Association Between Inflammatory Cytokines and Refractive Errors: A Bidirectional Mendelian Randomization Study

Purpose: This investigation aimed to elucidate the causal role of inflammatory cytokines in the risk of developing refractive errors. Methods: Genetic variants previously associated with inflammatory cytokines served as instrumental variables in genome-wide association studies (GWASs) of European ancestry. Bidirectional two-sample Mendelian randomization (MR) analyses were conducted using summary data from GWAS meta-analyses. Rigorous sensitivity analyses were performed to validate the reliability of the MR results. Results: We found that, for every unit increase in interleukin 1 receptor antagonist (IL1RA) and interleukin 2 (IL2), there was a corresponding decrease in the prevalence of myopic refractive errors by 0.235 (95% confidence interval [CI], 0.050-0.419 for fixed effects; 95% CI, 0.125-0.345 for random effects) and 0.132 (95% CI, 0.032-0.231 for fixed effects; 95% CI, 0.044-0.220 for random effects), respectively. No substantial causal associations were observed for IL1 alpha, IL1 beta, IL12p70, or monocyte chemoattractant protein 1 (MCP1) with refractive errors. Conversely, reverse MR analyses failed to indicate a causal influence of refractive errors on IL1RA and IL2. Conclusions: The present study offers evidence for a causal link between inflammatory cytokines and refractive errors, which could have significant implications for the early detection, surveillance, and management of refractive errors. Translational Relevance: Our study underscores the importance of IL1RA and IL2 in the prevention and management of refractive errors, suggesting the feasibility of strategies for early identification, continuous surveillance, and the deployment of focused therapeutic approaches.