Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis

There is still no agreement on total plasma homocysteine (tHcy) role in age-relatedmacular degeneration (AMD), the leading cause of new blindness in industrializedcountries. We performed a systematic review and meta-analysis of the publisheddata on the correlation between tHcy and AMD. MEDLINE/PubMed and ISIWeb of Sciences searches wer e performed according to MOOSE guidelines. Case–control studies were eligible for inclusion. Participants and controls were AMDpatients and subjects without AMD. The main outcome measure was wet AMD.Homocysteine level was the main exposure variable. Data were pooled using arandom-effects model. Twelve case–control studies were identified: 10 assessed wetAMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As forwet AMD , there was a total of 453 cases and 514 controls. Mean tHcy was onaverage 1.1 lmol/l (95% confidence interval [CI] = 0.96–1.25) greater in wetAMD cases, but there was evidence of extreme between-study heterogeneity(p < 0.001, I2= 91.8%). In a model homogenous for age, including six wet AMDstudies (214 cases, 274 controls), mean tHcy was on average 0.58 lmol/l (95%CI = 0.35–0.73) greater in the case group, a not statistically significant result(p = 0.144) associated with moderate heterogeneity (I2= 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might beassociated with wet AMD; however, this result should be interpreted cautiously,because of a marked between-study heterogeneity and the possible effect ofpublication bias. Future studies, preferably of cohort design, are necessary beforeany firm conclusions on the putative role of increased tHcy on AMD can be drawn