Assessment of causality between diet-derived antioxidants and primary open-angle glaucoma: a mendelian randomization study

Purpose: This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR).

Methods: Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, β-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure.

Results: We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854–1.199; P = 0.895) per natural log‐transformed β-carotene to 1.052 (95% CI, 0.911–1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801–1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870–1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits.

Conclusions: Our study did not support a causal association among six diet‐derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells.