Clinical profile and demographic distribution of pseudoexfoliation syndrome: An electronic medical record-driven big data analytics from an eye care network in India

Abstract

Purpose:

To describe the demographics and clinical profile of pseudoexfoliation syndrome (PXF or PES) in patients presenting to a multi-tier ophthalmology hospital network in India.

Methods:

This cross-sectional hospital-based study included 3,082,727 new patients presenting between August 2010 and December 2021. Patients with a clinical diagnosis of PXF in at least one eye were included as cases. The data were collected using an electronic medical record system.

Results:

Overall, 23,223 (0.75%) patients were diagnosed with PXF. The majority of the patients were male (67.08%) and had unilateral (60.96%) affliction. The most common age group at presentation was during the seventh decade of life with 9,495 (40.89%) patients. The overall prevalence was higher in patients from a lower socio-economic status (1.48%) presenting from the urban geography (0.84%) and in retired individuals (3.61%). The most common location of the PXF material was the pupillary margin (81.01%) followed by the iris (19.15%). The majority of the eyes had mild or no visual impairment (<20/70) in 12,962 (40.14%) eyes. PXF glaucoma was documented in 7,954 (24.63%) eyes. Krukenberg’s spindle was found in 64 (0.20%) eyes, phacodonesis in 328 (1.02%) eyes, and lens subluxation in 299 (0.93%) eyes. Among the surgical interventions, cataract surgery was performed in 8,363 (25.9%) eyes, trabeculectomy was performed in 966 (2.99%) eyes, and a combined procedure in 822 (2.55%) eyes.

Conclusion:

PXF more commonly affects males presenting during the seventh decade of life from lower socio-economic status and is predominantly unilateral. A quarter of the affected eyes are associated with glaucoma and the majority of the eyes have mild or no visual impairment.

Pseudoexfoliation syndrome (PXF or PES) has been established to be a systemic age-related, elastic microfibrillopathy with manifestations in the ocular system.[1] The first ever description of this disorder was in 1917 in a Thesis by Lindberg.[2] He had made a note of grayish material in the pupillary border in 50% of patients with glaucoma.[2] In 1926, the term “capsular glaucoma” was coined, as it was hypothesized that the material observed could have its origins in the lens anterior capsule.[3] However, by 1954, Dvorak–Theobald, proposed the term “pseudoexfoliation of the lens capsule” and differentiated it from true exfoliation of the lens capsule, with doubts on its origins, whereas finding deposits on the ciliary body and zonules as well.[4] Ultrastructural studies by transmission electron microscopy have shown the presence of PXF fibrils in the “non-pigmented ciliary epithelium, all cell types of the iris, pre-equatorial lens epithelium, trabecular endothelium, corneal endothelium, and vascular endothelial cells.”[5] Autopsy examinations have been conducted, showcasing the presence of PXF material in tissue specimens of the heart, lungs, liver, kidneys, skin, cerebral meninges of the cerebrum, and cerebellum.[6] It is characterized by the accumulation and deposition of fibrillar extracellular fibers that are intermingled with granules and microfibrils, all of which are embedded in an amorphous matrix.[6] Genetic studies first showed that multiple single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene has an association with PXF, whereas other studies have shown that environmental factors also have a major role to play: increased outdoor activities, exposure to the sun, especially when it is reflected off of ice, water, or snow and more daylight hours as in higher altitudes.[7] The prevalence of PXF has been reported in various regions and populations, including the South Asian region but a study involving a large number of patients has not been published to date. The purpose of the study is to present the clinical and demographic profile of PEX syndrome at a large multi-tier ophthalmology network in India using electronic medical record (EMR)-driven analytics.

Methods

Study design, period, location, and approval

This cross-sectional observational hospital-based study included all patients presenting between August 2010 and December 2021 to a multi-tier ophthalmology network located in India.[8] The patient or the parents or guardians of the patient filled out a standard consent form for electronic data privacy at the time of registration. None of the identifiable parameters of the patient were used for the analysis of the data. The clinical data of each patient who underwent a comprehensive ophthalmic examination were entered into a browser-based electronic medical records system (eyeSmart EMR) by uniformly trained ophthalmic personnel and supervised by an ophthalmologist using a standardized template.[9] The study adhered to the Declaration of Helsinki and was approved by the Institutional Ethics Committee.

Cases

A total of 3,082,727 new patients presented to the tertiary and secondary centers of the multi-tier ophthalmology network during the study period. The eyeSmart EMR was screened for patients with a documented ocular diagnosis of PEX syndrome or pseudoexfoliation glaucoma in one or both eyes by a trained glaucoma specialist. The diagnosis of PEX syndrome was based on the clinical findings of pseudoexfoliation material on slit-lamp examination, and the diagnosis of glaucoma was based on a combination of disc findings, intraocular pressure (IOP) values, and/or corresponding visual field changes. A total of 23,223 patient records were identified using this search strategy and were labeled as cases. A total of 32,290 eyes diagnosed with PEX syndrome in the above patients were further analyzed for clinical information.

Data retrieval and processing

The data of 23,223 patients included in this study were retrieved from the EMR database and segregated into an Excel sheet. The columns included the data on patient demographics, clinical presentation, ocular diagnosis, and treatment information and were exported for analysis. The Excel sheet with the required data was then used for analysis using the appropriate statistical software. Standardized definitions were used for occupation and socio-economic status.[10] The visual acuity was classified according to the World Health Organization (WHO) guidelines.[11]

Statistical analysis

Descriptive statistics using mean ± standard deviation and median with interquartile range (IQR) were used to elucidate the demographic data. All tables for age, gender, visual acuity, and clinical features were drawn using Microsoft Excel (Microsoft Corporation 2018. Redmond, USA). A Chi-square test (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP) was used for univariate analysis to detect significant differences in the distribution of demographic features between patients with PXF and the overall population.

Results

Prevalence

Of the 3,082,727 new patients who presented across the eye care network during the study period, 23,223 patients were diagnosed with PXF in at least one eye, translating into a prevalence rate of 0.75% (95% confidence interval [CI]: ±0.0075%) or 7,533/million population.

Age

The mean age of the patients was 66.16 ± 11.67 years, whereas the median age was 67 (IQR: 61–73) years. The most common age group of the patients was distributed between 61 and 70 years (n = 9,495; 40.89%), followed by 71 and 80 years (n = 6,747; 29.05%). The distribution of patients in each age decade is presented in Fig. 1.

Figure 1.

Decade-wise distribution of patients with pseudoexfoliation syndrome. X-axis = age in years, Y-axis = percentage of patients

Sex

There were 15,579 (67.08%) male and 7,644 (32.92%) female patients. The overall distribution of PXF syndrome was significantly greater in males (0.94%; 15,579/1,659,432) as compared to females (0.54%; 7,644/1,423,295) and was statistically significant (P ≤ 0.00001). Among the patients diagnosed with PXF, the mean and median age were 67.3 ± 10.95 and 68 (IQR: 62 to 74) years for men and 65.08 ± 11.07 and 66 (IQR: 60 to 71) years for women, respectively. The overall mode was 71 years in men and 66 years in women.

Urban-rural distribution

Of the 23,223 patients with PXF, 11,285 (48.59%) were from an urban locality, 10,128 (43.61%) were from a rural locality, and 1,810 (7.79%) patients presented from the metropolitan region. The overall prevalence of PXF in the urban community (0.84%; 11,285/1,341,267) was higher as compared to the rural (0.73%; 10,128/1,383,026), or metropolitan community (0.50%; 1,810/358,434) and was statistically significant (P ≤ 0.00001).

Socio-economic status

Of the 23,223 patients with PXF, there were 10,627 (45.76%) patients from the lower socio-economic class, 11,928 (51.36%) patients from the lower middle class, 481 (2.07%) patients from the upper middle class, and 187 (0.81%) patients from the upper class. The overall prevalence was significantly higher in the lower socio-economic strata (1.48%; 10,627/719,571) as compared to higher socio-economic strata (0.53%; 12,596/2,363,156) and was statistically significant (P ≤ 0.00001).

Occupation

Of the 23,223 patients with PXF, 4,911 (21.15%) were agricultural workers, 4,264 (18.36%) were homemakers, 3,595 (15.48%) were retired individuals, 3,100 (13.35%) were manual laborers, 2,324 (10.01%) were professionals, 150 (0.65%) were students, and in the remaining 4,879 (21.01%) patients, the occupational category was not available/applicable.

Systemic co-morbidities

Among the 23,223 patients, hypertension was documented in 2,323 (10%) patients, diabetes mellitus in 1,420 (6.11%) patients, asthma in 293 (1.26%) patients, coronary artery disease in 236 (1.02%), and thyroid disorders in 134 (0.58%) eyes.

Laterality

Of the 23,223 patients, 7,249 (31.21%) were affected in the left eye and 6,907 (29.74%) were affected in the right eye. In 9,067 (39.04%) patients, the affliction was bilateral in nature.

Location

In the 32,290 eyes, the most common location of the PXF material was the pupillary margin in 26,158 (81.01%) eyes, the rest of the iris in 6,184 (19.15%), a lens in 1,846 (5.72%), anterior chamber angle in 361 (1.12%), and cornea in 321 (0.99%) eyes.

Presenting visual acuity

Of the 32,290 eyes, 12,962 (40.14%) eyes had mild or no visual impairment (<20/70), 5,530 (17.13%) eyes had moderate visual impairment (>20/70 to 20/200), 1,381 (4.28%) eyes had severe visual impairment (>20/200 to 20/400), 6,106 (18.91%) 27 eyes had blindness (>20/400 to 20/1200), 2,585 (8.01%) eyes had blindness (>20/1200 to PL), 1,209 (3.74%) eyes had blindness (NPL), and in 2,517 (7.79%) eyes, the visual acuity was undetermined or unspecified. The mean logarithm of the minimum angle of resolution (logMAR) at presentation was 1.04 ± 1.12.

Optic disc findings

Among the 32,290 eyes, a cup-disc ratio of between 0.1 and 0.4 was documented in 10,398 (32.2%) eyes, 0.5–0.7 in 3,576 (11.07%) eyes, and >0.7 in 4,930 (15.27%) eyes. Notching of the disc was documented in 1,528 (4.73%) eyes, disc excavation in 470 (1.46%) eyes, rim thinning in 938 (11.79%) eyes, disc pallor in 1,511 (4.68%) eyes, and unspecified disc damage in 1,331 (4.12%) eyes.

Intraocular pressure

Among the 32,290 eyes, intraocular pressure (IOP) of between 1–9 mm of Hg was documented in 1,047 (3.24%) eyes, 10–21 mm of Hg in 25,715 (79.64%) eyes, 22–30 mm of Hg in 2,685 (8.32%) eyes, and > 30 mm of Hg in 2,416 (7.48%) eyes. The mean IOP was 16.97 ± 8.47 mmHg.

Ocular co-morbidities

Among the 32,290 eyes, cataract was seen in 18,792 (58.2%) eyes, phacodonesis in 328 (1.02%) eyes, crystalline lens subluxation in 299 (0.93%) eyes, intraocular lens (IOL) subluxation in 69 (0.21%), and Krukenberg’s spindle in 64 (0.20%) eyes.

Glaucoma

As shown in Table 1, glaucoma along with PXF was seen in 5,357 eyes (23.07%) with males making up the majority of the cases (4,013; 74.91%). Also, 1,978 eyes (8.13%) had IOP >21 mmHg without any glaucoma changes. However, there were 4,739 eyes (59.58%) who had IOP <21 mmHg with a diagnosis of glaucoma. A higher prevalence was seen in the age group of 61–70 years with 2,193 eyes (40.94%) being affected, closely followed by the age group of 71–80 years with 1,598 eyes (29.83%). Most patients had a cup-disc ratio >0.7, (4,796; 60.30%) and glaucomatous disc changes were seen as the following: a notch in 1,528 eyes (19.21%), disc excavation in 470 eyes (5.91%), rim thinning in 938 eyes (11.79%), disc pallor in 1,511 eyes (19%), and unspecified disc damage in 1,331 eyes (16.73%). Majority of the eyes, 5244 (65.93%) had bilateral glaucoma, and 2,710 (34.07%) had unilateral glaucoma.

Table 1.

The demographics in pseudoexfoliation and pseudoexfoliation glaucoma

Parameter	PXF	Percentage	PXF glaucoma	Percentage
Total patients	17866	76.93%	5357	23.07%
Male	11566	64.74%	4013	74.91
Female	6300	35.26%	1344	25.09%
Age groups
0-–10 years	29	0.16%	5	0.09%
11–20 years	79	0.44%	11	0.21%
21–30 years	144	0.81%	30	0.56%
31–40 years	260	1.46%	36	0.67%
41–50 years	750	4.20%	187	3.49%
51-60 years	2799	15.67%	875	16.33%
61–70 years	7302	40.87%	2193	40.94%
71–80 years	5149	28.82%	1598	29.83%
81–90 years	1235	6.91%	396	7.39%
91–100 years	119	0.67%	26	0.49%
Surgical procedures
Total cataract surgery	6694	27.51%	1669	20.98%
Phacoemulsification	2130	8.75%	842	10.59%
SICS	4460	18.33%	768	9.66%
ECCE	60	0.25%	30	0.38%
ICCE	44	0.18%	29	0.36%
Iris hooks	125	0.51%	26	0.36%
Combined (trabeculectomy + cataract) surgery	128	0.53%	694	8.73%
Trabeculectomy	158	0.65%	808	10.16%
Glaucoma valve surgery	14	0.06%	30	0.38%
GATT	2	0.01%	13	0.16%
Vitreoretinal surgery	631	2.59%	105	1.32%

Also, 1,838 eyes (5.69%) had already undergone a Yttrium aluminium garnet (YAG) peripheral iridotomy (PI) before presenting at our centers and 868 eyes (2.69%) underwent YAG PI at our centers. Among the PXF glaucoma cases, 694 eyes (8.73%) underwent a combined surgery (trabeculectomy + cataract surgery), 808 eyes (10.16%) underwent a trabeculectomy, 30 eyes (0.38%) underwent a glaucoma valve surgery, and 13 eyes (0.16%) underwent gonioscopy-assisted transluminal trabeculotomy (GATT). Three hundred two eyes (3.84%) in the PXF group underwent glaucoma surgery as shown in Table 1, these were the eyes that had PXF with another form of glaucoma other than PXF glaucoma.

Surgical treatment

Among the 32,290 eyes, cataract surgery was performed in 8,363 (25.9%) eyes, trabeculectomy in 966 (2.99%) eyes, combined procedure in 822 (2.55%) eyes, glaucoma valve in 44 (0.14%) eyes, and GATT in 15 (0.05%) eyes. The average follow-up of the patients was 260 ± 489 days with an average of 3.2 ± 4.9 visits.

Unilateral vs. bilateral cases

As shown in Table 2 for PXF, the gender and age prevalence were comparable, as were the examination findings and surgical rates.

Table 2.

The demographics in unilateral versus bilateral pseudoexfoliation syndrome

Parameter	Unilateral	Percentage	Bilateral	Percentage
Total patients	14156	60.96%	9067	39.04%
Male	9144	64.59%	6435	70.97%
Female	5012	35.41%	2632	29.03%
Age groups
0–10 years	27	0.19%	7	0.08%
11–20 years	74	0.52%	16	0.18%
21–30 years	150	1.06%	24	0.26%
31–40 years	249	1.76%	47	0.52%
41–50 years	715	5.05%	222	2.45%
51–60 years	2450	17.31%	1224	13.50%
61–70 years	5777	40.81%	3718	41.01%
71–80 years	3772	26.64%	2976	32.82%
81–90 years	865	6.11%	766	8.45%
91–100 years	78	0.55%	67	0.74%
Visual acuity
Mild or no visual impairment	5533	39.09%	7429	40.97%
Moderate visual impairment	2311	16.33%	3219	17.75%
Severe visual impairment	600	4.24%	781	4.31%
Blindness 3	2722	19.23%	2284	18.66%
Blindness 4	1199	8.74%	1386	7.64%
Blindness 5	611	4.32%	598	3.30%
Undetermined or unspecified	1180	8.34%	1337	7.37%
IOP
0–9 mmHg	543	3.84%	504	2.78%
10–21 mmHg	11215	79.22%	14500	79.96%
22–30 mmHg	1093	7.72%	1592	8.78%
>30 mmHg	1091	7.71%	1325	7.31%
Cup-disc ratio
0.1–0.4	4479	31.64%	5919	32.64%
0.5–0.7	1345	9.50%	2231	12.30%
>0.7	1894	13.38%	3036	16.74%
Disc changes
Notch	55	3.78%	993	5.48%
Excavation	155	1.09%	315	1.74%
Rim thinning	343	2.425%	595	3.28%
Unspecified disc damage	428	3.02%	903	4.98%
Disc pallor	619	4.37%	892	4.92%
Surgical procedures
Total cataract surgery	3893	27.50%	4470	24.65%
Phacoemulsification	1378	9.73%	1594	8.79%
SICS	2443	17.26%	2785	15.36%
ECCE	42	0.30%	48	0.26%
ICCE	30	0.21%	43	0.24%
Iris hooks	69	0.49%	82	0.45%
Combined (trabeculectomy + cataract) surgery	264	1.86%	558	3.08%
Trabeculectomy	333	2.35%	633	3.49%
Glaucoma valve surgery	20	0.14%	24	0.13%
GATT	5	0.04%	10	0.06%
Vitreoretinal surgery	430	3.04%	306	1.69%

Pediatric PXF

There were 75 eyes (0.32%) of pediatric PXF cases. Twenty-eight eyes (32.18%) of the 75 eyes had undergone vitreoretinal surgery, 3 eyes (3.45%) had an intravitreal triamcinolone injection procedure, 1 eye (1.15%) had undergone phacoemulsification surgery.

Discussion

This study sought to describe the clinical profile and demographic distribution of PXF in a large cohort of patients presenting to a multi-tier hospital network in India using electronic medical records-driven big data analytics. The primary purpose of the study was to determine the relative proportion and demographic profile of PXF in the clinical care setup. The overall prevalence was 0.75% in patients who presented between 2010 and 2021 (11 years). In our data, the disease was predominantly unilateral and affected males. It caused mild or no visual impairment in the majority of the affected eyes, and the PXF material was more commonly lodged in the pupillary margin. A quarter of the affected eyes were associated with glaucoma.

The prevalence rates of PXF vary quite considerably across different regions, races, and sex as shown in Table 3. Compounding this, criteria for diagnosing the condition along with the awareness and thorough observations of the examiner may skew prevalence rates. Initial studies showed a higher prevalence in the Scandinavian region with rates of up to 23%.[12] In Europe, the prevalence rates differ from region to region and across age groups with rates in Greece being 28.7%,[13] and in Finland 8.1% in less than 50 years of age, and 18.4% above 70 years of age.[14] Studies in Australia showed rates of 0.98% although they had excluded patients who underwent bilateral cataract surgery.[15] The most probable reasons for variations have been cited to be the definitions of PXF, examination procedures, environmental influences, and differences in the study population.

Table 3.

Prevalence and gender distribution of pseudoexfoliation in various studies

Study	No. of Patients	Prevalence	Age group	Avg. age	Gender distribution	Remarks
Framingham eye study[16]	34	1.8%	52–85		43.18% males	Population-based survey
“Pseudoexfoliation syndrome in Australian adults”[15]	42	0.98%	40–98			Population-based study
Hisayama Study[17]	50	3.4%	>50			Prospective cohort study
“Pseudoexfoliation syndrome in central Iran: a population-based survey”[18]	53	9.6%	40–91	61.8±9.4	48% males	Population-based survey
Saudi Arabia[19]	69	3.5%			50.72%	Hospital-based study
Andhra Pradesh eye disease study[20]	73	0.71%			47.15% Males	Epidemiologic study
Finnish population[14]	76	8.1% >50 years 18.4% > 70 years	>50 years			Population-based
Northern Sweden[12]	77	23%				Population-based
Reykjavik Eye Study[21]	108	10.7% 2.5% 50-59 years 40.6% >80 years	>50 years			Population-based
“Pseudoexfoliation in south India”[22]	108	3.8%				Population-based survey
Blue Mountains Eye Study[23]	120	2.3%	49–97			Population-based study
Beijing Eye Study[24]	176	5.82%	50–93	64.6±9.8		Population-based study
Ural Eye and Medical Study[25]	196	3.6%	40–94	58.1±10.2		Population-based study
Croatia[26]	188	3.6%	>45		33%	Hospital-based study
Thessaloniki Eye study[27]	269	11.9%				Population-based
Chennai Glaucoma Study[28]	290	3.73%	>40 years			Population-based
Aravind Comprehensive Eye Survey[29]	309	6.0%				Population-based cross-sectional study
Jordan[30]	962	4.9%		71.8±8.1	49.58%	Hospital-based
Current study	23223	0.75%	All ages	66.17±11.67	67.08%	Hospital-based

The odds of having PXF increase with increasing age and the prevalence of PXF has also been noted to rise with age.[15,16,21,23,31-33] The increase has been shown to be multifold, with odds increasing up to 5–6 times by the age of 70–80 years as compared to the age of 40 years.[26,31,33] In our data, the highest prevalence was between 61 and 70 years (n = 9,495; 40.89%) followed by 71 and 80 years (n = 6,747; 29.05%). This emphasizes the need for older individuals to be efficiently screened for PXF.

Differences in the prevalence according to gender have also been noted, with some studies showing a higher prevalence among women (although it has been argued that higher life expectance in women has skewed the results).[23,34,35] A number of other studies, however, have shown no sex predilection.[36–39] Our study showed a higher prevalence in males.

Exposure to solar radiation along with increased prevalence in outdoor occupations point toward the role of environmental factors in PXF.[40,41] It seems to be more prevalent in the rural setting, a factor that may also support the solar radiation theory.[33,42,43] Further, 21.15% of the cases in our study were agricultural workers, a part of the population who are constantly exposed to solar radiation.

Data on bilaterality and unilaterality are perplexing with a few studies reiterating that bilateral disease presentations are the most common.[44,45] Also, 60.96% of the patients had unilateral affliction in our study. Cases detected clinically to have unilateral disease have been shown to have deposits of PXF fibrils in the iris muscles and vessels, ciliary body, and trabecular meshwork on electron microscopy,[46,47] not forgetting extra-ocular tissue such as conjunctiva, the connective tissue of the orbit, extra-ocular muscles, vortex veins, and central retinal vessels.[48] Such evidence points to the fact that PXF is a predominantly bilateral disease with the most probable asymmetric presentation, hence emphasizing the fact that patients with unilateral disease should be carefully examined bilaterally, after dilatation of the pupil.

Alzheimer’s disease, dementia, and cognitive impairment seem to have an association with PXF.[49] Other systemic associations range from chronic obstructive pulmonary disease, hypertension, ischemic heart disease, aneurysms, and homocystinuria to cerebrovascular disorders.[23,50–54] The definitive pathomechanism is still unknown but some evidence points to PXF being a form of elastosis.[55] Hypertension was documented in 10% of our patients, diabetes mellitus in 6.11% of patients, asthma in 1.26% of patients, and coronary artery disease in 1.02%.

One of the first easily detectable changes of PXF in the eye, before dilatation of the pupils, remains the observance of PXF material at the pupil margin.[56] The constant friction of the iris with the lens causes the loss of pupillary ruff along with iris transillumination defects[57] with the presence of poorly dilating pupil or non-dilating pupils, the amount of dilatation corresponding to the amount of PXF.[58] It has also been described as “moth-eaten” appearance.[59] In our patients, PXF material was found at the pupillary margin in 81.01% of eyes. On the lens, there is the presence of white flakes on the anterior capsule, most often having a bull’s eye or target appearance, more clearly seen after dilatation of the pupil. A clear intermediate zone is seen, due to the rubbing of the iris on the anterior capsule, surrounded by a peripheral and central zone of deposition of fibrillar material.[60] Changes in the lens were seen in 5.2% of cases. The type of cataract in these patients has been reported to mainly be either nuclear[61] or subcapsular,[62] with unilateral patients having a more advanced cataract in the involved eye compared to the contralateral eye.[62]

The PXF fibrillar material has been demonstrated on the ciliary processes and zonules.[63] Evidence of zonular weakness in the form of phacodonesis[58,64] and subluxation/dislocation of the lens has been described in multiple papers,[65,66] along with a few descriptions of anterior subluxation in the form of shallowing of the anterior chamber and/or angle closure glaucoma.[67,68] Phacodonesis was seen in 1.02% of eyes, with crystalline lens subluxation in 0.93% of eyes, and intraocular lens subluxation in 0.21% of eyes in our patients.

Gonioscopy is an important examination in all cases, as it helps to diagnose an occludable or narrow-angle and reveals flaky white material, mostly in the inferior angle along with the patchy and increased pigmentation of the trabecular meshwork, at times with the presence of “Sampaolesi’s line.”[69] A correlation has been seen between a higher amount of pigmentation in the angle and higher IOP.[70,71] Therefore, there is a possibility to prognosticate cases according to the amount of pigmentation in the angle. Pupillary block due toanterior subluxation of the lens, has also been described in PXF which leads to iris bombe, which gets relieved after a peripheral iridotomy.[40] Also, 8.38% of our patients underwent a YAG PI.

One of the early associations of high IOP, glaucoma, and PXF was in the early manifest glaucoma trial, where it was seen that PXF patients with high IOP progressed to have glaucoma as compared to patients without PXF. PXF was therefore singled out as an independent risk factor for glaucoma.[72] Fluctuations in IOP seem to be one of the characteristic features of PEX with important implications in the management and prognostication of glaucoma.[73] Like other features of PXF, a predominant bilateral/asymmetric presentation is seen; however, increased fluctuations of IOP make for a worse prognosis and more severe/advanced glaucoma at the time of diagnosis as compared to primary open angle glaucoma (POAG).[72,74] Non-pressure mechanisms of optic nerve head (ONH) damage have been postulated due to findings of elastotic changes in the lamina cribrosa of patients with PXF and glaucoma. The prevalence of glaucoma among PXF subjects varies in different studies, with prevalence being 3.0%,[23] 8.3%,[33] 23.6%,[26] 30%,[75] and 30.3%,[76] with odds ratio also varying from 3.80[15] to 5.0,[23] Glaucoma seems to be more prevalent in higher age groups,[23] more so in men[77] as seen in our study as well. Leading to both angle closure and open-angle glaucomas, it is also a major cause of post-cataract surgery complications.[31]

Most glaucoma cases are intractable, only responding to medical management for a limited period. Most clinicians prefer using Prostaglandin Analogues (PGAs) for their first line of treatment due to their high efficacy and long duration of action, being quite suitable for the high spikes in IOP in PEX.[78] A few studies have shown the efficacy of medical management in cases of PXF, with PGAs, beta-blockers, and Carbonic anhydrase inhibitors (CAIs).[68,79] The use of pilocarpine, however, is not without caution as it may precipitate pupillary block in the already anteriorly subluxated cataract scenarios, along with the added disadvantages of possible posterior synechiae formation and cataract formation.[80]

Zonular weakness along with a malfunctioning blood ocular barrier means that patients with PXF who undergo surgical management (trabeculectomy) have higher rates of complications and failure.[81] However, newer studies have shown that there are no significant differences between trabeculectomy in POAG or PEX, most likely due to the increased use of antifibrotic agents.[82] In all, 1,847 eyes (5.72%) underwent glaucoma surgery in our study.

Because of the advent of cataract surgery, the rate of complications in PEX was always higher when compared to other cases with normal cataracts.[83] Cataract surgery was performed in 83,63 eyes (25.90%) of the patients.

Very few case reports are available with respect to pediatric PXF.[84–88] Ocular trauma and previous history of an intraocular procedure are common in these case reports, with the exact pathomechanism still unknown. An increase in inflammatory mediators, with a possible genetic and environmental influence, has been implicated in these pediatric cases. In our data, the number of pediatric PXF cases was 75 eyes (0.32%). Most eyes in our data had undergone vitreoretinal surgery.

Table 4 enlists all the salient findings of studies around the world in relation to PXF. Our study does have a few disadvantages, the first being that it is a retrospective study. The diagnosis of PXF is very observer dependent and this may be flawed as cases without any clinically detectable PXF have been shown to have PXF material on conjunctival biopsy.[31] Therefore, many cases of PXF in the population may be missed, skewing prevalence rates. Because it is a cross-sectional study, the relationship between PXF and glaucoma could not be ascertained, and for this, prospective studies are mandatory.

Table 4.

Table enumerating different studies along with the geographical location and the salient findings of the studies

Study	Geographical location	Salient findings*
Framingham Eye study	Framingham, USA	Bilaterality increased with age; mean IOP was higher in the eyes with PXF.
Pseudoexfoliation syndrome in Australian adults	Victoria, Australia	PXF is a highly specific predictor of glaucoma.
Hisayama Study[17]	Hisayama, Japan	Hypertension was more frequent in PXF.
Pseudoexfoliation syndrome in central Iran: a population-based survey”[18]	Falavarjan County, Central Iran	The highest number of cases between 51 to 60 years; the highest distribution of PXF material was on the anterior lens capsule; unilateral in 55% and bilateral in 45%; higher prevalence in males.
Saudi Arabia[19]	Riyadh, Saudi Arabia	Unilateral in 62.3% and bilateral in 37.7%; 45% had high IOP; 26% had cataracts; 62.3% had PXF material on the iris margin; 9.5% had occludable angles; direct association between poor vision and frequency of PEX.
Andhra Pradesh Eye Disease Study[20]	Andhra Pradesh, India	Prevalence was significantly increased in subjects with outdoor occupation; unilateral in 46.6% and bilateral in 53.4%; 58% had PXF on the pupillary margin; the prevalence of blindness was higher in PXF; 4.1% were blind due to glaucoma; no statistically significant association between glaucoma and PXF; increase prevalence of cataract with PXF.
Finnish population[14]	Kokar, Finland	The unilateral and bilateral diseases were equal in proportion; the prevalence of PXF with glaucoma was higher in males.
Northern Sweden[12]	Vasterbotten County, Sweden	Prevalence is higher in females; IOP was higher in PXF eyes; the risk of glaucoma increases with PXF.
Reykjavik Eye Study[21]	Reykjavik, Iceland	Higher frequency of PXF in females; IOP was higher in eyes with PXF.
“Pseudoexfoliation in south India”[22]	Tamil Nadu, India	Unilateral in 49.1% and bilateral in 50.9%; highest prevalence in the 60–69 age group; higher IOP in PXF eyes; the prevalence of OHT, OAG, occludable angles higher in eyes with PXF.
Blue Mountains Eye Study[23]	Blue mountains region, Australia	Unilateral in 52% and bilateral in 48%; highest prevalence in the 70–79 age group; higher prevalence in females; strong association between glaucoma and PXF.
Beijing Eye Study[24]	Beijing, China	Unilateral in 54.5% and bilateral in 45.5%; prevalence was significantly associated with shorter axial length, shorter anterior chamber depth, and increased IOP; association with glaucoma was inconclusive.
Ural Eye and Medical Study[25]	The Russian republic of Bashkortostan, Ural Mountains, Russia	Unilateral in 58.7% and bilateral in 41.3%; higher prevalence of PXF was associated with a higher prevalence of raised IOP and open-angle glaucoma; independent of any systemic parameters.
Croatia[26]	Koprivnica, Croatia	Patients with angle closure glaucoma were higher in females.
Thessaloniki Eye study[27]	Thessaloniki, Greece	The presence of PXF on the iris was associated with higher IOP.
Chennai Glaucoma Study[28]	Tamil Nadu, India	Unilateral in 59.3% and bilateral in 40.7%; prevalence is higher in the rural population; significant association with rural residents, manual workers, low BMI, cataracts, aphakia, and IOP.
Aravind Comprehensive Eye Survey[29]	Tamil Nadu, India	PXF was associated with elevated odds of POAG,
Jordan[30]	Amman, Jordan	Unilateral in 56.0% and bilateral in 44.0%; the prevalence of glaucoma (26.3%); bilateral glaucoma (72.7%); open-angle glaucoma (96.0%); males had a higher frequency of glaucoma; age, gender, laterality were significantly associated with glaucoma.
Current study	Telangana, Andhra Pradesh, Orissa, Karnataka; India	Increased prevalence between 61–70 years; greater distribution in males; overall prevalence was higher in the urban community and in the lower socio-economic strata; unilateral in 60.95% and bilateral in 39.04%; most common location of PXF was pupillary margin (81.01%); cataract was seen in 58.2%; glaucoma was present in 23.07% of the eyes; the prevalence of pediatric PXF was 0.32%.

*All studies had increased prevalence with age

Knowing the prevalence rates of PXF will aid in the planning of glaucoma-related eye care services and preventing blindness as the prospected future incidence is going to increase, given the aging of the population.

Conclusion

In conclusion, this study aimed to describe the epidemiology and clinical presentation of PEX syndrome in 3 million new patients presenting to a multi-tier ophthalmology hospital network in India. The findings show that PEX syndrome and PEX glaucoma more commonly affect males presenting during the sixth and seventh decades of life from lower socio-economic status and are predominantly unilateral. A quarter of the affected eyes were associated with glaucoma and the majority of the eyes had mild or no visual impairment.

Financial support and sponsorship

This study was funded by Hyderabad Eye Research Foundation

Conflicts of interest

There are no conflicts of interest.