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 dietderived circulating antioxidants, primary open -angle glaucoma (POAG), and glaucomarelated traits using two -sample Mendelian randomization (MR). Methods: Genetic variants associated with diet -derived circulating antioxidants (retinol, ascorbate, 0 -carotene, lycopene, alpha-tocopherol, and gamma-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 0 -carotene to 1.052 (95% CI, 0.911-1.215; P = 0.490) for 1 mu mol/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 gamma-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. Translational Relevance: This study provides valid evidence regarding the use of dietderived antioxidants for glaucoma patients.