Microsoft Word - Irfan Shafiq.doc 221 Original Article Pseudoexfoliation (PEX) Glaucoma Over the Age of 40 Years; a Hospital Based Study Irfan Shafiq, Khwaja Sharif-ul-Hasan Pak J Ophthalmol 2007, Vol. 23 No.4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . See end of article for authors affiliations …..……………………….. Correspondence to: Irfan Shafiq Eye Unit I, Dow University Health Sciences Civil Hospital Karachi Received for publication April’ 2007 …..……………………….. Purpose: To determine the prevalence of Pseudoexfoliation (PEX) glaucoma in patients over the age of 40 years who presented at eye department of Baqai Medical University hospital, Karachi for examination. Material and Method: This hospital based prospective case study was carried out at the department of Ophthalmology, Baqai Medical University Hospital, Karachi from August 2000 to January 2004. A total of 3195 patients of 40 years and above were examined on slit-lamp for evidence of PEX syndrome and glaucoma and those found to be having the disease were subjected to further thorough examination including visual acuity, Goldmann applanation tonometry, gonioscopy, slit lamp examination before and after dilatation of the pupil, fundus examination and visual field examination. Results: Out of 3195 patients 58 (1.81%) were found to be having PEX syndrome, out of which 21 patients showed PEX glaucoma. Out of 3195 patients 1807 (56.55%) males and 1388 (43.44%) were females. Male to female ratio of PEX was 2:1. The prevalence increased with advancing age. Conclusions: PEX syndrome and glaucoma is more common in males and increases with advancing age. hen an eye with Pseudoexfoliation (PEX) develops glaucoma the condition is referred to as pseudoexfoliative glaucoma, exfoliative glaucoma or capsular glaucoma1. Glaucoma results from combination of exotrabecular and endotrabecular PEX material, increased aqueous protein and deposition of PEX material on trabecular meshwork and corneal endothelial proliferation2. Study showed that eyes with PEX had a 5 fold increased risk of glaucoma. This risk was independent of other known glaucoma risk factors including intraocular pressure (IOP)3. The first description of PEX syndrome reported in Scandinavian literature in 1917, when Lindberg, a Finnish ophthalmologist described the appearance of flakes at the pupillary border of the iris in 30 out of 60 patients having chronic simple open angle glaucoma. He believed the flakes to be the result of earlier inflammation4. In 1925, Swiss ophthalmologist Alfred Vogt established the association of the condition with glaucoma and originated the term “Glaucoma Capsulare” for it5. Another Swiss author Malling in 1923 reported the presence of changes in the anterior lens capsule in 40% of his patients with chronic glaucoma and thought that exfoliation and glaucoma were associated6. In 1956, Sunde proposed the term “Exfoliation syndrome” to signify multiple tissues involvement as opposed to the previous belief that the anterior lens capsule is involved7. Streeten et al studied extra ocular sites for the evidence of PEX material and their study suggests that PEX may be the ocular manifestation of a systemic derangement in the elastic tissue synthesis closely related to elastosis8. Now it has been established that in Pseudoexfoliation syndrome there is bluish-white W 222 flaky material deposition at the pupillary border, membrane like deposits on the anterior lens capsule in the center and as granular deposits on the periphery of the lens. In the angle, on zonules and on ciliary processes, it is seen as white gray fluffy masses, while on the corneal endothelium it appears as gray small keratic precipitates (KPs)9. PEX material appears to be produced by the equatorial lens capsule, iris pigment epithelium and non-pigmented ciliary epithelium secondary to abnormal basement membrane produced by ageing epithelial cells10. The disease is of insidious onset with minimal symptoms, so the ophthalmologist should look for early signs when the patient either presents with monocular glaucoma or some other ocular problem11. There is also involvement of the conjunctiva, skin, heart, lung, liver, kidney, cerebral meninges and gall bladder and histological studies show that the material is deposited in these tissues12. The material has also been demonstrated in the walls of the short posterior ciliary arteries13. It is both histochemically and ultra structurally similar to amyloid10. PEX can cause glaucoma, poor pupillary dilatation, posterior capsular rupture, vitreous loss, phacodonesis10 and keratopathy14. As the disease was first described in the Scandinavian countries especially in Norway and Finland, the initial impression was that it was more prevalent in that region than elsewhere15. However a careful search for the disease in other countries led to accumulation of information from all over the world and the condition is reported from other countries16. Variations in the prevalence of PEX syndrome have been reported. In one study, Aasved reported incidence of PEX of 4.0% in England, 4.7% in Germany and 6.3% in Norway17. In Pakistan the prevalence has been reported as 1.2% in persons over 40 years of age and 5.1% in those over 60 years of age18. There are multiple factors affecting the prevalence of the disease. This is a disease of old age. The usual age prevalence is between 60 and 80 years of age19. Its prevalence steadily increases after the age of 60 with a mean age in early 70’s20. However with decreasing frequency it is also found in the young individuals and the youngest patient reported is at the age of 32 years from Pakistan21. It occurs equally in both sexes but is found some years earlier in males than females20. Hereditary factors in the form of autosomal dominant trait or X- linked with poor penetrance are postulated by some authors22. HLA linkage with PEX is identified for 14 antigens. Eleven antigens (HLA A1, A33, B8, B47, B51, B53, B57, B62, DR3, DR12, and DR13) are statistically significantly common in the PEX while three antigens (HLA B12, B17 and DR2) are significantly less common. This HLA association is evidence for a genetic component to the development of PEX23. Familial occurrence and hypothesis that PEX syndrome is genetically inherited are reported24. Clinical classification of the various stages of PEX is based mainly on the findings of the anterior lens capsule2. Suspect Early PEX (exfoliative material: precapsular layer) Masked PEX (posterior synechiae with other obvious cause) Definite Mini PEX (focal defects in precapsular layer nasally and superiorly) Classical PEX (late stage) (Figure I) Variable data is available regarding raised IOP and glaucoma in PEX syndrome. In one study ocular hypertension was present in 15% of patients having PEX syndrome, while glaucoma was present in 7% of patients having PEX syndrome25. Irvine in a review of literature reported the figures as 14%-90% from different authors4. In Pakistani survey 30% patients with PEX syndrome had an IOP more than 20mmHg18. The subsequent occurrence of raised IOP in patients having PEX syndrome and normal IOP at the initial examination is 5% at 5 years and 15% at 10 years26. If one eye has glaucoma and fellow eye shows PEX, the risk of glaucoma in the fellow eye within 5 years is about 50%26, while some reports put the figures at 7- 20% in 5 years and 9-24% in 10 years1. In those having bilateral PEX syndrome but unilateral glaucoma, 21- 26% will develop glaucoma in the other eye in next 5 years1. MATERIAL AND METHODS This prospective analytic study was undertaken at the department of ophthalmology, Baqai Medical University hospital Karachi from August 2000 to January 2004. Inclusion criteria, all patients 40 years of age and above came in eye O.P.D of Baqai Medical University hospital with various ocular problems. Exclusion criteria, patients below the age of 40 years. 223 A total of 3195 patients, 40 years of age and above attending the out patient department for various ocular problems were screened for PEX syndrome and PEX glaucoma. The initial examination consisted of slit-lamp biomicroscopy for evidence of PEX material on the edge of pupil or lens in undilated state and in those having suspicion of the disease, the pupils were dilated and repeat slit-lamp examination was performed (Figure 1,2). Those patients having PEX syndrome were further examined in detail, according to an examination protocol and all the findings were entered in the especially designed proforma for this study. The examination included complete history, general physical and systemic examination and full ocular examination. The ocular examination included visual acuity testing, slit-lamp examination of the anterior segment, transillumination, gonioscopy, applanation tonometery and fundus examination. Visual fields were recorded in those with high IOP and/or cupping of the disc (Figure 2). RESULTS Out of 3195 patients examined 1807 (56.55%) were males and 1388 (43.44%) were females. In age group 40-49 years, total 1332 patients were examined, 705 (52.92%) were males and 627 (47.07%) females. In age group 50-59 years, total 922 patients examined, 508 (55.09%) were males and 414 (44.90%) were females. In age group 60-69 years, 552 patients examined, 334 (60.50%) were males and 218 (39.49%) were females. In age group 70 and above, total 389 patients were examined, 260 (66.83%) were males 129 (33.16%) were females (Table 1). Table I: Total number of male and female patients examined in different age groups. Age Groups Males Females Total 40-49 years 705 627 1332 50-59 years 508 414 922 60-69 years 334 218 552 70 & above 260 129 389 Total Patients 1807 1338 3195 A total number of 6390 eyes of 3195 patients were examined for Pseudoexfoliation (PEX) syndrome and glaucoma. Those having PEX syndrome were 58 (1.81%) out of which 21 patients had PEX glaucoma (0.65%). Out of 58 patients with PEX syndrome 41 (70.68%) were males and 17 (29.31%) were females. Those having PEX glaucoma were 21 out of which 14 (66.66%) were males and 7 (33.33%) were females (Graph I & Table 2). In age group 40-49 years, total 1332 patients were examined and 5 cases (0.37%) of PEX syndrome and 1 case (0.07%) of PEX glaucoma were detected. In age group 50-59 years, total 922 patients were examined and 7 cases (0.75%) of PEX syndrome and 2 cases (0.21%) of PEX glaucoma were detected. In age group 60-69 years, total 552 patients were examined and 17 cases (3.07%) of PEX syndrome and 6 cases (1.08%) of PEX glaucoma were detected. In age group 70 and above, total 389 patients were examined and 29 cases (7.45%) of PEX syndrome and 12 cases (3.08%) of PEX glaucoma were detected (Graph II & Table 3). DISCUSSION Earlier prevalence studies are biased due to the detection of the condition in the Scandanavian countries and most of the earlier authors believed that the condition is more prevalent in the Scandanavian countries27. However one study of 2058 patients over age 60 examined by a single investigator in three countries, Aasved reported similar prevalences PEX of 4.0% in England, 4.7% in Germany and 6.3% in Norway17. Although wide variation in the prevalence of PEX syndrome and glaucoma have been reported, these variation may be due to differences in the definition of disease, population studied, age and sex distribution and examination techniques1. Studies from this subcontinent are those of Irvine 8% at Madras, India4, 9% cases from Simla India28 are available. In Pakistan the prevalence has been reported as 1.2% in persons over 40 years of age and 5.1% in those over 60 years of age18. Our figure of PEX syndrome and PEX glaucoma are 1.8% and 0.65% respectively in general population of 40 years and above are comparable to the other study in this part of the world of 1.2% in patients over 40 years of age. The increased prevalence in our study may be due to the higher number of elderly patients examined rather than true difference. In this study prevalence of 3.07% in persons 60-69 years age group and 7.45% in persons 224 70 years and above group is comparable to that of Aasvad’s study17 and study from Pakistan29. As the disease usually affects the elderly and a steady increase in prevalence occurs with advancing age20. Our data also supports this observation. The disease is thought to occur in an earlier age group in some communities, the youngest in our study is a 42 years old male having unilateral PEX syndrome. While from Pakistan a lady of 32 years of age is reported as the youngest21. Male or female preponderance is not yet settled, some studies have shown that PEX is more common among men, several American and European series have indicated that PEX is more common in women1. For Pakistan a previous study reported a male preponderance with a ratio of male to female of 3:118. Our study also substantiates the previous results and shows male preponderance with a ratio of male to female of 2:1. Laterality of the condition is also not settled and various reports speak of different figures 57% unilateral cases in one study, while figures from Pakistan are 20% unilateral in one18 and 25% in another study21. In our study the prevalence is unilateral in 34.37% of the patients. Variable data is available regarding glaucoma in PEX syndrome. Irvine in review of literature reported the figures as 14%-90% from different authors4. In Pakistani survey 30% patients with PEX syndrome had an IOP more than 20mmHg. Our study shows 36.2% association of glaucoma with PEX syndrome which is higher than data available. It may be due to late age of presentation of PEX syndrome. The fact that diagnosis of the condition depends on thoroughness of examination because the disease is asymptomatic. This may be the cause of differences in the prevalence reported by different authors. CONCLUSION Pseudoexfoliation glaucoma more commonly occurs in males and its prevalence depends on age and it increases with the age of patients. Table 2: Prevalence of Pseudoexfoliation glaucoma and syndrome in different gender. Gender Examined Pseudoexfoliation Syndrome Pseudoexfoliation Glaucoma No. of Eyes No. of Eyes No. of Patients No. of Eyes Prevalence (%) No. of patients No. of eyes Prevalence (%) Male 1807 3614 41 82 2.26 14 28 0.77 Female 1338 2776 17 34 1.27 7 14 0.52 Total 3195 6390 58 116 1.81 21 42 0.65 Table 3: Prevalence of Pseudoexfoliation glaucoma and syndrome in different age group. Age groups Examined Pseudoexfoliation Syndrome Pseudoexfoliation Glaucoma No. of Patients No. of eyes No. of Patients No. of eyes Prevalence (%) No. of Patients No. of eyes Prevalence (%) 40-49 years 1332 2664 5 10 0.37 1 2 0.07 50-59 years 922 1844 7 14 0.75 2 4 0.21 60-69 years 552 1104 17 34 3.07 6 12 1.08 70 & 389 778 29 58 7.45 12 24 3.08 225 above Total 3195 6390 58 116 1.8 21 42 0.65 Fig. 1: Schematic representation of clinical classification of PEX syndrome. Photograph showing membrane like deposition of PEX material on lens capsule. Photograph showing granular like deposition of PEX material at pupillary border. Fig. 2: Showing visual field defect in a patient with PEX glaucoma. 226 TOTAL NUMBER OF PATIENTS 3137 58 Patients without PEX Patients with PEX Graph 1: Showing total number of patients with and without Pseudoexfoliation (PEX) syndrome. 1327 5 915 7 535 17 360 29 0 200 400 600 800 1000 1200 1400 Number of Pts 40-4 9 Y ears 50-5 9 Y ears 60-6 9 ye ars 70 & abo ve AGE DISTRIBUTION OF PEX Pts without PEX Pts with PEX Graph 2: Showing pseudoexfoliation glaucoma in different age group. Author’s affiliation Dr. Irfan Shafiq Assistant Professor Eye Unit I, Dow University Health Sciences Civil Hospital Karachi. Prof. Khwaja Sharif-ul-Hasan Professor and Chairmen Ophthalmology Department Baqai Medical University Hospital Karachi. REFERENCES 1. Skuta GL. Pseudoexfoliation syndrome. In Tasman W and Jaegar E.A (eds) “Duane’s Clinical Ophthalmology”. Volume 3 chapter 54B. Philadelphia: J B Lippincott Company. 1997: 1-10. 2. Gottfried OH. Naumann, Ursula Schlotzer-Schrehardt & Michael Kuchle. 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