Risk of Retinal Vein Occlusion in Patients With Vitamin B12 Deficiency and Hyperhomocysteinemia: A Propensity-Matched Cohort Study Using TriNetX.

Purpose: To evaluate whether vitamin B12 deficiency with elevated homocysteine is associated with increased risk of retinal vein occlusion (RVO). Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Network (August 2005-August 2025). Adults (≥18 years) with vitamin B12 deficiency (International Classification of Diseases, Tenth Revision code D51.0-D51.9) and hyperhomocysteinemia (>15.00 µmol/L) were matched in a 1:1 ratio to controls without B12 deficiency and with homocysteine status unrestricted, using propensity scores for age, sex, race, ethnicity, body mass index, hypertension, diabetes, ischemic heart disease, and nicotine dependence. Patients with pre-index RVO were excluded. The primary outcome was incident RVO (central or branch) over 10 years, analyzed with risk ratios, odds ratios, hazard ratios, and Kaplan-Meier cumulative incidence curves. Results: After matching and exclusion of patients with prior RVO, 10 161 individuals were included (5070 with B12 deficiency and hyperhomocysteinemia, 5091 controls). The cohorts were well-balanced across demographics and comorbidities. Incident RVO occurred in 32 patients (0.63%) with B12 deficiency and hyperhomocysteinemia compared with 15 patients (0.29%) among the control group, corresponding to a statistically significant increased risk (risk ratio, 2.142 [95% CI, 1.162-3.951]; odds ratio, 2.149 [95% CI, 1.163-3.974]; both P = .012). Kaplan-Meier curves demonstrated a higher cumulative incidence of RVO in the B12 deficiency and hyperhomocysteinemia cohort (log-rank χ² = 7.551, P = .006; hazard ratio, 2.306 [95% CI, 1.249-4.260]). Conclusions: Vitamin B12 deficiency with hyperhomocysteinemia was associated with an increased RVO risk. These findings highlight a modifiable risk factor, and prospective studies are needed to assess causality and evaluate whether correction of vitamin B12 deficiency or hyperhomocysteinemia reduces RVO risk.