Ocular Pseudoexfoliation Syndrome and Vascular Disease: A Systematic Review and Meta-Analysis

Zhang X (2014) Ocular Pseudoexfoliation Syndrome and Vascular Disease: A Systematic Review and Meta-Analysis. PLoS ONE 9(3): e92767. doi:10.1371/journal.pone.0092767 Ocular Pseudoexfoliation Syndrome and Vascular Disease: A Systematic Review and Meta-Analysis Wei Wang 0 Miao He 0 Minwen Zhou 0 Xiulan Zhang 0 Pedro Gonzalez, Duke University, United States of America 0 Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University , Guangzhou , People's Republic of China Objective: Many studies have assessed the association between ocular pseudoexfoliation syndrome (PEX) and vascular disease and produced controversial results. We performed a meta-analysis of epidemiologic studies to evaluate this relationship. Methods: Eligible studies that reported the incidence of vascular disease among PEX and control groups were identified via computer searches and reviewing the reference lists of the key articles. The summary odds ratio (OR) and 95% confidence interval (CI) were pooled using a random-effects model. Meta-regression to assess heterogeneity by several covariates and a subgroup analysis on study design and population were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test. Results: Sixteen eligible studies involving 8,533 PEX patients and 135,720 control patients were included in the metaanalysis. All studies were performed primarily in whites with a mean age between 54.7 and 77.1 years. The overall combined ORs for patients with PEX compared with the reference group were 1.72 (95% CI: 1.31 to 2.26) for any vascular disease, 1.61 (95% CI: 1.22 to 2.14) for coronary heart disease, 1.59 (95% CI: 1.12 to 2.23) for cerebrovascular disease, and 2.48 (95% CI: 1.30 to 4.72) for aortic aneurysm. There was evidence of statistical heterogeneity; however, subgroup and sensitivity analyses showed this result to be robust. No evidence of publication bias was observed. Conclusions: The overall current literature suggests that PEX was associated with increased risk of vascular disease. Because of the limitations of the included studies and meta-analysis, the findings need to be confirmed in future research via welldesigned cohort studies. - Pseudoexfoliation syndrome (PEX) is an age-related disorder characterized by the production and accumulation of an abnormal pseudoexfoliation fibrillar material in various ocular tissues [1]. This syndrome affects about 0.230% of people older than 60 years worldwide [2]. Ocular manifestations of PEX have been well defined, such as pseudoexfoliation glaucoma (PEG), cataract formation, zonular instability, etc. Pseudoexfoliation fibers also have been identified in many extra-ocular tissues, such as the heart, lung, gall bladder, kidney, and cerebral meninges, so the search for systemic implications of this syndrome has attracted a great deal of attention [3]. Vascular disease is the leading cause of death worldwide. In recent decades, a number of epidemiological and experimental studies have assessed the association of PEX with vascular disease risk [4,5]. However, the results have been inconsistent. Some studies [615] have shown an association between PEX and increased systemic vascular risk, while others [1621] have indicated the opposite. An improved understanding of this issue may have important public health and clinical implications given the possibility that slit-lamp examination of the eye for the diagnosis of PEX may identify individuals with an increased vascular disease risk [22]. With recently accumulating evidence, our goal, therefore, was to evaluate the association between PEX and the risk of vascular disease by conducting a systematic review and meta-analysis of all available epidemiological studies. This study was conducted using a predefined protocol and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and the MetaAnalysis of Observational Studies in Epidemiology (MOOSE) guideline (Table S1) [23]. 1. Search Strategy The databases of PubMed, Embase, and Web of Knowledge were systematically searched for relevant articles published between 1966 and December 2013. Both medical search headings and open text fields were used to identify articles. No date or language restrictions were applied. The search terms for exposure were pseudoexfoliation syndrome and exfoliative syndrome, and the search terms for the outcomes were: cardiovascular disease, coronary artery disease, myocardial infarction, heart attack, coronary heart disease, vascular disease, ischemic heart disease, ischaemic heart disease, stroke, transient ischemic attack, transient ischaemic attack, vascular accident, aneurysm, and cerebrovascular disease. The search strategy was optimized for all consulted databases, taking into account the differences in the various controlled vocabularies as well as the differences of database-specific technical variations (e.g. the use of quotation marks). Once relevant articles were identified, their reference lists were searched for additional articles. 2. Inclusion and Exclusion Criteria A study was considered relevant if it reported quantitative estimates of the unadjusted and (or) multivariable adjusted (i.e. age, sex, serum cholesterol, blood pressure, current smoking, diabetes, family history, etc.) odds ratio (OR) with a corresponding 95% confidence interval (CI) for the log relative risk for vascular events. As few studies were eligible and as authors employed heterogeneous endpoints related to vascular disease, we defined a composite of major clinical vascular disease s as the primary endpoint for our meta-analysis. Vascular diseases include coronary heart disease (CHD, such as myocardial infarction, angina pectoris, and other ischemic heart disease), cerebrovascular disease (CVD, such as cerebral hemorrhage and stroke), aortic aneurysm, and peripheral vascular disease. Unpublished papers, nonhuman studies, letters/case reports, studies enrolling ,10 subjects or subjects age ,18 years, editorials, reviews, studies lacking raw data, and studies lacking a suitable control group, and studies using inadequate case definition were excluded. 3. Data Extraction and Quality Assessment Two reviewers independently extracted data using a standardized data-collection form, and any disagreements were discussed. The data collected included the first author, the year of publication, the study design, the population studied, the exposure and outcome evaluated, the number of cases and controls, the association measure, the point estimate and 95% CI, and any adjustment/stratification/matching variables. In studies with overlapping patients or controls, only the latest or the most complete were included. The qualities of included case-control studies were assessed independently by the same two investigators using the NewcastleOttawa Scale (NOS) [24]. The NOS uses a star rating system to judge quality based on thre (...truncated)