Pseudoexfoliation Syndrome and the Long-Term Incidence of Cataract and Cataract Surgery: The Blue Mountains Eye Study




Purpose


To assess whether the pseudoexfoliation syndrome (PXS) is associated with the long-term incidence of cataract or cataract surgery.


Design


Population-based cohort study.


Methods


The Blue Mountains Eye Study examined 3654 persons 49 years of age and older at baseline; 2564 were re-examined after 5 or 10 years, or both. PXS was recorded at the baseline eye examination by an ophthalmologist. Masked graders assessed lens photographs using the Wisconsin Cataract Grading System. Generalized estimating equation regression models were used to examine the association between PXS and cataract by eye.


Results


Eyes with PXS had a significantly greater prevalence of cortical cataract ( P = .02) and nuclear cataract ( P < .0001) than eyes without PXS. The association between PXS and cortical cataract, however, did not persist after further adjustment for age, gender, smoking, diabetes, steroid use, myopia, socioeconomic status, and open-angle glaucoma (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.53 to 1.46), whereas the association between PXS and nuclear cataract persisted after adjustment for the above confounders (OR, 1.90; 95% CI, 1.04 to 3.48). In addition, significant associations were found between the presence of PXS at baseline and the 10-year incidence of either nuclear cataract ( P < .0001) or cataract surgery ( P < .0001). These associations persisted after adjustment for the potential confounders listed above (OR, 3.25; 95% CI, 1.38 to 7.65; and OR, 4.09; 95% CI, 2.25 to 7.44; respectively). No significant cross-sectional or longitudinal associations were found between PXS and posterior subcapsular cataract.


Conclusions


Long-term follow-up data from this population-based older cohort suggest that the presence of PXS is associated with an increased risk of nuclear cataract and cataract surgery.


Cataract is the most frequent eye disease in the elderly population. Despite recent improvements in surgical techniques and subsequent outcomes, cataract remains the leading cause of mild to moderate visual impairment in the developed world.


Pseudoexfoliation syndrome (PXS) is characterized by the production and progressive accumulation of a fibrillar extracellular material in ocular and extraocular tissues. In the eye, PXS is characterized clinically by small white deposits of material in the anterior segment, most commonly on the pupillary border and anterior lens capsule. It is the most common identifiable cause of open-angle glaucoma, and in some countries accounts for most open-angle glaucoma cases.


Findings from previous cross-sectional studies examining the association between PXS and cataract have been inconsistent. Nevertheless, both the prevalence of PXS and cataract are strongly associated with age, and PXS is known to be associated with open-angle glaucoma, which, together with glaucoma surgery, can be independent risk factors for cataract. Therefore, the apparent association between PXS and cataract, reported by some previous studies could be the result of the confounding effects of age and open-angle glaucoma. In addition, longitudinal studies are needed to establish a causal association between preceding exposures and subsequent development of cataract.


We aimed in this study to assess associations between the presence of PXS at baseline examinations of the Blue Mountains Eye Study cohort and the prevalence and long-term incidence of cataract and cataract surgery, after adjusting for several potential confounders, including open-angle glaucoma.


Methods


Study Population


Details of the Blue Mountains Eye Study population and its methods are reported elsewhere. In brief, the Blue Mountains Eye Study is a population-based cohort study of vision and common eye diseases in an urban older population comprising 2 postcode areas in the Blue Mountains region, west of Sydney, Australia. This geographically well-defined area has a stable population that is reasonably representative of Australia in socioeconomic status and other measures. All residents 49 years of age or older of these 2 postcode areas were eligible and were invited to participate in the survey.


At baseline examinations (1992 through 1994), 4433 eligible residents were identified, of whom 3654 (82.4%) were interviewed and examined. Baseline differences between participants and nonparticipants were reported previously. All surviving participants were invited for re-examination after 5 years (1997 through 1999) and 10 years (2002 through 2004), with 2335 (75.1% of survivors) and 1952 (75.6% of survivors) returning for re-examinations at these times, respectively. Altogether, 2564 participants were followed-up at least once since their baseline examinations.


Comparisons of participants and nonparticipants at each follow-up examination have been reported previously. Nonparticipants were significantly younger ( P < .0001), were more likely to be current smokers ( P < .0001), and were more likely to have been diagnosed with diabetes ( P = .049). They also were more likely to report lower job prestige index ( P = .041) and were less likely to live in their own home ( P = .0006) than those who participated in follow-up examinations.


The study was approved by the University of Sydney and Western Sydney Area Health Service Human Research Ethics Committees. Written informed consent was obtained from all participants.


Procedures


An interviewer-administered questionnaire was used to collect detailed demographic and medical history data at each visit. All participants underwent detailed eye examinations. Slit-lamp lens photographs of each eye were obtained using Ektachrome 200 color film (Kodak, Rochester, New York, USA) on a Topcon SL-7E photograph slit-lamp camera (Topcon, Tokyo, Japan) to assess the presence of nuclear cataract. Retroillumination lens photographs were obtained using a Neitz CT-R cataract camera (Neitz Instruments, Tokyo, Japan) to assess the presence of cortical cataract and posterior subcapsular (PSC) cataract.


Presence of pseudoexfoliation was recorded at baseline eye examination as described previously. After pupil dilatation, a detailed high-magnification slit-lamp assessment of the anterior segment was performed by means of a narrowed slit beam by 1 observer (P.M.) on all participants. The anterior lens surface from each eye was scanned from left to right, looking specifically for early signs of PXS, including pregranular radial lines, as well as established granular deposits. Presence of specific anterior segment abnormalities was recorded, including the presence of exfoliative material on the anterior lens surface or on the pupil margin, with the latter useful in pseudophakic eyes.


Intraocular pressure was measured using applanation tonometry. Glaucoma was diagnosed from characteristic visual field loss combined with optic disc cupping and rim thinning without reference to intraocular pressure. Refractive error was assessed using autorefraction, followed by subjective best-corrected refraction. At the 5-year and 10-year follow-up visits, participants were re-examined in approximately the same order as that at baseline, using the same procedures and equipment.


The Wisconsin Cataract Grading System, first developed in 1990 for use in the Beaver Dam Eye Study, was followed closely in performing masked grading of all lens photographs obtained at each visit. Intergrader and intragrader reproducibility of the lens photograph grading was assessed using quadratic weighted κ statistics and was shown to be within an acceptable range in our study.


Incident cataract was defined as the appearance of nuclear, cortical, or PSC cataract subtypes in bilaterally phakic participants, in which the corresponding cataract subtype was not present in either eye at baseline. Similarly, incident cataract surgery was defined as cataract surgery performed in either eye of participants who were bilaterally phakic at baseline.


Progression of nuclear cataract was defined as an increase of 1.0 or more in the grading score of nuclear opacity. Progression of cortical cataract was defined as an increase of at least 10% of the lens area affected by the cortical cataract. Progression of PSC cataract was defined as an increase of at least 2% of the lens area affected by PSC cataract.


Statistical Analysis


SAS software (SAS Institute, Cary, North Carolina, USA) was used for data analysis. Generalized estimating equation regression models and eye-specific data were used to assess associations between the presence of pseudoexfoliation at baseline and the prevalence and 10-year incidence of cortical, nuclear, and PSC cataract or cataract surgery. Potential confounders adjusted for included age, gender, diabetes, smoking, steroid use, myopia, socioeconomic status, and open-angle glaucoma. Supplemental analyses using competing risk models considering competing event of death also were performed using subject-specific data and the SAS macros function. Findings are presented as odds ratios (ORs) with 95% confidence intervals (CIs).




Results


Table 1 shows the eye-specific prevalence of PXS stratified by age and gender. Of the 7308 eyes examined at baseline, 120 (1.64%) had PXS. In men, 38 (1.20%) of 3164 eyes had PXS, and in women, 82 (1.98%) of 4144 eyes had PXS. The prevalence of PXS increased steadily with age from 0% in the youngest group (49 to 54 years of age) to 6.25% in the oldest group (85 years of age and older) of the study population.



Table 1

Prevalence of Pseudoexfoliation Syndrome in the Blue Mountains Eye Study Population
































































Age Group (y) Male Female Total
n/N a % n/N a % n/N a %
49 to 54 0/430 0 0/540 0 0/970 0
55 to 64 6/1026 0.58 13/1318 0.99 19/2344 0.81
65 to 74 17/1054 1.61 31/1364 2.27 48/2418 1.99
75 to 84 14/558 2.51 22/746 2.95 36/1304 2.76
85 and older 1/96 1.04 16/176 9.09 17/272 6.25
Total 38/3164 1.20 82/4144 1.98 120/7308 1.64

a Number of eyes with pseudoexfoliation/total number of eyes.



Table 2 shows the cross-sectional association between PXS and either cataract or cataract surgery at the baseline examination. Eyes with PXS had a significantly greater prevalence of both cortical cataract ( P = .02) and nuclear cataract ( P < .0001) compared with eyes without PXS. The association between PXS and cortical cataract prevalence, however, did not persist after further adjustment for age, gender, smoking, diabetes, steroid use, myopia, socioeconomic status, and open-angle glaucoma (OR, 0.89; 95% CI, 0.53 to 1.46), whereas the association between PXS and nuclear cataract prevalence persisted after further adjustment for the above confounders (OR, 1.90; 95% CI, 1.04 to 3.48). No significant associations were found between PXS and the prevalence of either PSC cataract or cataract surgery ( P = .18 and P = .14, respectively).



Table 2

Associations between Pseudoexfoliation Syndrome and the Prevalence of Cataract, by Eye















































Cataract Type PXS Absent PXS Present Univariate P Value Multivariate Adjusted b Odds Ratio (95% Confidence Interval)
n/N a % n/N a %
Cortical 1182/6604 17.90 28/105 26.67 .02 0.89 (0.53 to 1.46)
Nuclear 705/4525 15.58 26/82 31.71 <.0001 1.90 (1.04 to 3.48)
Posterior subcapsular 258/6632 3.89 7/110 6.36 .18 NI
Cataract surgery 323/7175 4.50 2/120 1.67 .14 NI

NI = not included in the multivariate-adjusted model as the univariate model was not statistically significant; PXS = pseudoexfoliation syndrome.

Significant P values (<.05) appear in boldface.

a Number of eyes with cataract/number of eyes at risk.


b Adjusted for age, gender, diabetes, steroid use, smoking, myopia, socioeconomic status, and open-angle glaucoma.



Table 3 shows the associations between PXS at baseline and the 10-year incidence of the 3 cataract subtypes and cataract surgery. No associations were found between PXS and the incidence of cortical or PSC cataract ( P = .18 and P = .19, respectively). However, baseline PXS was associated significantly with the 10-year incidence of nuclear cataract ( P < .0001). This association persisted after adjusting for age, gender, smoking, diabetes, steroid use, myopia, socioeconomic status, and open-angle glaucoma (OR, 3.25; 95% CI, 1.38 to 7.65). In addition, PXS was associated significantly with the 10-year incidence of cataract surgery ( P < .0001). This association also persisted after adjusting for the potential confounders listed above (OR, 4.09; 95% CI, 2.25 to 7.44). When we repeated the analysis after excluding eyes with glaucoma, the association of PXS with nuclear cataract (adjusted OR, 3.22; 95% CI, 1.38 to 7.55) and cataract surgery (adjusted OR, 3.91; 95% CI, 2.10 to 7.26) remained significant. Furthermore, when the analysis was repeated using person-specific data, similar associations were observed between PXS and nuclear cataract (OR, 3.20; 95% CI, 1.37 to 7.48) and cataract surgery (OR, 4.12; 95% CI, 2.27 to 7.49; Table 4 ). Competing risk models incorporating the probability of competing event of death provided the same risk estimates for the associations (data not shown).



Table 3

Associations between Baseline Pseudoexfoliation Syndrome and the Long-Term Incidence of Cataract, by Eye















































Cataract Type PXS Absent PXS Present Univariate P Value Multivariate Adjusted b Odds Ratio (95% Confidence Interval)
n/N a % n/N a %
Cortical 641/3808 10.62 2/31 4.44 .18 NI
Nuclear 658/2730 16.04 15/26 45.45 <.001 3.25 (1.38 to 7.65)
Posterior subcapsular 191/4196 2.84 0/39 0.0 .19 NI
Cataract surgery 564/4841 11.65 26/56 46.43 <.0001 4.09 (2.25 to 7.44)

NI = not included in the multivariate-adjusted model as the univariate model was not statistically significant; PXS = pseudoexfoliation syndrome.

Significant P values (< .05) appear in boldface.

a Number with cataract/number at risk.


b Adjusted for age, gender, diabetes, steroid use, smoking, myopia, socioeconomic status, and open-angle glaucoma.


Jan 9, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Pseudoexfoliation Syndrome and the Long-Term Incidence of Cataract and Cataract Surgery: The Blue Mountains Eye Study

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