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.