Association between hyperhomocysteinemia and retinal vein occlusion in a high-altitude population: a case-control study

Abstract Objective To investigate the association between hyperhomocysteinemia (HHcy) and retinal vein occlusion (RVO) in a high-altitude population, evaluate the relationship between different degrees of homocysteine (Hcy) elevation and RVO, and describe the distribution of branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). Methods This hospital-based case-control study included 125 consecutive patients diagnosed with RVO and 125 healthy controls recruited from the same high-altitude region (≥ 2500 m) between July 2023 and March 2026. Demographic characteristics, cardiovascular risk factors, and laboratory parameters, including serum Hcy, folate, vitamin B12, lipid profile, hemoglobin, and hematocrit, were evaluated. HHcy was classified as mild (15–30 µmol/L), moderate (31–100 µmol/L), or severe (> 100 µmol/L). Patients with RVO were categorized as BRVO or CRVO. Multivariable logistic regression analysis was performed to identify factors independently associated with RVO. Results Patients with RVO had significantly higher serum Hcy concentrations than controls (18.26 ± 5.34 vs. 10.35 ± 3.12 µmol/L; P < 0.001), accompanied by significantly lower folate and vitamin B12 levels. HHcy was present in 68.0% of patients with RVO compared with 19.2% of controls ( P < 0.001). Mild HHcy predominated, accounting for 77.6% of all HHcy cases in the RVO group, whereas no cases of severe HHcy were observed. BRVO accounted for 78.4% of RVO cases and CRVO for 21.6%. The distribution of HHcy grades did not differ significantly between BRVO and CRVO ( P = 0.312). Multivariable logistic regression identified hypertension (OR 2.77, 95% CI 1.52–5.06), hyperlipidemia (OR 3.49, 95% CI 1.82–6.69), mild HHcy (OR 5.81, 95% CI 2.77–12.21), and moderate HHcy (OR 8.21, 95% CI 3.56–18.89) as factors independently associated with RVO (all P < 0.05). Conclusions Hyperhomocysteinemia was highly prevalent among patients with retinal vein occlusion living at high altitude, and both mild and moderate HHcy were independently associated with RVO. Elevated homocysteine was similarly distributed between BRVO and CRVO, suggesting a common pathogenic role across RVO subtypes. These findings support consideration of homocysteine assessment as part of the systemic evaluation of patients with RVO in high-altitude regions. Prospective multicenter studies incorporating genetic, nutritional, and environmental factors are warranted to clarify causal relationships and evaluate whether homocysteine-lowering interventions improve clinical outcomes.