Homocysteine and risk of wet age‐related macular degeneration: a meta‐analysis

Purpose: Wet age-related macular degeneration (AMD) is an important cause of vision loss. We performed a meta-analysis review of the literature to assess the role of plasma total homocysteine (tHcy) concentration a as risk factor for wet AMD. Methods: Data sources included PubMed searches and searching reference lists of relevant articles and reviews. The literature review was performed according to the guidelines of Meta-analysis of Observational Studies in Epidemiology (MOOSE). Case-control studies were eligible for inclusion. Meta-analysis summary estimates were obtained using a random-effects model to account for between-study heterogeneity. Results: 9 case-control studies were identified, for a total of 422 cases and 467 controls. The mean tHcy was on average 1.18 μmol/L (95% confidence interval [CI] = 1.03–1.33) greater in the wet AMD cases compared with the controls (P < 0.001), but patients’ and controls’ ages showed a high degree of between-study heterogeneity. After exclusion of the two studies with higher age heterogeneity, there were 243 cases and 277 controls and the mean tHcy was on average 0.7 μmol/L (95% CI = 0.52–0.88) greater in the wet AMD patients compared to the controls (P = 0.03). Conclusions: There is some weak evidence that elevated tHcy might be associated with wet AMD; however, this result should be interpreted cautiously because of a marked heterogeneity between the study estimates and the possible effect of publication bias on the tHcy findings.