lens. (figure 3b) discussion the association between cryptophthalmos and multiple congenital anomalies has been well described over the last century, with thomas describing the diagnostic criteria for fraser syndrome (stevens et al 1994, ramsing et al 1990, schauer et al 1990, berg et al 2001). the pathogenesis of this condition is unknown, with some studies documenting similarities with animal models showing vitamin a deficiencies and defects in programmed cell death (thomas et al 1986). prenatal diagnosis and subsequent management is still a challenge, especially in the developing world good prenatal screening can help physicians with recognition of some of its characteristics through ultrasonography (usg) examination of the eyes, digits, kidney, and lungs in utero (berg et al 2001). bilateral orbital reconstruction with corneal graft and anterior vitrectomy and lid reconstruction has been described for such cases, but the visual deficit usually persists due to clouding of corneal grafts (kanhere et al 1999, chaudhary et al 2010). in our case we deferred surgery, due to extensive anterior segment digenesis as figure 1: 6 month old child with bilateral complete cryptophthalmos figure 2: right and left ear a b figure 3: (a) coronal mri scan showing absence of crystalline lens (b) usg b-scan showing absence of crystalline lens. 188 evident on mri and usg b scan. also, the surgery is a staged procedure which requires continued care over a long period of time. we did not plan surgery in this patient because of the lack of infrastructure and expertise in managing this case, references berg c, geipel a, germer u (2001). prenatal detection of fraser syndrome without cryptophthalmos: case report and review of the literature. ultrasound obstet gynecol; 18: 7680. chaudhary ta, salman b, ahmad k (2010). a boy with bilateral complete cryptophthalmos in pakistan with subsequent blaming and shaming for his mother. pak j ophthalmol; 26 (1): 48-50 coulon p, lan pt, adenis jp, verin p (1994). bilateral complete cryptophthalmos. illustration with a case. review of the literature [in french]:j fr ophthalmol; 17: 505–512. gonzález-treviño jl, salcedo-casilla g, villanueva-martínez c, jair garcía-guerrero j (2008). criptoftalmos y ablefarón. presentación de un caso [in spanish]. rev mex oftalmol; 82(3):176-178 kanhere s, phadke v, mathew a, irani sf. cryptophthalmos(1999). indian j pediatr; 66: 805-808. ramsing m, rehder h, holzgreve w, meinecke p, lenz w (1990). fraser syndrome (cryptophthalmos with syndactyly) in the fetus and newborn. clin genet; 37: 84-96. schauer gm, dunn lk, godmilow c, eagle rc jr, knisely as (1990). prenatal diagnosis of fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks. am j med genet; 37: 583-91. seal hm, traboulsi ei, gavaris p, samango-sprouse ca, parks m (1992). dominant syndrome with isolated cryptophthalmos and ocular anomalies: am j med genet; 43: 785-788. slavotinek am, tifft cj (2002). fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. j med genet; 39: 623-33. stevens ga, mcclanahan c, steck a, shiel fo, carey jc (1994). pulmonary hyperplasia in the fraser cryptophthalmos syndrome. am j med genet; 52: 427-31. thomas it, frias jl, felix v, de leon l s, hernandez ra, jones m c, reynolds jf (1986). isolated and syndromic cryptophthalmos. am. j. med. genet; 25: 85–98. source of support: nil. conflict of interest: none farooqui et al isolated bl crytophthalmos nepal j ophthalmol 2016; 8(16): 186-188 inside text.pmd 64 lavaju p et al nep j oph 2010;2(3):64-67 rhabdomyosarcoma in an adult orbital rhabdomyosarcoma in an adult lavaju p1, das h1, shrestha (malla) p1, tiwari a2, sinha a3, upadhayaya p3 1department of ophthalmology, 2department of radiology, 3department of pathology b.p. koirala institute of health sciences, dharan, nepal abstract introduction: rhabdomyosarcoma is the most common primary orbital malignant tumor in children. orbital lesions represent about 10 % of all the cases of rhabdomyosarcoma. rhabdomyosarcoma is a rare cause of proptosis in adults. objective: to report a case of primary orbital rhabdomyosarcoma in a 45-year-old female. design: interventional case report. the main outcome measures are a rare cause of proptosis in an adult, discussion on treatment options and prognosis of rhabdomyosarcoma. result: the patient underwent total orbital exenteration and was referred for radiotherapy and chemotherapy. conclusion: rhabdomyosarcoma is a rare cause of proptosis in adults. it should be suspected in a case of rapidly-progressive proptosis in adults. keywords: rhabdomyosarcoma, proptosis, malignant tumors, radiotherapy, chemotherapy, orbital exenteration case reportcase reportcase reportcase reportcase report received: 08.07.2009 accepted: 29.12.2009 correspondence and reprint request to: dr poonam lavaju, md assistant professor department of ophthalmology b p koirala institute of health sciences dharan-18, sunsari, nepal e-mail: drpoonamlavaju@yahoo.com fax: 00977-25-520251 introduction rhabdomyosarcoma (rms) (from greek, rhabdo, meaning rod shape, and myo, meaning muscle) is the most common soft tissue sarcoma in children. though weber first described rms in 1854, a clear histologic definition was not available until 1946, when stout recognized the distinct morphology of rhabdomyoblasts. stout described rhabdomyoblasts as appearing in round, strap, racquet, and spider forms. as its name suggests, the tumor is believed to arise from primitive muscle cells (cripe tp, 2008). orbital rhabdomyosarcoma was first reported by bayer (henderson jw, 1973). rhabdomyosarcoma is the most common childhood primary soft tissue sarcomas of the orbits (porterfield jf & zimmerman le, 1962). orbital lesions represent about 10 % of all the cases of rhabdomyosarcoma (crist w et al, 1995). rhabdomyosarcoma is a rare cause of proptosis in adults. we report a rare cause of proptosis due to rhabdomyosarcoma in a 45-year-old female. case report a 45-year-old female presented with a gradual protrusion of the right eye of three-year duration. it was associated with gradually progressive diminution of vision for the last one year. the protrusion of the right eye was rapidly progressing for the last fifteen days, which was associated with pain, redness, discoloration of the central black part of the eye. there figure 1 right non-axial proptosis with exposure keratopathy and iris prolapse 65 lavaju p et al nep j oph 2010;2(3):64-67 rhabdomyosarcoma in an adult was no history of trauma, fever or any systemic problems. she had no history of thyroid disorder. she was not commenced on any treatment prior to hospitalization. figure 1 systemic examination did not reveal any abnormality. the best-corrected visual acuity was no perception of light (npl) in the right eye and 6\6 in the left. there was a non-axial proptosis (27mm) on the right side with the globe displaced infero-nasally. palpation revealed a firm non-tender mass in the superior and lateral quadrants of the orbit. there was complete exposure of the cornea with restriction of extraocular movements in all directions of gaze. the conjunctiva was chemosed and injected. the cornea was melted down due to exposure keratopathy with prolapsed iris tissue at the centre, which was covered with an exudative membrane. there was complete destruction of the anterior segment of the right eye. the inner details were not visible. the left eye examination was within normal limits. the regional lymph nodes were not palpable. the ct scan of the right orbit showed a homogenous orbital mass with erosion of the superior and lateral orbital walls and a deformed right globe with retinal detachment. the optic nerve sheath complex was normal. of alveolar rhabdomyosarcoma. the patient was referred for radiotherapy and chemotherapy. (figure 2 & 3) the patient underwent a right orbital exenteration under general anesthesia. intra-operatively, involvement of superonasal part of the orbital roof with csf leakage was detected. intra-operatively, the patient was commenced on intravenous antibiotics. histopathological analysis of the mass was conclusive figure 4 and 5 these figures show malignant round cell tumor revealing alveolar glandular trabecular and solid pattern with areas of necrosis and hemorrhages. the cytoplasm is deeply esinophilic with eccentrically placed nucleus. discussion rhabdomyosarcoma is a malignant neoplasm that is composed of cells with histologic features of striated muscle in various stages of embryogenesis (weiss sw & goldblum jr, 2001). it can occur in several sites in the body including the ocular region. orbital rhabdomyosarcoma accounts for about 25-35 % of head and neck rhabdomyosarcoma and for about 10-20 % of all the cases of rhabdomyosarcoma (crist w et al, 1995). metastatic disease to the orbit from more distant body sites has been reported (fekhat s et al 1993). primarily, rhabdomyosarcoma is a disease of young children with a mean age of 8 years at diagnosis (ashton n & morgan g, 1965). however, it can occur at any age, with cases reported in newborns (chams h et al 1987) and in infants and adults. it has been diagnosed in 35, 65 and 78-year-old patients (sood gc et al 1970). it has also been diagnosed during pregnancy in two nigerian women (olurin o, 1969). our patient presented at the age of the fifth decade. there is a slight predilection for disease in males, with a male-tofemale ratio of 5:3 (jones is et al 1966). microscopically, the four major histopathological types of rhabdomyosarcoma are pleomorphic, embryonic, alveolar and botryoid. the majority of orbital rhabdomyosarcomas are of the embryonal type. the alveolar and botryoid types are less common, and the pleomorphic type is extremely rare in the orbit. embryonal rhabdomyosarcoma is characterized histopathologically by spindle to round cells that show features of skeletal muscle in various stages of embryogenesis ( weiss sw, goldblum jr, 2001). our figure 2 & 3 ct scan of orbit showing homogenous orbital mass with erosion of superior and lateral orbital walls; and a deformed right globe with retinal detachment. optic nerve sheath complex was normal. 66 case showed malignant round cells with closet morphologic resemblance to the alveolar type. rhabdomyosarcoma shows strong tendency for local invasion, local recurrences and haematogenous and lymphatic spread. therefore, treatment of rhabdomyosarcoma includes a combination of both chemotherapy and radiotherapy (demirci h et al 2002). according to the intergroup rhabdomyosarcoma study groups i through iv, prognosis of the disease depends on several factors like the extent of the disease, tumor burden at diagnosis, primary site, patient age, histopathologic and cytopathologic type, cellular dna content and therapeutic response (maurer hm et al 1988). with regard to tumor burden at diagnosis, survival rates are 90 % for patients with clinical group i disease, 85 % for group ii, 70 % for group iii and 40 % for group iv disease (maurer hm et al 1988).tumor morphologic features are an important predictor of death. those patients with the alveolar cell type showed a 74 % 5-year survival, whereas those with the embryonal cell type demonstrated a 94 % 5-year survival (lanzkowsky p, 2000). a younger age (1-7 years) at presentation carries better prognosis (maurer hm et al 1988) than older age (>7 years). infants particularly those of less than 1 year of age with orbital rhabdomyosarcoma show poor prognosis, with death in 46 %.the reason for more aggressive behavior of rhabdomyosarcoma in infancy is unknown (kodet r et al 1997). until the late 1960s, orbital exenteration was generally considered to be the treatment of choice for orbital rhabdomyosarcoma (jones is et al 1966). however, the mortality rate for patients with orbital rhabdomyosarcoma continued to be greater than 70 % (knowles dm et al 1976). hence, orbital exenteration alone is rarely performed as a primary treatment today. it may be justified for extremely advanced disease that has destroyed the eye, as frequently seen in third-world and tumors resistant to irradiation and chemotherapy (shields cl et al 2001). the intergroup rhabdomyosarcoma study committee (irsg, the later group) organized in 1972, performed large collaborative randomized trials for treatment of rhabdomyosarcoma. since its inception, there have been four major trials, listed as studies i through iv (crist w et al1995). as a result of these trials, survival after treatment of rhabdomyosarcoma at all sites has improved from 25 % in 1970 to 70 % in 1991 (crist wm, kun le, 1991). orbital rhabdomyosarcoma has been recognized to display better life prognosis than rhabdomyosarcoma at other sites. before the treatment trials, patient survival with orbital rhabdomyosarcoma was poor, with approximately 30 % survival (knowles dm et al 1976). treatment generally consisted of orbital exenteration and various chemotherapy regimens. after trials i and ii, improved treatment regimens with chemotherapy and radiotherapy, usually avoiding exenteration, were successful, and the prognosis of orbital rhabdomyosarcoma strikingly improved to 93 % survival at 3 years ( wharam m et al 1987). according to the results of trial iv, the recommended treatment includes both chemotherapy and radiotherapy, with the exception of completely resected orbital tumors where only chemotherapy without radiotherapy is advised. treatment depends upon the group of the disease at presentation as classified by the irsg. current management of group iv orbital rhabdomyosarcoma depends on the location and extent of disease and generally consists of a combination of chemotherapy and radiotherapy delivered to the orbit and all involved sites of the tumor ( lanzkowsky p, 2000). recurrent tumors in the orbit are usually treated with orbital exenteration, sometimes supplemented with chemotherapy and radiotherapy (mannor ge et al 1997). the prognosis for patients with orbital rhabdomyosarcoma has greatly improved in recent years. based on trials i, ii, iii, and iv, survival with orbital rhabdomyosarcoma is now 93 % (kodet r et al 1997). our patient at the time of presentation had an extensive tumor with destruction of the globe and erosion of the superior and lateral walls. therefore she underwent orbital exenteration. despite the rarity of this tumor at this age, the possibility of occurrence of rhabdomyosarcoma in elderly people cannot be ignored as is evident from our patient. our clinical findings confirmed the diagnosis of rhabdomyosarcoma, and the patient was treated surgically and referred for radiotherapy and chemotherapy. the treatment outcome is not known to us because the patient was lost for follow-up and did not respond to written communication to her permanent address. lavaju p et al nep j oph 2010;2(3):64-67 rhabdomyosarcoma in an adult 67 conclusion rhabdomyosarcoma is a rare cause of proptosis in adults. however, it should be suspected as a cause of rapidly progressing proptosis in adults. references ashton n, morgan g (1965). embryonal sarcoma and embryonal rhabdomyosarcoma of the orbit. t clin pth 1965;18:699-714 chams h, rahisii f, sagdeghitari a (1987): a case of congenital rhabdomyosarcoma. orbit;7:133-5 crist wm, kun le (1991). common solid tumors of childhood. n engl j med;324:461-71. crist w, gehan ea, ragab ah et al (1995). the third inter-group rhabdomyosarcoma study. j clin oncol; 13: 610-630. demirci h, shields cl, shields ja (2002). orbital tumors in the older adult population. ophthalmology; 109:243–8. fekhat s, miller nr, lovry mc: alveolar rhabdomyosarcoma that metastasized to orbit. arch ophthalmol iii: 1993;1662-1664 henderson jw (1973). orbital tumors. 1 st sub-edition. w.b. saunders, philadelphia: 269-84. jones is, 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pun n shrestha,1 suresh r pant,1 bidya p pant1 1geta eye hospital, dhangadhi, kailali, 2institute of medicine, department of ophthalmology b.p. koirala lions centre for ophthalmic studies, 3kanti children hospital, maharajgunj, kathmandu, nepal abstract introduction: in some instances, the understanding of the ocular manifestations in childhood leukemia is not only important to establish the diagnosis but also reflects the disease state and prognosis. objective: to study the ocular manifestations of childhood acute leukemia among the children attending a tertiary-level hospital in nepal. materials and methods: a cross-sectional, descriptive study was undertaken at the b.p. koirala lions centre for ophthalmic studies (bpklcos) and kanti children hospital (kch), kathmandu, over a period of one-and-a-half years. children diagnosed with acute childhood leukemia referred to the bpklcos from the oncology unit of the kch and the emergency department of the tribhuvan university teaching hospital (tuth) were included in the study, using a non-probability sampling method. results: of the 71 cases with childhood acute leukemia, 55 (77.5%; 95% ci = 66% 85%) had acute lymphoblastic leukemia(all)whereas the other 16 (23%) had acute myeloblastic leukemia (aml). ocular involvement were seen in 33 cases (46%) and were more frequent in cases of aml as compared to those with all (p=0.001, or 5.0, 95% ci= 1.4 – 17.5). direct ocular involvement and secondary ocular involvement were observed in 12 (16.9%) and 29 (40.8%) subjects, respectively. ocular symptoms were present in only 11 cases (15.49%). cerebro-spinal fluid (csf) and bone marrow examination in cases with direct ocular involvement showed 10 cases (83.3%) positive for blast cells in the csf and 6 cases (50%) positive for blast cells in bone marrow.the most common secondary manifestation was retinal haemorrhage, seen in 23 cases (32.4%). conclusion: in view of the high asymptomatic ocular involvement and the significant visual morbidity, a routine ophthalmic examination is recommendedas an integral part of the medical examination in all cases of childhood acute leukemia. keywords: ocular manifestations, childhood acute leukemia, lymphoblastic leukemia, myeloblasticleukemia original article khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 received on: 05.01.2013 accepted on: 12.03.2014 address for correspondence dr ananda kumar sharma, md associate professor and head department of ophthalmology institute of medicine, b.p. koirala lion’s centre for ophthalmic studies, maharajgunj, kathmandu, nepal tel: +977-9851078622 e-mail: dr.anandasharma@gmail.com introduction leukemias are a group of heterogeneous neoplastic disorders of white blood cells which are the most frequent childhood cancers affecting children aged 2 to10 years. they are one of the ocular manifestations of childhood acute leukemia in a tertiarylevel eye centre of kathmandu, nepal deepak khadka,1ananda k sharma,2 jeevan k shrestha,2 gauri s shrestha2 pun n shrestha,3 suresh r pant,1 bidya p pant1 1geta eye hospital, dhangadhi, kailali, 2institute of medicine, department of ophthalmology b.p. koirala lion’s centre for ophthalmic studies, 3kanti children hospital, maharajgunj, kathmandu, nepal 198 leading causes of childhood cancer-related deaths.ophthalmic involvement can be classified into two major categories (sharma et al, 2004): primary or direct leukemic infiltration, and secondary or indirect involvement. the direct leukemic infiltration can be observed in three various patterns: (a) uveal infiltration, orbital infiltration, and neuro-ophthalmic signs of optic nerve infiltration (chaudhuri et al, 2013; lin h-f et al, 2005), (b) cranial nerve palsies, and (c) papilledema (nguyen et al, 2013). the secondary changes are manifested as retinal or vitreous haemorrhage, infections, and vascular occlusions due to hematologic abnormalities of leukemia such as anaemia, thrombocytopenia, hyperviscosity, and immune suppression. estimates of the occurrence of ophthalmic manifestations of leukemia vary from 9 to 90% (kinacid et al, 1983; reddy & menon, 1998). various ocular manifestations (reddy et al, 2003; alemayehu, 1996) have been reported, such as bilateral serous detachment of the retina, leopardspots pattern of the fundus (hine & kingham, 1979), sub-conjunctival haemorrhage (murthy et al, 2009), acute iridocyclitis with hypopion or hyphema (zakka ka et al., 1980), leukemic infiltration of the optic nerve (brown gc et al, 1981), vitreous infiltrates (zhioua, 2001), retinal haemorrhage, leukemic retinopathy (holt & gordon-smith, 1969) and proptosis (murthy et al 2009). diffuse iris infiltration results in heterochromiairidis and in nodular involvement that usually extends to the pupillary margin (jonston & ware, 1973). knowledge regarding the ocular manifestations of leukemia is important for the diagnosis and timely management of the disease, more so as they also often reflect the disease state of the body (kinacid & green, 1983; curto et al., 1989; ohkoshi & tsiaras, 1992; reddy & menon, 1998). this study, in nepal, will provide some baseline information about the ocular involvement in childhood leukemia. subjects and methods a hospital-based, cross-sectional, descriptive study was undertaken among 71 children with acute leukemia referred to the bpklcos during the period of january 2006 to july 2007 from the oncology unit of kanti children hospital (kch) and the emergency department of tribhuvan university teaching hospital. informed consent was received from all parents and caregivers. all children were examined by a team of ophthalmologists and ophthalmic residents irrespective of the presence or lack of eye symptoms. a detailed ocular evaluation was carried out in the eye centre and data were recorded on a specifically designed proforma. visual acuity was assessed by using the standard snellen’s chart and other age appropriate tests for children, e.g., catford drum, hotv chart, lea-symbols, were done. after performing the external eye examination with a torch light, the anterior segment examination of the eyes was performed with a slit-lamp bio-microscope. the fundus evaluation was carried out with a direct ophthalmoscope (heine beta-200) as well as with a binocular indirect ophthalmoscope with +20d lens after pupillary dilation with 0.5% tropicamide and 2.5% phenylephrine. intraocular pressure was measured either with an air puff tonometer or a hand-held perkins tonometer. orthoptics evaluation, hess screen charting, diplopia charting, computerized tomography (ct) scan, magnetic resonance imaging (mri) and ocular tissue biopsy were carried out whenever necessary. anterior and posterior segment photography were also done whenever needed. the ocular findings in the leukemic children were divided into two categories: i. direct ocular involvement, and, ii. secondary ocular involvement. direct ocular involvement included (a) orbital, adnexal and anterior segment invasion, (b) retinal infiltrates and vitreous seedlings, (c) neuro-ophthalmic signs of central nervous system (cns) leukemia, optic nerve invasion, cranial nerve palsies and khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 199 papilledema. the secondary ocular involvement findings include were lid ecchymosis, subconjuctival haemorrhage, vitreous haemorrhage, retinal haemorrhage, subretinal hemorrhage, cotton wool spots, vascular sheathings, roth’s spots, retinal vessel tortuosity, disc edema and others. cerebrospinal fluid (csf) analysis and bone marrow (bm) biopsy of patients with direct ocular involvement were performed. the data were processed and analyzed with spss 14.0 version. results of the 71 children with acute leukemia, 52 (73.2%) were males and 19 (26.8%) females. fifty five (77.5%; 95%ci = 66% 85%) children suffered from acute lymphoid leukemia (all) and sixteen (22.5%) had acute myeloid leukemia (aml). the mean age of the cases was 7.8±4 years for all and 10.7± 3.3 years for aml. only eleven children (15.4%) with leukemia had ocular complaints. all of them complained of diminution of vision with other associated ocular complaints such as ocular pain (2.8%), redness of eyes (2.8%) and other complaints such as eyelid swelling, deviation of eye, headache and drooping of upper eyelid in 5.6% of the cases. ocular manifestations were seen in 33(46.0%). among the 16 cases of aml, 12 cases (75.0%) had ocular involvement where as only 21cases (38.2%) had ocular involvement among the 55 cases of all examined. in the leukemic subjects, the patterns of ocular involvements were also analyzed. among them, 5.6% of the subjects had direct ocular involvement, 29.6% had secondary ocular involvement and 11.2% had both direct and indirect involvement. table 1: description of leukemia according to age, sex, symptoms, andocular manifestations total no (%) acute lymphoid leukemia no (%) acute myeloid leukemia no (%) p value odd (95% ci) gender males 52 (73.2) 38 (69.1) 14 (87.5) 0.14* 0.3 (0.1-1.6) females 19 (26.8) 17 (30.9) 2 (12.5) mean age (sd) years 8.5±4.0 7.8±4.0 10.7±3.3 0.05** symptoms 11 (15.4) 6 (10.9) 5 (31.2) 0.04* 3.8 (1.0-4.7) ocular involvement 33 (46.5) 21 (38.2) 12 (75.0) 0.00* 5.0 (1.4-17.5) ocular findings direct 4 (5.6) 3 (5.5) 1 (6.3) 0.89* 1.2 (0.1-12.2) secondary 21 (29.6) 13 (23.6) 8 (50.0) 0.037* 3.3 (1.0-10.5) both 8 (11.3) 5 (9.1) 3 (18.8) 0.27* 2.3 (0.5-11.1) *= chi-square test; **= unpaired t-test condition total acute lymphoid leukemia (all) acute myeloid leukemia (aml) cases (n=71) direct involvement (n=12) cases (n=55) direct involvement (n=12) cases (n=16) direct involvement (n=12) no (%) no (%) no (%) no (%) no (%) no (%) orbit,adnexae, and anterior segment manifestations chloroma (figure a) 1 (1.4) 1 (8.3) 1 (6.3) 1 (8.3) iris nodule 1 (1.4) 1 (8.3) 1 (1.8) 1 (8.3) glaucoma 1 (1.4) 1 (8.3) 1 (1.8) 1 (8.3) proptosis 2 (2.8) 2 (16.6) 1 (1.8) 1 (8.3) 1 (6.3) 1 (8.3) table 2: ocular manifestations in childhood acute leukemia khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 200 table 2 represents ocular manifestations in childhood acute leukemia. a total of 7% had direct orbital and anterior segment involvement including three cases (5.4%) of all and two cases (12.6%) of aml and total direct involvement in 41.7%. total retina and vitreous involvement was seen in 5.6% of cases and total direct involvement was reported in 33.3% (figure 1b). four cases of all with retinal and vitreous involvement developed whitish pupillary reflex due to massive leukemic infiltrates in the retina and vitreous and developed retinal detachment in a few days (figure 1c). neuro-ophthalmic signs of cns leukemia were seen in all cases with direct ocular involvement. optic nerve infiltration (figure 1d) was seen in 7%, cranial nerve palsies in 5.6% (figure 1e) and papilledema in 9.9% (figure 1f). some cases had more than one direct ocular involvement. when the patterns of secondary ocular involvements were analyzed (table 3), 32.2% had retinal, preretinal or sub-retinal hemorrhage whereas retinal vascular tortuosity (19.7%) and white-centered hemorrhage (12.7%) were also commonly noted. lid ecchymosis, abscess, vascular sheathing and cotton-wool spots were the rare presentations. table 3: secondary ocular manifestations in childhood acute leukemia table 4 represents the presenting visual acuity in the 71 cases (142 eyes) with childhood acute leukemia. visual acuity was recorded as less than or equal to 3/60 in 13 eyes (9.1%), and they were blind due to the ophthalmic manifestations of childhood acute leukemia. posterior segment involvement retinal infiltrate 2 (2.8) 2 (16.6) 2 (3.6) 2 (16.6) vitreous seedlings 2 (2.8) 2 (16.6) 2 (3.6) 2 (16.6) neuro-ophthalmology manifestations optic nerve infiltrate 5 (7.0) 5 (41.6) 4 (7.3) 4 (33.3) 1 (6.3) 1 (8.3) 3rd, 6th, 7th nerve palsy 4 (5.6) 4 (33.3) 3 (5.5) 3 (25.0) 1 (6.3) 1 (8.3) papilledema 7 (9.9) 7 (56.3) 5 (9.1) 5 (41.6) 2 (12.5) 2 (16.6) khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 table 4: presenting visual acuity inpatients with childhood acute leukemia 201 when the csf analysis and bm examination records were analyzed, 83.3% of patients with direct ocular involvement had csf positive for blast table 5. csf and bm findings in leukemias with direct ocular involvement discussion leukemias are the most frequent childhood neoplasm and one of the leading causes of childhood cancer-related deaths (kumar et al, 2006). in most of the studies of childhood acute leukemias, all were more common than aml. in this study of 71 cases with childhood acute leukemias, 77 % (n=55) were all and 23% (n=16) aml. this finding is similar to that of the study conducted by ridgeway et al (1976), in which 78% of the caseswere of all, 21% of aml and 1% of non-lymphocytic leukemia. chronic lymphoblastic leukemia (omoti et al, 2010) has been reported to be more common (40.4%) in adult leukemic patients, followed by chronic myeloid leukemia (29.8%), aml (19.1%) and all (10.6%). similarly, russo et al (2008) have also reported ocular manifestation in 66% of patients with aml and in 11.5% of all patients. orbital or ocular lesions were noted more commonly in patients with aml (66.6%) as compared to patients with all (15.1%). in our study, the age of the patients ranged from 8 months to 15 years with the mean age (sd) of 8.5±4.0 years, and the male-female ratio was 2.3:1. a study by reddy & menon (1998) on both childhood and adult leukemi as has reported a male-female ratio of 1.3:1. in this study, 15% of patients (n=11)with childhood acute leukemias presented with ocular symptoms.the most common presentation was diminution of vision, in 19.7% (n=14). one case presented with a sudden onset of ptosis and had a complete 3rd nerve palsy with pupillary involvement. massive intra-cranial bleed caused death in one of the children.one leukaemic patient with severe left lower lid abscess was found to have acute lymphoblastic leukemia (all). similarly, those who had headache were diagnosed to have papilledema. schachat et al, (1989) and reddy & menon (1998) reported ocular symptoms in 3% and 3.6% patients with acute childhood leukemia, respectively. we included all the sub types of childhood acute leukemia, irrespective of the duration and total (n=12) acute lymphoid leukemia (n= 8) acute myeloid leukemia (n=4) p* value or (95% ci) csf for blast cells 10 (83.33) 7 (75) 3 (83.3) 0.58 0.4 (0.01-9.3) bm for blast cells 6 (50) 4 (50) 2 (50) 1.0 1.0 (0.1-11.0) csf =cerebro-spinal fluid, bm =bone marrow cells whereas only 50% had bm positive for blast cells (table 5). khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 202 treatment. all the cases were constantly instigated for any ocular complaints as well. therefore, a high rate of symptoms is present in our study. in a study of a pathological series of leukemia, ocular involvement was reported in 80% (kinacid et al, 1983), whereas it was reported in the range of 790% in various clinical series (ridgeway et al, 1976; reddy & menon, 1998; schachat et al, 1989). in our clinical study, ocular involvement was noted only in 46% of patients (n=33). in our study, ocular involvement was more common in aml (81.2%) than in all (38%). similarly, reddy & menon (1998) have reported a more common ocular involvement in aml (41%) than in all (29.2%). direct ocular manifestations were seen in 16.9% (n=12) of our patients, which is much higher (3.0%) than in the schachat et al (1989) study. the higher prevalence in our study could be due to the enrollment of only newly-diagnosed cases. the chloroma or granulocytic sarcoma a rare ocular manifestation commonly seen in the m4 type of aml (champlin & gale, 1989) was also reported in our study. in our study, optic nerve involvement was seen in 41.66% of cases (n=5) with neurological manifestations of leukemia. the optic nerve invasion of the neoplasm was observed in 15.15% of cases(n=5). ridgeway et al (1976) reported that 31% of cases with acute childhood leukemia had optic nerve involvement. chaudhuri et al (2013) have also reported ischaemic optic neuropathy causing blindness in a case of all. in our study, of 33 cases with ocular involvement, 12.12% (n=4) had cranial nerve palsies and 21.21% (n=7) had papilledema. ridgeway et al (1976) reported papilledema in 25%. csf and bone marrow evaluations were also performed in 12 subjects of leukemias in this study. the csf for leukemic cells was found positive in 83.3% of cases (n=10) of direct ocular involvement and bone marrow involvement was noted in 50% (n=6) of these cases. in this study, no case of pseudohypopion was noted, as has been reported by the gomber et al (2008) study. in our study, secondary ocular manifestations were seen in 40.8% of cases (n=29), which is comparable with the schachat et al (1989) report, where they were seen in 39% of cases. among the secondary ocular manifestations, the most common manifestation was the retinal hemorrhage (32.4%), which was more common in aml (56.3%) than in all (25.5%). this finding is also comparable with the findings of the schachat et al (1989) report of 24% and the ridgeway et al (1976) report of 37%. the visual acuity was assessed in all the cases with childhood acute leukemia.among them,120 eyes had a visual acuity (va) of better than 6/18, 9 had less than 6/60 and 13 less than 3/60. three patients had ava of less than 3/60 in both eyes due to a dense subhyaloid premacular hemorrhage which was subjected to nd-yag laser hyaloidotomy resulting in an improved visual outcome (khadka et al, 2012). conclusion though ocular symptoms were reported in a small proportion of our cases of childhood acute leukemia, a significantly high rate of ocular manifestation was found in the visually asymptomatic cases of childhood leukemia in this study. ocular findings are more frequently observed in aml than in all.the posterior segment involvement causes visual impairment. routine ophthalmic examination is recommended in all childhood leukemias. acknowledgement we would like to thank dr kailash p shah, oncology unit kanti children hospital,and mr suresh sharma, chief ophthalmic technologist for providing the illustrative clinical photographs and mr chudamani basel, (m.sc), for the relevant laboratory investigations. references alemayehu w, shamebo m, bedri a, mengistu z (1996). ocular manifestations of leukemia in ethiopians. ethiop med j;34:217224. khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 203 allen ra, straatsma br (1983). ocular involvement in leukemia and allied disorders. arch ophthalmol; 27: 211-232. brown gc, shields ja, augsburger jj 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(2001). acute lymphoblastic leukemia and vitreous infiltration: a case study. j francais ophthalmol; 24:180-182. khadka d et al ocular manifestations of childhood acute leukemia nepal j ophthalmol 2014; 6(12): 197-204 text.pmd 83 guest editorial vision 2020: the meaning and the spirit of the right to sight initiative prof dr murthy vs gudlavalleti, msc, md 8 bedord square, gower street london wc1b3ra, uk vision 2020: the right to sight, the global initiative for the elimination of avoidable blindness, has become the fulcrum of all programs for control of blindness worldwide. just like the five blind men who perceived an elephant differently, policy makers, program planners, eye care professionals and the general population (the main stake holder) have different interpretations for what vision 2020 stands for. for many, it has replaced the national programs for control of blindness that have been in existence for over two decades. for some, it is the panacea of all that ails eye care services. for others it is the new mantra (formula) to get rid of unwanted blindness. there are also those who presume that after 2020, there is no need of any focus on avoidable blindness. with such a plethora of views, vision 2020 unfortunately is being marketed by many as the new strategy for eye care services. instead of using vision 2020 as a step to successfully climb the ladder for prevention of blindness; many countries have fallen into the trap of using vision 2020 as jargon. the laudable effort of the global alliance between the countries of the world (represented by the who) and the international eye ngos (represented by iapb) to use vision 2020 as the plank to ‘demystify’ eye care and emphasize the rights of all individuals to seek appropriate eye care and sound the bugle for those unnecessarily blind despite available technology will stand defeated if the basic premise for the clarion call goes unheeded. vision 2020 became a reality because of the realization that problems abound while resources are limited. a significant difference would be palpable if the available resources were to be used optimally. therefore, it was necessary to set priorities in both the relation to the diseases primarily responsible for blindness as well as to populations which had remained marginalized and beyond the ‘service net’. at a global level, it was possible to chart out a course of action with some benchmarks for individual countries to plan their strategies and activities. for planning at country level, an evidence base was essential. there is a need for evidence on prevalence and causes of blindness, availability and functionality of human resources and eye care infrastructure, integration of eye care with general health services, community perceptions on eye care, utilization patterns of existing eye care services, provider perceptions and needs and the political and administrative support to eye care before one could embark on need-based and situation-dependant strategies for the elimination of avoidable blindness. unfortunately, even in countries where such evidence was available, policy makers and program planners chose to ignore the same and instead devise plans based on ‘personal experience’, ‘anecdotal information’ and simple jugglery of setting targets based on past outputs. in every country in the south asia region, a vision 2020 national committee was formed, but in terms of functionality, most of the countries continued the same approach to problem solving without paying heed to new evidence available from scientifically soundresearch studies in either their country or a neighboring country. similarly, the planning for the future requirements for eye care personnel has hardly been based on the availability and effectiveness of available human resources but has depended on the numbers required by 2020 based on norms enunciated by the global vision 2020. how the gap between what was existing and what was required by 2020 was to be bridged has never been given adequate attention. how personnel could be made to work in rural and remote area and what facilities they would require to make them productive and happy are issues which need to be addressed. at the same time, case studies need to be undertaken to see why some populations access services and why others do not. gudlavalleti mvs nep j oph 2009;1(2):83-84 right to sight initiative 84 gudlavalleti mvs nep j oph 2009;1(2):83-84 right to sight initiative vision 2020 is about making services accessible to all populations in a country. it therefore means that additional efforts will be needed to increase access to populations that are not within easy reach compared to those populations who are within reach. there has been a tendency to reach those within easy reach than make efforts to reach the ‘unreached’. very often one hears about a plethora of ‘eye camps’ at the same site year after year while there are more needy areas where no eye care team ever ventures. the need to work with communities cannot be under-emphasized. identifying volunteers within communities who act as facilitators and counselors through simple training can go a long way in sustaining eye care services at no additional costs. however for maintaining their motivational levels, regular contact and due recognition for their efforts are essential. the most crucial aspect of vision 2020 which is often overlooked is that the strategy is targeted towards those ‘already blind’ and redresses their problem. most countries report on the number of cataract surgeries done in a year and not on the number of surgeries done on blind persons where the presenting vision in the better eye is < 3/60. in india nearly 5 million cataract surgeries have been reported in 2008. how many of these were done on blind persons is not known. many people take the path of least resistance by stating that even if people are operated before they go blind, they are being prevented from going blind in the future. what they forget is that the recommended cataract surgical output for elimination of avoidable blindness is only tenable when that number of surgeries is done only on blind persons and not otherwise. if this principle is not followed, then it will not be possible to eliminate avoidable blindness by 2020. another argument used is that surgery is being done on a ‘blind’ eye and therefore it is acceptable. there is nothing like a ‘blind’ eye as blindness only refers to presenting vision in the better eye and therefore connotes person vision. over the next 10 years, if professionals and program managers concentrate their efforts on identifying the most needy groups through a situational analysis and needs-assessment exercise and ensure that blind persons in these populations receive priority attention, it will go a long way in working towards the ethos and spirit of vision 2020, rather than using the laudable effort as marketable jargon. prof dr murthy vs gudlavalleti, msc, md 8 bedord square, gower street london wc1b3ra, uk source of support: nil. conflict of interest: none 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 text.pmd 114 original articleoriginal articleoriginal articleoriginal articleoriginal article received: 21.12.2008 accepted: 09.04.2009 correspondence and reprint request to: dr pragati gautam, md lumbini eye institute, bhairahawa rupandehi nepal e-mail: pragatigautam@hotmail.com ph no: 00977-9841252921 the factors associated with age related macular degeneration and quality of life of the patients in a tertiarylevel ophthalmic center in kathmandu gautam p1, shrestha jk2, joshi sn3 1consultant ophthalmologist, lumbini eye institute, 2professor and head, department of ophthalmology, 3associate professor bp koirala lion’s center for ophthalmic studies, kathmandu, nepal abstract introduction:age-related macular degeneration (armd) is a leading cause of blindness in the elderly population. objective:to frame a profile of patients with armd and find out the factors associated with it materials and methods: a cross-sectional study was carried out including a total of 75 patients with armd presenting to the out-patient department of a tertiary level ophthalmic center in kathmandu. the data pertaining to their demography, ocular and systemic history and the findings of clinical examination and laboratory investigations were analyzed. the quality of life was assessed based on their dependability on the others for daily activity. results: mean age of presentation of armd was 73 years ±7.93. of the total, 44 were male and 31 female. smoking was significantly associated with armd (p<0.01). 47 of the subjects had a sedentary lifestyle and 28 a non-sedentary lifestyle. sedentary life style was significantly associated with armd (p=0.028). 48 subjects were hypertensive. systemic hypertension was significantly associated with armd (p = 0.015). 45 had dry armd, 21 had wet armd and 9 of them had a mixed variety. thirteen out of the 75 study subjects were leading a normal life while 45 of them had some limitation (self-care only) and 17 of them were dependent on the others for their daily activity. the quality of life was not significantly different between dry and wet armd (p = 0.40). conclusion: sedentary life style, smoking and hypertension are the modifiable factors that are associated with armd. a significant number of people with the armd have a compromised quality of life. keywords: armd, associated factors, quality of life, macular degeneration introduction age-related macular degeneration (armd) is the leading cause of visual impairment in the elderly and the most common cause of blindness in western countries. the pathogenesis of age-related macular degeneration is poorly understood. as with other lateonset chronic diseases, susceptibility is influenced by age, ethnic background, and a combination of environmental and genetic factors. smoking status and family history are well-established risk factors (de jong ptmv, 2006). armd is a common ophthalmological disorder that can significantly impair a patient’s ability to function independently and potentially have a dramatic impact on health-related quality of life. this study was conducted in view of finding out risk factors that can be modified and how much burden this disease imposes on patients in their day-to-day life. materials and methods a cross-sectional study was carried out among 75 successive patients of armd attending the out-patient department of the b p koirala lion’s center for gautam p et al nep j oph 2009;1(2):114-117 age related macular degeneration 115 ophthalmic studies (bpklcos opd) from 2007 to june 2008. a structured questionnaire and format were used. an informed consent was obtained from the subjects included for the study. the data pertaining to their demography, ocular and systemic history and the findings of clinical examination and laboratory investigations were analyzed. the quality of life was assessed based on their dependability on the others for daily activity. the lifestyle was broadly divided into sedentary and non-sedentary. statistics data analysis was done using the latest version of spss 11.5 and ms excel. the p value was said to be significant when it was <0.05. confidence interval (ci) was set at 95%. results mean age of presentation of armd was 73 ± 7.93 years. the age ranged from 90 to 60 years. of 75 subjects, 44 (59%) were male and 31 (41%) female (table 1). the gender was not significantly (p =0.133) associated with armd. among them, 47 had a sedentary lifestyle and 28 non-sedentary. sedentary life style was significantly associated with armd (p=0.028). of 75, 48 (64 %) were found to be hypertensive. hypertension was significantly associated with armd (p = 0.015). eight study participants were diabetic. diabetes was not significantly associated with armd. diminution of visual acuity was the most common presenting symptom of armd. visual acuity was not significantly different between dry and wet armd (p = 0.34). lens opacity was the most common ocular disease found on examination. almost all of the study participants had either some form of cataract or were pseudophakic. nuclear cataract of more than grade ii together with armd was significantly associated with the poor quality of life (p = 0.018). type of armd forty-five (60%) subjects had dry armd, 21(28%) of them had wet armd and 9 (12%) of them had a mixed variety. the male subjects had dry, wet and mixed armd in a frequency of 24, 14 and 6 respectively. while for females, this was 21, 7 and 3 respectively. sex was not significantly associated with any form of armd (p=0.083). thirteen out of 75 study participants were leading a normal life while 45 of them had some limitation (selfcare only) and 17 of them were dependent on others for their daily activities. quality of life was not significantly different between dry and wet armd (p = 0.40). likewise quality of life was not significantly different between male and female (p =0.49). discussion armd is the leading cause of blindness in the elderly worldwide, affecting 30–50 million individuals. the prevalence of blindness is increasing significantly in asian countries, which could be due to urbanization of the populations, westernization of lifestyles and increasing disease awareness (wong ty et al, 2006). world health organization (who) statistics from the most recent who global eye disease surveys conducted in 2002 revealed that 8.7% of world-wide blindness is due to armd (world health organization, 2004), the third leading cause of world-wide blindness after cataract and glaucoma. conservatively, the who estimated that 14 million persons worldwide are blind or severely visually impaired because of armd. even though figures on the prevalence of armd vary greatly table 1 occupation distribution occupation exexfarmer teacher house social army service wife worker male 3 16 15 5 0 5 female 0 6 10 1 14 0 of the total 75 study participants, 53 (70.66 %) of them were smokers. smoking was significantly associated with armd (p<0.01). people who smoked had armd at the average age of 72 years compared to 77 years for those who did not smoke. mean age of presentation was significantly different (p <0.001) between smokers and nonsmokers. the ocular disease most commonly associated with armd was cataract, which was present in 34 of the total. two of them had cataract as well as glaucoma. presence of other ocular diseases was not significantly associated with any form of armd. history of ocular disease was also not significantly associated with the poorer quality of life in patients of armd (p =0.49). gautam p et al nep j oph 2009;1(2):114-117 age related macular degeneration 116 depending on the definition used, it is clear that the likelihood of developing the condition increases considerably with age. in a study done by seddon j (2008), the prevalence increased from 12.2 per cent in people aged 55-64 years to 18.3 per cent in those aged 65-74 years and 29.7 per cent in people aged over 74. in our study, sex was not significantly (p =0.133) associated with armd. male participants presented at mean age of 75 years and females presented at mean age of 71 years. sex was not a risk factor for armd. in some of the studies (klein r et al, 2006), it has been seen that more women are affected than men. however, the evidence is not strong since the larger number of women with armd may simply be a reflection of their greater longevity. generally, there does not seem a significantly increased risk for women as compared to men (smith w et al 2001). it is also worth noting that a study in japan has found the prevalence of armd to be higher in men than in women (miyazaki m et al 2003). in our study, sedentary life style was significantly associated with armd (p=0.028). this is in par with the areds study (age-related eye disease study group, 2001) which showed that as body mass index (bmi) increased, so did the risk for armd. further work needs to be completed before definitive conclusions can be made in this regard (amd special report cme newsletter, 2006). in the present study, smoking was significantly associated with armd (p<0.01). most of the smokers had smoked 5-10 cigarettes or more than 10 cigarettes per day. most of the smokers smoked for more than 10 years. people who smoked had armd at the average age of 72 years compared to 77 years for those who did not smoke. mean age of presentation was significantly different (p <0.001) between smokers and non-smokers. regarding sex difference in smoking, 77% of the male patients were smokers compared to 67% of female patients. this shows the same results as of some other studies which report that the most important avoidable risk factor for armd is smoking. evans et al (2005) studied more than 4,000 britons aged 75 and older and showed that those who smoked were twice as likely to have age-related macular degeneration as those who did not. numerous epidemiological studies have demonstrated the risk of smoking with regard to armd. hayman et al (2000) showed a 2.6 relative risk for male smokers, but no significant risk for female smokers. of the 75 armd patients included in our study, 48 were found to be hypertensive. hypertension was significantly associated with armd (p = 0.015). studies on hypertension and cardiovascular diseases and its association with armd have been inconsistent. in a case-control study, fred et al (2000) suggested that neovascular armd was associated with moderate to severe hypertension. however, non-neovascular armd was unrelated to hypertension in the same study. the framingham study (dawber tr et al, 1951) also indicated an association of armd with systemic hypertension. however, the beaver dam eye study (klein r et al 2002) showed no correlation between hypertension, cardiovascular diseases and armd. conclusion a sedentary life style, smoking and systemic hypertension are the factors associated with armd. further studies are required to confirm the cause and effect relationship of these findings. references age-related eye disease study group (2001). a randomized, placebo-controlled clinical trial of highdose supplementation with vitamins c and e, beta carotene, and zinc for age-related macular degeneration and visual loss. arch ophthalmol;119:1417-1436. amd special report cme newsletter (2007). volume 4. medscape ophthalmology. may 26, 2006 (assessed may 27, 2007) dawber tr, meadors gf, moore fej (1951). epidemiological approaches to heart disease: the framingham study. am j public health; 41:279286. de jong ptmv (2006). age-related macular degeneration n engl j med;355:1474-85. evans jr, fletcher ae and wormald rpl (2005). 28,000 cases of age-related macular degeneration causing visual loss in people aged 75 years and above in the united kingdom may be attributable to smoking. br j ophthalmol; 89:550-553. gautam p et al nep j oph 2009;1(2):114-117 age related macular degeneration 117 fred h, lambrou, jr, md and dessouki a, (2000). risk factors and prevention of age related macular degeneration. jacksonville medicine northeast florida medicine journal.. hyman l, schachat ap, he q, leske mc (2000). hypertension, cardiovascular disease, and age related macular degeneration. age-related macular degeneration risk factors study group. arch ophthalmol.;118:351-358 klein r, klein be, knudtson md et al (2006). prevalence of age-related macular degeneration in 4 racial/ethnic groups in the multi-ethnic study of atherosclerosis. ophthalmology;113:373–380 klein r, klein be, tomany sc, meuer sm, huang (2002). ten-year incidence and progression of agerelated maculopathy: the beaver dam eye study. ophthalmology. miyazaki m, nakamura h. et al (2003). risk factors for age related maculopathy in a japanese population: the hisayama study. br j ophthalmol;87:469-472 seddon j (2008). latest developments in genetic and nutritional factors associated with age related macular degeneration: keynote speech at vision 2005, tuesday 5 april 2005. smith w, assink j, klein r et al (2001). risk factors for age-related maculopathy. the visual impairment project. arch ophthalmol; 108:697-704. wong ty, loon sc, saw sm (2008). the epidemiology of age-related eye diseases in asia. br j ophthalmol; 90: 506-511. world health organization (2004). magnitude and causes of visual impairment. factsheet 282. gautam p et al nep j oph 2009;1(2):114-117 age related macular degeneration source of support: nil. conflict of interest: none for numbering.pmd 66 introduction eales' disease is an idiopathic inflammatory venous occlusion primarily affecting the peripheral retina of otherwise healthy young adults. it is the commonest cause of vitreous hemorrhage in young adults in the 2nd to 3rd decade of life in nepal. it is one of the major causes of visual impairment and blindness after diabetes in patients attending the vitreo-retina clinic at b.p. koirala lions centre for ophthalmic studies (personal experience of the authors). eales (1880, 1882)-a british ophthalmologist, described recurrent retinal hemorrhage in young adults. his seven patients were all young males with a common history of epistaxis, constipation and dyspepsia. he believed it to be a vasomotor neurosis with constriction of alimentary vessels and compensatory dilatation of those in the retinal and nasal vessels. eales did not describe retinal vasculitis. however, five years later, wadsworth (1887) described signs of retinal vasculitis. retinal vasculitis shrestha j k1, khadka d2, lamichhane g3, khanal s4 1department of ophthalmology, institute of medicine, bpklcos, kathmandu, nepal 2geta eye hospital, dhangadi, nepal, 3md res. department of ophthalmology, institute of medicine, bpklcos, kathmandu, nepal 4md res. department of ophthalmology, institute of medicine, bpklcos, kathmandu, nepal abstract retinal vasculitis is an idiopathic inflammatory venous occlusion primarily affecting the peripheral retina of otherwise healthy young adults. eales' disease is recognized as primary vasculitis of unknown etiology occurring in young adults. this article aims at the overall review of the etiopathogenesis, clinical presentations, pathology, management and prognosis of retinal vasculitis. key words: retinal vasculitis, eales' disease initially, eales' disease was described as periphlebitis retinae (elliot, 1948) because the affection was primarily of the mid peripheral retina. later studies showed that both the arteries and veins were involved (kimura et al 1956; keith-lyle and wybark, 1961) and hence, it was named "retinal perivasculitis". in the following century, henry eales has been honored with the eponym for the disease characterized by idiopathic recurrent vitreous hemorrhage in otherwise young and healthy adults. patients' profile eales' disease typically affects healthy young adults of 20-30 years of age (average 26.9). males account for 80%-90% of all cases (patnik and nagpal, 1998). in a study of 55 cases in the united states, there was equal involvement among male and female. in a study conducted in nepal (malla et al 1999) during 1993 to 1996 in a series of forty patients, 80% were between the age of 20 to 40 years and 90% of them were males. another study conducted in nepal (joshi et al 2000) showed that 54.34% of the subjects were in the age group of 21 to 30 years and the male to female ratio was 19:1 and the disease was bilateral in 56.1% of the subjects. however, duke elder has mentioned the possibility of bilateral involvement in 90% of cases. in review articlereview articlereview articlereview articlereview article nep j oph 2009;1(1):66-71 received: 07.12.2008. accepted: 21.12.2008 correspondence and reprint requests to: dr shankar khanal b p koirala lions center for ophthalmic studies tel: 00977-1-4720694 e-mail address: khanalshankar@hotmail.com 67 a retrospective study conducted by palmer et al (1996) at st. thomas hospital on 53 patients, 48 of those patients had bilateral disease and 5 had unilateral disease. eales' disease is now rare in developed countries but is commonly reported from the indian sub-continent. aetiopathogenesis eales' disease is recognized as a primary vasculitis of unknown etiology occurring in young adults (wadsworth, 1887). various studies have been done to identify the etiology which can be classified as follows. a) systemic disorders associated with eales' disease some authors have found association of tuberculosis with eales' disease; however, many authors have found no association between the two at all (patney et al 1965; stock, 1937). madhavan et al (2002) showed presence of tubercular bacilli in epiretinal membrane of eales' disease patients. eales' disease has been shown to be associated with hypersensitivity to tubercular protein because of the fact that 90% of the patients in their series were mantoux positive (donders, 1958; elliot, 1954). however, eales' disease has been found in mantoux negative patients as well and mantoux positivity is seen in 67% to 90% of normal population in this part of the world. some authors have shown the association of eales' disease with thrombangitis obliterens, neurological diseases (fielo and foster 1962; singhal and dastur 1976; opala et al 1988; masson et al 1988; gordon et al 1988), multiple sclerosis, cerebral stroke and hematological diseases (khan et al 1963; rahi et al 1969; jain et al 1970; bertrams et al 1989; bryselbout et al 1989; vanacore et al 1965; boase et al 1980; pathak et al 1977), such as acanthocytosis, coagulation disorders, etc. b ) immunological studies in eales' disease (stock, 1937; gilbert, 1935; finoof, 1924) the clinical picture of acute onset, steroid responsiveness, lymphocytic infiltration in histological study of the vitreous and epiretinal membrane and abnormal immunological parameters like low igm, high igg and iga all indicate an immunological mechanism involved in eales' disease. however, so far, a precise immunological mechanism has not been identified. c) biochemical studies in eales' disease several studies have been done on the serum and vitreous samples (rengarajan et al 1989; pratap et al 1976). studies have shown raised alpha-globulin and reduced albumin levels in the serum samples of patients with eales' disease (stanford et al 1987). stages of eales' disease although a universally accepted classification has not been worked out, the ophthalmoscopic findings have been conveniently divided into several stages, although there may be an overlap between these stages. eales' i (stage of inflammation) is characterized by localized areas of peripheral retinal edema with sheathing of the small caliber vascular arcades. minute retinal hemorrhage can be seen. in eales' ii disease (stage of ischemia), the same pathologic changes involve larger vessels and extend more posteriorly (fig 1). veins as well as arterioles can be sheathed. there are more widespread retinal hemorrhages and the vitreous body looks hazy. there are areas of retinal ischemia best seen on fundus fluorescein angiography. in the eales' iii stage (stage of neovascularisation), peripheral new blood vessels become apparent, with numerous and vitreous hemorrhages (fig 2). the hemorrhage frequently recurs. the final stage, eales' stage iv (stage of complication), is characterized by massive retinal proliferation protruding from the retinal surface into the vitreous cavity and associated with massive retinal and vitreous hemorrhages. with this advanced stage of the disease, the fibrous tissue components of the neovascular frond can also cause tractional or rhegmatogenous retinal detachment. shrestha j k et al nep j oph 2009;1(1):66-71 retinal vasculitis fig 1extensive vascular sheathing 68 pathology the clinical manifestations of the disease are due to three basic pathological changes inflammation, ischemia and neovascularisation and its sequale. the site of involvement is predominantly the peripheral retina. inflammation involves both the peripheral veins and arterioles, mainly the veins. histopathological studies have uniformly demonstrated infiltration of chronic inflammatory cells, especially lymphocytes. in addition, stock (1937) and gilbert (1935) have demonstrated acid-fast bacilli on the peripheral retinal lesions and perivascular sheath respectively. the immuno-phenotyping of the lymphocytic infiltrate in the epiretinal and sub-retinal membrane in eales' disease was found to be of predominantly t-cell type with few b cell type (biswas and rao, 1990). clinical features patients are asymptomatic if there is mild peripheral involvement only. symptomatic patients complain of blurred or decreased vision. a study of 150 patients with vasculitis showed two-third to have visual acuity of 6/18 or better and 20% worse than 6/18 in both eyes (graham 1989) on presentation. retinal ischemia leads to scotoma formation and associated vitritis often causes floaters. some patients may have defective color vision, difficulty in reading or metamorphopsia if the macula is involved. signs in the anterior chamber are mild but severe vitritis with inferior snowballs are often present in the vitreous. a review of the retinal signs in 67 patients with idiopathic retinal vasculitis showed that the most common retinal signs were peripheral vascular sheathing (64%) followed by macular edema (60%), retinal neovascularisation (16%), periphlebitis (15%) and retinal vein occlusion (10%)(graham et al 1989). many patients with retinal vasculitis have it associated with prominent uveitis, optic disc edema or cystoid macular edema. idiopathic retinal vasculitis is characterized by retinal phlebitis, peripheral nonperfusion and retinal neovascularisation. 1) retinal phlebitis fundus examination reveals venous dilatation in the periphery with tortuosity and discontinuity of veins. perivascular exudates are seen along the peripheral veins with characteristic venous sheathing. perivascular sheathing ranges from thin white lines limiting the blood columns to heavy exudation, and characteristically peripheral vessels are involved. though initially not involved, later, arteries are also attenuated. the involved vessels become obliterated and are better visualized with fluorescein angiography. 2) peripheral non-perfusion intra-retinal hemorrhage first appears in the affected area, followed by increase in vascular tortuosity with frequent collateral formation around occluded vessels. the vascular abnormalities at the junction between the perfused and non-perfused retina include micro aneurysm, veno-venous shunts, venous beading, and occasionally hard exudates (spitzans et al 1975; elliot, 1975). 3) neovascularisation this complication is observed in 80% of patients with eales' disease. the new vessels can form either on the disc (nvd) or elsewhere in the retina (nve). bleeding from the new vessel is common and recurrent and is the major cause of vision loss. in the favorable cases, no further episodes of bleeding occurs, but in recurrent cases, the fundus shows the evidence of old blood and fibrous organization, retinitis proliferens and even tractional retinal detachment. some patients may develop uveitis, complicated cataract, rubeosis iridis, and secondary neovascular glaucoma in the late stage of the disease. the macula is usually not involved despite extensive peripheral non-perfusion. this preserves the central vision. however, in some cases non-perfusion may extend to the macula and macular edema develops. fluorescein angiography being essentially a retinal vascular disease, the various manifestations of retinal vascular disease are ideally shown by ffa (malik and patnaik, 1973; theodosisadis, shrestha j k et al nep j oph 2009;1(1):66-71 retinal vasculitis fig 2neovascularisation at disc 69 1970). active vasculitis is characterized by staining of the vessel wall or frank extravasations. vascular sheathing due to gliosis without active inflammation does not show these features. venous stasis due to venous obstruction is manifested by engorged tortuous veins distal to the obstruction, engorgement of the capillary bed, micro-aneurysm and macular edema. it also helps monitoring the regression and disappearance of new vessels during treatment and follow up (fig 3). that patients do better with prednisolone 80 mg for 4 days, 60 mg for 4 days and 40 mg for a month and then tapering the dose thereafter. too rapid tapering may cause recurrence. few studies have highlighted the role of anti-tubercular therapy in eales' disease in patients with acute phlebitis with massive infiltration, nodule formation and obliteration of segments of veins. immunosuppressive therapy is reserved for steroidcontraindicated cases and non-responders. drugs used are alkylating agents (cyclophosphamide, chlorambucil), antimetabolites (methotrexate, azathioprine) or cyclosporine a. photocoagulation photocoagulation is mainly indicated for the ischemic and proliferative stages of eales' disease. stage i doesn't require photocoagulation whereas stage iv is too advanced for it. so the best time for photocoagulation is stage ii and stage iii of eales' disease (das and namperumalsamy, 1987). focal treatment at flat new vessel, sectoral laser at capillary drop out and direct treatment of neovascular frond in vitreous is quite effective (90% regression). anchoring photocoagulation using moderate power laser is preferred in preventing subsequent tractional retinal detachment (patnaik and kalsi, 1987). anterior retinal cryoablation this is indicated especially for stage ii and stage iii disease with hazy media, non-dilating pupil and recentonset hemorrhage. the results are encouraging. vitrectomy vitreous hemorrhage is the prime cause for impaired vision in eales' disease. despite the available therapeutic measures, vitreous haemorrhages are still common. the first episode of vitreous hemorrhage usually clears but recurrent vitreous haemorrhages may lead to formation of traction bands and membranes in the vitreous and subsequent complications. pars plana vitrectomy is indicated in vitreous hemorrhage that has not cleared in two to three months, tractional retinal detachment involving posterior pole, multiple vitreous membranes with or without tractional rd and combined tractional and rhegmatogenous retinal detachment. in one study, forty eyes of forty patients with vitreous hemorrhage due to eales' disease underwent simple vitrectomy (malla et al 1999). visual results were taken as criteria for improvement. more shrestha j k et al nep j oph 2009;1(1):66-71 retinal vasculitis management not all patients require therapeutic intervention. indications for treatment are vision-limiting vitritis, capillary destruction around foveal avascular zone, broad areas of capillary drop out in ffa and cystoid macular edema. the various modalities of management are the following. observations if vision is 20/40 or better, and the patient is not bothered by vitreous opacities, mild vascular changes, non to minimal cystoid macular edema and the disease process does not appear to be progressive, the patient can be closely followed-up. medical therapy corticosteroid is the mainstay of treatment in the stage of active inflammation characterized by perivascular sheathing and infiltrations. oral and periocular routes are the preferable ones and there is no role of topical steroids for posterior segment inflammation. the therapy is started with oral 1-2 mg/kg body weight then gradually tapered once vasculitis decreases. periocular steroid injection, particularly posterior sub-tenon injection, is recommended for unilateral disease and oral-steroid contraindicated cases. howe et al believed fig 3fa-peripheral retinal nonperfusion 70 than 36 eyes had visual improvements. of these, in 30 eyes, the vision improved to 6/6-6/24. visual improvement was better with few hemorrhagic episodes and a short duration of the disease. in our experience, early vitrectomy carries a better visual prognosis than waiting for the hemorrhage to clear. early vitrectomy gives early visual recovery and probably removes the noxious stimuli from the vitreous and the inflammatory debris. vitrectomy in eales' disease is found to be less risky than in diabetic retinopathy because of early and complete posterior vitreous detachment, though retinitis proliferans is fairly common in long-standing cases. conclusion usually patients with eales' disease have extensive antero-peripheral non-perfusion but spare macula. vitreous hemorrhage is the most common cause of visual loss. with the advent of sophisticated vitrectomy instruments, laser photocoagulation techniques and early vitrectomy in these patients, visual prognosis is usually good. the main sight-threatening complications are recurrent vitreous hemorrhage, tractional or rhegmatogenous 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(1988). eales' disease and multiple sclerosis. case report. (pol). neurologia i neurochirurgia polska. 22:340-342. palmer he (1996). visual outcome of patients with idiopathic ischemic and non ischemic retinal vasculitis. eye vol 10 part 3; 343-348. patnaik b, kalsi r (1987). understanding and management of eales' disease. acta xxv concilium ophthalogicum :2200. patney hl, garg mp (1965) aetiological study of eales' disease. j ind med assoc. 44:650. pathak sd, mehra ks, dube b (1977). blood fibrinolysis in eales' disease ( a follow up study). ind j ophthalmol. 25:9-11. patnik b, nagpal pn (1998). eales disease; clinical features, pathophysiology, etiopathogenesis; ophthalmology clinics of north america, vol 11, number 4, dec. pratap vb, mehra mk, gupta rk.(1976). shrestha j k et al nep j oph 2009;1(1):66-71 retinal vasculitis electrophoretic pattern of serum proteins in eales' disease. ind j ophthalmol. 23:14-16. rahi ah, nath k, gogi r. (1969). acanthocytosis in eales' disease. orient arch ophthalmol 7:269. rengarajan k, muthukkaruppan vr, namperumalsamy p.(1989). biochemical analysis of serum proteins from eales' patients. curr eye res. 8:1259-1269. stock w (1937). retinal haemorrhage due to miliary tuberculosis. klin monatsol augenh. 99:367-372. singhal bs, dastur dk (1976).eales' disease with neurological involvement. part i. clinical features in 9 patients. j neurol sci. 27:313-321. stanford mr, graham em, kasp e (1987). retinal vasculitis-correlation of animal and human disease. eye 1:69-77. spitzans m, meyer-schwickerath gt, stephen b. (1975). clinical picture of eales' disease. grafes arch clin exp ophthalmol. 194:73. theodosisadis g (1970). fluorescein anigography in eales' disease. am j ophthalmol. 69:271. vanacore, maselli e (1965). blood coagulation anomaly in a case of eales' disease. (corrector effect of corticosteriod treatment). ann ottamol clin ocul. 91:1132-1140. wadsworth (1887). recurrent retinal hemorrhage followed by the development of blood vessels in the vitreous. ophthalmic rev. 6:289. text.pmd 118 original articleoriginal articleoriginal articleoriginal articleoriginal article received: 16.12.2008 accepted: 05.05.2009 correspondence and reprint request to: dr pratap karki, md biratnagar eye hospital, morang, nepal e-mail: pkarki10@yahoo.co.in tel: 00977-21-533661 hospital-based community cataract surgery: comparison of visual outcomes between conventional extra-capsular cataract extraction and small incision cataract surgery karki p1, shrestha jk2, shrestha jb3 1consultant ophthalmologist, biratnagar eye hospital, morang, nepal 2 professor and head, department of ophthalmology, b.p koirala lion’s centre for ophthalmic studies (bpklcos) 3 associate professor, department of ophthalmology, b.p koirala lion’s centre for ophthalmic studies (bpklcos), kathmandu abstract introduction: the small-incision cataract surgery is gaining popularity among the ophthalmic surgeons. objective: to compare the visual outcome of conventional extra-capsular cataract extraction (ecce) and small-incision cataract surgery (sics) in a hospital based community cataract program. materials and methods: a prospective interventional study without randomization was carried out including the patients undergoing cataract surgery by either conventional ecce or manual sics. they were followed up for 6 weeks postoperatively. the visual outcomes were compared between the two groups. statistics: the statistical program epi-info version 2000 was used to analyze the data. mean values with standard deviations, 95% ci and p value were calculated. the p value of <0.05 was considered significant. results: of 85 patients, 44 (m: f=10:34) underwent ecce and 41 (m: f=15:26) sics (rr= 0.71, 95% ci=0.42-1.2, p value=0.16). unaided visual acuity on the 1st postoperative day in the ecce group was e”6/ 18 in 22.7%,<6/18-6/60 in 63.6 %,< 6/60 in 13.7%, whereas in the sics group, the same was e”6/18 in 70.7%,<6/18-6/60 in 22 %,< 6/60 in 7.3% (95% ci = 0.23 – 0.48, p=0.001). best corrected visual acuity on the 6th week follow-up in the ecce group was e”6/18 in 79.5%,<6/18-6/60 in 18.2 %,< 6/60 in 2.3% and in the sics group the same was 6/18 in 90.5% and <6/18-6/60 in 4.9% (95% ci=0.44 – 0.73; p=0.0012). conclusion: both ecce and sics are good procedures for hospital based community cataract surgery but within the 6 weeks postoperative period sics gives better visual outcome. remarkably higher number of female patients can be provided service in a hospital based community cataract programme as compared to males. keywords: cataract, small incision, extra-capsular introduction cataract is the most common cause of blindness and visual impairment globally. according to global data (who 2002, pascolini et al 2004), the prevalence of visual impairment due to cataract is 49.7%. nepal blindness survey (1980-81) showed that cataract and sequel accounted for 72% of blindness in nepal (brilliant ge, 1988). according to a recent study by sapkota et al (2006) prevalence of blindness due to cataract was found to be 60.5%. with the problem of cataract related blindness increasing in nepal as well as globally, tackling blindness due to this condition remains a major challenge. visual rehabilitation following phacoemulsification cataract surgery combined with foldable intraocular lens is remarkable. however, despite such improvements in surgical results, this method of surgery requires expensive equipment and lenses. the majority of the needy population requiring cataract surgery in our part karki p et al nep j oph 2009;1(2):118-122 community cataract surgery: conventional vs sics 119 of the world is not able to afford it. conventional extra-capsular cataract extraction and small-incision cataract surgery are both very good techniques for cataract extraction practiced in hospitals in all developing countries. in nepal both methods are used in community based surgical camps and in tertiary level centers, though the sics is gaining popularity amongst the ophthalmic surgeons (hennig et al 2003 & ruit et al 1999). our study was done to compare the visual outcomes of these two procedures in hospital based-community cataract surgery, where the patients were selected for surgery in a community and brought to the hospital for surgery. materials and methods all patients with age-related cataract who underwent cataract surgery with either conventional ecce or sics technique under the b p koirala lion’s center for ophthalmic studies (bpklcos), kathmandu community surgery program were eligible for the study. all surgeries were performed in community ot at bpklcos, teaching hospital. prior to the surgery, an informed consent was obtained from all of the patients. the patients of age less than 40 years were excluded. the other criteria for exclusion were pterygium, corneal opacities, uveitis, secondary cataracts, sub-luxated lens, uncontrolled systemic hypertension, diabetes mellitus, high myopia, amblyopia, retinitis pigmentosa, age-related macular degeneration, glaucoma, optic atrophy and other posterior segment diseases. this was a prospective interventional study without randomization. preoperative evaluation all patients were initially screened in camps or peripheral centers and brought for surgery to the bpklcos. basic eye examination was done using a torch and slit-lamp to assess eyelids and adnexa, lacrimal apparatus, conjunctiva, globe, cornea, anterior chamber, pupil, and lens. the cataract and the posterior segment were evaluated, where possible, after pupillary dilatation. intraocular pressure was measured using airpuff for screening and goldman applanation tonometry when required. lacrimal syringing was done to check for patency of the lacrimal apparatus. biometry was done to assess power of the intraocular lens required. b-scan was done in all cases to assess posterior segment. blood pressure and urine sugar were checked to screen for hypertension and diabetes. surgical technique all surgeries were performed under peri-bulbar anesthesia. ecce a posterior limbal incision was made after making a conjunctival flap from 10 o’clock to 2 o’clock positions. anterior capsulotomy and hydro-procedures were followed by nucleus removal by gentle expression using pressure-counter pressure technique. the cortex was aspirated with simcoe irrigating and aspirating cannula. posterior chamber intra-ocular lens (pciol) was implanted into the capsular bag. continuous sutures were applied using 10/0 nylon to close the wound. subconjuctival gentamycin and dexamethasone injection was given at the end of the surgery. the flap of conjunctival peritomy was positioned over the wound. sics a scleral frown incision 6.5 to 7.0 mm long was made superiorly 2.0-3.0 mm away from the limbus. tunnel construction was done using a crescent knife extending to 1-1.5 mm into the clear cornea. internal corneal incision was made using a 3.2 mm keratotome. the nucleus was prolapsed into the anterior chamber and removed with irrigating vectis under viscoelastic or directly extracted from the bag using a fishhook after hydro-procedures and nuclear rotaion. the cortex was aspirated with simcoe cannula and the pciol was implanted in the capsular bag. subconjunctival gentamycin and dexamethasone injection was given and conjuctival flap mobilized to cover the tunnel. 1st postoperative day and follow up all the patients were examined on the next day. visual acuity was measured and detailed examination done under slit-lamp. the patients were discharged with steroid and antibiotic combination eye drops. the patients were followed up 1 week and 6 weeks postoperatively. on the 6th week follow up, refraction and keratometry were done. postoperative medications were tapered according to the anterior chamber reaction. results of the patients eligible to participate in the study, 85 completed the 6 weeks follow up. 44 of them underwent conventional ecce and 41 karki p et al nep j oph 2009;1(2):118-122 community cataract surgery: conventional vs sics 120 underwent sics. the majority of patients in the study were female (70.6%), while only 29.4% were male. the mean age of the patients was 62.82±11.33 years. the range was from 40 to 90 years. comparison of the demographic profile of the patients undergoing conventional ecce and sics groups showed no statistically significant difference (table 1). most of the cataracts operated were immature (62.3 table 2 unaided visual acuity on 1st postoperative day visual acuity ecce sics rr 95%ci p value 6/6-6/18 22.7% 70.7% 0.33 0.23-0.48 0.001 6/24-6/60 63.6% 22% <6/60 13.7% 7.3% %), 36.5% mature and 1.2% hypermature. of the total 85 eyes operated, the majority (64.7 %) was blind, 15.3% had severe visual impairment and 20 % had visual impairment (table 1). on the first postoperative day the unaided visual status in the operated eye was 6/6-6/18 in 22.7%, <6/18-6/60 in 63.6 %, <6/60-3/60 in 4.6% and <3/60 in 9.1% in the table 3 comparison of outcomes between sics and ecce on 6th week postoperatively visual acuity ecce sics rr 95%ci p value good (6/6-6/18) 79.5% 95.1% 0.57 0.44 -0.73 0.0012 borderline (6/24-6/60) 18.2% 4.9% poor (<6/60) 2.3% 0% karki p et al nep j oph 2009;1(2):118-122 community cataract surgery: conventional vs sics table 1 demography and clinical profile description ecce sics sex male 10 15 female 34 26 relative risk(rr)= 0.71, 95% ci=0.42-1.2, p value=0.16 mean age (years) 63.14 ±12.3 62.59±10.3 operated eye right 21 21 left 23 20 type of cataract mature 18 13 immature 26 27 hyper-mature 0 1 rr= 1.5, 95% ci=0.76-1.73, p value=0.5 pre-operative visual status blind (<3/60) 31 24 severe visual impairment (<6/60-3/60) 7 6 visual impairment (<6/18 – 6/60) 6 11 rr= 1.5, 95% ci=0.8-3.12, p value=0.12 iol power +21.43±3.7d +21.74±2.3d 121 ecce group. while in the sics group, unaided visual acuity on the first postoperative day was 6/6-6/18 in 70.7 %, <6/186/60 in 22 %, <6/60-3/60 in 4.9%, and <3/60 in 2.4 %. visual outcome on the 6th week of follow-up by taking the best corrected visual acuity in the ecce group was good (6/6-6/18) in 79.5%, borderline (<6/18-6/60) in 18.2% and poor (<6/60-3/60) in 2.3%. in the sics group visual outcome taking best corrected visual acuity was good in 95.1% and borderline in 4.9%, while none had poor outcome (table 3). discussion community-based cataract surgery remains a big challenge for all developing countries like nepal. the objective to tackle the problem of cataract-related blindness, where surgery remains the only treatment, seems to be just out of our reach, despite our best efforts. the answer to the problem may lie somewhere between searching for a method to provide cost-effective surgical care with good outcome and the one with less complications. the geographical makeup of our country remains another barrier where we are almost relying on a singlecontact surgical care and where follow-up of the patients is extremely poor. conducting this study also faced the same challenges where a very few number of patients could possibly come for follow-up despite counseling. however, while in such circumstances conducting surgical camps may be one practical option, in areas accessible by transport, bringing patients to the hospital for surgery is another way of providing surgical care. hospital-based community cataract surgery not only provides better opportunity to give good surgical care but, in our opinion, also encourages the patients to come to the hospital for better care in the future. the inclusion of a higher number of female patients (70.6%) in our study was in contrast to the one by sapkota et al (2006) in nepal which shows a higher cataract surgical coverage among men (68.1%). the study done by r venkatesh et al (2005) also had more female patients (54%) compared to males (46%). the mean age in our study (62.82±11.3 years) was similar to 63.4 years in the study by ruit et al (1999) in nepal. in a study done in bpklcos by heng et al 2004 (unpublished work, personal communication) had similar mean age of 63.62±10.17 years. the sics group in our study showed significantly better visual rehabilitation on the first post-operative day with the majority, 70.7% having unaided vision of e”6/18, while most patients in the ecce group had the unaided vision of < 6/18 in 63.6%. the study done by hennig et al (2003) showed similar results with unaided visual acuity of e” 6/18 in 76.8% of the sics group. in the 6th week of follow-up best corrected visual acuity was also significantly better in the sics group as compared to the ecce group, with 95.1% having vision of e”6/ 18 as compared to 79.5% in the ecce group. the study done by gogate et al (2003) had 86.7% in the ecce group with the visual acuity of 6/18 or better and 89.8% in the sics group showing similar results in both groups as compared to our study (gogate et al 2003). a study done by venakatesh et al (2005) showed 94% best corrected visual acuity of e” 6/18 in the sics group which is comparable to our results. gurung a et al (2009) have also reported consistent findings that a more rapid recovery of good vision can be achieved with manual sics than with conventional ecce in the immediate postoperative period. the study done by shrestha et al (2001) assessing outcome of ecce in surgical camps showed best corrected visual acuity of e”6/18 in 59.5%, which was less than the outcomes of both the ecce and sics in our study, thus stressing the advantage of hospital-based community cataract surgery. conclusion visual rehabilitation is quicker and better with sics with significantly better unaided first postoperative day vision. best-corrected visual acuity after 6 weeks is also much better with sics. both conventional ecce and sics remain cost-effective methods of cataract surgery which can be done under similar settings. karki p et al nep j oph 2009;1(2):118-122 community cataract surgery: conventional vs sics 122 hospital-based community cataract surgery programme provides better opportunity to serve the female patients. references gogate pm, deshpande m, wormald r p, deshpande r and kulkarni s r (2003). extracapsular cataract surgery compared with manual small incision cataract surgery in community eye care setting in western india: a randomised controlled trial br j ophthalmol; 87:667-672. gurung a, karki db, shrestha s, rijal ap (2009). visual outcome of conventional extra-capsular cataract extraction with posterior chamber intra-ocular lens implantation versus manual small incision cataract surgery. nep j oph; 1:13-19. hennig a, j kumar, d yorston, foster a (2003). sutureless cataract surgery with nucleus extraction: outcome of a prospective study in nepal. br j ophthalmol;87:266-270. brilliant ge (1988). epidemiology of blindness in nepal. report of 1981 nepal blindness survey. chelsea, mi: seva foundation. pascolini d, mariotti sp, pokharel gp, pararajasegaram r, etya’ale d, negrel ad, resnikoff s (2004). global update of available data on visual impairment: a compilation of population based studies. ophthalmic epidemiol; 11 (2):67-115. ruit s, tabin gc, steven a. nissman bs, paudyal g and gurung r (1999). low-cost high-volume extracapsular cataract extraction with posterior chamber intraocular lens implantation in nepal. am j ophthalmol; 135:1887-1892. shrestha j k, pradhan ym, snellingen t (2001). outcomes of extracapsular surgery in eye camps of eastern nepal. br j ophthalmol; 85:648–652. venkatesh r, muralikrishnan r, balent lc, prakash sk, n venkatesh prajna (2005). outcomes of high volume cataract surgeries in a developing country. br j ophthalmol; 89:1079-1083. sapkota y d, pokharel g p, nirmalan p k, dulal s, maharjan i m, prakash k (2006). prevalence of blindness and cataract surgery in gandaki zone, nepal. br j ophthalmol; 90:411-416. karki p et al nep j oph 2009;1(2):118-122 community cataract surgery: conventional vs sics source of support: nil. conflict of interest: none for numbering.pmd 32 original articleoriginal articleoriginal articleoriginal articleoriginal article efficacy of latanoprost in management of chronic angle closure glaucoma kumar s1, malik a2 singh m3, sood s4 1associate professor, 2 assistant professor, 4professor, department of ophthalmology, government medical college and hospital, chandigarh, 3senior lecturer, department of ophthalmology, ram manohar lohia hospital, delhi abstract background: chronic angle closure glaucoma is often managed surgically. aim: to study the effect of latanoprost 0.005% on intraocular pressure in subjects diagnosed as having chronic angle closure glaucoma. materials and methods: forty patients participated in the study. baseline examination included visual acuity, refraction, slit-lamp examination, intraocular pressure, anterior and posterior segment examination, gonioscopy and perimetry. patients were treated with latanoprost 0.005% once daily at bedtime. iop was recorded at baseline, 2weeks, 4 weeks, 8 weeks and 12 weeks after starting the treatment. results: the mean age of the study sample was 56.45 years (40-70 years). there were 18 males and 22 females in the study. mean iop at baseline was 24.55±3.63. mean iop decreased to 17.27±3.19 at 2 weeks, 15.27±3.07 at 4 weeks, 14.60±3.06 at 8 weeks and 14.47±2.66 at 12 weeks. there was a statistically significant reduction in mean iop (41.03%) at 12 weeks as compared to those of the baseline iop (p=0.000). there was no significant difference in iop reduction in eyes with different degrees of angle closure by peripheral anterior synechiae. conclusion: latanoprost, a prostaglandin analogue, is effective in reducing iop in chronic angle closure glaucoma patients and its efficacy is not affected by the degree of angle closure by peripheral anterior synechiae. key words: latanoprost, chronic angle closure glaucoma, intraocular pressure, peripheral anterior synechiae introduction glaucoma accounts for approximately 5.1 million of the blind people in the world, with more than half of these residing in asia (quigley, 1996; thylefors et al 1995; dandona et al 2000). primary angle closure glaucoma (pacg) is considered the most common form of glaucoma in asia. most glaucoma research has been focused on populations with a preponderance of primary open angle glaucoma (poag), whereas treatment modalities for chronic angle closure glaucoma (cacg) remain less studied. in cacg, gradual asymptomatic angle closure results in diminished aqueous outflow through the angles and a subsequent rise of the intraocular pressure (iop). laser iridotomy remains the appropriate initial therapy for cacg to received: 12.08.2008. accepted: 14.11.2008 correspondence and reprint requests to: dr archana malik assistant professor, department of ophthalmology government medical college and hospital, chandigarh, india-160032 email: drarchanag2002@yahoo.com fax: 0091-172-2607707 nep j oph 2009;1(1):32-36 33 eliminate any element of pupillary block. topical medications should only be added if iridectomy alone is insufficient to control iop. latanoprost, a prostaglandin f2-alpha analogue, has proven to be an effective ocular hypotensive drug in subjects with poag and ocular hypertension (mishima et al 1996, watson & stjernschantz 1996). its main mechanism for reducing iop is an increase in the uveoscleral outflow (toris et al 1993). very few studies have investigated the efficacy of latanoprost in reducing iop in subjects with cacg (aung et al 2005, kook et al 2005, chew et al 2002, aung et al 2000, hung et al 2000, chen et al 2006). the mechanism of action of latanoprost in eyes with closed angles is not established. it is not known whether the iop-reducing effect of latanoprost varies with the extent of angle closure and whether latanoprost is effective in eyes with extensive peripheral anterior synechiae (pas). this study was carried out to see whether latanoprost was effective in reducing iop in patients with cacg and whether the extent of pas affected its action. materials and methods forty subjects participated in a 12-week study conducted across 2 centers in india. informed consent was obtained from all subjects and the study was carried out in accordance with the world medical association's declaration of helsinki. chronic angle-closure glaucoma was defined as optic neuropathy with a corresponding visual field defect, chronically raised iop, an anterior chamber angle in which the trabecular meshwork was not visible for at least 180° on gonioscopy, and with evidence of pas in the angle. patients included were those who were 40 years of age or older with unilateral or bilateral primary cacg, who had undergone peripheral iridotomy (pi) at least one month before, had iop greater than 21mmhg after the pi, and current control with one or two pressure-reducing medications on two consecutive visits. patients excluded were those who had undergone previous intraocular surgery (pi excluded)/trauma to the eye, patients on oral drugs known to affect the iop, uveitis, causes of secondary angle closure and pregnant or nursing women. at the pre-study visit, which took place 5 weeks before the baseline visit, medical and ocular history was taken and subjects were assessed for eligibility. visual acuity, refraction, iop, anterior and posterior segment (cup-disc ratio) examination, gonioscopy (shaffer's grading, degrees of pas recorded) and perimetry were carried out. all existing iop-lowering therapy was discontinued. patients were required to complete a minimum washout period before the start of the study: 4 weeks for prostaglandins, 3 weeks for b-adrenergic antagonists, 2 weeks for adrenergic agonists, 5 days for cholinergic agonists and carbonic anhydrase inhibitors. the right eye was taken as the study eye in all subjects. iop was measured with a goldmann applanation tonometer. at each time point, three measurements were performed in each eye, and the mean of three measurements was used in the statistical analyses. iop was recorded at baseline, 2 weeks, 4 weeks, 8 weeks and 12 weeks after starting the treatment. statistical analysis was done using one-way anova test. static and dynamic gonioscopy were performed at baseline and at 12 weeks. the examination was carried out at the lowest level of illumination that permitted a view of the angle and at high magnification. the drainage angle was graded according to shaffer's grading in each quadrant and the degrees of pas were recorded for each patient. best-corrected snellen visual acuity, systemic blood pressure, and pulse rate were determined at each visit, and a slit-lamp examination was performed. the presence of cells and flare in the anterior chamber was investigated during slit-lamp examination. patients were instructed to administer one drop of latanoprost at 8.00 pm everyday. patients were instructed about punctal occlusion after administering the drops. adverse events were monitored carefully throughout the study. results in total, 40 patients entered the study. the mean age of the study sample was 56.45 ± 7.87 (40-70) years. there were 18 (45.0%) males and 22 (55.0%) females. vertical cup-disc ratio, shaffer's grade and degrees of peripheral anterior synechiae (pas) are shown in table 1. mean iop at baseline was 24.55 ± 3.63 (20-34) mmhg. mean iop decreased to 17.27 ± 3.19 (12-26) at 2 weeks, 15.27 ± 3.07 (10-24) at 4 weeks, 14.60 ± 3.06 (10-24) at 8 weeks and 14.47 ± 2.66 (10-22) at 12 weeks kumar s et al nep j oph 2009;1(1):32-36 latanoprost in chronic angle closure glaucoma 34 (fig.1). there was 41.03% (10.07 ± 0.71 mmhg) reduction of iop at the end of 12 weeks. repeated measure one-way anova revealed statistically significant reduction in mean iop at 12 weeks as compared to at baseline {wilks' test [f 4,156] = 48.773, p=0.000}. the maximum reduction of iop (29.63%) was seen in the first 2 weeks, though significant decrease was seen thereafter also till the end point of study. fig. 2 shows scatter plot of final iop at 12 weeks versus baseline iop. kumar s et al nep j oph 2009;1(1):32-36 latanoprost in chronic angle closure glaucoma table 2. decrease in iop in eyes with different degrees of pas degrees of iop at iop at 12 pas baseline w e e k s <180 25.88 ± 4.35 13.64 ± 2.14 180-270 24.38 ± 2.02 14.61 ± 3.15 >270 22.50 ± 3.17 15.70 ± 2.49 tables table 1. vertical cup-to-disc ratio, shaffer's grade and degrees of pas parameter no. of study subjects (n= 40) vertical cup-to-disc ratio mean (sd) 0.59 (0.17) range 0.3-0.9 shaffer's grade 0 6(15.0) 0-i 7(17.5%) i-ii 21(52.5%) ii-iii 6(15.0%) iii-iv 0 degrees of pas <180 17(42.5%) 180-270 13(32.5%) >270 10(25.0%) t ime (weeks) 128420 io p ( m m h g) 30 28 25 23 20 18 15 13 10 figures fig.1 line graph showing iop change from baseline to 12 weeks fig.2 scatter plot showing final iop (mmhg) at 12 weeks versus baseline iop (mmhg) 12 week iop 2624222018161412108 b as el in e io p 36 34 32 30 28 26 24 22 20 18 degrees of pas >270.00180270<180.00 io p 30 25 20 15 10 5 0 baseline iop iop af ter treatment fig.3 bar diagram depicting change of iop (mmhg) with different degrees of peripheral anterior synechiae (pas) on comparing the decrease in iop in eyes with different degrees of pas, no significant difference was found between the three groups by repeated measure one-way anova {wilks' test [f 8, 68] = 1.744, p=0.104}. table 2 and fig.3 depict the decrease in iop in the three groups with different degrees of pas. 35 latanoprost was well tolerated in our patients. most of the adverse events were reported as mild. the most common ocular adverse events found were that of conjunctival hyperemia and ocular discomfort. discussion this study shows that latanoprost is effective in reducing iop in cacg patients and its efficacy is not affected by the degree of angle closure by pas. though higher iop reduction was seen in eyes with lesser degrees of pas, it was not statistically different from those with greater degrees of pas. laser iridotomy is the still the first line of management in cacg to eliminate any element of pupillary block and topical medications should only be added if the iridectomy alone is insufficient to control iop. the exact mechanism of action of latanoprost in eyes with closed angles is not known. the main mechanism of action of prostaglandin analogs in the reduction of iop has been shown to be increased uveoscleral outflow of aqueous humor (toris et al 1993). they act on specific ciliary muscle prostanoid receptors and thus lead to increased biosynthesis of matrix metalloproteinases, which can cleave extracellular matrix components (lindsey et al 1997). this alters the collagen content in the ciliary muscle, thereby reducing the hydraulic resistance in the uveoscleral pathway. in cacg, latanoprost may gain access to the ciliary body through the still-open part of the anterior chamber angle to increase uveoscleral outflow. it is also possible that it is able to increase outflow of aqueous through the pas in closed angles, explaining its efficacy in eyes with up to 12 clock hours of pas. another possibility is that latanoprost gains access to the uveoscleral outflow through other routes such as through the posterior chamber between the iris and lens, the iris root itself, or the sclera. evidence for this is suggested by the finding that topical prostaglandin treatment induces matrix metalloproteinases and reduces collagens in the sclera and iris root (sagara et al 1999). the preliminary study by chew et al (2002) in cacg patients demonstrated a 34.2% decrease in iop at 2 weeks with latanoprost as opposed to 29.63% reduction seen in our study. our study was comparable to a study done by aung t et al (2005). demographic characteristics were similar in both the studies. mean vertical cd ratio was 0.59 ± 0.17 as compared to 0.61 ± 0.2 in our study. 80% of our patients had shaffer's grade less than or equal to 2 while in theirs 72% patients had < grade 1; and 10 patients in our study had more than 270 degrees of pas as compared to 15 patients in their study having more than 8 clock hours of pas. the mean iop levels at baseline and at week 12 were 24.55 ± 3.63 and 14.47 ± 2.66 respectively in our study (corresponding values in their study were 25.2 ± 6.0 mmhg and 17.7 ± 5.3 mm hg). mean reduction of iop was considerably higher in our study (41.03%) as compared to their study (29.7%). no particular reason for this could be elucidated. mean iop reduction in patients with >270 degrees of pas was 30.2% in our study which was comparable to 31% in patients with >8 clock hours of pas in their study. they noticed a higher hypotensive response in eyes with greater angle closure. though there was significant decrease in iop in eyes with variable degrees of pas, our study showed a higher iop reduction in patients with lesser degrees of pas, but the difference was not statistically significant. conclusion our study demonstrates that latanoprost does reduce iop in cacg patients and significant reduction is also seen in patients with >270 degrees of pas showing that the amount of angle closure does not reduce the action of latanoprost. acknowledgements no grants or sponsorships have been requisitioned for this study. the authors do not have any proprietary or financial interest in any procedure or product mentioned in this manuscript. references aung t, chan yh, chew ptk, exact study group (2005). degree of angle closure and the intraocular pressure-lowering effect of latanoprost in subjects with chronic angle-closure glaucoma. ophthalmology 112:267-271. aung t, wong ht, yip cc et al (2000). comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma: a preliminary study. ophthalmology kumar s et al nep j oph 2009;1(1):32-36 latanoprost in chronic angle closure glaucoma 36 107:1178-83. chen mj, chen yc, chou ck, hsu wm(2006). comparison of the effects of latanoprost and travoprost on intraocular pressure in chronic angle-closure glaucoma. j ocul pharmacol ther 22:449-54. chew ptk, hung pt, aung t(2002). efficacy of latanoprost in reducing intraocular pressure in patients with primary angle-closure glaucoma. survey of ophthalmology 47:125-128. dandona l, dandona r, mandal p et al(2000). angle-closure glaucoma in an urban population in southern india. the andhra pradesh eye disease study. ophthalmology 107:1710-6. hung pt, hsieh jw, chen yf, wei t(2000). efficacy of latanoprost as an adjunct to medical therapy for residual angle-closure glaucoma after iridectomy. j ocul pharmacol ther 16:43-7. kook ms, cho hs, yang sj, kim s, chung j (2005) . efficacy of latanoprost in patients with chronic angle-closure glaucoma and no visible ciliary-body face: a preliminary study. journal of ocular pharmacology and therapeutics 21: 75-84. lindsey jd, kashiwagi k, kashiwagi f(1997). prostaglandin action on ciliary smooth muscle kumar s et al nep j oph 2009;1(1):32-36 latanoprost in chronic angle closure glaucoma extracellular matrix metabolism: implications for uveoscleral outflow. surv ophthalmol 41:53. mishima hk, masuda k, kitazawa y, et al.(1996) a comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. a 12-week study. arch ophthalmol 114:929 -32. quigley ha(1996). number of people with glaucoma worldwide. br j ophthalmol 80:389-93. sagara t, gaton dd, lindsey jd et al (1999). topical prostaglandin f2 alpha treatment reduces collagen types i, iii, and iv in the monkey uveoscleral outflow pathway. arch ophthalmol 117:794-801. thylefors b, negrel ad, pararajasegaram r, dadzie ky(1995). global data on blindness. bull world health organ 73:115-21. toris cb, camras cb, yablonski me (1993). effects of phxa41, a new prostaglandin f2 alpha analogue on aqueous humour dynamics in human eyes. ophthalmology 100:1297-304. watson p, stjernschantz j, latanoprost study group (1996). a six month randomized, double-masked study comparing latanoprost with timolol in openangle glaucoma and ocular hypertension. ophthalmology 103:126-37. page 145-153.pmd 145 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation __________________________________________________ received on: 02.02.2010 accepted on: 14.05.2010 correspondence and reprint request to:dr sudesh kumar arya, professor, department of ophthalmology, government medical college and hospital, chandigarh, india e-mail: aryasudesh@yahoo.co.in � review article role of amniotic membrane transplantation in ocular surface disorders arya sk, bhala s, malik a, sood s department of ophthalmology, government medical college and hospital, chandigarh, india. abstract the advent of amniotic membrane (am) and limbal stem cell grafts have transformed the treatment of diseases resulting in ocular surface failure. the current success may be attributed to cryopreservation of human am, which retains its properties and renders the amniotic epithelial cells nonviable and thus nonimmunogenic. its unique properties have prompted its application in a large number of ocular ailments. the present article reviews the properties of am and its uses in ophthalmic practice. keywords: amniotic membrane transplantation, ocular surface disorders, chemical injury, dry eye introduction: regenerative medicine is a new field based on the use of stem cells to generate biological substitutes and improve tissue functions. the three essential factors involved are: stem cells, which retain the capacity to renew themselves and may be able to restore damaged tissue with high proliferability and differentiability; the scaffolds that support them; and growth and differentiation factors. the advent of amniotic membrane (am) and limbal stem cell grafts have transformed the treatment of diseases resulting in ocular surface failure. history in 1910 davis was the first to report the use of fetal membranes as surgical material in skin transplantation (davis 1910). since then the use of amniotic membrane in surgery has been expanded. the earliest use in ophthalmology dates back when de rotth (1940) used fetal membranes, both chorion and amnion, in treating conjunctival defects. fresh membrane was used as a dressing. sorsby & symmons (1946) used dried and chemically processed human am for chemical burns involving the eye. for almost 5 decades thereafter, it was unheard of until kim & tseng (1995) propelled it into the limelight by using noncryopreserved human am as a xenograft in rabbit eyes. the current success may be attributed to cryopreservation of human am, which retains its properties and renders the amniotic epithelial cells nonviable and thus nonimmunogenic. its unique properties have prompted its application in a large number of ocular ailments. anatomy the human am is the innermost layer of the placenta and has a single layer of ectodermally derived columnar cells attached to a basement membrane with an underlying layer of mesenchyme. histologically the amnion is a 0.02 mm to 0.5 mm five layered membrane.the epithelium consists of a single layer of cuboidal cells with a large number of microvilli on the apical surface. the basement membrane is a thin layer composed of a network of reticular fibers. histochemically the basement membrane closely resembles that of the conjunctiva. the compact layer contributes to the tensile strength of the membrane. the fibroblast layer is the thickest layer of the am made up of a loose fibroblast network. the outermost layer of the amnion is the spongy layer. functions the structural integrity, transparency and elasticity of the amniotic basement membrane make it currently 146 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation the most widely accepted tissue replacement for ocular surface reconstruction. the am has several properties that render it extremely useful in ocular surgery: 1. promotes epithelialization: am acts like a basement membrane and facilitates the migration of epithelial cells (lee & tseng 1997). it reinforces adhesion of basal epithelial cells, promotes epithelial differentiation, prevents epithelial apoptosis, and improves corneal sensitivity and tear film stability; it also produces growth factors that promote epithelial cell growth. the am can be used to promote non-goblet cell differentiation of the conjunctival epithelium. 2. inhibits fibrosis: fibroblasts are normally responsible for the scarring associated with wound healing and are activated by transforming growth factor (tgf b). amniotic membrane downregulates tgf-b and the receptor expression by fibroblasts and thus reduces fibrosis like in conjunctival and pterygial fibroblasts (tseng et al 1999). 3. antiinflammatory and antiangiogenic factors: the am probably acts as a barrier against the tear film resulting in a reduced amount of inflammatory cells and hence the amount of inflammatory mediators (chen et al 2000). tissue inhibitors of metalloproteinase inhibitors (timps) 1, 2, 3, and 4 interleukin (il)-10; and il-1 receptor antagonist anti-inflammatory factors along with endostatin (inhibit endothelial cell proliferation, angiogenesis and tumor growth) are present in human am. in addition, the presence of proteinase inhibitors promote wound healing. 4. antimicrobial and antiviral properties: am seems to have antimicrobial properties that decrease the risk of postoperative infection (talmi et al 1991). it also contains cystatin e, an analogue of cysteine proteinase inhibitors, which has complementary antiviral properties. its antimicrobial and possible antiviral properties warrant further studies. 5. high hydraulic conductivity: the am has a high hydraulic conductivity, thus facilitating its use in bleb repair following glaucoma-filtering surgery. the non-immunogenicity of the am was thought as am did not express hla-a, -b, or -dr antigen since after transplantation it did not undergo rejection (adinolfi et al 1982). subsequent studies by several authors have shown class 1 antigen and co-manifestation of class 1a (hla-a, -b, -c, -dr) and class 1b (hla-g and hla-e) antigens in amniotic epithelium and in mesenchymal cells and fibroblasts of human am. the technique of human am processing and cryopreservation with dulbecco modified eagle medium and 50 % glycerol recommended by the fda renders all the amniotic cells nonviable and hence its immunogenicity is of no consequence. in addition, the human am appears to be an immuneprivileged tissue despite the expression of class 1a and 1b antigens and contains immunoregulatory factors that include hla-g and fas ligand. human am also has the ability to suppress t lymphocytes. procurement and preservation the current success may be attributed to cryopreservation of human am, which retains its properties and renders the amniotic epithelial cells nonviable and thus nonimmunogenic (mejia et al 2000). amniotic membrane is obtained from donors undergoing caesarean section, who are negative for hiv, hepatitis and syphilis. different protocols exist for the processing and storage. according to kim et al (1995) the placenta is cleaned with balanced salt solution containing a cocktail of antibiotics (50 mg/ml penicillin, 50 µg/ml streptomycin, 100 mg/ml of neomycin as well as 2.5 mg/ml of amphotericin b) under sterile conditions. the amnion is separated from the chorion by blunt dissection. the separated membranes are cut in different sizes placed on nitrocellulose paper strips with the epithelial side up. dulbecco modified eagles medium/glycerol (1:1) is used for cryopreservation and the tissues are frozen at -80 degrees until further use. amnion stored in 50-85 % glycerol is reliable and effective for over a year, with the added advantage of antibacterial properties. lyophilized ams were found to be impermeable to different strains of bacteria bacillus, escherichia coli, pseudomonas, citrobacter, flavimonas and staphylococcus. before use, the membrane is thawed by warming the 147 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation container to room temperature for 10 minutes. this technique of cryopreservation followed by thawing renders all the amniotic epithelial cells nonviable and the tissue nonimmunogenic. hyper-dry amnion at present, in most cases, cryopreserved amniotic membrane tissue has been used clinically for membrane grafts. the immunogenicity of cryopreserved tissue is generally thought to be less than that of fresh tissue. the low-grade inflammatory responses were observed when viable amniotic epithelial cells were present (akle et al 1981) suggesting that live amniotic membrane is immunogenic. to overcome these problems, a novel dried amniotic membrane (hyper-dry amnion), using far-infrared rays and microwaves, in addition to ãirradiation for sterilization can be prepared. there is still a lack of appropriate indications or scientific evidence based on randomized comparative studies to prove that its use is better than other alternative therapies. uses in ophthalmology persistent epithelial defect and neurotrophic ulcer the management of a persistent epithelial defect is aimed at treatment of the underlying disease process, control of inflammation, and protection of the surface. the am has several properties that promote epithelialization and reduce inflammation.multiple layers of am restore stromal thickness in deep and perforated noninfectious ulcers and probably provides a substrate for collagens and growth factors for epithelial healing. (fig 1, 2, 3 & 4).the limitations of amt include continuous tissue destruction beneath the graft, the need for adequate stem cells at the limbus and normal keratocytes in the surrounding tissue, and intact sensory innervation for healing (prabhasawat et al 2001). am has been used as an adjunct to fda-approved fibrin glue for management of corneal perforations up to 2 mm. the am provides better adhesion to the surrounding epithelium and prevents dislodgment of the glue. sheild ulcers since the am enhances epithelialization, and has antiscarring and antiinflammatory properties, it was used in 7 eyes of 4 patients with grade ii and iii shield ulcers unresponsive to conventional treatment (sridhar et al 2001). it helps in early healing. fig 1: preoperative photograph showing persistent epithelial defect fig 2: postoperative photograph showing healed epithelial defect after amt fig 3: preoperative photograph showing persistent epithelial defect after deep anterior lamellar keratoplasty (dalk). fig 4: photograph showing healed epithelial defect after amt 148 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation infectious keratitis amt has been used effectively in microbial keratitis of bacterial, parasitic, and fungal etiology, although the duration of therapy prior to amt and the time to resolution following amt are not mentioned (kim et al 2001). monitoring the disease process beneath the membrane may be difficult (fig 5, 6 & 7). bullous keratopathy amt has been used for alleviating pain in eyes with symptomatic bullous keratopathy with poor visual potential. relief of pain ranged from 88 % to 90 % over a period of 4 weeks to 45 months (mejia et al 2002). the exact mechanism of action of am in reduction of pain is unknown. this property has been observed in patients with severe skin burns. several of the properties described earlier promote ocular surface epithelial healing and cell adhesion. band keratopathy patients with band keratopathy experience ocular pain due to corneal epithelial breakdown and ocular surface instability. in a series of 16 eyes with band keratopathy, superficial keratectomy with or without ethyline diamine tetra-acetic acid (edta) chelation followed by amt resulted in an improved ocular surface and a pain-free postoperative course in 15 (93.75 %) eyes (anderson et al 2001). photorefractive keratectomy and phototherapeutic keratectomy amt following excimer laser photorefractive keratectomy in rabbit eyes demonstrated no effect on epithelial healing, reduced influx of inflammatory cells, decreased keratocyte apoptosis, decreased keratocyte proliferation, reduced late subepithelial fibroblast hyperplasia, and more regular architecture of corneal lamellae, thus resulting in reduced corneal haze (choi et al 1998). there is only 1 report of amt in human eyes for reducing subepithelial fibrosis following severe corneal haze and regression after phototherapeutic keratectomy and laser-assisted epithelial keratomileusis (lee et al 2003). in all 3 eyes, visual acuity improved to 20/40 from less than 20/100, with minimal haze after epithelial debridement, phototherapeutic keratectomy, and amt. chemical injuries in the acute stage, severe ocular surface inflammation and epithelial breakdown may progress to tissue melting. the aim of treatment is to reduce inflammation, promote epithelialization, and prevent fig 5: preoperative photograph showing corneal fistula fig 6: postoperative photograph showing healed corneal fistula after amt fig 7: perforated corneal ulcer with amt 149 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation tissue necrosis, thereby avoiding the scarring sequelae and debilitating visual loss that ensues in the chronic stages. in mild to moderate chemical injuries, amt restores corneal and conjunctival surfaces. it prevents symblepharon formation in severe burns (meller et al 2000) (fig 8,9,10 &11). in severe cases, owing to extensive ocular surface inflammation with deep stromal ischemia and near-total destruction of the limbal stem cells, the am may at best reduce inflammation, prevent further stem cell damage, and prevent symblepharon formation in the acute stages. conjunctival surface reconstruction conjunctival autograft and mucous membrane grafts have been used in ocular surface reconstruction despite the poor cosmesis, risk of infection, limited availability, and scarring at the donor sites (neuhaus et al 1982). it was used successfully for ocular surface reconstruction in ocp and steven johnson syndrome (sjs) patients and has been used as a “substrate” for conjunctival defects after the excision of cicatricial tissue, excision of dysplasia and tumors, acute toxic epidermal necrolysis, conjunctivochalasis, ocular cicatricial pemphigoid and stevens-johnson syndrome. the ability of am to reduce scar and reduce inflammation and promote epithelialization described earlier are beneficial in ocular surface reconstruction. the other benefits of am in ocular surface reconstruction include improved cosmesis, ability to monitor local recurrence of tumor beneath the transplanted am when used following excision of ocular surface squamous neoplasia or malignant melanoma as compared with the thicker buccal mucous membrane grafts, reservation of eyelashes due to amt on the lid margin in toxic epidermal necrolysis (ten), and entropion reversal due to release of cicatricial tissue (john t et al 2002). fig 8: preoperative photograph showing symblepharon fig 9: postperative photograph after symblepharon release with amt fig 10: preoperative photograph showing symblepharon fig 11: postperative photograph after symblepharon release with dalk and amt 150 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation the factors responsible for failure are dry eye (calonge m 2001), previous treatment with mitomycin-c or beta irradiation resulting in unhealthy conjunctiva surrounding the am, uncontrolled systemic pathology resulting in ocular surface inflammation necessitating the use of immunosuppression, and total destruction of conjunctival epithelial stem cells. partial limbal stem cell deficiency in unilateral cases with partial lscd, limbal stem cell transplantation is not always required. the patient may be kept under close observation, subjected to repeated mechanical debridement also known as sequential sector conjunctival epitheliectomy (ssce) or amt. the am was effective in reducing symptoms, restoring the ocular surface stability, and improving vision in a majority of patients with limbal stem cell deficiency ranging from 90 to 330 degrees who were followed up for 12-34 months (dua hs 1998 ). pterygium: ( fig 12 &1 3) the ability of am to suppress normal conjunctival and pterygium body fibroblasts among its other properties (vide supra) has prompted its use in management of pterygium.following a modification of the surgical technique, recurrences of 3 % and 9.5 % for primary and recurrent pterygia respectively were reported (solomon et al 2001). results were comparable to those following conjunctival autograft (ma dh et al 2000), and much less than that for bare sclera technique (10.7 % versus 38.7 %) (tekin nf et al 2001). amt has been used in combination with conjunctival or limbal autograft, and intraoperative mitomycin c.amt has been recommended as the first line of management for primary pterygium, especially for double-headed pterygium to cover a large conjunctival defect or to preserve superior bulbar conjunctiva for future glaucoma surgery (ti & tseng 2002). cultured stem cells the am has been used for culturing conjunctival epithelial cells to promote a predominantly conjunctival nongoblet epithelial phenotype with expression of microvilli, intercellular junction, and increased density of desmosomes and hemidesmosomes. the am preserved conjunctival epithelial progenitor cells for goblet and nongoblet fig 12: preoperative photograph of pterygium fig 13: postperative photograph after pterygium excision with amt cell differentiation. goblet cell differentiation requires a more stringent environment and may depend on fibroblasts, although further studies are needed to explore this aspect (meller et al 2002). regrafting of cultured corneal epithelium using am was done and successful surface reconstruction for over a year was achieved with cultivated allolimbal stem cells on am in 3 eyes with failed cultivated limbal stem cell transplants due to epithelial rejection (nakamura t et al 2003). cultured limbal and conjunctival epithelium was used for bilateral ocular surface disorders. the ocular surface remained stable with improvement in vision at 1-year follow-up (sangwan vs et al 2003). amt was used for filtering blebs as an adjunct to glaucoma-filtering surgery as a substitute for antifibrotic therapy (barton k et al 2001). the am was placed beneath the scleral flap to inhibit scarring 151 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation (budenz dl et al 2000). cicatricial entropion may be due to chronic blepharoconjunctivitis, trachoma, burns, chemical injuries, trauma, and systemic mucocutaneous disorders like stevens-johnson syndrome and ocular cicatricial pemphigoid. it promoted rapid epithelialization of the bared tarsus within 2 weeks but did not prevent subsequent lid margin keratinization or tarsal shrinkage. surgical technique am may be used either as a graft (inlay) or a patch (overlay) or in multiple layers. if preserved at -80°c, it should be thawed to room temperature before use.the membrane is usually sutured with the epithelial side up and the mesenchymal side down to facilitate adherence to the ocular surface (dua & azuara-blanco, 1999). it is thus important to identify the 2 surfaces of the membrane. while placing the membrane on nitrocellulose paper, the basement membrane side is allowed to face up or a suture may be tied with the knot indicating the basement membrane. blunt forceps or a surgical sponge may be used to identify the mesenchymal side since the forceps draw a vitreous-like strand from this side and tends to adhere to a surgical sponge. the loose epithelium around the epithelial defect and slough within the base of the corneal lesion is removed. the am is spread onto the surface ensuring that no blood or fluid is trapped underneath it and sutured to the cornea with 10-0 monofilament nylon sutures and to the conjunctiva with 8-0 or 9-0 vicryl sutures. inlay technique: the am is trimmed a little larger than the size of the defect, anchored in place with the basement membrane side facing up. it thus functions as a basement membrane on which the corneal epithelium can grow overlay technique: (fig14). the am is spread over the whole cornea and the perilimbal area and anchored with 10-0 monofilament sutures at the limbus and occasionally the mid-peripheral cornea with a running 10-0 polygalactin suture. it functions as a bandage contact lens and also acts as a barrier to protect the cornea from inflammatory cells and proteins in the tear film (letko e et al 2001).the inlay and overlay techniques may be combined, ie, first an inlay graft followed by an overlay patch. multilayered technique: (fig 15). in cases of deep ulceration, multiple pieces of am may be used to fill up the defect. the orientation of these pieces does not matter. the most superficial piece is placed with the basement membrane side up and sutured as an inlay graft enabling corneal epithelium to grow over it (kruse fe et al 1999). fig 14: overlay technique of amt postoperative care a large hydrophilic bandage contact lens may be placed after surgery. topical steroids and antibiotics are used until epithelialization is complete and inflammation subsides. the translucent membrane enables observation of the healing epithelial defect beneath it. in the presence of excessive inflammation, it disintegrates faster and may have to be repeated several times (petersen et al 2001). fig 15: multilayered filling technique of amt 152 arya s k et al nep j oph 2010;2(4):145-153 amniotic membrane transplantation conclusion am has been used for a variety of conjunctival and corneal disorders with varying success rates. due to its ability to promote epithelialization and reduce inflammation and scarring, it appears to have a beneficial effect on persistent epithelial defects, neurotrophic ulcers, shield ulcers, chemical injury, pterygium excision, and conjunctival surface reconstruction. its role in bullous keratopathy, band keratopathy, glaucoma-filtering surgery, and entropion has to be further evaluated. the am devoid of epithelial cells provides an excellent substrate for culturing limbal stem cells and conjunctival epithelial cells. this may be attributed to the production of several growth factors that promote epithelial growth and its ability to preserve and maintain the existing progenitor cells. thus, patients with limbal stem cell deficiency, either partial or total, may benefit from transplantation of am alone or limbal stem cells cultured on am. the results of long-term clinical studies in this area are awaited. hyper-dry-amnion and cell sheets will also be attractive materials in the field of tissue engineering. references adinolfi m, akle ca, mccoll i et al (1982). expression of hla antigens, [beta] 2 microglobulin and enzymes by human amniotic membrane. nature; 295:325-327. akle ca, adinolfi m, welsh ki, leibowitz s, mccoll i (1981). immunogenicity of human amniotic epithelial cells after transplantation into volunteers. lancet; 2:1003–1005. anderson df, prabhasawat p, alfonso e et al (2001). amniotic membrane transplantation after the primary surgical management of band keratopathy. cornea; 20:354-361. barton k, budenz dl, khaw pt et al (2001). glaucoma filtering surgery using amniotic membrane transplantation. invest ophthalmol vis sci; 42:1762-1768. budenz dl, barton k, tseng scg (2000). 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interest: none untitled 82 acknowledgementacknowledgementacknowledgementacknowledgementacknowledgement a. peer-reviewers the editorial board acknowledges the scientific contributions of the following peer-reviewers. acknowledgement nep j oph 2010;2(3):82 1. prof s k arya, india 2. dr sandeep kumar, india 3. dr basanta raj sharma, nepal 4. dr martin spencer, canada 5. dr folkert tegelberg, the netherlands 6. dr suman thapa, nepal 7. prof chet raj pant, nepal 8. dr sanjay kumar daulat thakur, india 9. dr hrishikesh das, india 10. prof joginder chugh, india 11. dr alpesh shah, india 12. dr sanjay kumar singh, nepal 13. prof s p shrestha, nepal 14. prof sudesh subedi, nepal 15. prof christian mardin, germany 16. prof rakesh maheshwari, amu, india 17. prof. r r shukul, amu, india 18. prof yogesh gupta, amu, india 19. prof bhagawat prasad nepal, nepal 20. prof o k malla, nepal 21 prof j k shrestha, nepal 22. dr chundak tenzing, usa 23. dr steve waller, usa 24. dr saroj gupta, india 25. dr a hennig, nepal b. support for publication the nepal ophthalmic society sincerely acknowledges the continued-support of the eye care foundation, the netherlands in publishing the nepalese journal of ophthalmology. for numbering.pmd 2 original articleoriginal articleoriginal articleoriginal articleoriginal article introduction leprosy is a chronic disease, which may result in cosmetic stigma, various malformations and disability in humans. ocular involvement in leprosy is frequent (10-50%) and is responsible for 5% of blindness worldwide (kagame, 1983; hobbs, 1971). pattern and determinants of ocular complications in leprosy patients in eastern nepal javvadhi s1, das h1, agrawal s2 departments of 1ophthalmology and 2dermatology, b p koirala institute of health sciences dharan, sunsari, nepal abstract background: ocular complications of leprosy can lead to blindness. objective: to report the pattern and determinants of ocular complications in patients with leprosy from eastern nepal. methods: a cross-sectional study was carried out analyzing one hundred and eighty six patients of leprosy presenting between jan 2002-nov 2004. all the patients were categorized using who and ridley and jopling classification. after determining bacillary indices in all of them, a detailed ocular examination was carried out. independent risk factors were determined for ocular involvement. results: ocular complications were found in 30.65 % of the leprosy patients; lagophthalmos (17.74%) was the most frequent followed by uveitis (8.60%). most of the patients having visual loss had it due to corneal complications and none of the patients with uveitis had vision <6/18. the patients released from treatment (83.33%) and those currently on treatment (31.63%) had higher occurrence of complications. risk factors for ocular involvement were higher bacillary index, longer disease duration (p=0.031, rr=1.109, 95% ci=1.009-01.218) and decreased corneal sensation (p=0.001, rr=3.564; 95% ci =2.014-6.306). higher schirmer values (p=0.012, rr=0.935, 95% ci=0.888-0.985) were found to be protective for ocular complications. stastics: spss ver 10.0 was used for data analysis. the p value of <0.05 was considered as significant. conclusions: the prevalence of complications is high in patients released from treatment for leprosy. cornea-related complications are the most important cause of visual disability and blindness. risk factors for ocular complications are higher bacillary index, longer disease duration and decreased corneal sensation. key words: leprosy, nepal, ocular complications and risk factors of various reported ocular complications due to leprosy, the potentially sight-threatening ones are iridocyclitis and its sequelae, corneal anesthesia, lagophthalmos and exposure keratitis, leprous keratitis, scleritis, scleral perforation and secondary glaucoma (lubbers et al 1994, rathinam et al 2008). the pattern of ocular complications may differ from one part of the world to the other. the factors determining the complications include type of leprosy (paucibacillary and multi-bacillary), age of the patients, multidrug therapy (mdt) coverage, socioeconomic received: 14.04.2008. accepted: 06.05.2008 correspondence and reprint requests to: dr s javvadhi department of ophthalmology b p koirala institute of health sciences, dharan, sunsari, nepal e-mail: ophth_eye@yhaoo.com fax : 00977-25-520251 nep j oph 2009;1(1):2-8 3 status and availability of eye care services (courtright & lewallen, 1998; gupta et al 2007). the prevalence of leprosy in nepal is reported to be 4.4/10,000 population, making it an important public health problems (hmg nepal report, 2002). considerable difference in the prevalence of ocular complications in patients with leprosy between the preand post-mdt era has been reported (malla et al1981; brandt et al1981; knuuttila, 1998; nepal, 2004). moreover, the pattern of ocular complications is not known. this study was carried out to report the prevalence and pattern of ocular complications of leprosy in patients from the eastern region of nepal. materials and methods the patients with leprosy (either on treatment or released from treatment) presenting between jan 2002 and nov 2004 to the b p koirala institute of health sciences were included in this study. the majority of leprosy patients from the eastern part of nepal attend this institute as it is the only tertiary care hospital in this region with modern dermatological and eye care facilities. all the patients were subjected to detailed dermatological evaluation, which included history pertaining to duration of symptoms, duration of treatment and lepra reactions. bacillary indices (bi) were determined by skin-slit smear examinations (from 6 predetermined sites, namely one from each ear lobe and medial part of eyebrow and from the skin lesions). ophthalmic history included determination of presence or absence of diminution of vision in the past or ocular redness with or without pain. best-corrected visual acuity measurement and detailed slit-lamp bio-microscopy were performed for every patient. uveitis was classified as active or inactive. active uveitis was defined as eyes having > 5 cells in the anterior chamber with or without presence of flare or keratic precipitates (kps), whereas inactive uveitis was defined as eyes having either iris pearls, patchy iris atrophy, fine multiple peripheral anterior synechiae (pas) on gonioscopy, ectropion uveae, diffuse loss of iris pattern, heavily pigmented trabecular meshwork (>180 degrees or presence of pigmentation in the superior trabecular meshwork without any history of trauma or surgery) and kps or posterior synechiae in the absence of cells. in all except 10 eyes (5 eyes with phthisis bulbi, 3 with perforated ulcers and one each with interstitial keratitis and corneal opacity), intraocular pressure (iop), schirmer test, tear break-up time and corneal sensations were determined. intraocular pressure (iop) was determined using the goldmann applanation tonometer and an average of three readings for each eye was recorded. schirmer test and tear break-up time (tbut) were determined using standard means. iop, schirmer and tbut values in both the eyes were averaged for analysis; in cases where measurement in one eye was not possible, the available eye was considered for evaluation. all patients were tested for any facial weakness. the corneal sensation was determined using a cotton wisp. decrease in corneal sensation in any of the four corneal quadrants was classified as abnormal. syringing was performed in all to evaluate the lacrimal apparatus. leprosy was classified using both who (1988) and ridley and jopling (1966) immunological classifications. the patients were divided into multibacillary (bi>0) and paucibacillary types (bi=0) (who, 1988). the patients grouped according to ridley and jopling classification were further categorized into tuberculoid type (tt), intermediate type (bb, bt & bl) and (ll) lepromatous type (dharmendra, 1985). statistics spss ver 10.0 was used for data analysis. the student's 't' test was used for continuous variables, mann-whitney rank sum test and chi square test for categorical variables. multivariate analysis and logistic regression were used to determine the independent risk factors. the p value of < 0.05 was taken as significant. results demography one hundred and eighty six patients with leprosy were evaluated [136 (73.02%) males and 50 (26.88%) females]. the mean age was found to be 37.0753 ± 15.179 years (range 6-72 years). the mean duration between onset of the disease symptoms and diagnosis of the disease was found to be 2.76 ± 4.87 years (range=1 month to 40 years). at the time of evaluation, 52.69% of the patients were javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy 4 receiving mdt, 9.68% had been released from treatment (rft) and 37.63% were not on any treatment. leprosy type the dermatological diagnoses at the time of presentation were: tt (10.75%), bt (49.46%), bb (2.15%), bl (13.98%) and ll (23.66%). the mean bi was 1.36±2.04 (95% ci=1.06-1.66). paucibacillary disease was found in 58.06% of the patients. type 1 lepra reaction was encountered in 5 patients and type 2 in 2 patients, but none of the patients had any evidence of eye involvement at the time of presentation. ocular involvement (table 1) ocular involvement due to leprosy was found in 57 (30.65%) patients (94 eyes; 20 unilateral and 37 bilateral). lagophthalmos (17.74%) was the most common complication encountered followed by uveitis (8.60%). loss of iris pattern (7 eyes), ectropion uveae (6 eyes), peripheral anterior synechiae (5 eyes), and pigmented trabecular meshwork (2 eyes) were found in isolation and were categorized as inactive uveitis. corneal complications were identified in 64 eyes, which included prominent corneal nerves (32.81%), superficial punctuate keratitis (21.86%), interstitial keratitis (18.75%), corneal opacity (18.75%) and perforated corneal ulcers (4.69%). details of the other complications are given in table 1. ocular complications were not related to age, gender, paucibacillary or multi bacillary involvement and treatment status. however, they were found to be independently associated with patients having bi > 5 and longer disease duration (table 3). though the treatment status was not related to ocular complications, 11 (5.9%) of the newly-diagnosed patients and 15 (83.33%) of the 18 patients released from treatment were found to have complications. patients with the disease in the lepromatous (p=0.006, rr=0.244 95% ci=0.089-0.669) end of the spectrum had complications less frequently than those on the tuberculoid. variables considered for the regression analysis were: sex, bi, paucibacillary/multibacillary status, diagnosis, disease duration, treatment status, average schirmer values, tbut and corneal sensation. javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy table 1 ocular complications of leprosy sn complications number of complications 1 uveitis inactive uveitis 20 1. iris pearl 4 2. loss of iris pattern (7) 15(7†) 3. ectropion uveae (6) 8(6†) 4. pas (5) 6(5†) 5. pigmented tm (2) 4(2†) 6. posterior synachieae 2 active uvietis 6 2 corneal lagophthalmos 34 corneal opacity 12 prominent corneal nerves 21 interstitial keratitis 12 superficial punctuate keratitis 14 perforated ulcer 3 trichiasis 2 3 sclearal nodular scleritis 2 4 extraocular madarosis 8 dacryoadenitis 6 phithisis bulbi 5 total (no of complications) 145 investigations 1 intraocular pressure (eyes) 6 10 mm hg 11(6‡) 2 corneal sensations (eyes) decreased (abnormal) 54 (25‡) 3 schirmer values (eyes) < 5 mm 10 (0‡) 5-10 mm 21 (8‡) 4 tbut (eyes) < 5 s 8 (2‡) † isolated findings in eyes categorized as uveitis ‡ findings in eyes without any ocular complications 5 javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy table 2 variables with and without ocular complications variables patients with ocular patients with no p value complications complications patients (total = 186) 57 129 age mean (95% ci) 39.597(35.145 42.048) 35.105 (30.958 -39.2526) p = 0.365 sd 13.008 15.630 median 36 34 sex males 50 86 p = 0.005 females 7 43 disease duration mean (95% ci) 4.287(2.233-6.341) 2.126(1.456-2.795) p = 0.004 sd 7.740 2.523 median 1.5 1 treatment on treatment 31 67 p=0.001 released from treatment 15 3 not on treatment(new patients) 11 59 bi mean (95%ci) 1.719 (1.171-2.268) 1.158(0.600-1.716) p = 0.074 sd 2.068 2.103 median 1 0.00 paucibacillary 27 81 p= 0.048 multibacillary 30 48 schirmer mean (ci) 14.456(12.430-16.479) 17.0(15.129-18.871) p = 0.036 sd 7.489 6.920 median 13 15 tbut mean 13.283(11.911-14.655) 16.302(14.915-17.689) p = 0.003 sd 4.978 5.033 median 14 16 iop mean (ci) 12.943(12.107-13.779) 13.00(12.283-13.717) p = 0.612 sd 3.035 2.602 median 12 13 sensations (eyes, 176) abnormal 25 29 p = <0.001 normal 59 249 intraocular pressure (iop) mean iop in the right and left eye was 13.044 ± 2.848 mm of hg (6-26 mm hg) and 13.167 ± 2.793 mm of hg (8-20 mm of hg) respectively. eleven (3.04%) eyes had iop < 10 mm of hg, of which 6 had no complications related to leprosy. there was no statistically significant difference in iop in eyes with ocular complications or patients with multibacillary or paucibacillary involvement. 6 superficial punctate keratitis associated with lagophthalmos (19 eyes), interstitial keratitis and corneal opacity (10 eyes each); and the remainder were due to phthisis bulbi (5) and perforated corneal ulcer (3). none of the patients with uveitis had vision <6/18. discussion the majority of the visual disability and blindness in leprosy patients is produced by corneal and uveal diseases. a higher cure rate is possible in patients with leprosy after the induction of mdt (lewallen et al 2000), though a substantial number of them continue to suffer from leprosy-related disability due to the earliersustained nerve or tissue damage following treatment. there is evidence that chronic uveitis may be progressive in patients thought to be bacteriologically cured (lewallen et al 2000). ocular complications are more frequently reported in developing countries. the majority of patients come from rural areas, are poor and have less access to health care facilities. in this series of 186 patients evaluated over a period of around 3 years, we found the prevalence of ocular complications to be 30.65%. earlier studies from this region showed a prevalence rate of 37.3% (lubbers et al 1994), which is similar to ours. however, studies done by nepal et al in 2004 showed a somewhat higher prevalence (57%), which may be attributed to geographical factors. earlier studies from nepal reporting the higher prevalence probably replicate the pre-mdt era with poorer control of the disease (malla et al 1981; brandt, 1981; hogeweg, 2005). studies done later from the same region and other parts of the world showed a prevalence similar to ours (knuuttila, 1998; orefice et al 1998; fytche 1981), suggesting better ocular disease control with mdt. though it is reported that multi-bacillary disease is more prevalent in east and south-east asian countries, data from the health survey in nepal showed otherwise (courtright and lewallen, 1998), which may be due to the fact that the majority of our patients had paucibacillary disease. it is also known that there is a higher incidence of paucibacillary disease in the endemic zones (indian subcontinent and africa), probably due to better cellmediated immunity (courtright and lewallen, 1998). in the present study, ocular complications were javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy table 3 variables for regression analysis variables rr 95% ci p lower higher value 1 bi (bacillary 0.091 index) 1 0.486 0.117 2.028 0.323 2 0.409 0.091 1.830 0.242 3 0.208 0.046 0.944 0.042 4 0.514 0104 2.530 0.413 5 5.952 1.047 33.828 0.044 6 0.292 0.046 1.849 0.191 2 diagnosis 0.010 non0.729 0.078 6.787 0.782 lepromatous intermediate 0.618 0.126 3.024 0.553 lepromatous 0.244 0.089 0.669 0.006 3 disease 1.109 1.009 1.218 0.031 duration (increasing) 4 schirmer 0.935 0.888 0.985 0.012 values (increasing) 5 decreased 3.564 2.014 6.306 0.000 corneal sensation tear film mean schirmer values were found to be higher in eyes with no ocular complications (p=0.012, rr=0.935, 95% ci=0.888 0.985). values of 5-10 mm were detected in 21 eyes (8 of them had no ocular complication). abnormal tbut (<5s) was encountered in 2 eyes which did not have any complications due to leprosy. corneal sensation decreased corneal sensation was observed in 54 eyes (14.51). it was more commonly found in eyes with ocular complications (p=0.001, rr=3.564; 95% ci=2.014-6.306). visual acuity according to the who criteria for the visually impaired, we found 6 (3.23%) patients having visual impairment (6/60-6/24) and 2 (1.08%) each with severe blindness (<3/60) and moderate blindness (3/60-5/60). forty seven (12.63%) eyes were found to have vision of less than 6/18 (6/60-6/18=23 eyes, 5/60-3/60=11 eyes and <3/60 in 13 eyes). of these, the majority were due to 7 encountered more frequently in patients who had been released from treatment (83.33%, table 2) and those on treatment (31.63%), though the treatment status was not found to be an independent risk factor. gupta et al 2007 have reported similar observations in a study from mid-nepal. none of our patients presenting with lepra reactions had ocular complications at the time of presentation. the large number of patients with complications among those who had been released from treatment may be due to the higher incidence of neural (viith and vth cranial nerves) complications. in general, regular monitoring of patients released from treatment may help reduce the incidence of blindness due to ocular complications. lubbers et al (1984) in a study from nepal reported 5% prevalence of leprosy-related sight-threatening complications in newly diagnosed patients of leprosy as compared to 15.71% in our study. we cannot find a plausible explanation for the difference. the most common ocular complications reported in leprosy patients are corneal followed by uveitis (courtright and lewallen, 1998). our series also had a higher prevalence of lagophthalmos and corneal complications than reported in other studies of this region. a high prevalence of lagophthalmos (32.5%) is commonly reported among leprosy patients with multibacillary disease (courtright et al 1995). unlike our data, patients with leprosy from india and nepal having paucibacillary disease were found to have a lower prevalence of lagophthalmos, though a study in similar leprosy patients from pakistan reported a higher prevalence of lagophthalmos (25.17%) and ectropion (9.01%), (khan et al 2002). higher prevalence of lagophthalmos among paucibacillary patients is generally reported early in the course of the disease. patients with facial patches and reversal reaction also have a higher prevalence of lagophthalmos (courtright and lewallen, 1998), though this was not found to be the case in our series. decreased corneal sensation was more prevalent in our patients with ocular complications, which may have a cause effect relationship. uveitis is common among leprosy patients, particularly in those with a longer duration of the disease, inadequate treatment and with the multi-bacillary type (courtright and lewallen, 1998). most of the studies generally underestimate the prevalence of uveitis either due to improper methods of examination, miotic pupils or co-existing corneal lesions. histopathological studies of the iris of leprosy patients with no ocular findings have revealed inflammatory changes (brandt et al 1990). lower prevalence (1-4.3%) of chronic uveits is reported in leprosy patients from various regions of nepal and china (courtright and lewallen, 1994; lubbers, 1995). a recently-conducted study from western nepal reported prevalence of uveitis to be 7.79% (nepal et al 2004). the higher prevalence of uveitis in our study may be attributed to a more detailed evaluation and inclusion of subtle features suggestive of uveitis. lower intraocular pressure has been reported in patients of leprosy as a result of plastic iridocylcitis (karacorlu, 1991) or autonomic dysfunction (hussain et al 1990). this study, however, did not find any decrease in iop in patients with ocular complications. visual disability was seen exclusively in patients with corneal disease in our series. none of the eyes with uveitis had vision of <6/18. a shorter disease duration may be responsible for the lower prevalence of uveitisrelated visual impairment. patients without ocular complications were found to have higher schirmer values. lower schirmer values reflect poor aqueous production, which is a result of autonomic dysfunction and is commonly observed in multi-bacillary disease (courtright and lewallen, 1998; koshi et al 2001). conclusion corneal complication is the most common cause of blindness among the patients with leprosy in eastern nepal. the prevalence of complications is high in patients released from treatment for leprosy. the determinants for ocular complications of leprosy are longer disease duration, high bacillary index, decreased corneal sensation and lower schirmer values. references brandt f, kist p, wos j (1981). ocular findings in leprosy: results of a survey in the green pastures leprosy hospital, nepal. klin monatsbl javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy 8 augenheilkd 178(1):55-8. brandt f, zhou hm, shi zr, rai n, thuladar l, pradhan h (1990). histopathological findings in the iris of dapsone treated leprosy patients. br j ophthalmol 74(1):14-8. courtright p, lewallen s (1998). ocular manifestation of leprosy. in: gordon j johnson, darwin cm, robert weale, ed. the epidemiology of eye disease.1st edn. 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group system. international journal of leprosy 34:255-73. samanta sk, das d (2007). recent advances in ocular leprosy. ind j lepr 79: 135-50. world health organization (1982). report of study group chemotherapy of leprosy for control programs. world health organization technical report series 675. world health organization (1988). who expert committee on leprosy. sixth report technical reprot series 768. javvadhi s et al nep j oph 2009;1(1):2-8 ocular complications in leprosy 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 book of jan 2014.pmd 122 ocular myocysticercosis: an unusual case of ptosis punita kumari sodhi professor in ophthalmology guru nanak eye centre affilaited with maulana azad medical college new delhi email: punitasodhi222@gmail.com dear editor, the authors agarwal et al (2013) have reported a case with ocular myocysticercosis wherein the cysticercus cyst was located in the levator palpebrae superioris (lps) and superior rectus muscle complex. the cysticercus cyst involving the lps muscle is infrequently reported and chan and looi (2010) have reported the sixth case of involvement of the lps muscle. the extraocular muscles have a good vascular supply and thus these are the frequent sites for the location of the cysticercus cyst during orbital involvement. inside the orbit, the orbital lesions have been found to be localized more often on the nasal side, which may be due to the course of the ophthalmic artery, which after giving off the lacrimal branches, runs along the medial side of the orbit and divides into its terminal branches (malik et al, 1968). even in the ct scan picture shown by agarwal et al, the cysticercus cyst appears to be located medially. the lateral branch of the ophthalmic artery supplies the lateral and superior rectus muscles, the levator muscle of the upper lid, and the superior oblique muscle while the medial branch of the ophthalmic artery, which is the larger of the two, supplies the inferior and medial rectus muscles and the inferior oblique muscle. in the above case, there is involvement of the superior rectus and levator palpebrae superioris muscles which are supplied by smaller branch of the ophthalmic artery. the superior rectus has been earlier reported by rath et al (2010) in their review of 171 patients of orbital cysticercosis to be the most frequently involved extraocular muscle, i.e. in 33.3 %, among all extraocular muscle involvements. it is obvious that the case presented by agarwal et al (2013) specifically highlights the role of radiological studies while treating a case of ptosis. in the case reported by chan and looi (2010), the lps action was reduced to 3 mm in the affected eye as compared to 13 mm in the normal eye. it would have been better if the authors had given the measurements of the ptosis and of the lps action, so that magnitude of affection of the lps action by this pathology could have been documented and which could have conspicuously added to the existing literature for giving guidelines in the management of patients of ptosis specifically if they come from an area which is endemic for cysticercus infestation. references agrawal s, ranjan s, mishra a (2013). ocular myocysticercosis: an unusual case of ptosis. nepal j ophthalmol; 5 (10): 279-81. chan ew and looi a (2010). cysticercosis of the levator palpebrae superioris. ann acad med singapore;39(12):938-2. malik, s.r.k., gupta, ak. and chaudhari, s. k., 1968. amer. jour. ophthal; 66, 1168. rath s, honavar sg, naik m, anand r, agarwal b, krishnaiah s, sekhar gc (2010). orbital cysticercosis: clinical manifestations, diagnosis, management, and outcome. ophthalmology ;117(3):600-5. sodhi pk ocular myocysticercosis nepal j ophthalmol 2014; 6 (11):122 letter to the editor source of support: nil. conflict of interest: none 123 optical coherence tomography in diabetic macular edema: sub-retinal fluid pattern and related risk factors aditi gupta, rajiv raman, tarun sharma shri bhagwan mahavir vitreoretinal services, 18, college road sankara nethralaya, chennai-600 006, tamil nadu, india email: guptaaditi_dr@yahoo.com dear editor we read with interest the article by ahmadpour-baghdadabad m et al (2013) in which the authors studied the association of various patterns of diabetic macular edema (dme) with the risk factors of dme based on the optical coherence tomography (oct) findings. in a retrospective cross-sectional study, we too evaluated the systemic risk factors associated with sub-retinal fluid (srf) pattern of dme. we compared 37 eyes with srf pattern of dme (designated cases) versus 30 eyes having dme (sponge like retinal swelling or cystoid macular edema) without srf (designated controls) on spectral domain-oct. we too found that the srf pattern was more common in males than in females (84.8 % of cases were males versus 66.7 % of controls). we did not find an association of hba1c (mean hba1c of 6.73 in cases versus 6.71 in controls, p = 0.859) and anemia (mean hb of 10.71 in cases versus 11.77 in controls, p = 0.118) with the srf pattern of dme. there was no significant difference between the presence of hypertension among cases and controls (diagnosis of hypertension found in 72.7 % of cases and in 66.7 % of controls, p = 0.634). however, we did find a positive association between high systolic (sbp) and diastolic blood pressures (dbp) and the srf pattern of dme. on measuring the levels of blood pressure in all cases and controls, both the sbp (mean sbp 147.84 in cases versus 141.0 in controls, p = 0.039) and the dbp (mean dbp 85.24 in cases versus 81.47 in controls, p = 0.043) were found to be raised in patients with srf pattern of dme in comparison to dme without srf. the reason for this can be unreported hypertension in the cases or higher uncontrolled blood pressures in the hypertensive cases than in the hypertensive controls. the occurrence of srf in dme can be secondary to excessive leakage in the retina or to a poorly functioning retinal pigment epithelium (rpe). raised blood pressure can lead to increased retinal leakage as well as ischemic damage to the rpe. we reported the presence of outer retinal communications, seen as defects in the outer border of the elevated retina in eyes with srf pattern of dme (gupta a et al, 2013). these defects may represent a path for the flow of fluid and proteins from intra-retinal cysts or from the outer layers of the edematous retina into the sub-retinal space. in conclusion, we congratulate ahmadpour-baghdadabad m et al on their study and support their findings. we also recommend measuring the sbp and dbp in subjects with srf pattern of dme besides evaluating a history of hypertension. it might be helpful to provide a more aggressive control of blood pressures in subjects with the srf type of dme than in dme without srf. gupta a et al oct in diabetic macular edema nepal j ophthalmol 2014;6(11):123-124 letter to the editor 124 references ahmadpour-baghdadabad m, manaviat m, shojaoddiny-ardekani a (2013). optical coherence tomography in diabetic macular edema: patterns and related risk factors. nepal j ophthalmol; 5(10):190-4. doi: 10.3126/nepjoph.v5i2.8727. gupta a, raman r, mohana kp, kulothungan v, sharma t (2013). communications between intraretinal and subretinal space on optical coherence tomography of neurosensory retinal detachment in diabetic macular edema. oman j ophthalmol;6 (3):183-188. source of support: nil. conflict of interest: none gupta a et al oct in diabetic macular edema nepal j ophthalmol 2014;6(11):123-124 for numbering.pmd 25 original articleoriginal articleoriginal articleoriginal articleoriginal article effectiveness of sedation in dacryocystorhinostomy surgery tuladhar s1, adhikari s1, bhattarai b k2 departments of 1ophthalmology and 2anesthesiology and critical care b p koirala institute of health sciences, dharan, sunsari, nepal abstract background: chronic dacryocystitis is a common ophthalmic problem almost always requiring surgery as the only definitive treatment. aim: to compare the perioperative outcome of external dcr surgery under local anesthesia with and without sedation. subjects and methods: one hundred consecutive patients with chronic dacryocystitis undergoing dacryocystorhinostomy (dcr) surgery were randomly divided into two groups using computer generated random table. group a underwent dcr under local anesthesia (la) without sedation and group b under la with sedation. the outcome parameters were intra-operative pain, surgeon's comfort, intra-operative complications and duration of surgery. statistical analysis: spss version 11.5 software was used. chi square test was used to compare the difference between the groups. results: there were 50 patients in each group. the mean age ± sd of the patients was 34.4±12.12 years (95% ci=28.89-38.55 years). sixty-nine percent of them were female. significantly higher number of patients experienced pain in group a as compared to group b (100% vs 50%, p<0.001) surgeon's discomfort was significantly present in group a as compared to group b (70% vs 10%), (p=0.00001). blood loss was significantly more in group a than in group b (p=0.017). there was no significant difference in the duration of surgery. the post operative success rate in both the groups was comparable after six months of followup. conclusion: the use of sedation with la improves the perioperative outcome of dcr surgery in terms of patient's pain, surgeon's comfort and intra-operative complications. key words: dacryocystitis, dacryocystorhinostomy, sedation nep j oph 2009;1(1):25-31 received: 07.06.2008. accepted: 10.10.2008 correspondence and reprint requests to: dr sarita tuladhar (dhakal) department of ophthalmology b p koirala institute of health sciences, dharan, sunsari, nepal phone: 025-525555 ext 2320 (office) e-mail: drtuladharsarita@yahoo.com introduction dacryocystitis is an inflammation of the lacrimal sac secondary to obstruction of the naso-lacrimal duct (nld). it can be acute or chronic. the definitive treatment (dalgesh et al 1967) of chronic dacryocystitis due to nld obstruction for duration greater than one year is dacryocystorhinostomy (dcr). the principle of dcr is anastomosing the lacrimal sac to the nasal mucosa of the middle nasal meatus. toti (1904) first described dcr. the best known technique for dcr was described by dutemps and bourget in 1920 (duffy et al 2000). it can be performed with or without silastic tube intubation. the former has been reported to improve the success rate of the procedure (duffy et al 26 2000; o, donnell et al 2001). caldwell et al (1993) described the intra-nasal approach for dcr. currently endoscopic intra-nasal dcr is available (massaro et al 1990). gonnering et al (1991) have described the performance of successful intranasal dcr by using either the argon laser, potassium-titanyl-phosphate: yag laser, or a co2 laser for tissue removal. the overall success rate of external dcr is better than that of the endonasal dcr (zaman et al 2003). external dcr can be carried out under general anesthesia (ga) or local anesthesia (la) with or without use of sedation. it is commonly done under la on outpatients basis (benger et al 1992; dresner et al 1991). la provides anesthesia and excellent hemeostasis for the operation (fanning, 2000). the commonly used la in dcr is 2% lignocaine with or without 1:200,000 adrenaline or a mixture of 2% lignocaine and 0.5% bupivacaine in equal parts. the advantage of adding adrenaline to plain lignocaine is that it maintains better homeostasis, prolongs the duration of action of la and allows the use of higher dose. a number of sedatives can be used in conjunction with la. the commonly used ones are pethidine (1-2 mg/ kg body weight intramuscularly) and promethazine (1 mg/kg body weight intra-muscularly). also, midazolam (1-2 mg) or droperidol (0.5 mg) intravenously, along with a modest dosage of alfentanil (125-250 microgram intra-venously), may be given (fanning, 2000). ketamine in a dose of 0.1-0.2 mg/kg combined with midazolam may also be given (fanning, 2000). this combination produces excellent amnesia as well as analgesia. in the past, dcr used to be carried out under ga, but nowadays it is mostly done under la except in children (<15 years of age). many studies have compared the outcome of dcr under local anesthesia versus general anesthesia. no published report comparing the outcome of dcr surgery with or without the addition of sedatives is available. this study was carried out to compare the efficacy of dcr surgery under la with and without sedatives. subjects and methods one hundred consecutive patients with chronic dacryocystitis undergoing dcr surgery from march 2007 to february 2008 were randomly divided into two groups: a and b, using computer-generated random table. group a underwent dcr under local anesthesia without sedation and group b with sedation. the drugs used for sedation were pethidine (1 mg/kg) im with promethazine (0.5mg /kg), which were given im in the deltoid region half an hour before giving local anesthetics. the local anaesthetic used was 2% lignocaine with adrenaline 1:200,000. the maximum dosage of lignocaine for a healthy adult is 7 mg/kg or 500 mg for a 70 kg person. this corresponds to 25 ml of 2% solution. all patients with nld obstruction with chronic dacryocystitis and above 15 years of age undergoing dcr surgery were included in the study. the exclusion criteria were failed dcr, canalicular block and bleeding disorders. other pathological conditions for exclusion criteria were atrophic rhinitis, rhinosporidosis, deviated nasal septum, hypertrophied turbinates, nasal polyp and malignancies. similarly, acute dacryocystitis, pyocele, encysted mucocele, post traumatic lid and bony deformity were also excluded. the research proposal was approved by the institutional review board and ethics committee. an informed consent was obtained from all the patients included in the study. the operation was performed in the operation theatre with resuscitation facility, ambu bag, oxygen supply and drugs required for cardiopulmonary resuscitation, with preparedness for possible problems occurring during the operation due to sedatives. preoperative blood pressure and pulse were measured. intra-operatively, at least three readings were taken and postoperative vitals and blood pressure were taken before shifting the patient to the ward. technique of local anesthesia the delineating incision with a marking pencil was made. the local anesthetic agents were injected subcutaneously, parallel and anterior to the lacrimal crest in the lacrimal sac fossa, superior and posterior to the medial canthal tendon. steps of external dcr surgery the middle nasal mucosa was packed with sterile ribbon gauge soaked in 2% lignocaine with 1:200,000 adrenaline. a straight vertical incision was made tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery 27 medial to the inner canthus, avoiding the angular vein. the anterior lacrimal crest was exposed by blunt dissection. the periosteum was divided from the spine on the anterior lacrimal crest to the fundus of the sac and reflected forwards. the sac was reflected laterally from the lacrimal fossa. the anterior lacrimal crest and the bone from the lacrimal fossa were removed. a probe was introduced into the lacrimal sac through the lower canaliculus and the sac was incised in the 'h' shaped manner to create two flaps. a vertical incision was made in the nasal mucosa to create anterior and posterior flaps. the posterior flaps were excised. the anterior flaps were sutured together and suspended to the overlying muscle with vicryl® 6/0. the medial canthal tendon if divided during surgery was re-sutured to the periostium. the skin incision was closed with interrupted vicryl® sutures. the procedure was done by surgeons with more than 3 years of experience in doing external dcr surgery using the same surgical technique. postoperative evaluation syringing was done on the first postoperative day after removal of the nasal pack. systemic oral antibiotic was given starting from one day before surgery for 7 days and topical for two weeks. a nasal vaso-constrictor drug was given for two weeks. the patients were discharged on the second post-operative day. measurement of outcomes pain score of the patients 0 no pain 0 3 mild pain 4 6 moderate pain 7 9 severe pain 10 maximum pain imaginable on completion of the surgery, the patient was asked to grade the severity of pain experienced during the surgery on a 0-10 numerical rating scale ('o' representing no pain and 10 representing worst pain imaginable). the rated values were categorized for analysis. surgeon's comfort score during surgery this was also done by the visual analogue scale. 0______________________________10 this is a 0-10 scale where 0 means no discomfort and 10 means maximum discomfort or surgery not possible without second analgesics. the numerical rating of surgeon's discomfort was done as follows. 0 no discomfort 0 3 minimal discomfort 4 6 moderate discomfort 7 9 severe discomfort 10 surgery not possible in case the patient in group a had unbearable pain and the surgeon's discomfort was so severe that surgery could not be continued, intravenous sedatives were given and surgery continued. intra-operative complications hemorrhage-intra-operative blood loss was measured by counting the number of average sized gauge pieces. a fully-soaked-standard sized gauge piece was considered to be equivalent to three to five ml blood loss. injury to adjacent structures like angular vein, ethmoidal artery, csf leakage and any other complications, if present, were noted. duration of surgery the duration of surgery from the beginning of cleaning and draping to the application of the eye pad and bandaging was noted. post-operative complications, if any, were also noted. definition of successful surgery: a patent lacrimal passage on syringing and or the patient free of symptom was considered successful surgery. follow-up the post-operative variables were evaluated on the 1st post-operative day, at 1st week, 6 weeks, 3 months and 6 months. results patient characteristics seventy-two percent of the patients belonged to the age group 21-40 years. the mean age ± sd of the patients was 34.4±12.12 years (95% ci=28.89-38.55 years). the mean age in group a was 34.06±12.04 years (95% ci=28.55-38.21 years) while in group b was 34.74±12.30 years (95% ci=29.23-38.89years). both groups were comparable (p value=0.78). most of the patients (69%) were female. the female: male ratio in tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery 28 group a was 3.5:1 while in group b was 3.4:1 (p=>0.05). 62% of the study populations were house wives, 11% students, 10% farmers, 6% labors, 3% businessmen, 3% tailors and 2% service holders. sixty percent of the study population was from india and 40% from nepal. among the nepalese, 16% were from sunsari district and the remaining from near-by districts of eastern nepal. twenty-two patients in group a and 28 in group b had dacryocystitis in right eye, while 25 in group a and 20 in group b had it in left eye. three patients in group a and 2 in group b had bilateral disease. of the total, 5% had bilateral involvement. the mean duration of symptoms in group a was 1.34±0.88 years (95% ci=1.2-1.9 years) while in group b it was 1.13±0.89 years (95% ci=0.99-1.69 years). there was no difference in duration of symptoms in the two groups (p=0.24). changes in vital signs (pulse rate and blood pressure) are given in table 1. intra-operative pain in group a, all patients (50) had pain while in group b, 50% (25patients) had pain and 50% (25 patients) did not have pain (p=<0.001). grading of pain in group a, 2% of patients had maximum pain imaginable, 32% had severe pain, 34% had moderate pain, 32% had mild pain, while in group b, 8% patients had severe pain, 20% had moderate pain and 72% had mild pain (p value <0.001). surgeon's discomfort in group a, the surgeon had no or minimal discomfort in 15 cases, and moderate discomfort or more in 35 cases; while in group b, the surgeon had no or minimal discomfort in 45 cases and moderate discomfort or more in 5 patients (p value 0.00001). comparison of blood loss in group a, 29 patients had less than 20 ml of blood loss, and 21 patients had > 20 ml while in group b, 40 patients had less than 20 ml of blood loss and 10 patients had > 20 ml (p value 0.017). tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery table 1 comparison of pre-operative, intra-operative and post-operative vitals characteristic categories mean ± sd p value group a group b preoperative systolic bp 120.2±13.78 125±11.65 0.06 vitals (mmhg) diastolic bp 78.16±8 77.2±8.34 0.55 (mmhg) pulse rate 83.36±7.9 83.76±9.47 0.81 (per minute) intra-operative systolic bp 126.28±14 127.76±13.56 0.59 vitals (mmhg) diastolic bp 82.72±6.96 81.04±8.26 0.27 (mmhg) pulse rate 88.6±9.37 84.76±8.14 0.03 (per minute) postoperative systolic bp 125.8±13.72 127.2±13.25 0.60 vitals (mmhg) diastolic bp 81.28±9.4 80.00±7.42 0.45 (mmhg) pulse rate 86.52±10.32 82.76±8.67 0.04 (per minute) table 2 grading of intra-operative pain groups number mild moderate severe maximum of pain patients imaginable group a 5 0 32% 34% 32% 2 % group b 2 5 72% 20% 8 % 0 % p-value 0.001 table 3 surgeon's discomfort groups no or minimal moderate discomfort discomfort or more group a 15 35 group b 45 5 p value 0.00001 29 duration of surgery the duration of surgery in group a was 82.5±6.2 minutes while in group b 77.5±5.9 minutes (p value=0.08). success rate of surgery (among the followed-up patients) 1st pod: 100% in both groups 7th pod: 94% in group a 96% in group b 6 weeks: 87.9% in group a 90.1% in group b 3 months: 83.3% in group a 88.9% in group b 6 months: 87.5% in group a 92.35% in group b follow-up rate 7th pod: 100% in both groups. 6 weeks: 66% in group a 66% in group b 3 months: 36% in group a 36% in group b 6 months: 16% in group a 26% in group b discussion since tear secretion decreases with age, the actual prevalence of nld blockade reported in older people may just be an underestimation. dalgesh et al (1967) in a large series of normal subjects older than 40 years observed the incidence of nld obstruction in males and females to be 9% and 10% respectively. after 90 years of age, the prevalence was reported to be 35-40%. other studies have supported this fact. in older age, the lacrimal system loses elasticity and fails to flush the debris which is collected through the complex and this might be one of the reasons for increased prevalence in these age groups. ali and ahmad (2002) reported that 70.8% of the patients of chronic dacryocystitis were in the age group 31-50 years. similarly, dresner et al (1991) reported the highest disease prevalence in age group 30-60 years. according to a study by zaman et al, 80% of the patients with chronic dacryocystitis were in the age group 41-60 years (zaman et al 2003). according to the recent study by badhu et al (2005) in eastern nepal, the mean age of patients with chronic dacryocystitis was 27.4±13.7 years (95% ci=26.34 to 28.46 years). as expected, we also found similar results. the mean age group of our patients was 34.4±12.12 years (95% ci=28.89-38.55 years). 71% of them belonged to the 21-40 years group. we couldn't explain the difference in the age of presentation as reported in the literature from the western and neighboring countries. it is likely that some genetic, environmental, hormonal or some unidentified insults may be responsible. most of the authors have reported that the disease is more common in females. it has been suggested that females have a nasolacrimal duct of smaller length and size. also, the angulation of the canal where obstruction is more likely is more in females. these anatomical factors might be a reason why this condition is more common in females. the association of chronic dacryocystitis with serious gynecological pathology or hysterectomy due to de-epithelization is reported by zolli and stanon. they reasoned it to be due to hormonal imbalance (zolland et al 1973). the fact that the disease is more prevalent in the younger age group contradicts this hypothesis (badhu et al 2005). we did not study the socioeconomic status of the patients though some studies report a higher prevalence in patients of a lower socioeconomic class. we studied the occupation, which can be taken as one of the arms of socioeconomic status. most of our patients were housewives. since two-third of our study population was female, it is no surprise that housewives were found to be commonly affected. we think it is a chance association rather than a cause effect. a larger sample with involvement of different professions would confirm whether profession has any role in its pathogenesis. the published study from this part of nepal reported a higher incidence in patients coming from subtropical lowlands with monsoon climate (badhu et al 2005, 2006). in our study, the majority of the patients were from subtropical lowlands of nepal and india. while analyzing the nasolacrimal duct involvement, we found that most (95%) of the patients had unilateral involvement. fifty percent of the patients had it on the right side and 45% on the left side. but as described in the literature, dacryocystitis is more common in the left tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery 30 eye compared to the right eye (delaney et al 2002). the cause of right preponderance in our study may be due to the small sample size. the mean duration of symptoms was 1.23±0.8 years (95% ci=1.09-1.79 years).the symptoms of the patients varied from 6 months to 3 years. the duration of the symptoms mentioned in the literature is variable, the maximum reported being 50 years. in our study, there was an increase in intraoperative blood pressure and pulse rate in both the groups. however, the increase in pulse was significantly higher in group a than in group b. the increase in intraoperative and postoperative blood pressure and pulse in group a compared to group b can be explained as the group a patients had more pain compared to group b. in group a, all patients complained of pain, while in group b, 50% of the patients had pain. the severity of pain was more in group a compared to group b. (p value <0.001). in group a, the surgeons rated moderate or more discomfort in 35 cases while in group b, moderate or more discomfort was rated only in 5 cases. discomfort was significantly higher in group a, compared to group b (p value <0.001). the significant difference in pain and comfort can be explained by the fact that only local anesthesia was given in group a while in group b, local anesthesia with sedatives was given. the amount of blood loss was more in group a compared to group b (p=0.017). the more hemorrhage in group a can be explained by the surgeon's discomfort and the intraoperative pain experienced by the patients. the duration of surgery in both groups was comparable (p value=0.08). this is because the duration of surgery depends on the surgeon's skill. on the 7th pod, 1 patient in group a and 2 patients in group b had wound infection. according to yazici and meyer (2002), postoperative wound infection in dcr surgery can be controlled by selective use of antibiotics preoperatively and postoperatively. all the patients were given preand post-operative antibiotics in our study. poor personal hygiene and inadequate cleaning of the wound may be the cause of the wound infection. success of surgery is defined as patent lacrimal passage on syringing and free of watering. all the patients in both the groups had patent lacrimal passage on syringing on the first postoperative day. after six months, 87.5% of the patients in group a and 92% of the patients in group b had patent syringing. the success of conventional primary external dcr with or without mucosal flap is 85% to 99%. the success rate reported from this part of nepal is 88.6% (badhu et al 2005). in our study, the success rate was comparable on the 1st pod, 7th pod and at 6 weeks. but success rate was more in group b than in a after 6 weeks. this is due to the inequality in the follow-up rates in the two groups. attempts were made to increase the follow-up rate by explaining about the need of post-operative syringing and evaluation. the low follow-up rate may be due to the low socioeconomic condition, transportation difficulties and tendency of the patients not to return for follow-up once their symptoms are relieved. conclusion the demographic patterns and success rate of dcr surgery are similar to the previous reports from this part of the world. the use of sedatives improves the outcome of dcr surgery in terms of patient's pain, surgeon's comfort and intraoperative complications. references ali a, ahmad t a (2002). dacryocystorhinostomya review of 51 cases. pak j ophthalmol 18; 4:122-8. badhu b p, karki b s, khanal b, dulal s, das h (2006). microbiological patterns of dacryocystitis. ophthalmology 113 (12): 2377, p 1-2 badhu b, dulal s, kumar s, s.k.d. thakur, a. sood, h. das (2005). epidemiology of chronic dacryocystitis and success rate of external dacryocystorhinostomy in nepal. orbit 24:79-82. benger r (1992). day-surgery external dacryocystorhinostomy. aust n z j ophthalmol 20: 243-245. caldwell gw (1993). two new operations for obstruction of the nasal duct with preservation of tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery 31 the canaliculi and an incidental description of a new lacrimal probe. med j 57: 581. dalgesh r, mannor ge, milalan al, barret l (1967). idiopathic acquired lacrimal drainage obstruction. br j ophthalmol 51: 643 delaney ym, khoosabeh r, lagalla r, ponte f, mc lean cj et al (2002). external dcr for the treatment of the acquired partial nasolacrimal duct obstruction in adults. br journal of ophthalmology 86: 533-535 dresner s c, klussman k g, meyer d r et al (1991). outpatient dacryocystorhinostomy. ophthalmic surg 22: 222-2224. duffy mt, mass r, parlak m, koorneef l, bosmak s, et al (2000). advances in lacrimal surgery. current opin ophthalmol 11(5):352-6. fanning gl (2000). local anesthesia for dacryocystorhinostomy. current anaesthesia and critical care 11:306-309. gonnering rs, lyon db, and fischer jc (1991). endoscopic laser-assisted lacrimal surgery. am j ophthalmol 111: 152. massaro bm, gonnering rs, harris gj (1990). endonasal laser dcr. a new approach to nasolacrimal duct obstruction. arch. ophthalmol 108:1172. tuladhar s et al nep j oph 2009;1(1):25-31 sedation in dcr surgery o donnell b, shah r, harris gj, rose ge, puukula p et al (2001). dacryocystorhinostomy for epiphora in the presence of a patent lacrimal system. clin experiment ophthalmol 29(1):27-29. toti a (1904). nuovo metodo conservatore di cura radicale delle suppurazioni croniche del sacco lacrimale (dacrio cistorhinostomia). clin moderna (firanze) 10.385. yazici b, meyer dr (2002). selective antibiotic use to prevent postoperative wound infection after external dacryocystorhinostomy. ophthal plast reconstr surg 18 (5):331-5. zaman m, babar tf, saeed n (2003), a review of 120 cases of dacryocystorhinostomies (dutemps and bourguet technique). j aub med coll abbotabad 15:10-12. zolland s nl, oguya jh, pratt ll, kominek p, novak v (1973). cancer of the lacrimal sac. presentation of five cases and review of the literature. ann otol rhionol 82; 2:153-61. 128 direct microscopy in suppurative keratitis: a report from tertiary level hospital in nepal pooja gautam rai1, meenu chaudhary2, ananda kumar sharma2, vijay gautam1 1sagarmathachoudhary eye hospital, lahan, siraha, nepal 2bpklcos, tuth, iom, kathmandu, nepal abstract introduction: infective keratitis is an ocular emergency that requires prompt diagnosis for appropriate management. this study was done todetermine the sensitivity, specificity and predictive values of gram stain and potassium hydroxide (koh) wet mount in the diagnosis of suppurative keratitis. materials and methods: a prospective hospital based study of all patients with clinically diagnosed suppurative keratitis presenting between january 2011 and june 2012 was carried out. corneal scrapes were taken and subjected to direct microscopy and culture.results: corneal scrapings were obtained from 108 eyes with suppurative keratitis. direct microscopy was positive in 39.2% of cases and organisms were grown in 50.9 % of the cases. bacteria were responsible in 76.4% and fungi in 23.6%. of the bacterial isolates, 66.7% was staphylococcus aureus and of the fungal isolates, 30.7% was aspergillus species. sensitivity in vitro showed that cefazolin, chloramphenicol and ofloxacin were most effective against bacteria. sensitivity of gram stain in detecting bacteria was 50% (95% ci, 34.43 to 65.56) and specificity was 77.3% (95% ci, 65.0 to86.3) and sensitivity of koh wet mount in detecting fungi was 53.8% (95% ci, 26.12 to79.6) and specificity was 98.9% (95% ci, 93.44 to 99.9). positivity of direct smear (65.1%) was found to be higher among eyes with larger ulcers (>2mm) than eyes with smaller ulcers (<2mm). conclusion: direct microscopy is of great diagnostic value in the management of suppurative keratitis and it is recommended in all ophthalmic clinics without exception for establishing timely, appropriate and effective treatment. keywords: corneal ulcer, suppurative keratitis, microbiological diagnosis, direct microscopy. original article received: 24/04/16 accepted: 26/06/16 address for correspondence dr. pooja gautam rai, md sagarmatha choudhary eye hospital, lahan, siraha, nepal phone: 00977-9862051477 fax: 00977-33-560492 email: drpoojarai15@gmail.com introduction corneal ulceration is defined as a loss of the corneal epithelium, with underlying stromal infiltration and suppuration associated with signs of inflammation with or without hypopyon (whitcher jp et al, 2001). infective keratitis is an ocular emergency that requires prompt diagnosis for appropriate management to ensure the best visual outcome for the patient. without adequate treatment, corneal infection leads to blindness through corneal scarring and endophthalmitis (resnikoff s et al, 2004). a clinical diagnosis of infective keratitis does not give an unequivocal indication of the causative organisms because a wide range of organisms can produce a similar clinical picture rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 mailto:drpoojarai15@gmail.com 129 (ostler hb, 1993; florakis gj, 1997; liesegang tj, 1980). direct microscopic examination and culture for the detection of causative organisms are the two important microbiological investigations that are widely used. although culturing of microbial pathogens is considered to be the gold standard, direct microscopic evaluation of smears provides immediate information about the causative organisms. several techniques have been used for the direct microscopic identification of microbes from corneal scrapes using stains like gomori’s methenamine silver (xie l et al, 2001),periodic acidschiff (sharma s et al, 1998),calcofluor white and fluorescein conjugated lectins (robin jb et al, 1986) yield accurate results, but are time consuming and require special infrastructures. in addition, the cost of each test makes them inapplicable in primary, secondary and even in most tertiary centers. the conventional techniques, potassium hydroxide (koh) wet mount, gram stain and giemsa stain, are widely used for the rapid detection of microbes (xie l, 2001; sharma s, 2002); however, owing to misinterpretation, presence of artefacts, and lack of detection of candida and other yeasts, the sensitivity of these methods is highly variable (xie l, 2001; rosa rh, 1994; rao na, 1989; o’day dm, 1996; vajpayee rb, 1993). in addition, molecular diagnosis of pathogenic agents is a newer technology for accurate identification of the causative agents (gaudio pa et al, 2002) but is inapplicable to all patients with corneal ulcer, as it is more expensive. also, cultures require a longer time depending on the organisms (24 hours to 3 weeks). hence, examination of a smear can provide results in a short span of time, enabling clinician to start empirical treatment (hagan m et al, 1995).in a study commissioned by the who southeast asia regional office in new delhi (who/searo), it was estimated that 6 million corneal ulcers occur annually in the 10 countries of south-east asia region encompassing a total population of 1.6 billion (gonzales ca et al, 1996). these estimates are based on the data from 4 countries where the incidence of corneal ulceration ranged from as low of 113 per 100,000 in india (upadhyay mp et al, 2001)to as high as 799 per 100,000 in nepal (erie jc et al, 1993). suppurative keratitis is one of the leading causes of corneal blindness in nepal. prompt diagnosis and initiation of appropriate management could reduce severe visual loss and restrict corneal damage. lack of microbiological laboratory facilities and initiation of primary treatment without etiological diagnosis are the main challenges in the management of corneal ulcers in the developing countries like nepal. hence, there is a great need to perform simple methods of diagnosis like direct microscopy as it is easy, economic, less time consuming and can be carried out without sophisticated technicalities. to the best of our knowledge only a few reports are available in nepal with regard to the sensitivity and specificity of the direct microscopy till date. this study has been undertaken to emphasize the role of direct microscopy and its importance as a simple method in the management of suppurative keratitis. materials and methods this prospective hospital based study included all the diagnosed cases of suppurative keratitis attending the bpklcos, kathmandu over a period of 18 months (1st january 2011 to 30th june 2012). informed consent was taken from all the patients. typical or suspected viral ulcer, interstitial keratitis, neurotrophic ulcer, mooren’s ulcer, any ulcer associated with systemic or metabolic disease, patients not willing to participate, small children and small ulcers from which enough sample could not be scraped for examination and patient who were not evaluated as per the protocol ,were excluded from this study. patients already on rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 130 antimicrobials at the time of presentation were advised to stop medication for 48 hours before inclusion in the study. detailed clinical history, general physical examination and detailed ophthalmological examination were carried out in all the subjects as per ourstudy protocol. the location of the ulcer was recorded as central, paracentral or peripheral or total. the shape, margins and the size of the ulcer were recorded. the size of the epithelial defect after staining with 2% fluorescein was measured with variable slit on the slit-lamp bio-microscope and recorded in millimeters on a standardized form. firstly, the longest dimension of the defect was determined and then the dimension perpendicular to the first was measured. in a similar fashion the size and depth of the stromal infiltrate was recorded. stromal infiltrate was looked for their colour, depth and margin along with surrounding corneal haze. the corneal ulcer depth was evaluated as <20%, 20-50% or >50% of the total corneal thickness. corneal vascularisation was looked for and labeled as superficial or deep. a sketch of each ulcer was also drawn on the form using standardized frontal and cross sectional diagrams. corneal sensation was assessed in all the cases. ultrasound a and b scan were done in cases where the posterior segment could not be viewed to rule out the presence of vitritis and/or endophthalmitis. photographic documentation was done whenever it was felt necessary. microbiological evaluation corneal scraping was performed under magnification of a haag streit slit lamp bio-microscope or konan operating microscope 700. the affected eye was anesthetized with a topical 0.5% proparacaine hydrochloride. the kimura’s spatula or no.15 bard parker blade was scraped over the surface of the suppurative area first to remove the superficial necrotic material then in a series of short, moderately firm strokes to sample both the leading edges and the base of each infiltrated area in one direction from the peripheral margins towards the center of the suppurative area. the material obtained was initially smeared onto clean sterile labeled glass slides for 10% koh wet mount and gram stain. giemsa stain was not included in the study. the material obtained by the next scrape was inoculated directly onto the surface of solid media such as blood agar, chocolate agar and sabouraud’s dextrose agar in rows of c-shaped streaks and also inoculated into depth of liquid medium such as brain heart infusion broth. the order in which the specimen was prepared was: slide for gram stain and koh wet mount was prepared first, followed by inoculating the sample onto the solid media and lastly onto the liquid media. laboratory procedures smears were prepared by scraping the ulcer and gently transferring the material on the spatula on to the sterile glass slide over an area of approximately 1 cm in diameter. the glass slide was marked on the opposite side with a permanent marker to obviate the need to search for area smeared under the microscope. two slides were prepared, one for gram staining and the second for koh wet mount. the specimen was then viewed with 10x objective and 100x oil-immersion objective of a microscope (nikon, japan, 183382). all inoculated media were incubated aerobically. the inoculated sabouraud’s dextrose agar was incubated at 27ᵒc, examined daily and discarded at 3 weeks if no growth was seen. the inoculated blood agar, chocolate agar and brain heart infusion broth were incubated at 37ᵒc, examined daily and discarded at 7 days if no growth was seen. for the entire bacterial isolates antimicrobial sensitivity test was performed by kirby bauer disc diffusion method. processing, reading of the results and zone size interpretation have been performed as per nccls (clsi) guidelines (wayne, pa., 2006). rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 131 treatment protocol initial therapy was decided on the basis of smear report. if it was negative, then on the basis of patient’s history and clinical examination, therapy in the form of broad spectrum antibacterial or antifungal was started. after availability of culture sensitivity report, if needed treatment was changed to a suitable antibiotic or antifungal. bacterial corneal ulcer for mild corneal ulcerfluoroquinolones (ofloxacin) eye drops was started every hour for 2-3 days. then it was tapered according to clinical response of the corneal ulcer. for moderate to severe corneal ulcerduo-therapy consisting of reconstituted cefazolin 50mg/ml and fortified gentamycin 14mg/ml eye drops were used.however, sensitivity of the organism to an antibiotic was of prime importance in selecting a suitable antibiotic. fungal corneal ulcers for mild fungal corneal ulcers5% natamycin eye drops were started every hour and tapered according to the clinical response. for moderate to severe fungal corneal ulcers5% natamycin eye drops and systemic itraconazole (100mg bd) for 21 days or fluconazole (150mg bd) for 2 weeks were given. adjuvant therapy all patients with suppurative keratitis were given atropine 1% eye drop, anti-glaucoma therapy if needed, vitamin c along with antibacterial or antifungal therapy. in severe corneal ulcers not responding to the above treatment or in impending corneal perforation, treatment was modified in the form of systemic antibacterial or antifungal therapy. for perforated corneal ulcer, bandage contact lens with tissue adhesive for smaller perforations (<2 mm)and therapeutic penetrating keratoplasty for larger perforations were done. data processing and analysis detail findings were recorded in the performa developed for this study. pearson chi-square test was used for the analyses of categorical data. the 95% confidence interval limits were provided and p value ≤0.05 was considered statistically significant. spss software version 18 for windows was used for statistical analysis. results one hundred and eight patients with the clinical diagnosis of suppurative keratitis meeting the inclusion criteria were included in the study. the mean age of the patients was 46.76 ± 18.27 years, ranging from 14 – 89 years. the median age of the patients was 50 years. in this study 52% (n=56) cases were female and 48% (n=52) cases were male. majority of the patients 77 (71%) were from the hilly region of nepal followed by those from the terai region (26%). corneal ulcers occurred throughout the year in nepal, in this study it was seen that a slightly more number of patients presented to the centre during the spring season. corneal ulcers were more prevalent in the agricultural workers (n=51, 47.2%). the median duration of presentation was 7 days (inter-quartile range was 11.75 days). about 32% patients presented between 4 to 7 days of onset of symptoms. history of corneal injury was the most common risk factor, encountered in 43 eyes (39.8%). trauma with vegetative matter was found to be the most common predisposing risk factor in 23 patients (21.3%) and 20 patients (18.5%) had a history of trauma with non vegetative matter. most of the patients were using topical eye drops at the time of presentation (n=74, 68.5%) among them 9 (8.3%) subjects were documented to be using steroid eye drops. out of 108 specimens examined, direct microscopy was positive in 43 (39.8%) rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 132 specimens and culture was positive in 55 (50.9%). table 1 shows the yield percentage of direct smear and culture method. table 1: yield percentage methods positive yield negative yield bacteria fungus direct smear 39.8% 60.2% 83.7% 16.3% culture method 50.9% 49.1% 76.4% 23.6% fifty-five (51%) ulcers measured more than 2mm in diameter. in this study it was seen that smear positivity was seen in 50.9% ulcers those were larger than 2mm in size (p value =<0.02) as shown in table 2. table 2: ulcer size vs. smear positivity ulcer size number of cases smear positive percentage less than 2 mm 53 15 28.3% more than 2 mm 55 28 50.9% culture was positive in 55 samples. out of the 55 samples, in 42 eyes (76.4%) bacteria were identified and 13 eyes (23.6%) showed fungal growth. no mixed organism was isolated from any eye. out of the 42 bacterial isolates, 67% (n=28) grew staphylococcus aureus , 28% (n=12) grew streptococcus pneumonia and 5% (n=2) grew streptococcus viridians. pseudomonas species, e.coli, filamentous bacteria or acinetobacter were not isolated in this study. out of the 13 fungal isolates 4 (30.75%) grew aspergillus, 3 (23.1%) each grew fusarium and penicillium. candida species or any dematiaceous fungiwere not isolated in this study. table 3 shows the different organisms isolated. table 3: organisms isolated bacteria 42 fungus 13 staphylococcus aureus 28 aspergillus spp. 4 streptococcus pneumonia 12 fusarium spp. 3 streptococcus viridans 2 penicillium spp. 3 acremonium spp. 1 rhodotorula spp. 1 others 1 the sensitivity of gram stain in detecting bacteria was 50% (95% ci 34.43 to 65.56) and the specificity was 77.3% (95% ci 65.0 to 86.3). hence, the positive predictive value of gram stain was 58.3% and the negative predictive value was 70.8% as shown in table 4. the sensitivity of koh wet mount in detecting fungi was 53.8% (95% ci 26.12 to 79.6) and specificity was 98.9% (95% ci 93.44 to 99.9). hence, the positive predictive value of koh wet mount was 87.5% and negative predictive value was 94%, also shown in table 4. table 4:sensitivity and specificity of direct smears methods grams stain koh wet mount sensitivity 50% 53.8% specificity 77.3% 98.9% positive predictive value 58.3% 87.5% negative predictive value 70.8% 94% most of the patients were managed well with medical therapy but few required surgical intervention. table 5 shows the overall treatment outcome. table 5:treatment outcome outcome culture result total bacteria (n=42) fungus (n=13) negative (n=53) healed scar 22 5 15 42 adherent leucoma 9 1 12 22 worsening/ no response 5 2 10 17 evisceration 0 1 3 4 keratoplasty 2 3 7 12 no follow-ups 4 1 6 11 results of different previous studies have been compared with the results of this study in table 6. rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 133 table 6: comparison with previous studies studies bharathi mj et al, 2006 gopinathan u et al, 2009 dunlop aas et al, 1994 feilmeier mr et al, 2010 current study culture yield % total 69.4% 60.4% 81.7% 40% 50.9% bacteria 46.7% 51.9% 58.6% 39% 76.4% fungus 49.7% 38.2% 41.4% 61% 23.6% mixed 3.6% 9.9% (5%) 0% 0% smear yield % total 74% 70.5% 70.4% 34.6% 39.8% bacteria 48.1% 60.4% 50% 41% 83.7% fungus 48.5% 39.6% 50% 59% 16.3% mixed 3.4% 0% (6%) 0% 0% koh wet mount sensitivity 99.3% 89.8% 97.9% 80.5% 53.8% specificity 99.1% 93.7% 96.8% 98.9% 98.9% positive predictive value 98.5% 94% 95.8% 87.5% grams stain sensitivity 100% 56.6% 61.7% 75% 50% specificity 97.6% 97.8% 89% 97.3% 77.3% positive predictive value 95.7% 84% 80.6% 58.3% most common microorganism bacteria streptococcus pneumonia staphylococcus epidermidis streptococcus pneumonia streptococcus pneumonia staphylococcus aureus fungus fusariumspp fusariumspp aspergillus fumigatus aspergillusspp aspergillusspp discussion in our study of 108 patients with clinically diagnosed suppurative keratitis, the mean age of the patients was 46.76 ± 18.27 years ranging from 14 to 89 years. while evaluating the age distribution of the patients it was seen that 79 (73.1%) of the patients were between 21 to 60 years of age, which is the most productive socioeconomic population of nepal. this was similar to a study conducted by m.p. upadhyay et al in nepal, where corneal ulcers were found to be least common in patients below 10 years and over 71 years of age (upadhyay mp et al, 1982). similarly, in a study conducted by u. gopinathan et al it was seen that the mean age of patients with bacterial keratitis was 41.20 ± 20.36 years and that of patients with fungal keratitis was 30.90 ± 15.28 years, indicating a relatively increased occurrence of corneal infections in the middle age group (gopinathan u et al, 2009) . in another study conducted by lavaju p et al, it was seen that ulcers were more prevalent in the middle age groups, between 2140 years of age (50%) (lavaju p et al, 2009). presentation in this age was more common due to the fact that persons belonging to this age group are more active and involve themselves in outdoor activities. another factor could be that they are also the earning member of the family so are brought more frequently to the hospital (saeed a et al, 2009). in this study females were affected more (52%) than males (48%) similar to that seen in a study conducted by m.p. upadhyay et al where 63.9% of patients with corneal ulcer were females and 36.1% were males (upadhyay mp et al, 1982). while a study conducted by samar k basak et al in west bengal, india showed that majority of the patients were males (70.6%) and 29.4%were females (basak sk et al, 2005). in another study done by m.p. upadhyay et al between september 1985 and august 1987 showed that the males and females were equally affected rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 134 (upadhyay mp et al, 1991). in our study females seemed to be affected more than males because there is a significant contribution of the female population to the agricultural labour force in the country and also that a significant number of the male population venture to foreign countries in search of employment. although corneal ulcers occur in all seasons of the year, a slightly more number of patients (30.6%) presented to the hospital in the spring season between the months of march and may. a study done by m.p. upadhyay (upadhyay mp et al, 1982) et.al saw that corneal ulcers seemed to be more frequent during monsoon (june to august) and autumn (september to november) seasons, when 84 cases (63.2%) were seen. majority of keratitis cases were seen in the agricultural group (47.2%) similar to other studies done by upadhyay mp et al (upadhyay mp et al, 1991), lavaju p et al (lavaju p et al, 2009) 75% in nepal and samar k basak et al (basak sk et al, 2005) 57.6%; but a marked contrast was found in a study done in ghana (hagan m et al, 1995)where only 16.1% were involved in agricultural activity. the median day of lag before presentation to our eye centre was 7 days, with the interquartile range of 11.75 days. more than half of the patients (57.4%) presented to the hospital before 7 days of onset of symptoms contrary to the study conducted by samar k basak (basak sk et al, 2005) where the majority of patients (51.8%) were seen between 2-3 weeks of their illness. the findings in our study can be correlated with the regional distribution, where it was seen that the majority of patients came to hospital from the hilly region of nepal which falls in and around the kathmandu valley, where the tertiary eye centre is located. corneal injury has always been identified as a cause of microbial keratitis. in our study, a history of corneal injury was present in 43 eyes (39.8%). similarly, a history of trauma could be elicited in 82.7% of cases of corneal ulcer in the study conducted by upadhyay m.p et al (upadhyay mp et al, 1982). whereas y w ibrahim et al (ibrahim yw et al, 2009) and matthew green et al (green m et al, 2008) found that a significant number of patients had contact-lens use as the main risk factor (31% and 22% respectively). majority of the patients were using topical drops at the time of presentation to the hospital (n=74, 68.5%), of them 13% had received a combination therapy (antibiotics and antifungals). this reflects the tendency of general practitioners and ophthalmologists at the primary and secondary eye centres to prescribe a cocktail of drugs and refer patients to tertiary eye centres only when empirical treatment failed. almost 16% had received antibiotics alone; many of them had received insufficient dosage, demonstrating the tendency of medical practitioners to treat the condition inadequately. ushagopinathan et al (gopinathan u et al, 2009) found 10% of patients using steroids similar to our study where 8.3% had received topical steroids, and many of them had acquired them as an over the counter drug from a local chemist, showing a lack of awareness of the disease and its complications. in the total of 108 cases, 43 patients (39.8%) showed positive findings in direct microscopy and 55 patients (50.9%) were culture positive. these findings were comparable to other studies done in nepal (feilmier mr et al, 2010) where smear microscopy was positive in 34.6% of cases and 40% of the cases showed growth in the culture, ghana (hagan m et al, 1995) where 57.3% were culture positive. similarly matthew green et al (green m et al, 2008) found gram stain was positive in 83 cases (33%) and cultures were positive in 164 (65%) cases and negative in 89 (35%) cases. the lower rate of isolation in our study could be attributed rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 135 to empirical use of topical antibiotics before presentation to our hospital and our inability to employ enriched and selective media. use of additional media would help determine the pattern of microbes more fully, which in turn would permit the selection of antimicrobials that will have the best chance of curing corneal ulcers (upadhyay mp et al, 1982). bacteria wereisolated in 42 (76.4%) samples and fungus in 13 (23.6%) of culture-positive samples. none of the isolates showed mixed organisms or acanthameoba. out of these, staphylococcus aureus was isolated in the majority i.e.,28 patients (67%), followed by streptococcus pneumoniae in12 cases (28.6%). aspergillus species was seen as themost common isolates accounting for 4 (30.7%) of fungal isolates. staphylococcus aureus was the most commonly isolated bacterial organism representing 70% of all positive bacterial growth and aspergillus was seen as the most common of the fungal isolates (66.6%) in a study done by samar k basak et al(basak sk et al, 2005) and staphylococcus aureus was also the most common bacterial organism isolated and aspergillus the most common fungi in a study conducted by aartitewari et al (tiwari a et al, 2012). ashok narsani kumar (narsani ak et al, 2009) and colleagues also found that the most frequent organism isolated among the 240 cases of corneal ulcer was staphylococcus aureus (n=75, 60%). a study done by lavaju p et al (lavaju p et al, 2009) showed that among the 44 patients of infective keratitis culture positivity was observed in 20 (45.5%) samples. staphylococcus aureus was the most commonly isolated bacteria (70%) in this study also. penny asbell et al (asbell p et al,1982) also found staphylococcus to be the most common isolate (239 cases, 48%), coagulase positive staphylococcus was twice as common as coagulase negative staphylococcus (33% and 16% respectively). whereas m. p. upadhyay et al (upadhyay mp et al, 1982) found pneumococcus to be the single most important isolate, contributing to 60.4% of corneal ulcers; staphylococcus was responsible for 24.5%. among the fungi, aspergillus species was the most common (40.0%). feilmeier mr et al (feilmeier mr et al, 2010) reported fungi in 61% of the cases, of which aspergillus species was most commonly isolated (35%) and among the bacteria streptococcus pneumoniae was most commonly isolated (69%). antibiotic sensitivity in vitro showed that cefazolin, chloramphenicol and ofloxacin were most effective (100%) effective against the bacteria. gentamycin which is commonly used along with cefazolin for the treatment of suppurative keratitis was seen to be effective (100%) against staphylococcus aureus and streptococcus viridians and 83.5% of streptococcus pneumonia was sensitive to it. it was also seen that staphylococcus aureus was 96.4% sensitive to ciprofloxacin as seen in a report (goldstein mh et al, 1999) which shows a rapid increase in staphylococcus aureus resistance to ciprofloxacin. m.p. upadhyay et al (upadhyay mp et al, 1982) found that carbenicillin, chloramphenicol, cephaloridine, methicillin and lincomycin were most effective against bacteria. in our study it was seen that tobramycin was not as effective against the bacterial isolates, contrary to this lailaakter et al (akter l et al, 2009) found that lomefloxacin, tobramycin and gentamycin were more effective drugs against most of the gram-positive and gram-negative bacteria. the disc susceptibility method provides quantitative measurements that are critical for epidemiology and drug resistance surveillance. although this approach is both fast and cost effective (hindler j et al, 1995), resistance criteria apply only to systemically achieved drug levels, which are different from those achieved with topical treatment. direct microscopy (gram stain + koh wet mount) was positive in 65.1% of the ulcers rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 136 (n=28) which were greater than 2mm in size (p value <0.016). similar findings were seen in a study done by bharathi mj et al (bharathi mj et al, 2006) which showed that the positivity of koh was 44.46% and gram stain was 77.37% among eyes with larger ulcers (>2mm). in another study by savitri sharma et al (sharma s et al, 2007) it was also seen that in ulcers with the infiltrate size of <2.5mm square, the smear negativity was 79.3% while the smear positivity rate was just 49.0%. although culture was used as a gold standard for detecting pathogens in this study, smear microscopy was also effective for rapid identification of micro-organisms. it was seen that the sensitivity of gram stain in detecting bacteria was 50% (95% ci, 34.43 65.56) and specificity was 77.3% (95% ci, 65.0 86.3), thus the positive predictive value of gram stain was 58.3% and negative predictive value was 70.8%. the sensitivity of koh wet mount in the detection of fungi was found to be 53.8% (95% ci, 26.12 79.6), specificity was 98.9% (95% ci, 93.4 99.9). its positive predictive value was 87.5% and negative predictive value was 94%. in a study done by m j bharathi et al, the sensitivity of gram stain in detecting bacteria was 100% and specificity was 97.6% and sensitivity of koh in detecting fungi was 99.3% and specificity was 99.1% (bharathi mj et al, 2006). prashant garg et al found the sensitivity and specificity of gram stain in detecting bacteria to be 56.6% and 97.8% respectively and sensitivity and specificity of koh in detecting fungi was 90.6% and 94.3% respectively (gopinathan u et al, 2009). a study done by michael r et al in nepal, gram stain was 75% [95%, confidence interval (ci), 0.632–0.841] sensitive and 97.3% specific (95% ci, 0.951– 0.986) in identifying bacterial organisms. koh wet mount was 80.5% sensitive (95% ci, 0.718–0.871) and 98.9% specific (95% ci, 0.971–0.997) in identifying the presence of fungal elements (feilmeier mr et al, 2010). similarly, another study done by aartitewari et al shows the smear sensitivity corresponding to 64.4% and specificity to 93.8% for bacteria and for fungi, smear sensitivity was 75.6% while specificity was 100% (tiwari a et al, 2012). matthew green et al found in their study, the sensitivity of gram stain in identifying causative organisms as 53% and specificity as 89% (green m et al, 2008). aas dunlop et al did a study on 142 cases of infective corneal ulcer where gram stain had a sensitivity of 62%, specificity of 65%, positive predictive value of 84% and negative predictive value of 37% in detecting bacteria (dunlop aas et al, 1994). the factors which may have contributed to our findings are the size of the corneal ulcers, scraping technique, amount of scraped material and the ability to detect microorganisms in the field of microscopic examination of the scraped material. however, our findings do indicate that smear microscopy is a very important diagnostic test that provides rapid etiologic information and allows for initiation of the most appropriate antimicrobial therapy at the time of presentation. this is particularly important in developing countries such as nepal, where follow-up is not always feasible and culture techniques are not always available. conclusions corneal ulcer is an ocular emergency that requires prompt and appropriate management for restoration and better visual outcome. this study was designed to find out the efficacy of available direct microscopic techniques in the detection of microbes from corneal scrapes which could lead to timely and appropriate treatment of the suppurative corneal ulcers. among the microbiological aetiology established, bacterial isolates were three times more frequent than the fungal isolates. this study found that there is a change in the trend of bacteria isolated from the cases of suppurative keratitis over the past decade. rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 137 about 10% difference was found between the direct microscopy of corneal smear and culture results. the sensitivity and specificity of gram stain and koh wet mount in our study were comparable to what was found in most other studies. there was a statistically significant association between the smear positivity and the size of the corneal ulcers. it was observed that direct microscopy of corneal smear was an important diagnostic tool in the management of suppurative keratitis. hence, the practice of performing direct microscopy in all the cases of infective keratitis should be emphasized and made mandatory in all the ophthalmic clinics. references akter l, salam ma, hasan b, et al (2009). etiological agents of suppurative corneal ulcer: study of 56 cases bangladesh j med microbiol; 03 (01): 3336. asbell p, stenson s (1982). ulcerative keratitis survey of 30 years’ laboratory experience. arch ophthalmol ; 100:77-80. basak sk, basak s, mohanta aet al (2005). epidemiological and microbiological diagnosis of suppurative keratitis in gangetic west bengal, eastern india. indian j ophthalmol;53:17-22. bharathi mj, ramakrishnan r, meenakshi r, , et al(2006). microbiological diagnosis of infective keratitis: comparative evaluation of direct microscopy and culture results .br j ophthalmol; 90:1271–1276. dunlop aas, wright ed, howladert sa, et al (1994). suppurative corneal ulceration in bangladesh: a study of 142 cases examining the microbiological diagnosis, clinical and epidemiological features of bacterial and fungal keratitis australian and new zealand journal of ophthalmology; 22(2): 105-10 erie jc, nevitt mp, hodge do, et al (1993). incidence of ulcerative keratitis in a defined population from 1950-1988. arch ophthalmol; 111:1665–1671. feilmeier mr, sivaraman kr, oliva m, et al (2010). etiologic diagnosis of corneal ulceration at a tertiary eye center in kathmandu, nepal. cornea; 29(12): 1380-5 florakis gj, moasami g, schubert h, et al (1997). scanning slit confocal microscopy of fungal keratitis. arch ophthalmol;115:1461–3 gaudio pa, gopinathan u, sangwan v, et al (2002). polymerase chain reaction based diagnosis of fungi in infected corneas. br j ophthamol; 86:755–60. goldstein mh, kowalski rp, gordon yj (1999). emerging fluoroquinolone resistance in bacterial keratitis. a 5-year review. ophthalmology;106:1313–18. gonzales ca, srinivasan m, whitcher jp, et al (1996). incidence of corneal ulceration in madurai district, south india. ophthalepidemiol.; 3:159–166 gopinathan u, sharma s, garg p, et al (2009). review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: experience of over a decade. indian j ophthalmol; 57:273-9. green m, apel a, and stapleton f (2008). risk factors and causative organisms in microbial keratitis cornea;27:22–27. hagan m, wright e, newman m, et al (1995). causes of suppurative keratitis in ghana.br j ophthalmol; 79: 1024–8. hindler j(1995). antimicrobial susceptibility testing of gram negative bacteria: meeting the challenge of increasing resistance and decreasing budgets. clinical microbiology newsletter;17(10):77-80. ibrahim yw, boase dl, cree ia (2009). epidemiological characteristics, predisposing factors and microbiological profiles of infectious corneal ulcers: the portsmouth corneal ulcer study. br j ophthalmol;93:1319–1324. lavaju p, arya sk, khanal b, et al (2009). demograhic pattern, clinical features and treatment outcome of patients with infective keratitis in the eastern region of nepal. nepal j ophthalmol;1(2):101-106 rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 138 liesegang tj, forster rk (1980). spectrum of microbial keratitis in south florida.am j ophthalmol; 90:38–47. narsani ak, jatoi sm, lohana mk, et al (2009). hospital –based epidemiology, risk factors and microbiological diagnosis of bacterial corneal ulcer. int j ophthalmol;2(4):362-366 o’day dm, burd em (1996). fungal keratitis and conjunctivitis: mycology. in:smolin g, thoft ra, eds. the cornea: scientific foundations and clinical practice. 3rd ed. boston: little, brown & co, 1996, p.229– 39. ostler hb (1993)diseases of the external eye and adnexa. baltimore: williams &wilkins, 1993,p.173–91. rao na (1989). a laboratory approach to rapid diagnosis of ocular infections and prospects for the future. am j ophthalmol; 107:283 91. resnikoff s, pascolini d, elya’ale d, et al (2004). global data on visual impairment in the year 2002. bull world health org.; 82: 844–855.robin jb, nielson s, tronsdale md (1986). fluorescein-conjugated lectin identification of a case of human keratomycosis. am j ophthalmol; 102:797–8. rosa rh, miller d jr, alfonsa ec (1994). the changing spectrum of fungal keratitis in south florida. ophthalmology; 101:1005–13. saeed a, d’arcy f, stack j, et al (2009). risk factors, microbiological findings and clinical outcomes in cases of microbial keratitis admitted to a tertiary referral centre in ireland. cornea; 28(3):285-92. sharma s, silverberg m, mehta p, et al (1998). early diagnosis of mycotic keratitis: predictive value of potassium hydroxide preparation. indian j ophthalmol; 46:31–5. sharma s, kunimoto dy, gopinathan u, et al (2002). evaluation of corneal scraping smear examination methods in the diagnosis of bacterial and fungal keratitis. a survey of eight years of laboratory experience. cornea; 21:643–7. sharma s, taneja m, gupta r, et al (2007). comparison of clinical and microbiological profiles in smear-positive and smear-negative cases of suspected microbial keratitis. indian j ophthalmol; 55:21-5. tiwari a, sood n, vegad mm, mehta dc (2012). epidemiological and microbiological profile of infective keratitis in ahmedabad; indian j of ophthalmol;60(4): 267-72 upadhyaymp ,rai nc , brandt f, shrestha rb (1982). corneal ulcers in nepal graefe’s arch clin exp ophthalmol; 219:55-59. upadhyay mp, karmacharya pc, koirala s, et al (1991). epidemiologic characteritiscs, predisposing factors, and etiologic diagnosis of corneal ulceration in nepal. am j ophthalmol; 111:92-99. upadhyay mp, karmacharya pc, koirala s, et al (2001). the bhaktapur eye study: ocular trauma and antibiotic prophylaxis for the prevention of corneal ulceration in nepal. br j ophthalmol.; 85:388–392. vajpayee rb, angra sk, sandramouli s, et al (1993). laboratory diagnosis of keratomycosis: comparative evaluation of direct microscopy and culture results. ann ophthalmol; 25:68–71. whitcher jp, srinivasan m, upadhyay mp (1994).society for microbiology. corneal blindness: a global perspective. bull who 2001, 79: 214–21. wayne,pa. performance standards for antimicrobial disc susceptibility test, 9th ed. approved standard m2-a9. clinical and laboratory standards institute. 2006. xie l, dong x, shi w (2001). treatment of fungal keratitis by penetrating keratoplasty. br j ophthalmol; 85:1070–4. source of support: nil. conflict of interest: none rai et al direct microscopy in suppurative keratitis nepal j ophthalmol 2016; 8(16): 128-138 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 403 forbidden forbidden you don't have permission to access this resource. apache/2.4.54 (ubuntu) server at www.nepjol.info port 443 issue 6 final.pmd 99 the macular edema malla ok professor and head department of ophthalmology kathmandu medical college, sinamangal, kathmandu, nepal retinal vascular diseases, mainly diabetic retinopathy (dr) and retinal venous occlusions (rvo), account for the majority of blinding retinal conditions seen at retina clinics today. the implications of the rising numbers of patients who are being diagnosed with diabetes are significant to our profession, as many of these people will experience resultant visual loss. treating our patients with diabetes is also complicated by medical issues such as hypertension, both of which are coming up in an epidemic form in this part of the world. macular edema (me) is the single most important cause of profound visual loss in these retinal vascular diseases (the branch vein occlusion study group 1984; central vein occlusion study group 1993, 1995, 1997). the results of the diabetic retinopathy clinical research network (drcr.net) study comparing focal/grid laser photocoagulation treatment with intravitreal triamcinolone therapy in 2008 supported grid laser photocoagulation as the gold standard in therapy for diabetic retinopathy (dr). research, however, continues to be geared to finding effective pharmacologic and surgical treatments. me in dr and rvo affects mainly the neuro-retina and the photo-receptors are involved only in the later stages of the disease process, unlike in age related macular degeneration (amd) where the retinal pigment epithelial cells and photoreceptors are damaged first. thus, in dr and rvo, early intervention is more likely to restore vision. vascular endothelial growth factor (vegf) antagonists have gained attention in recent years as vegf has been shown to play a crucial role in the pathogenesis of diabetic macular edema (dme). ranibizumab (lucentis), a humanized, monoclonal antibody fragment and an anti-vegf, is being investigated in several trials to assess its efficacy in the treatment of dme. to date, ranibizumab appears to be effective in reducing optical coherence tomography (oct) central retinal thickness (crt) and improving vision early (geeta 2009). dr richard rosen shares his experience using the iq 577 yellow laser at a less power and shorter pulse duration for improving vision after one treatment in a 58-year-old man with dme. pars plana vitrectomy (ppv) and removal of the posterior hyaloid may be promising for selected cases of dme, mainly in conditions associated with vitreo-macular traction (vmt) (hikichi et al 1997, kaiser et al 2001, lewis et al 1992, harbour et al 1996).there is no shortage of exciting news from researchers searching for an effective pharmaceutical treatment for dme. promising new anti-angiogenic and antiinflammatory therapies may soon offer hope to diabetic patients. the me, though traditionally managed with laser photocoagulation, results in little or no improvement in visual acuity in patients with central retinal vein occlusion (crvo) and modest improvement relative to observation in branch vein occlusion (the branch vein occlusion study group 1984; the central vein occlusion study group 1995). vegf has been implicated in the patho-physiology of rvo. anti-vegf has been shown to be effective in reducing me. a prospective open-label study of intra-vitreal ranibizumab malla ok the maculat edema nepal j ophthalmol 2011; 3 (6):99-101 guest editorial 100 in patients with significant me associated with perfused crvo showed a mean decrease in crt on oct with improvement in visual acuity (pieramici et al 2008). in a study of bevacizumab for management of rvo, many patients responded with initial vision improvement, 71 % for branch retinal vein occlusion (brvo) and 56 % for crvo, with most of the improvement occurring after the first injection. there was regression in vision in all patients, but more regression occurred for patients with crvo than with brvo. however, even with the regression, patients were still significantly improved from the baseline (dev and bhatia, 2009). rvo requires a varied approach depending upon the case. anti-vegf agents can be used with success as the first line therapy for crvo and brvo and in combination with laser. two approved intra-vitreal agents available till date are bevacizumab and ranibizumab. the difference in the efficacy of ranibizumab and bevacizumab still remains to be seen but most extensive data are available regarding the uses of ranibizumab from brvo and cruise trials. the us food and drug administration (fda) has approved ranibizumab for the treatment of me following rvo. both the 0.3 mg and 0.5 mg doses of ranibizumab clinically and statistically improved vision in brvo and crvo according to the results of the brvo and cruise trials (the central vein occlusion study group, 1995). in a study done in nepal, thirty four eyes with me due to rvo treated with intra-vitreal bevacizumab (1.25mg) at 6 weeks interval and followed-up for 7.5 ± 4.8 months, showed a significant improvement both in visual acuity and me (thapa and poudyal, 2010). although we have many more treatment options available to us in 2010 for rvo, they only suppress the macular edema, thereby buying time so that the body can re-canalize the vessel that is occluded. the treatment with an injection of anti-vegf prior to laser application is important as it decreases the area requiring treatment. similarly, because it decreases the thickness of macula, the precision of laser burn placement is more accurate using less power (pieramici 2010). hypoxia-regulated genes play an important role in ocular neo-vascularization and macular edema. the role of vegf in the pathogenesis of macular edema is particularly important, and most efforts thus far have been directed at suppressing it (peter 2010). references dev s, bhatia h (2009). benacizumab for the management of retinal vein occlusion. retina today; 4(2): 56-57. harbour j w, smiddy we, flynn hwjr, rubsamen pe (1996). vitrectomy for diabetic macular edema associated with athickened and taut posterior hyaloids membrane. am j ophthalmol; 121(4):405413. hikichi, fujio n, akiba j et al (1997). association between the short term natural history of diabetic macular oedema and the vitreomacular relationship in type ii diabetes mellitus. ophthalmology; 104(3):473-478. kaiser pk, riemann cd, sears je, lewis h (2001). macular traction detachment and diabetic macular edema associated with posterior hyloidal traction. am j ophthalmol; 131(1):44-49. lalwani g a (2009). anti-vegf therapy in diabetic macular edema. retina today; 4(6):45-47. lewis h, abrams gw, blumenkranz ms, campo rv (1992). vitrectomy for diabetic macular traction and edema associated with posterior hyaloids traction. ophthalmology; 99(5): 753-759. peter a (2010). molecular targets for retinal diseases. retina today; 5:4-7 pieramici d (2010). anti vegf for recurring macular edema. retina today; 5:72-76. malla ok the maculat edema nepal j ophthalmol 2011; 3 (6):99-101 101 pieramici dj, grey sm, rubio r (2008). intravitreal ranibizumab(lucentis) in macular edema secondary to retinal vein occlusion: the design of the brvo and cruise trials. paper presented at:american society of retina specialists meeting; maui, hawaii. pieramici dj, rabena m, castellarin aa et al (2008). ranibizumab for the treatment of macular oedema associated with perfused central retinal vein occlusions. ophthalmology; 115(10): 47-54. thapa r, poudyal g (2010). intravitreal bevacizumab for treatment of macular oedema secondary to retinal vein occlusion. the 25th apao congress, poster sl 1-282, panel 282. the branch vein occlusion study group (1984). argon laser photocoagulation for macular oedema report. am j ophthalmol; 98:271-282. the central vein occlusion study group (1995). evaluation of grid pattern photocoagulation for macular oedema in central vein occlusion. the central vein occlusion study group m report. ophthalmology; 102(10):1425-1433. source of support: nil. conflict of interest: none malla ok the maculat edema nepal j ophthalmol 2011; 3 (6):99-101 untitled-1.pmd 3 stilma j s prevention of ocular firework injuries nepal j ophthalmol 2012; 4(7):3-4 received on: 04.11.2010 accepted on: 13.12.2011 address for correspondence: dr jan s stilma, emeritus professor of ophthalmology, university medical centre, utrecht, the netherlands and honorary consultant sierra leone. hooivaartsweg 4, 8459 et luinjeberd | the netherlands tel. (+31)-0513-528 707 e-mail: j.stilma@hetnet.nl guest editorial prevention of ocular firework injuries stilma j s emeritus professor department of ophthalmology university utrecht, the netherlands worldwide, the display of fireworks belongs to great festivals to commemorate religious or national events. the display is a joy for thousands or millions of people attending those events. however, some are affected by serious eye casualties. during the 1996 1997 indian diwali celebrations, 42 fireworks-related eye injuries were reported in chandigarh (arya, 2001). rashid reported 34 eye injuries during the aidik fitri celebration in malaysia. patients ranged between 2 and 43 years of age, 70 % of them being 12 years old or below (rashid et al, 2011). china is well-known for firework displays during new year’s eve, the spring festival and lately during the olympic games at beijing. at wuhan university, 25 eyes were treated during the spring festival in 2009 (jing, 2010). what can we learn from these and other reports? fortunately, a systemic review on the incidence, outcome and prevention of ocular firework trauma has been published (wisse et al, 2010). seventeen of these articles could be used for calculating trauma severity and vision loss. the combined data of 7,767 eye traumas were studied. what did we find? victims were male (77 %) and often bystanders (47 %). young people under the age of 20 years were affected in more than 67 % of the cases. most of the trauma is mild and temporary. however, 18 % accounted for penetrating eye trauma, globe contusions and burns. severe vision loss (< 10/200) was found in 16 %, including no light perception in 6 %. treatment is difficult because of infection, bleeding, loss of tissue and recurrent retinal detachment. enucleation was performed on average in 4 % and in a maximum of 17 %. in conclusion, ocular fireworks pose a severe risk of vision loss especially to young innocent bystanders. reduced vision of one eye will affect social life and binocularity necessary for many jobs. young people are affected for many expected life years. what can ophthalmologists do? since the treatment options are limited, we need to focus on prevention. indeed, an editorial on ocular traumatology was called ‘prevention, prevention, prevention’ (kuhn, 2010). but what does ‘prevention’ mean in ocular fireworks trauma? the only proven method to reduce ocular firework trauma is restrictive legislation of the personal sale and use of fireworks. this should be combined with the display of firework by professionals only. this method 4 source of support: nil. conflict of interest: none stilma j s prevention of ocular firework injuries nepal j ophthalmol 2012; 4(7):3-4 has been proven effective in several countries (wisse, 2010). this scientific truth is easier said than implemented for various reasons. first of all, democratically-elected governments will, by nature, follow the majority of their flock and not a minority of their ophthalmologists. second, large financial interests are involved in the sale of fireworks. thirdly, great festivals are an integral part of human culture. the way forward for ophthalmologists is to make the public aware of the side effects of personal firework. for example, ask a patient permission to show the effects of his or her eye injury in your local newspaper or television. a child or a well-know person is most effective for this purpose. motivate all ophthalmologists in your country to register all eye injuries during a festival. the registration paper should be as short as possible and web-based in order to get a maximal and quick response. ideally, you can report on the national scale of injuries the following day. emphasize your joy and commitment to great festivals, but in a professional and organized way. contact other medical colleagues to join you in a national publication campaign. plastic surgeons are confronted with the loss of fingers or hands or face injury. concerning politics, it is our experience in the netherlands that the top-down approach did not work, has not, yet. the prohibition of certain types of fireworks did not reduce the number of works trauma. on the contrary, an increase of firework trauma was seen after the increase of the maximum-allowed explosive powder from 250 to 500 grams in 2007 in the netherlands. the problem is that, internationally, thousands of different legal fireworks devices exist, not to mention the innumerable illegal homemade fireworks. the bottom-up approach has yielded some success. some small villages or towns have decided to discourage private fireworks and promote a central display of fireworks. it is a long way, but don’t forget the fight against smoking. in europe, it has taken 10 20 years before the public domain has become smoke free. a smoker has become an outcast in pubs and restaurants. so here we have the challenge for us ophthalmologists if we want to help the future victims of ocular firework injuries: come out of your clinics and don’t give up! any more suggestions and reactions are welcome. references arya sk, malhotra s, dhir sp, sood s (2001). ocular fireworks injuries. clinical features and visual outcome indian j ophthalmology;49:189-90 kuhn f (2010). ocular traumatology: prevention, prevention, prevention... graefes arch clin exp ophthalmol; 248:299-300 rashid ra, heidary f, hussein a et al (2011). ocular burns and related injuries due to fireworks during aidil fitri celebration on the east coast of the peninsular malaysia. burns; 37:170-173. wisse rpl, bijlsma wr, stilma js (2010). ocular firework trauma: a systemic review on incidence, severity, outcome and prevention. br j ophthalmol;94:1586-1591 jing y, yi-qiao x, yan-ning y, ming a, an-huai y, lian-hong z (2010). clinical analysis of fireworkrelated ocular injuries during spring festival 2009. graefes arch clin exp ophthalmol; 248: 333-338. << /ascii85encodepages false /allowtransparency false 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port 443 78 a biannual peer-reviewed academic journal of nepal ophthalmic society kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 original article comparative study of latanoprost (0.005%) and bimatoprost (0.03%) in primary open angle glaucoma neyaz kausar1 , kamala thapa2 1national academy of medical sciences, nepal eye hospital, kathmandu, nepal 2shree birendra hospital, chhauni, kathmandu, nepal abstract introduction: glaucoma can cause vision loss by damaging the optic nerve and increased intraocular pressure is one of the primary risk factors. materials and methods: this was a hospital based, prospective, comparative, single masked (observer masked) study conducted on patients attending glaucoma department of nepal eye hospital within a period of 1 year from february 2020 to january 2021. the sample size was 50. specially designed proforma was used to collect the patient. patients falling are divided in group a and group b randomly, patients using latanoprost were placed in group a and patients using bimatoprost were placed in group b. the examination procedure included history taking, snellen visual acuity, refraction, gonioscopy, iop measurement, slit lamp biomicroscopy and fundoscopy with 90 diopter lens. results: among fifty patients 33 (66%) were males and 17 (34 %) were females, 35 (70%) belonged to urban and 15 (30%) from rural population. maximum number of patients were in the age group of 16-30 years i.e. 15 (30%), second highest group was 61-75 years of age group i.e. 14 (28%) , 11 i.e. 22% of patients were of 46-60 years of age group. nine (18%) of patients were 31-45 years of age group and 1 i.e. 2% was above 75 years of age. twenty percent presented with hypertension, 14 % with diabetes mellitus and 66% with no systemic history. ten percent had family history of glaucoma and 90% patients had no family history . twenty-eight percent of patients had a family history of smoking and 72% had no history. the mean iop of group a (0.005% latanoprost) patients initially before the start of the treatment was 27.16 mm hg, at sixth month iop was 17.24 mm hg, mean difference was 9.92 mm hg and p value was < 0.001. the mean iop of group b (0.03% bimatoprost) patients initially before the start of the treatment was 26.88 mm hg , at the sixth month the iop was 15.88 mm hg , and the mean difference was 11.00 mm hg and p value was < 0.001. there was a significant difference in iop at first visit and 6 months in both groups, p<0.001. (the t-test is used.) however, the mean difference of group b, 11.00, is greater than group a, 9.92. conclusion: male gender, increasing age, urban population, hypertension, diabetes mellitus, and high intraocular pressure were the most prevalent risk factors. the most important factor is early detection of signs and symptoms and measurement of diurnal intraocular pressure. key words: bimatoprost, intraocular pressure, latanoprost, primary open angle glaucoma. financial interest : nil received : 18.04.2021 conflict of interest : nil accepted : 23.06.2022 corresponding author dr. neyaz kausar national academy of medical sciences, nepal eye hospital, tripureshwor, kathmandu e-mail: drneyaz2002@yahoo.com access this article online website: www.nepjol.info/index.php/nepjoph doi: https://doi.org/10.3126/nepjoph.v14i2.43026 copyright © 2022 nepal ophthalmic society issn: 2072-6805, e-issn: 2091-0320 this work is licensed under a creative commons attribution-noncommercial-noderivatives 4.0 international license (cc by-nc-nd). 79nepalese journal of ophthalmology kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 introduction glaucoma is a group of diseases that can cause vision loss and blindness by damaging the optic nerve. increased intraocular pressure (iop) is one of the primary risk factors of glaucoma. iop is raised by increased resistance to aqueous humor outflow. by definition primary glaucoma is not associated with ocular disorder that causes increased resistance to aqueous outflow or angle closure. the primary glaucoma usually affects both eyes. one of the leading causes of irreversible blindness in the world is glaucoma. glaucoma occurs in all segments of population with significant health and economic consequences, making it a major health problem. those with low vision confront visual disability in daily and social life (stamper rl et al, 1999). primary open angle glaucoma has characteristically an adult onset and is bilateral and symmetrical disease and it occurs in the elderly and tends to run in families. inheritance is said to be multifactorial and polygenic. diabetes and myopia also occurs more frequently in persons with glaucoma than in the general population (stamper rl et al, 1999). worldwide 37 million people are blind, with 12.3% (4.4) million attributed to glaucoma. the commonest type of glaucoma in caucasians and africans is poag and it also constitutes about half of the primary glaucoma seen in asians and eskimos (george a. cioffi et al, 2008). figures for developing world, where approximately 90% of world blind live and expected to increase significantly during the last decade as world population ages (jack j kanski, 2008). glaucoma can manifest in various patterns, many are asymptomatic until advanced stage. some may manifest as acute rise of intraocular pressure, while others may be congenital or secondary to trauma or secondary to various systemic and ocular diseases. as there is irreversible damage to the optic nerve head and visual field loss is the cause of glaucoma leading to blindness, much emphasis is given for early diagnosis. glaucoma is also the major cause of blindness in nepal. according to the national blindness survey (nbs), it is the 4th major cause of bilateral blindness in nepal (neupane mp, 1996). latanoprost is a prostaglandin analog and is a potent intraocular pressure lowering medication available today and has become one of the most useful anti glaucoma agents. latanoprost is supplied in 0.005% concentration which is administered in a single dose daily. latanoprost increases the outflow of aqueous through the uveoscleral pathways. it decreases the intraocular pressure (iop) by 25-32%. after administration it goes to peak at 10-14 hours, its wash out time is 4-6 weeks and maximum intraocular pressure lowering effect may take up to 6 weeks to occur. ocular side effects of latanoprost are increased pigmentation of eyelashes and iris, hypertrichosis, blurring of vision, keratitis, cystoid macular edema, anterior uveitis, hyperemia of conjunctiva, reactivation 80 a biannual peer-reviewed academic journal of nepal ophthalmic society of herpes keratitis, foreign body sensation, eye ache and irritation in eyes. systematically its side effects are flu like symptoms, joint pain, muscle pain and headache. latanoprost has a method of action that appears to be both pressure dependent and pressure independent. it has been shown that latanoprost results in increased spaces between the muscle fascicles within the ciliary body, presumably increasing aqueous flow and uveoscleral flow. latanoprost penetrates the cornea after being hydrolyzed by corneal esterase. bimatoprost is a prostaglandin analog and increases the outflow of aqueous fluid and lowers intraocular pressure. bimatoprost is absorbed through the cornea. it lowers intraocular pressure after four hours and lasts for 24 hours. a peak blood plasma concentrations is reached in 10 minutes and plasma protein binding is 88%. the biological half-life of bimatoprost is 45 minutes. drug excreted thru kidney is 67% and thru feces is 25%. the side effects of bimatoprost is conjunctival hyperemia, burning sensation, discomfort and permanent darkening of the iris. materials and methods this was a hospital based, prospective, comparative, single masked (observer masked) study on the patients attending glaucoma department of nepal eye hospital, kathmandu, nepal. patients who were given 0.005% latanoprost and patients who were given 0.03% bimatoprost, were randomly selected and study duration was one year. fifty cases of which % (25 cases were given 0.005% latanoprost and 25 cases were given 0.03% bimatoprost). inclusion criteria: diagnosed cases of primary open angle glaucoma, ocular hypertension with iop >24 mm hg and up to 35 mm hg and patients above 16 years of age. exclusion criteria: patients with iop greater than 35 mm hg, patients with normal intraocular pressure, patients with physiological cups, patients of congenital glaucoma , angle closure glaucoma, secondary glaucoma and who underwent filtering surgery were excluded. results there was a significant difference in iop at first visit and 6 months in both groups, p<0.001. (the t-test was used). however the mean difference of group b, 11.00 greater than group a, 9.92. on the basis of geographical distribution, out of fifty patients in this study 35 (70%) are urban and 15 (30%) are from rural populations. out of 50 patients, maximum numbers of patients were within the 16-30 years of age group i.e. 15 (30%), second highest group was 61—75 years of age groups it comprise 14 (28%) of patients, 11( 22%) of patients are of 46—60 years of age groups, 9 (18%) of patients are from 31—45 years of age group and only 1(2%) patient were from more than 75 years of age groups. kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 81nepalese journal of ophthalmology figure 1: age distribution of patients. figure 3: geographical distribution of patients. figure 3: geographical distribution of patients. figure 2: sex distribution of patients. figure 4: systemic disease in patients. figure 4: systemic disease in patients. pe rc en ta ge 35 30 25 20 15 10 5 0 16-30 31-45 46-60 61-75 >75 age in years pe rc en ta ge 70 60 50 40 30 20 10 0 hypertensioin dibetic mellitus no systemic disease 30 20% 18 14% 22 66% 28 male urban history of smoking family history of glaucomna female rural no history of smoking no family history of glaucoma 2 30% 28% 90% 66% 70% 72% 10% 34% kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 82 a biannual peer-reviewed academic journal of nepal ophthalmic society among fifty poag patients, 33 (66%) are males and 17 ( 34 %) are females, shows the result of this study. a study done at bp koirala lions center for ophthalmic studies on patients of glaucoma, among the primary open angle glaucoma patients 55.33% were males and 44.64% were females (neupane mp, 1996). in a framingham and barbados eye study males had a higher rate of primary open angle glaucoma (boldi fc, 1998). out of 50 (20 %) patients presented with hypertension, 7 (14 %) patients presented with diabetes mellitus and 33 (66 %) patients presented with no systemic history. study done at b p koirala lions centre for ophthalmic studies on association of primary open angle glaucoma with diabetes mellitus, out of 49 primary open angle glaucoma cases 5 had diabetes mellitus accounting for 10.2%. hence this study showed quite a large difference comparatively (khatri bb, 1999). among 50 patients 5 (10%) patients have a family history of glaucoma and 45 (90%) patients have no family history of glaucoma. it has been reported that 2.5 % of patients with primary open angle glaucoma are hereditary (dunbar hh et al, 1998). konavera et al suggested there is no association of family history, sex, hypertension, diabetes and refraction with poag and also shows disease has an early onset in cases with positive family history of glaucoma (konareva-kostianeva m, 1998). of 50 patients, 14 (28%) of patients have a history of smoking and 36 (72 % ) of patients have no history of smoking. s bonovas, k filioussi, a tsantes and v peponis’ study shows epidemiological association between cigarette smoking and primary open-angle glaucoma, a results suggest that current smokers are at significantly increased risk of developing poag.10 out of 50 patients 20 i.e. 40% of patients presents with complain of headache, 27 i.e. 54% of patients presents with complain of blurring of vision, 2 i.e. 4% of patients presents with complain of eye ache and 1 i.e. 2% of patients presents with complain of watering (bonovas s et al, 2004). discussion recent data from several studies show the clinical relevance of patients achieving specific low target pressures. according to advanced glaucoma intervention study (agis), glaucoma table 1: iop at first visit and six month visit. mean iop at first visit mean iop at 6 month mean difference p value group a 27.16 17.24 9.92 <0.001 group b 26.88 15.88 11.00 <0.001 kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 83nepalese journal of ophthalmology is an optic neuropathy which is associated with retinal ganglion cell death and results in visual field loss. increased intraocular pressure is a primary risk factor for the glaucoma and is a prime target for therapy. recently, a large, randomized clinical trial demonstrated that the risk of progression of glaucomatous visual field loss is reduced at lower iops (agis investigators, 2000). in addition, results from the ocular hypertension treatment study (kass m.a. et al, 2002) showed that a 20% iop reduction from baseline decreased the risk of developing optic disk cupping and/or visual field loss in ocular hypertensive patients from 9.5% to 4.4%. both bimatoprost and latanoprost have been shown to be effective iop-lowering agents in double-masked clinical comparisons with timolol (brandt j.d. et al, 2001; sherwood m et al, 2001; alm a et al, 1995; camras cb et al 1996; watson p et al 1996). two short-term, randomized, clinical comparisons of bimatoprost and latanoprost suggest, however, that bimatoprost provides better iop control than latanoprost (the latanoprost study group, 1996; dubiner h et al, 2001). it is also important to assess the differences observed between the treatment groups in a clinical trial. the clinical significance of the greater iop lowering achieved with bimatoprost can be analyzed by the number of patients reaching specific target pressures. clinicians define a desired iop range as a goal of glaucoma therapy (gandolfi s et al, 2001). glaucoma patients with iops consistently below 18 mm hg had no discernible additional visual field loss over a 6-year follow-up period. similarly, a study by mao and associates (singh k et al, 2000) found that all eyes with a mean iop of 16 mm hg remained stable, and eyes with higher iops showed an increasing risk of disease progression. glaucoma patients with iops consistently lower than 18 mm hg had no additional visual field loss over a 6-year follow-up period. similarly, a study by mao and associates (mao lk et al, 1991) found that all eyes with a mean iop of 16 mm hg remained stable, whereas eyes with higher iops showed an increasing risk of disease progression. conclusion male gender, increasing age, urban population, hypertension, diabetes mellitus, and high intraocular pressure were the most prevalent risk factors for primary open angle glaucoma. the most important factor is early detection of signs and symptoms of poag and measurement of diurnal intraocular pressure. the study shows that bimatoprost (0.03%) provides better iop control compared to latonoprost (0.005).. nepjoph kausar n and thapa k comparative study of latanoprost and bimatoprost in poag nepal j ophthalmol 2022; vol 14(28):78-85 84 a biannual peer-reviewed academic journal of nepal ophthalmic society references agis investigators (2000). the advanced glaucoma intervention study (agis): 7. the relationship between control of intraocular pressure and visual field deterioration. am j ophthalmol, 130, pp.429-440. alm a, stjernschantz j and scandinavian latanoprost study group (1995). effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning: a comparison with timolol. ophthalmology, 102(12), pp.1743-1752. boldi fc (1998). glaucoma. american academy of ophthalmology. bonovas s., filioussi k., tsantes a. and peponis v. 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