Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia

center dot 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. center dot DESIGN: Two-sample MR analysis. center dot 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 x 10-3 in at least 3 MR models. The ,B represents the change in outcomes (SER in diopters; axial length in millimeters; and choroidal thickness in SD) per SD unit increase in FA levels. center dot RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 ( ,B, 0.32-0.34), omega-3-total FA ratio ( ,B, 0.31-0.44), docosahexaenoic acid (DHA) ( ,B, 0.36-0.46), DHA-total FA ratio ( ,B, 0.37-0.53), PUFA-total FA ratio ( ,B, 0.07-1.003), and degree of unsaturation ( ,B, 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 ( ,B, 0.05-0.13; P <= .045 in >= 2 models). center dot 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. (Am J Ophthalmol 2024;268: 368-377. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)