To present the clinical profile of patients with pseudoexfoliation (PXF) and describe its association with pseudoexfoliation glaucoma and cataract surgery complications at a university hospital in Jordan.
Electronic chart search was performed among patients aged ≥ 50 years who attended the Jordan University Hospital between January 2015 and March 2018, to identify patients with pseudoexfoliation. Data derived from history and ophthalmic examination regarding laterality of pseudoexfoliation, presence of glaucoma, glaucoma surgery, cataract, cataract surgery, lens instability, and complications of cataract surgery were collected and analyzed.
Of 19,753 patient records searched, 962 (477 male and 485 female) had PXF (4.9%). The mean (SD) age was 71.8 (8.1) years. Pseudoexfoliation was unilateral in 539 patients (56.0%). The mean age of patients with clinically bilateral PXF was significantly higher than those with clinically unilateral PXF (p = 0.001). Pseudoexfoliation glaucoma was present in 237 of 962 (25.4%) patients with PXF and was significantly associated with clinically bilateral PXF (p < 0.001) and male gender (p = 0.001). In 454 (48.9%) patients (638 eyes) who underwent cataract surgery, there was no statistically significant difference in the rate of intraoperative complications between PXF eyes and the fellow eyes of clinically unilateral PXF eyes (p = 0.37), or between patients with clinically unilateral and clinically bilateral PXF (p = 0.78).
In this large hospital-based study, the frequency of PXF was 4.9%. Glaucoma was present in one fourth of patients and was significantly associated with clinically bilateral PXF and male gender. Cataract surgery complication rates were not statistically different between PXF and the fellow eyes of clinically unilateral PXF eyes. Surgeons need to be aware of the potential increased risk of intraoperative complications in both groups.
Key Summary Points
|Why carry out this study?|
|Pseudoexfoliation syndrome is the most common cause of secondary open-angle glaucoma and is associated with increased risk of cataract surgery complications.|
|Pseudoexfoliation syndrome is known to be a bilateral disease despite the presence of clinically apparent unilateral cases.|
|This study aimed to assess the frequency of pseudoexfoliation in a large number of patients attending a university teaching hospital and to describe its association with glaucoma and cataract surgery complications.|
|What was learned from the study?|
|Glaucoma was present in nearly one fourth of patients with pseudoexfoliation. Cataract surgery complications did not differ between eyes with pseudoexfoliation and clinically no pseudoexfoliation.|
|Surgeons need to be aware of the potentially increased risk of intraoperative complications in eyes with pseudoexfoliation as well as fellow eyes clinically labeled as normal eyes in patients with clinically unilateral pseudoexfoliation.|
Pseudoexfoliation (PXF) syndrome is a disease in which extracellular fibrillar material is deposited on the surface of many ocular structures and in the connective tissues of many visceral organs. This material is composed of elastic fiber components, basement membrane and extracellular matrix components, and blood-derived and immune-related proteins [1, 2]. The disease is associated with lysyl oxidase-like-1 (LOXL1) gene abnormality  with resultant abnormal chemical and mechanical properties of elastic tissues such as the lens zonules, trabecular meshwork, and lamina cribrosa . Other epigenetic and environmental factors may be involved as well .
In the eye, pseudoexfoliation material (PXM) accumulates on the lens surface, iris, ciliary body, zonules, corneal endothelium, and trabecular meshwork. In addition, pupillary ruff atrophy and increased trabecular meshwork pigmentation are present. Clinically, the appearance of white dandruff-like material associated with iris transillumination defects, inadequate pupil dilation, lens instability, and corneal endothelial abnormalities are well-recognized features, but the high risk of developing pseudoexfoliation glaucoma (PXG)  and the increased risk of cataract surgery complications are the most important clinical implications of the disease.
Overall, PXF is the most common identifiable cause of open-angle glaucoma and is usually associated with higher intraocular pressure (IOP) levels . Although not all patients with PXF will develop glaucoma, a significant percentage will develop glaucoma, which is thought to be more difficult to manage and has higher treatment failure than primary open-angle glaucoma . The risk of developing glaucoma in PXF is three times that for patients without PXF for the same high IOP (above 21 mmHg) .
PXF is also associated with an increased risk of cataract, cataract surgery , and cataract surgery complications, including intraoperative vitreous loss, postoperative IOP spikes, capsular phimosis, inflammation, and corneal decompensation . The cataract in PXF is commonly dense nuclear  and frequently coexists with glaucoma, sometimes necessitating combined cataract and glaucoma surgery.
The prevalence of PXF differs widely among populations ; however, the highest rates have been reported from Scandinavian countries, Greece , and sub-Saharan Africa , while PXF tends to occur much less frequently in Asian populations . In the Middle East, rates ranging from 3.5 to 9.1% in hospital-based studies [16–18] have been reported. The differences in prevalence rates probably reflect the complexity of all factors involved in the pathogenesis of PXF, apart from differences in study design and examiners’ ability to detect early cases.
In this study, we present the clinical profile of 962 patients with pseudoexfoliation syndrome and describe the association with glaucoma and cataract surgery complications in a teaching university hospital in Jordan.
Study Design and Population
The study was a retrospective electronic chart review of patients with pseudoexfoliation syndrome. We conducted a search in the electronic medical records database system at the Jordan University hospital (Amman, Jordan) to identify all new and consecutive patients aged 50 years or older with pseudoexfoliation syndrome who attended the eye outpatient clinic between January 1, 2015, and March 30, 2018. The study was conducted according to the principles of the Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board at the Jordan University of Science and Technology (Approval number 20200251).
To find patients with pseudoexfoliation, we entered the following search terms: pseudoexfoliation, pseudoexfoliation glaucoma, PXF, PEX, and PXG.
All available demographic and clinical data for each patient with pseudoexfoliation were retrieved and entered on a spreadsheet. Demographic data included age and gender. Clinical data derived from history and ophthalmic examination regarding the presence of diabetes mellitus (DM), laterality of pseudoexfoliation, glaucoma, ocular hypertension (OHT), glaucoma surgery, cataract, cataract surgery, signs of lens instability, and complications of cataract surgery were also collected. Patients with ambiguous diagnoses or significantly incomplete data regarding important diagnostic entities were excluded.
Pseudoexfoliation was considered present when typical PXM was present at the pupil, lens surface, or other intraocular structures. When no PXM was seen in one eye after pupil dilation, the eye was considered clinically non-PXF, and the case labeled as clinically unilateral PXF.
Pseudoexfoliation glaucoma (PXG) was defined as the presence of PXF and clinical glaucomatous optic neuropathy manifested as focal or diffuse neuroretinal rim thinning, retinal nerve fiber layer defects, or peripapillary atrophy, with corresponding glaucomatous visual field defects manifested as nasal step, temporal wedge defect, classic arcuate defect, paracentral defect, generalized visual field constriction, or retinal nerve fiber layer defects on optical coherence tomography (OCT). PXF patients with prior surgical intervention for glaucoma or currently receiving glaucoma topical medications and meeting the above definition of glaucoma were considered PXG cases. Ocular hypertension was defined as intraocular pressure above 21 mmHg with no evidence of glaucomatous optic nerve damage, glaucomatous visual field abnormality, retinal nerve fiber layer abnormality on OCT, and the absence of secondary causes of high intraocular pressure.
Cataract was defined as the presence of any degree of lens opacity. Cataract surgery was performed by a consultant or senior resident under consultant supervision. When the outcome of cataract surgery was a sulcus intraocular lens (IOL), anterior chamber IOL, or aphakia, as documented in the operative notes, cataract surgery was considered complicated.
Data were analyzed using IBM SPSS version 24 software. We used mean (standard deviation) to describe continuous variables and used count (percentage) to describe categorical variables. We performed independent-samples t tests to compare mean age between groups. The chi-square (
χ2) test was used to analyze the difference between categorical variables. Logistic regression was used to analyze factors associated with glaucoma and cataract surgery complications. A p value of 0.05 or less was considered statistically significant.
The electronic medical records (EMR) search included 19,753 patients aged 50 years or older. A total of 962 (4.9%) patients were found to have pseudoexfoliation syndrome and were included in the study. The mean (SD) age of the 962 patients was 71.8 (8.1) years (range 50–95 years). Nearly half of the patients (46.9%) were aged 70–79 years. Age and gender distribution are shown in Table Table1.1. There was no statistically significant mean age difference between men and women (t = 1.42, p = 0.162). Three hundred and fifty-seven patients (37.1%) had DM. PXF was clinically unilateral in 539 (56.0%) patients, and clinically bilateral in 423 (44.0%) patients. Of the patients with clinically unilateral PXF, 17 patients had lost the other eye due to either trauma or previous complicated intraocular surgery (total eyes: 1385 PXF eyes, 522 clinically non-PXF eyes). The mean age of patients with clinically bilateral PXF (72.8) was significantly higher than those with clinically unilateral PXF (71.0) (t = −3.351, p = 0.001), but no gender difference was found between clinically unilateral and clinically bilateral cases (
χ2 = 1.447, p = 0.229). Combined cataract and glaucoma were present in 248 (25.8%) patients.
Age and gender distribution of 962 patients with PXF
Overall, glaucoma was present in 253 (26.3%) patients and was bilateral in 184 (72.7%) of the glaucoma cases. Open-angle glaucoma was the most common type, occurring in 243 patients (96.0%). Of all glaucoma patients, 230 (90.9%) patients were medically controlled, and 23 patients underwent surgery to control IOP. Table Table22 shows the characteristics of glaucoma and glaucoma procedures performed.
Characteristics of glaucoma and glaucoma procedures performed
|Presence of glaucoma||Glaucoma 253 (26.3%), ocular hypertension 7 (0.7%), normal 702 (73.0%)|
|Glaucoma side||Unilateral 69 (27.3%), bilateral 184 (72.7%)|
|Glaucoma type||Open-angle 243 (96%), secondary 7 (2.8%), angle-closure 3 (1.2%)|
|Glaucoma procedures||Bilateral trabeculectomy 8, unilateral trabeculectomy 10, unilateral Ahmed valve 5|
After excluding patients with secondary glaucoma (neovascular and post-complicated intraocular surgery), patients with lost eyes, and patients with OHT, 932 patients with PXF remained (a total of 1864 eyes: 838 eyes of 419 clinically bilateral PXF patients, and 513 PXF eyes and 513 clinically non-PXF eyes of 513 patients with clinically unilateral PXF). Pseudoexfoliation glaucoma (PXG) was present in 237 of 962 (25.4%) patients with PXF, of whom 55 (23.2%) had unilateral glaucoma, and 182 (76.8%) had bilateral glaucoma. There was a significant gender difference in the frequency of glaucoma (
χ2 = 10.963, p = 0.001); men (n = 140, 30.2%) had a higher frequency of glaucoma than women (n = 97, 20.7%). The frequency of glaucoma was also significantly different between clinically bilateral PXF cases (n = 139, 33.2%) and clinically unilateral PXF cases (n = 98, 19.1%) (
χ2 = 24.080 p < 0.001). Bilateral glaucoma was more common in clinically bilateral PXF (n = 133, 95.7%) compared to clinically unilateral PXF (n = 49, 50%) (
χ2 = 67.309 p < 0.001). No significant differences were found in relation to the presence of DM (
χ2 = 2.069, p = 0.150) or to the mean age between patients with or without glaucoma (t = 1.278, p = 0.201).
We ran binary logistic regression using four predictors (age, gender, DM status, and laterality of PXF) to predict glaucoma status. The whole model was significant (
χ2(4) = 39.848, p < 0.001). The model also showed a good fit as evidenced by no significance of the Hosmer–Lemeshow test (
χ2(8) = 14.317, p = 0.074). Age, gender, and laterality were significantly associated with glaucoma among patients with pseudoexfoliation. Patients with clinically bilateral PXF were 2.149 times as likely to have glaucoma (odds ratio [OR] 2.15) as those with clinically unilateral PXF. Male gender was also associated with higher odds of glaucoma (OR 1.649), whereas increased age was less associated with glaucoma (OR 0.980). Table Table33 shows the results of logistic regression analysis for the prediction of glaucoma.
Binary logistic regression for prediction of glaucoma
|Variable||OR||95% CI for OR|
CI confidence interval, OR odds ratio, PXF pseudoexfoliation, DM diabetes mellitus
Cataract and Surgical Complications
Cataract was present in 928 (96.5%) patients, of whom 454 (48.9%) underwent cataract extraction in either one or both eyes (unilateral/bilateral: 270:184 patients). Of the total 638 eyes that underwent surgery, PXF was present in 499 (78.2%) eyes. Of all PXF study patients, 50 (5.2%) patients had iridodonesis or phacodonesis in either one or both eyes. Sixty-one of 499 (12.2%) eyes with PXF had cataract surgery complications, while 21 of 139 (15.1%) clinically non-PXF eyes developed complications. Table Table44 shows the distribution of cataract surgery complications among eyes with PXF and fellow eyes of clinically unilateral PXF. The difference in the frequency of complications between the two groups was not significant (
χ2(1) = 0.807, p = 0.37). There was also no difference in complication rate between patients with clinically unilateral pseudoexfoliation (n = 37, 15.6%) and clinically bilateral pseudoexfoliation (n = 36, 16.6%) (
χ2(1) = 0.08, p = 0.78).
The distribution of cataract surgery complications among eyes with PXF and fellow eyes of clinically unilateral PXF
|Complicated cataract surgery n, %||Total|
|None||AC IOL||Sulcus IOL||Aphakia|
|Fellow eyes of clinically unilateral PXF||118||11||7||3||139|
PXF pseudoexfoliation, AC anterior chamber, IOL intraocular lens
In binary logistic regression, age, laterality of PXF, DM status, gender, and lens instability were entered in the model to predict cataract surgery complications. The whole model was significant (
χ2(5) = 21.54, p < 0.01), and Hosmer–Lemeshow goodness of fit was not significant (
χ2(8) = 7.42, p = 0.492). Gender and age were the only variables with a significant effect on predicting cataract surgery complications. Male gender was associated with lower odds of cataract surgery complications (OR 0.494), and increased age was associated with a greater likelihood of cataract surgery complications (OR 1.060). Table Table55 shows the results of logistic regression analysis for the prediction of cataract surgery complications.
Binary logistic regression for prediction of cataract surgery complications
|Variable||OR||95% CI for OR||p|
|Laterality of PXF||1.025||0.611||1.721||0.925|
CI confidence interval, OR odds ratio, PXF pseudoexfoliation, DM diabetes mellitus