Abstract
PURPOSE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis. DESIGN: Two-sample MR analysis. METHODS: Exposures are genetically predicted plasma levels of 18 fatty acid (FA)-related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on plasma levels of 18 FA-related traits (n=115,006), refractive spherical equivalent (n=351,091), axial length (n=69,945), and choroidal thickness (n=44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used 5 MR models and considered results statistically significant if the Bonferroni-corrected P value was ≤2.78 ×10(-3) in at least 3 MR models. The β represents the change in outcomes (SER in diopters; axial length in millimeters; and choroidal thickness in SD) per SD unit increase in FA levels. RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 (β, 0.32-0.34), omega-3-total FA ratio (β, 0.31-0.44), docosahexaenoic acid (DHA) (β, 0.36-0.46), DHA-total FA ratio (β, 0.37-0.53), PUFA-total FA ratio (β, 0.07-1.003), and degree of unsaturation (β, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance (P ≤ .035 in ≥2 models). Higher levels of omega-3, DHA, DHA-total FA ratio, PUFA-total FA ratio, PUFA-monounsaturated FA ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness (β, 0.05-0.13; P ≤ .045 in ≥2 models). CONCLUSION: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration.