December 2008 no white pages.indd ABSTRACT Objective: Pseudoexfoliation (PEX) syndrome is one of the leading causes of secondary open angle glaucoma and blind- ness. This study explored whether in PEX eyes, preoperative changes in corneal endothelial cell morphology might be a risk factor for postoperative corneal decompensation. Methods: One hundred twenty six eyes of 69 preoperative cataract patients (43 males, 26 females) were enrolled in this cross-sectional study from the Ophthalmology Department at Sultan Qaboos University Hospital between 2003-2005. All patients were subjected to confocal biomicroscopy. Results: The mean age of patients with PEX eyes was 63.2 years. One hundred and eight (85.7%) eyes with PEX had endothelial cell counts within the normal range (650-3500/mm²). The qualitative morphology of the endothelium of PEX corneas was highly abnormal in term of polymegathism and pleomorphism. Twelve eyes had endothelial cell counts higher than normal for that age group. Only 6 eyes had endothelial cell counts lower than normal. The mean value for the pleomorphism was found to be significantly lower than normal and for polymegathism significantly more than normal. The relationship between pleomorphism and polymegathism was stronger for males than for females and stronger for patients under 60 years than patients over 60 years. The same relationship between pleomorphism and polymegathism showed a stronger relationship for the glaucoma group as compared to the non-glaucoma group. Conclusion: This study revealed that corneal decompensation in PEX eyes can occur in presence of abnormalities in polymegathism and pleomorphism, even when the endothelial cell counts may be normal. Key Words: Pseudoexfoliation; Pleomorphism; Polymegathism; Confoscan. Quantitative and Qualitative Corneal Endothelial Morphology of Omani Patients with Pseudoexfoliation Syndrome *Upender K Wali,1 Abdullah S Al-Mujaini,1 Nadia S Al-Kharusi,1 Alexander A Bialasiewicz,1 Syed G Rizvi2 Departments of 1Ophthalmology, 2Family Medicine and Public Health, Sultan Qaboos University, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: wali@squ.edu.om مبتالزمة املصابني العمانيني املرضى لدى قرنية العني بطانة خاليا وضع الكاذب لعدسة العني التقشر ريزفي سيد بيالسويتز، أليكاسندر نادية اخلروصي، ايني، والي، عبداهللا أوبندار املصابة العني أن حيث ، والعمى الثانوي األزرق باملاء اإلصابة إلى املؤدي الرئيسي العني السبب لعدسة الكاذب التقشر متالزمة امللخص: الهدف: تعتبر ــة الدراس الطريقة: في هذه العملية. بعد القرنية تدهور تؤدي إلى قد قبل العملية القرنية ــا بطانة خالي في تغيرات يرافقها من وما ــة املتالزم ــك بتل جامعة ــفى العيون مبستش أمراض ــم قس في األبيض املاء عملية نزول إجراء قبل 26 أنثى) و (43 ذكرا 69 حالة ل 126 عينا ــة مت دراس املقطعية عمر متوسط النتائج: بلغ الدقيق. العني احليوي مجهر بواسطة فحصهم مت كل املرضى 2005 ميالدية. 2003 إلى بني الفترة قابوس في السلطان -1650) العني بطانة في خاليا ــا تعدادا طبيعي (85.7%) 108 عينا أظهرت 63.2 عاما. ــني الع ــة الكاذب لعدس ــر املصابني مبتالزمة التقش املرضى خاليا تعداد كان فقد ــكالها. أش وتعدد اخلاليا حجم اختالف ناحية من كبيرة بصورة طبيعي غير كان اخلاليا فقد لنوع ــبة بالنس 3500/ملم² ). أما متوسط كان كما ل6 عيون. املستوى الطبيعي من أقل ، بينما كان التعداد في تلك الفئة العمرية الطبيعي املستوى من أعلى 12 عينا ل البطانة وتعدد حجم بني كانت العالقة الطبيعي. ــتوى املس من اخلاليا أقل حجم ، بينما كان عن الوضع الطبيعي ملحوظ ــكل أعلى بش اخلاليا ــكال أش تعدد أيضا كبيرة العالقة هذه كانت كما 60 عاما. أعمارهم تتعدى الذين للمرضى كبيرا كان كما باإلناث ، الذكور مقارنة املرضى في كبيرا اخلاليا أشكال الكاذب ميكن التقشر املصابة مبتالزمة للعني القرنية تدهور أن الدراسة هذه اخلالصة: تبني املصابني. غير األزرق مقارنة باملرضى باملاء املصابة الفئة بني طبيعيا. اخلاليا كان تعداد وان حتى أشكالها تعدد وفي اخلاليا في حجم طبيعية غير عالمات يظهر أن الدقيق. العني مجهر ، العني بطانة خاليا حجم العني ، بطانة خاليا أشكال تعدد ، العني لعدسة الكاذب التقشر الكلمات: متالزمة مفتاح SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL NOVEMBER 2008, VOLUME 8, ISSUE 3, P. 300-305 SULTAN QABOOS UNIVERSITY© SUBMITTED - 29TH MARCH 2008 ACCEPTED - 21ST JULY 2008 C L I N I C A L A N D B A S I C R E S E A R C H Q UA N T I TAT I V E A N D Q UA L I TAT I V E C O R N E A L E N D O T H E L I A L M O R P H O L O G Y O F O M A N I PAT I E N T S W I T H P S E U D O E X F O L I AT I O N S Y N D R O M E 301 SINCE 1917 WHEN THE FINNISH ophthalmologist Lindberg first described thepseudoexfoliation (PEX) syndrome, the main intraocular production sites of PEX material have been identified as the epithelial cells of the lens cap- sule, the iris, the non-pigmented ciliary epithelium, and the trabecular meshwork, as well as the corneal endothelial cells.1 Since PEX is also associated with hypoxia of the anterior segment, it seems pertinent to acquire more knowledge of the in vivo morphology of corneal endothelial cells in addition to the existing histopathological features in order to predict prob- lems for intraocular surgery in these eyes. The PEX syndrome is a systemic disease with mainly ocular manifestations.1 Its most common systemic mani- festations include ischaemia, infarctions and strokes involving the myocardium, bowels and intracranial structures. Epidemiologically, PEX has a wide geo- graphical distribution with the highest incidence in countries prone to ultra-violet light, in northern lati- tudes and at high altitudes.2, 3 The prevalence of PEX is variable: USA (1.6%), Germany (4.0%), England (4.7%), France (5.5%), Nor- way (6.3%), Saudi Arabia (13%), Finland (20%), and Iceland (25% - in more than 60 years of age). The risk of developing glaucoma in PEX is 20-77%.1, 4 Aasved found a nine fold increase in prevalence of PEX in first degree relatives over age of 40 years compared to the general population, suggesting an autosomal domi- nant inheritance.5 This study was commenced with the aim of high- lighting the importance and need for preoperative evaluation of corneal endothelial cells in PEX eyes in the Omani population undergoing cataract, or other intraocular anterior segment surgery. M E T H O D S A total of 69 adult patients (43 males and 26 females) and 126 eyes (78 male eyes and 48 female eyes), who met the inclusion and exclusion criteria, were enrolled in this study. The inclusion criterium was patients aged 40 years and above. Eyes with any other corneal pathology or prior surgery that would prevent reliable confocal microscopy were excluded. All patients were subjected to refraction, applana- tion tonometry, slit-lamp biomicroscopy, gonioscopy and fundus examination. Eyes confirmed to have PEX on the anterior lens capsule, iris and/or endothelium before or during mydriasis were subjected to a con- focal microscopic examination (Confoscan 2, Nidek Japan). Patients diagnosed with glaucoma were exam- ined by frequency-doubled perimetry (MatrixR, Zeiss- Humphrey), Humphrey automated perimetry and OCT 2 papillometry (OCT 2 Nidek). Confocal biomicroscopy was done under topical anesthesia (benoxinate 0.4%) using sterile transparent gel as a coupling medium. The confocal microscopy outcome of corneal en- dothelium was assessed in terms of endothelial cell count, polymegathism and pleomorphism. The en- dothelial cell count was calculated on the basis of a sample size which was different for different eyes and compared with age-matched mean values for other studies in the normal population. The pleomorphism and polymegathism values were defined against normal values of >59.0 for ple- omorphism and <30.0% for polymegathism, which means that a normal healthy cornea should have at Advances in Knowledge • Ocular Pseudoxfoliation syndrome induces structural changes in the morphology of the cornea that directly reflects the high risk of postoperative corneal decompensation. • Confocal scans can help the surgeon predict this possibility and so properly counsel the patient prior to the surgery. • This can make postoperative management more specific and result oriented. Application to Patient Care • The study shows the importance of confocal biomicroscopy in ocular pseudoexfoliation syndrome. • Patient care can be more predictive and specific if the corneal status is known preoperatively. • This can make postoperative management more specific and result oriented. U P E N D E R K WA L I , A B D U L L A H S A L - M U J A I N I , N A D I A S A L - K H A R U S I , B I A L A S I E W I C Z A A A N D S Y E D G R I Z V I 302 least 60% endothelial cells with regular shape or hex- agonality and should not have abnormal endothelial cell sizes or areas (normal 312-320 micron square) in more than 30% of cells. The Statistical Package for the Social Scienes (SPSS software, Version 10) was used for the analysis of the data and to make the figures. The Student’s t-test was applied to test the significance difference between the means of the groups for the variables under study and the chi-square test was used to compare the categori- cal variables. A p-value of .05 or less was taken as sig- nificant. Selection of the type of regression curve is based on the R2-values for different types of regression [Table 4]. A higher degree curve was preferred only when the difference in R2 -values was significant. R E S U L T S Sixty nine patients (43 males, 26 females), with 126 eyes diagnosed to exhibit ocular PEX on slit-lamp bi- omicroscopy, were selected for morphometric analysis of corneal endothelium by Confoscan 2 (Nidek). All the patients were of Omani origin. The patient characteristics were as follows, [Table 1]: The mean age of the patients was 63.45 ± 7.40 years for males and 62.77 ± 7.85 years for females. Of 126 PEX eyes the majority of patients (42.9%) belonged to age group 61-70 years, followed by 38.1% in 51-60 years age group, 15.9% in >70 years age group and 3.2% aged <50 years. The mean age for patients with PEX glaucoma was 60.81 years as compared to 64.65 years in patients with PEX without glaucoma, suggest- ing a younger age group for PEX glaucoma. The endothelial cell count [Tables 1 & 2] was as follows: Seventy eight male PEX corneas had a mean endothelial cell counts of 2463.18 ± 485.28 cells/mm² compared to 2470.21 ± 544.93 cells/mm² for 48 female PEX corneas; this difference was not found to be sta- tistically significant (p = 0.942). The overall mean en- dothelial cell count for all 69 patients with 126 PEX eyes was 2465.86 ± 506.68 cells/mm². The endothe- lial cell count of PEX eyes in this study was found to be within the normal range in 86.5%. Only 3.2% of PEX eyes had endothelial cell counts less than age- matched normal eyes. A total of 10.3% PEX eyes had endothelial cell counts that ranged even higher than that of age-matched control eyes. Most frequently (62 PEX eyes) the endothelial cell counts ranged between 2000-2500 cells/mm², and six eyes even had endothe- lial cell counts of more than 3500 cells/mm². The mean endothelial cell count for the PEX eyes with glaucoma (48) was 2438 ± 503.4 (1579-3974) compared to 2483 ± 511.2 (1595-4239) in PEX eyes without glaucoma (78); this difference was also not found to be statisti- cally significant (p = 0.629). As far as pleomorphism and polymegathism [Ta- ble 1 & 2] were concerned the following results were found. The pleomorphism (loss of hexagonality) data were abnormal in 122 PEX eyes (96.8%). Only four PEX eyes had pleomorphism of 60 and above (normal > 59.0%). Similar changes in cell density and hexago- nality have been reported by Hatorri.6 Forty three PEX eyes had pleomorphism values in the range of 20-30. The mean pleomorphism for 126 eyes was 34.63% ± 11.92 (normal >59.0%). In spite of having slightly and statistically non-significant lower endothelial cell counts compared to females, the males showed better, though statistically non-significant, pleomorphism values (34.70% ± 11.90) compared to females (34.52% ± 12.12). Males (78) Females (48) Total (126) PEX with Glaucoma (48) PEX with no Glaucoma (78) Age 63.45 ± 7.40 (49 - 84) 62.77 ± 7.85 (41 - 76) 63.19 ± 7.55 60.81± 8.33 (41 - 84) 64.65 ± 6.67 (49 - 76) Endothelium 2463.18 ± 485.28 (1579 - 3974) 2470.2± 544.9 (1595 - 4239) 2465.9 ± 506.7 2438.0 ± 503.4 (1579 - 3974) 2483.0 ± 511.2 (1595 - 4239) Pleomorphism 34.70 ± 11.90 (7.70 - 69.80) 34.52 ± 12.12 (16.2 - 59.8) 34.63 ± 11.92 37.09 ± 12.43 (16.2 - 65.4) 33.12 ± 11.44 (7.7 - 69.8) Polymegathism 57.89 ± 15.66 (28.3 - 103.5) 60.10 ± 18.14 (30.7 - 105.1) 58.73 ± 16.61 59.69 ± 16.79 (30.0 - 105.1) 58.14 ± 16.58 (28.3 -105.1) Each cell display; Mean ± SD and (Minimum value, Maximum) Table 1: Characteristics of 126 PEX eyes Q UA N T I TAT I V E A N D Q UA L I TAT I V E C O R N E A L E N D O T H E L I A L M O R P H O L O G Y O F O M A N I PAT I E N T S W I T H P S E U D O E X F O L I AT I O N S Y N D R O M E 303 The eyes with PEX glaucoma had more pleomor- phism (37.09 ± 12.43) than eyes with PEX without glaucoma (33.12 ± 11.44) [Table 1]. Polymegathism was very frequent in 124 PEX eyes (98.4%) exhibiting abnormal size and area of endothe- lial cells (average area of a normal endothelial cell is 312-320µ²). The normal value for polymegathism is <30.0%. In this study, only two eyes had normal cell size/area, or had polymegathism <30.0%. The mean value for polymegathism in 126 eyes was 58.73% ± 16.61 (normal <30.0%). Females showed more abnor- mal values for polymegathism (60.10% ± 18.14) than males 57.89 ± 15.66), although it was not a statistically significant result. Eyes with PEX glaucoma had more polymegath- ism (59.69 ± 16.79) than PEX eyes without glaucoma (58.14 ± 16.58) [Table 1]; however, this difference was not significant. The quadratic relationship of pleomorphism on polymegathism displayed a strong inverse relationship. Classifying this relationship into different categories, it was observed that this relationship is stronger for males (R2 = 0.638) than females (R2 = 0.602). The same association was found stronger in the under 60 years old age group (R2 = 0.727) as compared to above 60 years old age group (R2 = 0.581). Classify- ing the same relationship according to glaucoma ver- sus non-glaucoma groups, it was observed that eyes with PEX glaucoma exhibit a stronger relationship (R2 = 0.766) than PEX eyes without glaucoma (R2 = 0.604), [Table 4]. However, the relationship between endothelium and polymegathism was not as strong as the relation- ship between pleomorphism and polymegathism. Even the cubic regression of endothelium on polymegath- ism did not exhibit a strong relationship for the same categories: gender groups: males (R2=0.121) versus fe- males (R2 = 0.167); age groups: <60 years (R2 = 0.129) versus > 60 years (R2 = 0.129), and glaucomas: (R2 = 0.142) versus non-glaucomas (R2 = 0.121) [Table 4]. PEX-glaucoma eyes were then compared with non- glaucomatous eyes. The mean age of PEX patients with glaucoma (60.81 years ± 8.33) was found to be signifi- cantly lower than the mean age of the PEX patients without glaucoma (64.65 years ± 6.67, p = 0.005); also, among the ≤60 years old age group (52 eyes), 55.8% were glaucoma cases, compared to only 25.7% glauco- ma cases among > 60 year old age group (74 eyes). This difference was also found to be statistically significant (p = .001), evidencing a trend for the predominance of PEX glaucoma in the younger age group, maybe due to earlier and better means of diagnosis. PEX glaucoma seems more common among males (41%) than in females (33.3%), however, this difference was not found to be statistically significant. The mean endothelial cell count for PEX glaucoma eyes (2438.0 ± 503.43 cells/mm²) was less than for non- glaucomatous PEX eyes (2483 ± 511.46 cells/mm²). Higher values for pleomorphism were found in eyes with PEX glaucoma (37.09 ± 12.43) compared to PEX eyes without glaucoma (33.12 ± 11.44). Polymegath- ism was slightly more prevalent (59.69 ± 16.79) in PEX Factor Normal High Low Endothelium 108 (85.7%) 12 (9.5%) 06 (3.2%) Pleomorphism 04 (3.2%) Not applicable 122 (96.8%) Polymegathism 02 (1.6%) 124 (98.4%) Not applicable Table 2: Abnormal values/cells of different factors in 126 PEX eyes Factors/variables Pearson correlation Significance Endothelium versus Pleomorphism - 0.246 p = .005 Endothelium versus Polymegathism 0.072 Not significant Pleomorphism versus Polymegathism - 0.683 p < .000001 Table 3: Correlations and their significance U P E N D E R K WA L I , A B D U L L A H S A L - M U J A I N I , N A D I A S A L - K H A R U S I , B I A L A S I E W I C Z A A A N D S Y E D G R I Z V I 304 glaucoma compared to PEX eyes without glaucoma (58.14 ± 16.58); the above mentioned differences were not found to be statistically significant [Table 1]. The statistical evaluation is shown in Table 2. Ac- cording to Pearson’s 2-tailed correlation significance, the following parameters revealed statistically signifi- cant values (p = .005 or p <.005): 1. Pleomorphism and polymegathism for age groups <60 years versus >60 years in PEX eyes 2. Pleomorphism and polymegathism for male and female PEX eyes versus non-PEX eyes. 3. Pleomorphism and polymegathism for glaucoma- tous versus non-glaucomatous PEX eyes. A significant inverse relationship was found between endothelium and pleomorphism (p = .005) and a very strong inverse relationship was observed between en- dothelium and polymegathism (p < .00001) [Table 3]. D I S C U S S I O N This study has shown in vivo that the corneal endothe- lium is significantly affected quantitatively and quali- tatively by cells producing pseudoexfoliation material. Similar changes have been reported by Miyake et al.7 PEX eyes with glaucoma have more polymegathism than PEX eyes without glaucoma. The qualitative changes of the corneal endothelium by PEX, in the form of degenerating, irregular, loosely adherent cells have also been reported by Schlotzer et al.8 Seitz and Naumann have reported 85% polymegathism in PEX endothelial cells compared to 98.4% in our study.9 In another series, the same authors have reported 77% pleomorphism compared to our data of 96.8%. The difference could be due to more severe PEX in our patients. This study, however, revealed more pleomor- phic values for PEX eyes with glaucoma than PEX eyes without glaucoma. In contrast to their data, this study shows normal age-matched cell counts in most of the PEX eyes. Most of the recent series from different countries show a fe- male preponderance of PEX; however, reports from Ethiopia,10 Greece11 and Oman4 show that males are affected more than females. Notwithstanding, these data may be biased since the diagnoses have mainly been done on clinical grounds. Our study has revealed PEX glaucoma in a younger age group which means that these patients should be followed up early in life. The present study shows less endothelial cell counts in the PEX eyes with glaucoma as compared to PEX eyes without glaucoma. The difference, how- ever, is not significant. This observation is supported by Knorr et al.12 Thus, even though endothelial cell counts may be normal in age-matched PEX eyes, the latter may exhibit significant morphological changes with respect to their size/area (polymegathism) and shape/hexagonality (pleomorphism). This could be the reason for PEX keratopathy with subsequent early and rapid corneal decompensation.13 Since cataract is the most common anterior segment intraocular sur- gery performed world wide, the implications of PEX on corneal endothelial cells are quite demanding.14,15 The overall incidence of intra-operative complica- tions in PEX eyes has been reported to be 4-7% de- pending on the preexisting pathology. The general clinical opinion is that in PEX eyes a prolonged cor- neal recovery after intraocular surgery is frequent. This study has shown that corneal endothelial cell anomalies may provide a morphological basis for this event. The data clearly emphasises the importance of preoperative confocal analysis of PEX corneas. Table 4: R2 values for different type of regression curves Type of regression Regression curve of: Linear Quadratic Cubic Pleomorphism on Polymegathism Males and Females Age ≤ 60 yrs. and Age > 60 yrs, Glaucoma and No glaucoma 0.467 0.461 & 0.484 0.586 & 0.406 0.643 & 0.402 0.619 0.638 & 0.604 0.725 & 0.573 0.765 & 0.604 0.625 0.648 & 0.603 0.727 & 0.581 0.765 & 0.623 Endothelium on Polymegathism Males and Females Age ≤ 60 yrs. and Age > 60 yrs. Glaucoma and No glaucoma 0.017 0.070 & 0.001 0.010 & 0.038 0.002 & 0.036 0.060 0.077 & 0.099 0.039 & 0.075 0.068 & 0.065 0.124 0.121 & 0.167 0.129 & 0.129 0.142 & 0.121 Q UA N T I TAT I V E A N D Q UA L I TAT I V E C O R N E A L E N D O T H E L I A L M O R P H O L O G Y O F O M A N I PAT I E N T S W I T H P S E U D O E X F O L I AT I O N S Y N D R O M E 305 C O N C L U S I O N Pseudoexfoliation in Omani population is associated with increased corneal endothelial pleomorphism and polymegathism predisposing to early corneal decom- pensation after intraocular, mainly cataract, surgeries, even when the endothelial cell counts may be within normal limits. A C K N OW L E D G ME N TS The authors have no commercial or proprietary inter- est in any of the equipment mentioned in the study. No financial support has been received from any source during this study. R E F E R E N C E S 1. Schlotzer-Schrehardt UM, Koca MR, Naumann GO, Volkholz H. Pseudoexfoliation syndrome. Ocular mani- festations of a systemic disorder? Arch Ophthalmol 1992; 110: 1752-1756. 2. Forsius H. Exfoliation sybdrome in various ethnic pop- ulations. Acta Ophthalmol 1988; 66:71-85. 3. Allingham RR, Loftsdottir M, Gottfredsdottir MS, Thorgeirsson E, Jonasson F, Sverisson T. Pseudoexfolia- tion syndrome in Icelandic families. Br J Ophthalmol 2001; 85:702-707. 4. Bialasiewicz AA, Wali U, Shenoy R, Al-Saeidi R. Patients with secondary open angle glaucoma in pseudoexfolia- tion (PEX) syndrome among a population with high prevalence of PEX: clinical findings, morphological and surgical characteristics. Ophthalmologe 2005; 102:1064- 1068. 5. Aasved H. Study of relatives of persons with fi- brillopathia epithelio capsularis (psedoexfoliation of the lens capsule). Acta Ophthalmol 1975; 53:879-886. 6. Hattori Y. Corneal endothelial examination of Pseu- doexfoliation Syndrome. Nippon Ganka Gakkai Zasshi 1990; 94:957-963. 7. Miyake K, Matsuda M, Inaba M. Corneal endothelial changes in Pseudoexfoliation Syndrome. Am J Oph- thalmol 1989; 108:49-52. 8. Schlotzer-Schrehardt UM, Dorfler S, Naumann GO. Corneal endothelial involvement in Pseudoexfoliation syndrome. Arch Ophthalmol 1993; 111:666-674. 9. Seitz B, Muller EE, Langenbucher A, Kus MM, Nau- mann GO. Endothelial Keratopathy in Pseudoexfolia- tion Syndrome: Quantitative and Qualitative mor- phometry using automated video image analysis. Klin Monatsbl Augenheilkd. 1995; 207:167-175. 10. Pseudoexfoliation syndrome in Ethopian glaucoma pa- tients. East Afr Med J 1999; 76:278-280. 11. Correlation between age-related macular degeneration and pseudoexfoliation syndrome in the population of Crete (Greece). Arch Ophthalmol 1999; 117:664-669. 12. Knorr L, Junemann A, Handel A, Naumann GO. Mor- phometric and Qualitative changes in corneal endothe- lium in Pseudoexfoliation syndrome. Fortschr Ophthal- mol; 1991; 88:786-789. 13. Gottfried OH, Naumann GO, Ursula Schlotzer-Schre- hardt. Keratopathy in Pseudoexfoliation syndrome as a cause of corneal endothelial decompensation. Ophthal- mology 2000; 107:1111-1124. 14. Wirbelauer C, Anders V, Pham DT, Wollensak J . Cor- neal endothelial cell changes in Pseudoexfoliation syn- drome after cataract surgery. Arch Ophthalmol 1998; 116:145-149. 15. Brooks AM, Grant G, Robertson IF, Gillies WE. Pro- gressive Corneal endothelial cell changes in anterior segment disease. Aust NZ J Ophthalmol 1987; 15:71- 78.