Causal association between glaucoma and risk of retinal vascular occlusion: a Mendelian randomization study

Retinal vein occlusion (RVO) leads to visual impairment, and risk factors may include glaucoma. Although some studies suggest a relationship between glaucoma and RVO, it is unknown whether this association is causal. We performed Mendelian randomization (MR) analyses to evaluate the causal contribution to RVO of five genetically predicted glaucoma conditions.

We conducted two-sample univariable MR analysis using inverse variance weighting, weighted median, and MR-Egger methods. We obtained publicly available datasets of genome-wide association studies (GWAS) meta-analyses for glaucoma as the exposure and a GWAS for RVO in the Finn Gen biobank study as the outcome.

Genetically predicted glaucoma was causally associated with RVO risk (beta = 0.267, standard error [SE] = 0.052, odds ratio [OR] = 1.306, 95% confidence interval [CI]: 1.181-1.445). This association was supported by sensitivity analyses using weighted median (beta = 0.211, SE = 0.075, OR = 1.235, 95% CI: 1.067-1.429), weighted mode (beta = 0.491, SE = 0.132, OR = 1.633, 95% CI: 1.261-2.116), and MR-Egger (beta = 0.3900, SE = 0.138, OR = 1.476, 95% CI: 1.128-1.933) methods. MR analyses using the validation dataset obtained consistent results.

Our results indicated that glaucoma is likely causally associated with an increased risk of RVO. The current findings may help in determining the underlying mechanisms via which glaucoma affects the risk of RVO.