|Year : 2012 | Volume
| Issue : 2 | Page : 231-236
Ocular clinical profile of patients with pseudoexfoliation syndrome in a Tertiary Eye Care Center in South India
Swetha S Philip, Sheeja S John, Arathi R Simha, Smitha Jasper, Andrew D Braganza
Department of Ophthalmology, Christian Medical College, Vellore, India
|Date of Web Publication||21-Apr-2012|
Swetha S Philip
Department of Ophthalmology, Schell Campus, Christian Medical College, Vellore- 632 001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose:To study the clinical profile of pseudoexfoliation (PEX) syndrome in a hospital setting.
Materials and Methods: A case series of patients with PEX, with and without glaucoma attending the general ophthalmology clinic of a tertiary care center in South India. All patients underwent a complete ophthalmologic evaluation including recording diurnal variation of tension (DVT), gonioscopy and visual field assessment.
Results: The study cohort comprised 529 patients (752 eyes). There were 296 (56%) females. The highest number of patients (261 patients) was from the age group between 60 and 69 years. Of 752 eyes, 57.8% eyes had unilateral PEX and 72% had established PEX. Gonioscopy showed open angles in 98.1% of eyes. Intraocular pressure (IOP) greater than 21 mmHg in at least 1 of 4 measurements was recorded in 5.7% eyes. DVT was normal in 96.4% of unilateral PEX eyes, similar to fellow non-PEX eyes. Pseudoexfoliation glaucoma occurred in 1.9% of eyes and 4.7% of eyes were glaucoma suspects. There was no correlation between the stage of PEX and increased IOP. Mean central corneal thickness of PEX eyes was 522 ± 27μ. Pupillary dilatation in 90.5% eyes with early PEX was ≥ 7 mm.
Conclusions: A small percentage of PEX eyes had raised IOP, and the number of eyes with glaucomatous optic neuropathy was even lower. PEX eyes did not demonstrate wide fluctuations in IOP. No correlation was found between raised IOP and stage of PEX. There was good pupillary dilatation in early stage PEX eyes suggesting that all PEX eyes may not have poor pupillary dilatation and related complications.
Keywords: Diurnal Variation of Tension, Glaucoma, Pseudoexfoliation, Pupillary Dilatation
|How to cite this article:|
Philip SS, John SS, Simha AR, Jasper S, Braganza AD. Ocular clinical profile of patients with pseudoexfoliation syndrome in a Tertiary Eye Care Center in South India. Middle East Afr J Ophthalmol 2012;19:231-6
|How to cite this URL:|
Philip SS, John SS, Simha AR, Jasper S, Braganza AD. Ocular clinical profile of patients with pseudoexfoliation syndrome in a Tertiary Eye Care Center in South India. Middle East Afr J Ophthalmol [serial online] 2012 [cited 2019 Jun 26];19:231-6. Available from: http://www.meajo.org/text.asp?2012/19/2/231/95259
| Introduction|| |
Pseudoexfoliation (PEX) syndrome is an idiopathic, generalized disorder that is characterized by the accumulation of fibrillar extracellular material in ocular tissues.  PEX predisposes to a number of ocular co-morbidities, the most severe being glaucoma. , PEX occurs worldwide and prevalence rates vary from 10 to 20% of the general population over the age of 60 years.  Hospital-based studies from India have reported a prevalence rate between 1.8  and 7.4%  in adults over 45 years of age. Although there is no established sex predilection for PEX, , a female preponderance has been previously reported.  Unilateral PEX occurs in 48-76%  of patients and converts to bilateral disease in up to 50% of patients within 5 to 10 years. 
Pseudoexfoliation glaucoma (PXG) accounts for approximately 25% of all open angle glaucomas worldwide.  The prevalence of PXG as reported by population-based surveys from South India vary between 7.5 and 13%. , PXG has a more serious clinical course and a worse prognosis than primary open angle glaucoma (POAG). , Compared to POAG, PXG is typically associated with higher mean intraocular pressure (IOP), greater diurnal variations, marked pressure spikes, greater severity of optic neuropathy and more rapid visual field loss.  PEX is also associated with poor pupillary dilatation and is a risk factor for zonular dialysis  and vitreous loss during cataract surgery.  Central corneal thickness (CCT) is known to have an impact on IOP,  but there is no consensus on the central corneal thickness in PEX eyes. ,
The purpose of the current study was to document the ocular clinical profile of patients with PEX attending the general ophthalmology clinic of a tertiary care center in South India. This study also assessed the practical problems that PEX posed in the management of cataract and diagnosis of POAG.
| Materials and Methods|| |
This was a case series of patients with PEX who presented at a tertiary care eye center in South India, from May 2005 to May 2008. During this period, 1,40,338 patients were screened in the outpatient clinic of the center and outreach cataract and ocular morbidity screening camps. The study was approved by the Institutional Review Board and informed consent was obtained from all participants.
Patients identified with PEX were recruited. Patients with PEX material on the corneal endothelium, pupillary margin, angle or on the lens were included. Exclusion criteria were previous intraocular surgery in the eye with PEX, use of anti-glaucoma medications or topical/systemic steroids within the last six months, history of ocular trauma, uveitis, corneal scars, lens-induced glaucomas and any other ocular pathology that could have led to secondary glaucoma.
Ocular examination in all patients was performed by one ophthalmologist (SSP) who performed a slit-lamp examination, diurnal variation of tension (DVT) with Goldmann applanation tonometer, gonioscopy with Goldmann two mirror indirect gonioscope and dilated fundus examination using +90 D lens. Visual field assessment was performed using Humphrey's Field Analyzer-II (HFA-II, 30-2 SITA standard, Carl Zeiss AG, Jena, Germany). Central corneal thickness (CCT) was measured by ultrasound pachymetry (Tomey AL-3000 Optimetrics Inc., Florida, USA). The mean of three repeat central corneal thickness readings was used for CCT analysis. The IOP was recorded with a Goldmann applanation tonometer mounted on a Zeiss slit-lamp biomicroscope. The DVT was performed during working hours (between 8:00 AM and 5:00 PM) at two hourly intervals. A single tonometer was used for the study. It was calibrated weekly as part of the routine maintenance protocol of the department. Normal diurnal variation of IOP was defined as IOP variation (between the maximum and minimum IOP recorded during the DVT) of ≤ 4 mmHg.  The mean IOP of a particular eye was calculated from four recordings of IOP during the DVT. A difference in mean IOP between the PEX eye and the fellow non-PEX eye of > 4 mmHg was considered clinically significant. 
The established stage of PEX was defined as the presence of white, flaky, dandruff-like material at the pupillary margin and/or on the anterior lens capsule.  Early (brown stage) PEX was defined as small specks of radial, brown, pigmented lines on the anterior lens capsule.  We defined PXG as IOP > 21 mmHg in PEX eyes with optic disc changes (CDR ≥ 0.7). POAG was defined as IOP >21 mmHg, glaucomatous disc changes and typical glaucomatous field defects in the presence of an open angle without a secondary cause.  Primary angle-closure glaucoma (PACG) was defined as IOP >21 mm Hg or glaucomatous optic disc damage with visual field loss and an occludable angle or synechial closure.  Gonioscopic grading of the angle was performed based on the structures visualized.  An occludable angle was defined as non-visibility of the pigmented posterior trabecular meshwork in ≥ 75% of the angle circumference in the primary position without manipulation, in the presence of low illumination.  Normal tension glaucoma (NTG) was defined as IOP ≤ 21 mmHg with glaucomatous optic disc damage and visual field loss in the presence of open angles.  Glaucomatous optic neuropathy was diagnosed with two or more of the following features: vertical CDR ≥ 0.7, asymmetry in CDR > 0.2 between the two eyes, characteristic glaucomatous excavation of the neuroretinal rim and typical wedge nerve fiber layer defects.  Eyes with hazy media due to cataract, which precluded optic disc assessment, were excluded from the analysis. In our study, we defined visually significant cataract as decreased vision in the presence of a cataract without any other ocular pathology.
We assessed pupillary dilatation in all patients because poor pupillary dilatation and related complications in cataract surgery are well documented in PEX. , After instilling mydriatic (combined tropicamide 0.8% and phenylephrine 5% ophthalmic solution) in the eye, pupillary dilatation was assessed using a slit-lamp in a dark room with the pupil dilated and not reacting to maximum illumination. The illumination system of the slit-lamp was placed horizontally and the slit beam was adjusted according to the pupillary dilatation, and the measurement was read off the scale on the slit-lamp. A pupillary dilatation of ≥ 7 mm was considered good.
Visual field assessment was performed in all patients. Patients with clinically significant cataract, who could not perform the test, were excluded from the statistical analyses.
Data were analyzed using MedCalc® software, (version 22.214.171.124, 2007; MedCalc Software bvba, Mariakerke, Belgium). Test of proportion (critical ratio, z test) to detect disproportion in the sex distribution of patients was used. Student's t-test (paired t-test) was used to determine whether mean IOP was significantly different in unilateral PEX compared to the fellow non-PEX eye. Independent sample t-test was used to compare the CCT in PEX and non-PEX eyes. IOP values in early and established stages of PEX were analyzed using Mann-Whitney test to look for any correlation between the stage of PEX and IOP. Comparison of means was used to analyze the pupillary dilatation in eyes with PEX. A P value < 0.05 was considered as statistically significant for all tests.
| Results|| |
A total of 655 patients with PEX were considered eligible to participate in the study, of which 529 patients agreed to participate. The demographics and ocular features of patients enrolled in the study are summarized in [Table 1]. Of the 529 patients (752 eyes) in the study, 306 patients (57.8%) had unilateral PEX. In the unilateral cases, 295 (96.4%) eyes had diurnal IOP variation ≤ 4 mmHg, which was within the normal range and comparable to the fellow non-PEX eyes. There was no statistically significant difference in the mean IOP between eyes with PEX and non-PEX eyes (P = 0.20, Student's t-test).
|Table 1: Demographics and ocular features of patients with pseudoexfoliation|
Click here to view
Raised IOP > 21mm Hg in at least one of four recordings during DVT occurred in 43 (5.7%) of 752 eyes. Thirty six (83.7%) of 43 eyes had established PEX. There was no correlation between the stage of PEX and IOP (P = 0.5, Mann-Whitney test) [Figure 1]. The mean CCT in PEX eyes was 522 ± 27 μ which was comparable to CCT of fellow non-PEX eyes (P = 0.97, independent sample t-test) [Table 1].
|Figure 1: Box-plot representation of intraocular pressure (IOP) data in early and established pseudoexfoliation (PEX) showing no correlation between the stage of PEX and IOP (Mann-Whitney test; P = 0.5)|
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Stereoscopic examination of the optic disc was possible in 634 of 752 (84.3%) eyes as significant cataract precluded detailed optic disc assessment in the remaining eyes [Table 2]. [Figure 2] shows the association of raised IOP with optic disc changes.
|Table 2: Distribution of cup-disc ratio among patients with pseudoexfoliation|
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The mean pupillary dilatation was 5.8 mm ± 1.07 in the 542 eyes with established PEX. Five hundred and twenty four (96.7%) of 542 eyes with established PEX had pupillary dilatation of ≤ 6 mm, 14 (2.6%) eyes had pupillary dilatation of 6.5mm and 4 (0.7%) eyes had ≥7 mm dilatation. In eyes with early PEX, the mean pupillary dilatation was 7.14 mm, of which 190 (90.5%) eyes had pupillary dilatation of ≥ 7 mm, 13 (6.2%) eyes had dilatation of 6.5 mm, 4 (1.9%) eyes had 5 mm dilatation and 3 (1.4%) eyes had 4 mm pupillary dilatation. The difference in pupillary dilatation between patients with established and early PEX was statistically significant (P < 0.001).
| Discussion|| |
PEX has a greater prevalence in the older population. ,, Hence, data on the clinical profile of PEX is important due to the increasing age of general population in many parts of the world. In the current study, most of our patients with PEX were between 60 years and 69 years, which is comparable to the previously published reports. ,, The incidence of PEX tends to increase with age, and is less common below the age of 60 years.  The majority (74%) of the patients in our study had established PEX at first diagnosis while less than a third (28%) had early PEX. There are conflicting reports of gender differences in PEX. ,,, We found a male to female ratio of 1:1.27.
Our study showed that PEX eyes did not experience wide variations in diurnal IOP, contrary to the conclusions of previous studies. , DVT recordings in the majority (96.4%) of patients with unilateral PEX showed an IOP variation of ≤ 4 mmHg, which was normal and comparable to the fellow eyes without PEX. Even in non-glaucomatous eyes with PEX, several authors have found that the mean IOP was significantly higher than that of non-PEX eyes.  However, these previous studies reported a narrow range of difference in IOP between PEX and non-PEX eyes (1.02-1.29 mmHg), , which may not be clinically significant.
Patients with PXG have higher IOP with greater fluctuations and marked spikes that likely cause more severe optic neuropathy compared to patients with POAG.  PXG develops in approximately 50% of patients with PEX syndrome over time  and is recognized as the most common type of secondary open angle glaucoma.  The PEX patients in our study had a lower prevalence and severity of glaucoma when compared to previous reports of PEX. ,,,, One possible explanation for the difference is that PEX may have a different clinical profile based on racial or geographic origin. There is relative paucity of data regarding early PEX. To the best of our knowledge, there is no literature available on the strength of association between the stage of PEX and IOP. In our study, we found no correlation between the stage of PEX and IOP (P = 0.5).
In the eyes where stereoscopic disc assessment was possible, we found 93.4% (592/634) eyes were non-glaucomatous. This is comparable to a previous study from South India, in which 92.5% of the study population was non-glaucomatous.  In our study, high IOP (>21mm Hg) was recorded only in 5.7% (43 out of 752 eyes). Of the 634 eyes in which optic disc assessment was possible, features of glaucoma (raised IOP and CDR ≥ 0.7) were seen in 12 (1.89%) eyes. However, there were 30 eyes (4.7% of 634 eyes) with a CDR of ≥ 0.7 but normal IOP. The IOP and CDR were similar in all the fellow eyes. It is therefore possible that the 30 patients with suspicious discs and normal IOP in both the PEX and fellow eyes were cases of normal tension glaucoma, with PEX being a coincidental finding. Similarly, there were two patients with unilateral PEX, who had raised IOP with glaucomatous optic neuropathy in both the PEX and fellow eyes. Were these patients actually cases of POAG with coincidental PEX? We could not definitively diagnose normal tension glaucoma or POAG due to the lack of reliable visual field data in our study population. However, it is clinically possible for a patient with POAG to also have PEX. The latter may not be contributing to the mechanism of glaucoma at all. A definitive diagnosis of PXG could be made in such patients in the future by specialized genetic testing of myocilin levels. 
Our study had only 14 (1.86%) eyes with occludable angles and none of the patients presented with closed angles. This is in sharp contrast to other studies which have reported higher incidences of closed and occludable angles. , Different samples sizes (22 patients Dhanraj and Sundaramurthy study  versus 529 patients in our study) may account for the difference. Poor pupillary dilatation is generally considered to be associated to PEX. Cataract surgery is often associated with more complications in PEX eyes due to the presence of weak zonules, stiff iris and poor pupillary dilatation. However, there is no literature regarding the association between early PEX and pupillary dilatation. In our study, we found a significant difference in pupillary dilatation between eyes with early and established PEX. For example, 90% of eyes with early PEX had a pupillary dilatation of ≥ 7 mm and 96.7% of eyes with established PEX had pupillary dilatation of ≤ 6 mm. This observation indicates that not all stages of PEX have poor pupillary dilatation which may be extremely important and reassuring to surgeons planning cataract surgery on patients with early PEX.
The major drawback of our study was that we were unable to document reliable visual fields in many of our patients with visually significant cataract. Hence, visual field could not be used as a reliable indicator of disc damage caused by raised IOP. Therefore, these data were ignored in the analysis.
In conclusion, in our study, only a small percentage of patients with PEX had raised IOP and an even lower number of patients had features consistent with glaucoma. In patients with unilateral PEX, the mean IOP as well as the DVT was comparable to the fellow non-PEX eyes. This raises the possibility that PEX may be a coincidental finding in patients with asymmetric POAG /normal tension glaucoma. The true incidence of PXG may in fact be much lower. We found no correlation between the stage of PEX and the presence of high IOP. Good pupillary dilatation was found in early PEX. Further population-based longitudinal studies would be required to unravel the natural history of PEX in Indian eyes.
| References|| |
|1.||Naumann GOH, Schlötzer-Schrehardt U, Küchle M. Pseudoexfoliation syndrome for the comprehensive Ophthalmologist. Intraocular and systemic manifestations. Ophthalmology 1998;105:951-68. |
|2.||Schlötzer-Schrehardt U, Naumann GO. Pseudoexfoliation Glaucoma. In: Grehn F, Stamper R, editors. Essentials in Ophthalmology. Heidelberg: Springer Verlag Berlin; 2004. p. 157-76. |
|3.||Schlötzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol 2006;141:921-37. |
|4.||Sood NN. Prevalence of pseudoexfoliation of the lens capsule in India. Acta Ophthalmol (Copenh) 1968;46:211-4. |
|5.||Lamba PA, Giridhar A. Pseudoexfoliation syndrome (prevalence based on random survey hospital data). Indian J Ophthalmol 1984;32:169-73. |
|6.||Arvind H, Raju P, Paul PG, Baskaran M, Ramesh SV, George RJ, et al. Pseudoexfoliation in South India. Br J Ophthalmol 2003;87:1321-3. |
|7.||Krishnadas R, Nirmalan PK, Ramakrishnan R, Thulasiraj RD, Katz J, Tielsch JM, et al. Pseudoexfoliation in a rural population of southern India: the Aravind Comprehensive Eye Survey. Am J Ophthalmol 2003;135:830-7. |
|8.||Karger RA, Jeng SM, Johnson DH, Hodge DO, Good MS. Estimated incidence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Olmsted County, Minnesota. J Glaucoma 2002;12:193-7. |
|9.||Kozart DM, Yanoff M. Intraocular pressure status in 100 consecutive patients with exfoliation syndrome. Ophthalmology 1982;89:214-8. |
|10.||Henry JC, Krupin T, Schmitt M, Lauffer J, Miller E, Ewing MQ, et al. Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure. Ophthalmology 1987;94:545-52. |
|11.||Ritch R. Exfoliation syndrome-the most common identifiable cause of open-angle glaucoma. J Glaucoma 1994;3:176-7. |
|12.||Ritch R. Exfoliation syndrome. Curr Opin Ophthalmol 2001;12:124-30. |
|13.||Konstas AG, Stewart WC, Stroman GA, Sine CS. Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 1997;28:111-7. |
|14.||Skuta GL, Parrish RK 2nd, Hodapp E, Forster RK, Rockwood EJ. Zonular dialysis during extra capsular cataract extraction in pseudoexfoliation syndrome. Arch Ophthalmol 1987;105:632-4. |
|15.||Naumann GO. the Erlanger Augenblatter- Group. Exfoliation syndrome as a risk factor for vitreous loss in extra capsular cataract surgery. Acta Ophthalmol 1988;84:129-31. |
|16.||Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: A review and meta-analysis approach. Surv Ophthalmol 2000;44:367-408. |
|17.||Ozcura F, Aydn S, Dayanr V. Central corneal thickness and corneal curvature in Pseudoexfoliation syndrome with or without glaucoma. J Glaucoma 2011;20:410-3. |
|18.||Hepsen IF, Yaðci R, Keskin U. Corneal curvature and central corneal thickness in eyes with pseudoexfoliation syndrome. Can J Ophthalmol 2007;42:677-80. |
|19.||Chandler. Grant's Glaucoma. Examination of the eye in Glaucoma. In: Epstein DL, editor. Philadelphia: Lea and Febiger; 1986. p. 31. |
|20.||Becker- Shaffer's. Diagnosis and Therapy of the Glaucoma. In: Hoskin HD, Micheal A. editors. St Louis: Mosby International; 1989. p. 79. |
|21.||Thomas R, Nirmalan PK, Krishnaiah S. Pseudoexfoliation in Southern India: The Andhra Pradesh Eye Disease Study. Invest Ophthalmol Vis Sci 2005;46:1170-6. |
|22.||Jerndal T. New perspective on exfoliation syndrome and associated glaucoma. Semin Ophthalmol 1989;4:41-5. |
|23.||Jacob A, Thomas R, Koshi SP, Braganza A, Muliyil J. Prevalence of primary glaucoma in an urban south Indian population. Indian J Ophthalmol 1998;46:81-6. |
|24.||Thomas R, Thomas S, Chandra Shekar G. Gonioscopy. Indian J Ophthalmol 1998;46:255-61. |
|25.||Collaborative Normal -Tension Glaucoma Study group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998;126:487-97. |
|26.||Ritch R, Schlötzer-Schrehardt. Exfoliation Glaucoma. In: Weinber RN, Kitazawa Y, editors. Glaucoma in the 21 st century. London: Harcourt Health Communications: Mosby International; 2000. p. 171-9. |
|27.||Hiller R, Sperduto RD, Krueger DE. Pseudoexfoliation, intraocular pressure, and senile lens changes in a population-based survey. Arch Ophthalmol 1982;100:1080-2. |
|28.||Ringvold A, Blika S, Elsås T, Guldahl J, Brevik T, Hesstvedt P, et al. The Middle-Norway eye-screening study. I. Epidemiology of the pseudo-exfoliation syndrome. Acta Ophthalmol (Copenh) 1988;66:652-8. |
|29.||Mitchell P, Wang JJ, Hourihan F. The relationship between glaucoma and pseudoexfoliation: The Blue Mountains Eye Study. Arch Ophthalmol 1999;117:1319-24. |
|30.||Ekstrom C. Prevalence of pseudoexfoliation in a population 65-75 years of age. Acta Ophthalmol 1987;65:9-10. |
|31.||McCarthy CA, Taylor HR. Pseudoexfoliation syndrome in Australian adults. Am J Ophthalmol 2000;129:629-33. |
|32.||Howell KG, Vrabel AM, Chowdhury UR, Stamer WD, Fautsch MP. Myocilin levels in primary open-angle glaucoma and pseudoexfoliation glaucoma human aqueous humor. J Glaucoma 2010;19:569-75. |
|33.||Dhanraj Rao AS, Sundaramurthy SK. Gonioscopy In Brown Stage Pseudoexfoliation. Asian J Ophthalmol 2006;8: 270. |
|34.||Ritch R, Schlötzer-Schrehardt U. Exfoliation syndrome. Surv Ophthalmol 2001;45:265-315. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]