European Journal of Cardiovascular Medicine

Pseudo exfoliation syndrome (PEX), initially described by Dvorak-Theobald¹ in 1953, is Characterised by the diffuse deposition of grey-white flakes in the anterior ocular segment without prior exposure to heat (infrared irradiation), as opposed to true exfoliation, in which the eye has been subjected to intense heat, often as an occupational hazard². The latter is distinguished by the deposition of material on the anterior lens surface, frequently in the shape of a conspicuous circular flap, the so-called double ring sign or capsulorrhexis masquerade³. The accumulating substance in PEX is comparable to amyloid⁴ and may be the result of a disrupted basal membrane metabolism. Pseudo exfoliative material was found in several extra-ocular areas in prior research, which led to the theory that PEX is essentially a systemic disease with clinical implications for multiple organ systems ⁵. Anterior segment parameters such as Central Corneal thickness (CCT), Anterior chamber angle (ACA), Anterior chamber Depth (ACD), Anterior chamber volume (ACV), Intraocular pressure is crucial for the diagnosis, evaluation and prevention of Pseudo exfoliative glaucoma. Also, complications like endothelial decompensation, and phacodonesis that arise during or after cataract surgery can be reduced. Analyzing the anterior segment parameters in individuals with pseudoexfoliation syndrome was the purpose of the current study

This is a hospital based, cross-sectional study. A total of 50 patients both males and females aged 45 years and above with Pseudo exfoliation syndrome, attending outpatient department of Ophthalmology Sri Venkateswara Ram Narayan Ruya Government General Hospital (SVRRGGH), Sri Venkateswara Medical College, Tirupati were included in this study.

Study design: Cross sectional study.

Duration of the study: one year from the date of Institutional scientific and ethics committee approval from January 2021 to December 2021.

Sample size: 50 Patients .

Source of data: Department of Ophthalmology, SVRRGG Hospital

Inclusion Criteria

1. Patients aged 45 years and above with Pseudo exfoliation syndrome, attending out patient department of Ophthalmology SVRRGGH, Tirupati.
2. Those who give informed and written consent to participate in the study

Exclusion criteria

1. Those who are glassblowers, steelworkers, blacksmiths and bakers by occupation as true

exfoliation may be seen in them.

2. Patients with uveitis and trauma with
3. Patients with corneal diseases affecting central corneal thickness.
4. Patients with secondary glaucoma.

Methodology

After obtaining the approval of the institutional scientific and ethical committee,  a written and informed consent was taken from the patients in his/her vernacular language. A detailed history was taken regarding chief complaints, and duration of illness was taken. Clinical examination of the patient included a detailed general physical examination and systemic examination, followed by an Ophthalmological examination.

• Refraction and recording of best corrected visual acuity in both eyes.
• Detailed S/L examination of the anterior segment using Carl Zeiss Meditec AG 0.7740 Jena Germany.
• IOP measurement using Goldmann applanation tonometry (Zeiss AT 030-Carl Zeiss, Jena Germany).
• Central corneal thickness measurement using Pachymeter. (Ultrasonic Pachymeter-Pachette 2, DGH Technology, INC., Exton, PA, USA)
• Estimation of the angle of the anterior chamber using Indentation Gonioscopy with ZEISS 4 mirror handheld gonio lens.
• Keratometry with Autorefractory Kertometer (POTEC-PRK 5000).
• Anterior chamber depth, volume, lens thickness measurements using Ocular biometry (AXIS NANO ultrasound A-scan biometer- Quantel Medical).

Statistical analysis: Data was collected on predefined cases proforma and transcribed into MS- Excel spreadsheets. All the entries were double-checked to minimise the data entry errors. Data were expressed as mean with standard deviation (SD) for continuous variables and frequencies with percentages for categorical variables. All the statistical analysis was performed using Epi Info 7.2.0.1, Centres for disease control , CDC, Atlanta, Georgia . P-value < 0.05 is considered statistically significant.

50 patients both males and females aged 45 years and above with Pseudo exfoliation syndrome were studied at SVRRGG Hospital, Tirupati by conducting cross-sectional observational study to analyse the anterior segment characteristics of pseudo exfoliation syndrome.

Table 1: Age distribution

Table 1 displays the distribution of participants by age, with 4% in the 41–50 age group, 34% in the 51–60 age group, 42% in the 61–70 age group, and 20% in the 71–80 age group. The study population's average age was 64.18 ±7.67 years.

Table 2: Gender distribution

In our study, the males were more than females 68% and 32% respectively (Table 2) . among these patients 74.3% of males had bilateral PEX and 25.7% had Unilateral disease. 73.3% of females had bilateral PEX and 26.75% had unilateral PEX (table 3) with p value of 0.94 which is not significant .

Table 3: Distribution based on Laterality and Gender

.

Table 4:  Distribution based on Laterality and Age

Bilateral involvement is observed more in the age groups of 61-70 years i.e., 48.6% followed by 37.8% in 51-60 years and 13.5% in 71-80 years Table 4).

Unilateral involvement is observed mostly in the 71-80 years age group i.e., 38.5% followed by 23.1% each in 51-60 years and 61-70 years age group, 15.4% in 41-50 years age group.

This observation was statistically significant.

Open angle glaucoma is seen in 52%, Angle closure glaucoma I n12%, 2% with secondary ACG subluxated lens, 6% with Occludable angle. In PEX patients 75.7% of bilateral involvement had glaucoma and 61.5% of unilateral involvement had glaucoma.There was no statistical significance for this finding.

Table 5: Gender Incidence and Glaucoma

In patients with PEX  glaucoma 72.2% (n=26) were male and 27.8% n=10)  were female. This finding lacked statistical significance (table 5)

Cornea findings  in Pseudo exfoliation syndrome showed 92%(n=46) with clear cornea, 4%(n=2) with clear and pigmented cornea, 2%(n=1) with corneal edema, 2%(n=1) with spheroidal degeneration.

The anterior chamber findings in Pseudo exfoliation syndrome showed  80% (n=40) with normal findings, 16%(n=8) had Shallow findings, 4% (n=2)had irregular findings.

Table 6: Iris findings in Pseudo exfoliation syndrome

Among patients of PEX  28% had normal iris findings, 40% had Exfoliation material on iris , 2% with Exfoliation and Iridodonesis and 32% had exfoliation and Pupillary ruff defects(Table 6). 14% (n=7) had normal pupils , 80% had Exfoliation material at the pupillary boarder  (n=40), 6% (n=3)had Exfoliation at pupillary border and RAPD with varying grades (Table 7)

Table 7: Pupil findings in PEX

 Pupil findings, 14% (n=7) had normal findings, 80% had Exfoliation material at pupillary border (n=40), 6% (n=3)had Exfoliation at pupillary border and RAPD with varying grades (Table 7).

In   50% (n=25) had <6mm dilatation of pupil  and 50% (n=25)had >6mm Dilatation. When PEX patients were evaluated for lens changes 2% had Aphakia, 2% had Hyper mature cataract, 34% had Immature cataract, 6% had mature cataract, 48% had nuclear cataract, 6% had PCIOL.

Table 8: Gonioscopy findings in Pseudo exfoliation syndrome

On performing Gonioscopy in Pseudo exfoliation syndrome by using  Shaffer’s grade grade 0 seen  in 4% (n=2), Grade I in 6%(n=3), Grade 2 in 4%(n=2), Grade 3 in 24%(n=12), Grade 1P in 6%(n=3), Grade 2P in 2%(n=1) and Grade 3P in 54%(n-27).

The mean intraocular pressure in pseudo exfoliation syndrome was 23.18 ± 12.03 mm Hg, with 54%(n=27) having IOP < 21 mm oh Hg and 46% (n=23) having IOP >22 mm Hg .

Pseudo exfoliation syndrome has been described to occur worldwide. Reported prevalence rates of pseudo exfoliation vary widely in different geographic locations. The results may vary depending on the population's age, racial and ethnic makeup, patient selection, clinical diagnosis criteria, thoroughness of examination, and prospective versus retrospective data collecting.

The most common identifiable specific entity currently causing pseudo exfoliation syndrome, a systemic disorder, is development of glaucoma. 

It commonly affects the elderly with higher intraocular pressure as pseudo exfoliation glaucoma is more severe than Primary open angle glaucoma, reduction in Intraocular pressure (IOP)  helps to prevent in glaucoma progression.

The diagnosis, assessment, and prevention of pseudo exfoliative glaucoma depend heavily on anterior segment parameters like Central Corneal Thickness (CCT), Anterior Chamber Angle (ACA), Anterior Chamber Depth (ACD), Anterior Chamber Volume (ACV), and Intra Ocular Pressure.

Also, complications like endothelial decompensation, phacodonesis that arise during or after cataract surgery can be reduced. A cross-sectional observational study was conducted on individuals aged 45 years and above, diagnosed with pseudoexfoliation syndrome, who visited the Ophthalmology outpatient department at SVRRGGH, Tirupati to analyse the anterior segment characteristics in the above said population.

After taking a detailed history , assessment of visual acuity all patients were examined the variables measured were IOP, Central Corneal thickness (CCT) , and Gonioscopy to grade the angles and anterior chamber depth.

40% were in the 51–60 age range, 34% were in the 51–60 age range, 42% were in the 61–70 age range, and 20% were in the 71–80 age range with average age of 64.18 + 7.67 years and this is in accordance with other studies ^6,7,8,9

The majority of studies showed a male preponderance for pseudo exfoliation syndrome.

Laterality

In the present study, 74% had bilateral exfoliation and 26% had Unilateral Exfoliation. 74.3% of males had Bilateral exfoliation and 25.7% had Unilateral exfoliation. Among females 73.3% had Bilateral involvement and 26.75 had unilateral involvement. Bilateral involvement is observed more in the age groups of 61-70 years i.e.,  48.6% followed by 37.8% in 51-60 years and 13.5% in 71-80 years.

Unilateral involvement is observed mostly in 71-80 years age group i.e., 38.5% followed by 23.1% each in 51-60 years and

61-70 years age group, 15.4% in 41-50 years age group. Yazgan et al¹⁰ Out of 118 eyes evaluated, 43 eyes (in 29 subjects with bilateral PEX and in 14 subjects with unilateral PEX,Henry J et al⁷347 participants in which 225 cases were identified unilateral whereas 122 with bilateral pseudo exfoliation.

Philip et al⁸unilateral pseudo exfoliation with 57.8% followed by bilateral with 42%. Triveni et al⁹ Among 103 cases, majority of the patients was affected with a unilateral pseudo exfoliation with 91.26% and 8.24% with bilateral pseudo exfoliation.

In our study open angle glaucoma, angle closure glaucoma and secondary angle closure glaucoma was observed in 52% ,12% and  2% respectively. 6% had Occludable angles.

Based on Glaucoma and laterality of Pseudo exfoliation, 75.7% of bilateral involvement had glaucoma and 61.5% of unilateral involvement had glaucoma. Based on Gender and Pseudo exfoliation with Glaucoma, 27.8% of pseudo exfoliation with glaucoma patients were female and 72.2% had male pseudo exoliation. Glaucoma in pseudo exfoliation is associated with an open angle and normal anterior chamber depth. The blocking of the filtering meshwork by pseudo exfoliation material and pigment, build-up of pseudo exfoliation material in the juxtacanalicular area, and degradation of Schlemm's canal are the most plausible mechanisms. In the majority of the time, angle closure glaucoma is coincidental.

The most common reason is pupillary block brought on by a confluence of increased iris rigidity or thickness, posterior synechiae, and anterior lens movement brought on by zonular weakness.

Iris is more rigid, aqueous pressure in the posterior chamber causes the iris to bulge at the weakest point which is the root, producing a pseudo plateau iris.

The tendency of these eyes from posterior synechiae increases the frequency and severity of pupillary block and miotic-induced angle closure.

Study also observed that 47.5% showed gonioscopy Sampaolesi's line. Al- Saleh, S.A., et al¹⁰, study reported that pseudo exfoliation material in the angle showed 23.9% right eye of the patients and 14.9% of left eye.

Hence it can be inferred that delay in the diagnosis of pseudo exfoliation can converts ocular hypertension patients to glaucoma.

Studies have reported that among pseudo exfoliation patients, a significant change in the corneal thickness at the apex, centre and Periphery.

The study was done by Gunes et al¹¹PXS and control group comparison, the mean corneal thicknesses at the apex point (536 ± 31 and 560 ± 31 µm, respectively, p=0.001), at the centre of the pupil (534 ± 31 and 558 ± 33 µm, respectively, p=0.001), and at the thinnest point (528 ± 30 and 546 ± 27 µm, respectively, p=0.005) were significantly thinner in PXS patients.

Sekeroglu et al¹²study showed no discernible difference between the mean corneal densitometry values at anterior 120 μm, central, and posterior 60 μm of the cornea in all concentric radial zones (P>0.05 for all).

Triveni et al⁹ study on slit-lamp examination observed that 17.90%  of eyes had pigments on the corneal endothelium, and  4.46% had phacodones is Sharma, P. et al ,  conducted a study in a population of 93 pseudo  exfoliation patients in which 49.4% showed pigments on the corneal endothelium and 8.23% have  phacodonesis.

Presence of the corneal endothelial pigments and phacodonesis helps to identify patients with pseudo exfoliation.

Scattered flakes of pseudo exfoliation material may be observed on endothelium.

Central corneal thickness is also greater in eyes with pseudo exfoliation

Anterior chamber findings

In our study 80% had normal anterior chamber depth, 16% had shallow anterior chamber depth and 4% had irregular depth  which is comparable to Bozkurt et al

According to research done by Acar et al¹³ Als were higher in those with PES While Doganay et al¹⁴ study showed significantly lower anterior chamber depth. Bozkurt et al¹⁵ found that there were no noticeable differences in the centre values of the 3.0, 5.0, or 7.0mm anterior chamber volume, anterior chamber angle width, CCT, or PD.Gunes et al⁴⁴showed there were no significant differences between the PXS and control eyes' mean values for keratometry, anterior chamber angle, depth, corneal

volume, or anterior chamber volume. Mohammadi et al¹¹ study was that when compared to the eyes of control subjects, the anterior chamber depth in eyes with PEXG was substantially shallower

In our study, based on anterior chamber findings, 80% had normal findings, 16% had Shallow findings, 4% had irregular findings. These results were corroborated by research by Doganay et al.¹⁴ and Mohammadi et al.¹⁶

Increased trabecular pigmentation is a prominent sign of pseudo exfoliation which is of more variegated appearance and is apparent in all patients with clinically evident disease  Pigment is characteristically deposited on the Schwalbe's line and sometimes as a wavy line (or) lines anterior to Schwalbe's line (Sampaolesi's line).

Although anterior chamber depth is normal in most patients, in some studies show 9%to 18% have occludable angle and 14% have angle closure on basis of peripheral anterior synechiae

Iris findings

In the current research, 27% had normal findings, 39% had Exfoliation material, 2% with Exfoliation and Iridodonesis and 32% had exfoliation and Pupillary ruff defects.

In his ultrastructural investigation on phoney exfoliation, Thomas Hammer noted that on electron microscopy the muscle cells seemed thinner and rarefied in comparison to normal eyes, and they were separated by expanded intercellular gaps that were overflowing with microfibrillar material. In 3 of the 5 contralateral eyes, typical PEX fibres were seen within these intercellular gaps. Myofilaments clumped together and deteriorated cell organelles could be seen in some areas of the muscle cells' electron-lucent vacuolar cytoplasm.

The anterior part of the pigment epithelium contained membrane structures that resembled whirls.

These changes included a noticeable multilayering and thickening of the endothelial basement membrane as well as an excessive build-up of microfibrils with a diameter of 10 to 12 nm and fibrillar-granular extracellular material in the perivascular region.

Although mature PEX fibres were not found, the perivascular matrix in 2 cases contained PEX fibres at various levels of development.

Adventitial cells, in particular pericytes, underwent degenerative alterations that were characterised by vacuolation of their cytoplasm and an abundance of pinocytotic vesicles; electron-dense extracellular granules formed around the vessel's periphery.

Next to the lens the pseudo exfoliation material is most prominent at the pupillary border in 32 -94% of patients it tends to more prominent in eyes maintained on miotic therapy.

Pigment loss from the iris sphincter region is a hallmark of pseudo exfoliation which is reflected in iris sphincter region as motheaten pattern transillumination, defect near the pupillary border.

Pigment particles, larger than those found in pigment dispersion syndrome are deposited in a whorl like fashion on the anterior stroma at the sphincter

Pigment is deposited evenly over the iris surface, in contrast to its collection in iris furrows in pigment dispersion syndrome.

Pupil findings

13% had normal findings, 80% had Exfoliation material, 7% had Exfoliation and RAPD. Based on Pupil dilatation, 51% had <6mm dilatation and 49% had >6mm Dilatation

In a study conducted by Triveni et al⁹ observed that 59.82% of patients were presented with degranulation of pupillary ruff.

In a study conducted by Rao AD et al observed pupillary ruff among 56%. In Rao et al study, pupillary ruff atrophy was common. According to research by Sharma, P. et al. (1959), 84.7% of patients could be distinguished by the pseudo exfoliation material on their pupillary margins.  In the study population, 91.7% of eyes had pseudo exfoliation material on the anterior capsule of the lens, and 65.13 % of eyes had anterior lens capsule PXF in the pupil. The most well-known symptom of pseudo exfoliation syndrome is granular whitish deposition of pseudo exfoliation material on the anterior lens surface.

Three zonules, as first described by VOGT, are distinctive.The hallmark of pseudo exfoliation syndrome is its presence on the lens. Intrinsic capsular changes are present in the equatorial zones leading to the conclusion that the material is produced in these areas.

Intraocular pressure

In Yazgan et al⁶study the mean IOP was 23.18 ± 12.03mmHg

In Gunes et al¹¹study the mean IOP was 23.18 ± 12.03mmHg

In Triveni et al⁹ study the mean IOP was 21.98 ± 12mmHg

In Rao et al study the mean IOP was 18±3.4 among patients with unilateral pseudo exfoliation whereas it was 20±1.2 among those with bilateral pseudo exfoliation. Thomas et al reported that mean Intraocular pressure was 24.14±1.4mmHg. With the above findings we can infer that Increased intraocular pressure is highly correlated with pseudo exfoliation and care should be taken to frequently evaluate patients with pseudo exfoliation for glaucoma  

1. Pseudo exfoliation is more common bilaterally than unilateral
2. The anterior chamber angles are narrowest in PEXG eyes than in those with just pseudo exfoliation syndrome
3. Dilatation of pupil is less in those with pseudo exfoliation
4. Delayed diagnosis of pseudo exfoliation can convert ocular hypertension patients to glaucoma
5. Clinicians may be able to better manage the condition if it is identified early.

Conflict of interest: NIL

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