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

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.