Repurposing Antihypertensive Drugs for the Prevention of Glaucoma: A Mendelian Randomization Study

Purpose: Several antihypertensive drugs have been used for the treatment of glaucoma. However, the effect of hypertension and antihypertensive drugs on glaucoma is still unclear. Methods: Leveraging large-scale genome-wide association study summary statistics for glaucoma (Ncase = 4737, Ncontrol = 458,196), blood pressure (BP) (N = 422,771), and intraocular pressure (IOP) (N = 31,269), the genetic correlation and causal relationship of genetically assessed IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 12 types of antihypertensive drugs with glaucoma were evaluated using linkage disequilibrium score (LDSC) regression, univariate mendelian randomization (MR), and multivariable MR. Results: LDSC results showed a suggestive association of glaucoma with SBP (R_g = 0.12, P = 0.0076) and DBP (R_g = 0.17, P = 0.02). In univariate MR, genetically elevated BP in participants was not identified to lead to an increased glaucoma risk (SBP: odds ratio [OR], 1.05 [95% confidence interval {CI}, 0.91–1.21]; P = 0.52; DBP: OR, 1.07 [95% CI, 0.93–1.23]; P = 0.34). The results of univariate MR were replicated in multivariable MR (SBP: OR, 0.95 [95% CI, 0.71–1.29]; P = 0.75; DBP: OR, 1.13 [95% CI, 0.85–1.51]; P = 0.41). Furthermore, there was insufficient evidence to suggest that antihypertensive drugs were associated with glaucoma. Conclusions: Together, controlling BP may not help prevent and treat glaucoma, and antihypertensive drugs may neither treat nor worsen glaucoma. Translational Relevance: Treating with antihypertensive drugs should not be used as an intervention for patients with glaucoma.