OCULAR CLINICAL PROFILE OF PATIENTS WITH PSEUDOEXFOLIATION SYNDROME AND PSEUDOEXFOLIATION GLAUCOMA AT TERTIARY CARE CENTRE IN KASHMIR

1. Postgraduate Scholar, Department of Ophthalmology, GMC Srinagar. 2. Associate Professor, Department of Ophthalmology, GMC Srinagar. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 05 October 2021 Final Accepted: 10 November 2021 Published: December 2021

Pseudoexfoliation syndrome (PEX) was initially described by a Finnish ophthalmologist, John Lindberg in 1917 1 .It represents a common age related systemic disorder affecting approximately 10% to 20% of the general population over age 60 and involving both genetic and nongenetic factors in its etiopathogenesis 2,3 . It is characterised by pathologic accumulation of an abnormal fibrillar extracellular material in the anterior segment of the eye and in various extraocular tissues 4 . Progressive obstruction of the aqueous humor outflow pathways by abnormal pseudoexfoliation material deposits cause chronic pressure elevation, optic nerve damage and subsequent development of open angle glaucoma in eyes with PEX syndrome, a condition known as pseudoexfoliation glaucoma(PEXG) 5 . It accounts for a majority of glaucoma cases in some countries and for approximately 25% of PEXG is mostly bilateral and asymmetric; if compared to primary open angle glaucoma it presents a worse prognosis due to higher fluctuations in IOP levels and more severe optic nerve and visual field damage in affected eyes. Furthermore patients with PEXG usually present higher levels of IOP compared to those affected by POAG; moreover, various studies report a higher percentage of failure of medical management (prostaglandins, betablockers, adrenergic agonists, and carbonic anhydrase inhibitors) for PEXG patients.

Lens:
PEX is usually diagnosed by slit lamp examination that allows observing accumulation of whitish material deposits on the lens capsule. The typical bull's eye pattern disposition is probably due to the movement of the iris on the anterior lens surface, creating a double concentric ring aspect. Therefore, it is important to examine the anterior capsule of the lens after pupillary dilation, and in most cases the presence of three different areas is observed 25 .
It has been observed that patients with PEX present a higher percentage of nuclear cataract 26 .Cataract development seems to be related to the age of patients, although, in patients with unilateral PEX, cataract appears to be more advanced on the affected rather than the unaffected eye.

Cornea:
Slit lamp examination may demonstrate the presence of pseudoexfoliative material and pigment on the corneal endothelium that can be erroneously interpreted as inflammatory precipitates 27 . Confocal microscopy has demonstrated the presence of a lower number of endothelial cells in affected eyes and a consequent higher rate of guttae, which may probably be due to intermittent elevated levels of IOP.
Other non specific changes of the corneal endothelial cells include rarefaction and thinning of the cells, cytoplasmic vacuolization, phagocytosis of melanin granules, and abnormal extracellular matrix production.

Aqueous Humor and Anterior Chamber:
Aqueous humor production in PEX affected eyes has been demonstrated to be reduced and associated with a disrupted blood-aqueous barrier with a consequent presence of higher levels of aqueous protein concentration, as well as sudden changes in levels of acid phosphatase, alpha1-lipoprotein and ceruloplasmin, cellular/plasma fibronectin, transferrin, alpha1-antitrypsin, and growth factors.

Iris:
Presence of pseudoexfoliative material is frequently observed on the anterior and posterior surface of the iris 28 .Irregular borders, due to the rubbing of iris against the lens and presence of grayish material deposits, characterize the aspect of pupil margin in PEX. In most cases this is associated with poor or absent pupillary dilation as a result of atrophic and/or fibrotic changes in the iris sphincter muscle. Recent studies described various cases presenting iris ischemia and neovascularization, as a consequence of the deposition of pseudoexfoliative material on the vascular endothelium of the iris.

Zonules and Ciliary Body:
Weakness of the zonules is one of the main aspects of PEX representing an important cause of complication during cataract surgery. It is thought that this zonular fragility can be caused by accumulation of pseudoexfoliative material on the ciliary processes and zonules, which may lead to phacodonesis 29 .

Angle:
Gonioscopy represents one of the fundamental examinations, which should be performed in patients with PEX. Changes in both the aspect and depth of the angle commonly occur in PEXG affected patients. Pigment and flecks of pseudoexfoliative material can be observed over the structures of the angle, especially along the Schwalbe line, where the pigment dispersion pattern is named "Sampaolesi's line" 30 .

Patients And Methods:-
This cross sectional study was conducted at postgraduate Department of Ophthalmology Government Medical College Srinagar, after obtaining clearance from the institutional ethical committee from October 2018 to October 2020 over a period of two years. A total of 200 patients were included in the study. These include 100 patients with pseudoexfoliation syndrome (PEX) and 100 with pseudoexfoliation glaucoma(PEXG).
PEX: these patients exhibited deposits of exfoliative material on the anterior lens capsule and/or iris during slit lamp examination, in one or both eyes PEXG: in addition to exfoliative material these patients showed the characteristic optic disc damage Prior to clinical examination, a questionnaire was administered including demographic data, ophthalmologic, and medical history. In particular, subjects were queried whether they had ever been diagnosed with hypertension, diabetes mellitus, any cardiovascular disease.

Examination
Comprehensive ocular examination was performed for all eligible candidates which included the following parameters: 1.Visual acuity test was performed at a distance of 6 meters using Snellen's or illiterate E charts. The lowest line read successfully was taken as the visual acuity for the eye. 2. Refraction/ retinoscopy( using Heine Beta 200 streak retinocope). 3. Intra ocular pressure was measured using Goldman applanation tonometer. 4. Gonioscopy was performed with a two-mirror lens and the angle was graded according to Shaffer system as:  Pupil was dilated, unless contraindicated because of the risk of angle closure, to note the three zones of exfoliation material on the lens capsule. Lens-exfoliation material, cataractous or not, phacodonesis, subluxation or dislocation of lens. Cataracts were classified morphologically as nuclear sclerosis(NS), cortical and posterior subcapsular(PSC). 6. Stereoscopic examination of the optic disc and peripapillary area was performed at the slit lamp using a 78-D lens. The following disc features evoked suspicion of glaucomatous damage: • vertical cup disc ratio (CDR >0.5) in either eye • asymmetry of CDR > 0.2 between the two eyes • thin or notched neuroretinal rim, or disc hemorrhage • nerve fiber layer defect with the corresponding characteristic changes in the visual field. 7.
Measurements of the central corneal thickness (CCT) was performed on each eye using specular microscope(Topcon SP-1P,Tokyo,Japan).

Statistical analysis
Data was entered in Microsoft Excel 2010 and analyzed by using SPSS version 23. Categorical variables were summarized as frequencies and percentages whereas, continuous variables were summarized as mean and standard deviation. We used logistic regression for calculating odds ratio. Chi-square test and t-test were used wherever appropriate. P value<0.05 was considered statistically significant.

Results:-
The present study was conducted in the Department of Ophthalmology, Government Medical College, Srinagar from October 2018 to October 2020.This was a cross sectional study in which 200 patients were included (100 with PEX and 100 with PEXG). The mean age in PEX group was 62.98 ± 6.664years and majority of patients were in the age group of 60 to 70 years , whereas the mean age in PEXG group was 65.32± 6.628years and majority of patients were in the age group of 60 -70 years . Distribution of age is given in table 1 and 2.   Most of the patients were involved in outdoor activities in both groups and mostly were from rural areas in both PEX and PEXG groups as shown in table 4 and 5.  Bilateral involvement was in majority of patients in both PEX(73 patients) and PEXG(80 patients) groups.In PEXG group glaucoma was present bilaterally in 72% of patients. Table 6 shows laterality of pseudoexfoliative material in patients and table 7 shows laterality of glaucoma in PEXG patients.  Regarding site of exfoliation , deposition of material at anterior lens capsule was predominant in both PEX and PEXG group, followed by pupillary border. Descriptive data regarding site of exfoliation is given in table 8: In the present study most of the patients had visual acuity of less than 6/60 in both PEX and PEXG groups and nuclear type of cataract was common in both groups. The descriptive data regarding visual acuity and type of cataract is given in table 9 and table 10:   In our study no glaucomatous damage was seen in PEX group and 30 (15%) eyes in the PEXG group. However, early glaucomatous changes was seen in 130(65%) eyes and advanced glaucomatous damage in 40(20%) eyes in the PEXG group. In our study, the gender distribution was 72.50% males and 27.50% females .This is comparable to the studies conducted by Min Sagong et al 33 and YetkinYaz et al 34 , with malegender being predominant in their studies. There was a statistically significant difference in gender distribution showing a male predilection for the disease.
In the present study, the cases with outdoor and indoor activity were 72.50% and 27.50% respectively. Similar observations were also reported by Ravi Thomas et al 35 . The association of occupation with pseudoexfoliation can be explained by the fact that the people engaged in outdoor activities are more exposed to the environmental factors like solar radiations which may be a risk factor for the disease.
In our study, pseudoexfoliation was present in 353 eyes of 200 cases. Out of 200 cases it was unilateral in 47(23.5%) and bilateral in 153(76.5%). It was present on pupillary margin in 125(35.41%) eyes, on anterior lens capsule in 175(49.58%) eyes and in both locations combined in 53(15.01%) eyes. The results are contrary to that seen by Alan P Rotchfordet al 36 , who observed that maximum patients had pseudoexfoliation at pupillary border. However, our observations are in agreement with Ravi Thomas et al 35 . In their study, exfoliative material was present on anterior lens capsule in 42.9%, on pupillary margin in 33.9% and in both locations in 23.2% of eyes.
In our study, predominant cataract was nuclear cataract(49.47). Higher percentage of nuclear cataract was also observed in the study conducted by K Kaljurand et al 37 . In their study nuclear cataract predominated in eyes with pseudoexfoliation(57.6% ).Similar observations were also made by J. Hietanen et al 38 .
In the present study, majority of the eyes (58%) were blind (distance visual acuity of < 6/60) , followed by visual impairment in 28%. Our results were comparable to the study conducted by Ravi Thomas et al 35 . They found that 43.5% of eyes withpseudoexfoliation were blind and 31.6% of eyes were visually impaired. Similar observations were made by Allan P Rotchfordet al 36 .
In the present study, the median CDR in PEX group was 0.2(range 0.1-0.3), in PEXG group it was 0.6(range 0.4-0.8). Glaucomatous atrophy was seen in 40 eyes in PEXG group. These observations were comparable to study conducted by YetkinYaz et al 34 . In their study median CDR in PEX and PEXG group was 0.2 and0.6 respectively. Similar results were obtained by KKaljurand et al 37

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In our study, the mean IOP was 17.26mmHg in PEX group and 24.39mmHg in PEXG group. YetkinYaz et al114, in their study had found similar results with mean IOP in PEXG group 22.25mmHg, and 14mmHg in PEX group. Our results were also comparable to studies conducted by Allan P Rotchfordet al 36 and J. Hietanen et al 38 .
Several studies have pointed that cornea is thinner in pseudoexfoliation (Miyake K et al 39 , and Ozcura F et al 40 ). These alterations are secondary to changes in endothelial cells because corneal thickness is an indirect indicator of endothelial function. The mean central corneal thickness in pseudoexfoliation patients has been reported as 507±25µm(Ventura AC et al 41 ), 528±30 µm(Puska P et al 42 ) which was comparable to our study (531.80±19.127µm).

Conclusion:-
The prevalence of PEX is found to increase with age. Patients with PXG had more severity of optic nerve damage at presentation. Therefore a careful assessment for detection of PEX is warranted and regular follow-up of patients is desired to minimize the extent of optic nerve damage. Majority of PXF Patients were rural residents. Increased prevalence of PXF was seen in patients exposed to outdoor activity. Pseudoexfoliation syndrome may cause a spectrum of serious ocular and surgical complications. The problems related to cataract surgery are mainly initiated by zonular instability and, to some degree, by insufficient pupillary dilation. Thus awareness of the structural and functional features of this disorder may help avoid or minimize most of them. The early recognition of the syndrome has increased the percentage of favourable outcomes in operative procedures, through careful consideration with preoperative preparation, surgical awareness and postoperative follow-up