Meta-analysis of plasma homocysteine, serum folate, serum vitamin B 12, and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease

Abstract

Purpose To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B 12levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. Design Meta-analysis of literature. Methods A MEDLINE search was performed to identify all published case–control studies of plasma tHcy levels, serum folate and vitamin B 12 levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B 12 standard differences and odds ratios (OR) of TT genotype between cases and controls. Results In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P < .001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P < .001). Serum folates, but not vitamin B 12 levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P < .001; and −0.060; 95% CI = −0.024, 0.104; P = .474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P = .054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P = .060). Conclusions Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B 12 levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B 12 should be considered for affected persons.