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

Can Can Xue; Hengtong Li; Xing-Xuan Dong; Marco Yu; Zhi Da Soh; Crystal Chun Yuen Chong; Chen Jiang; Helene Choquet; Nazlee Zebardast; Seyedeh Maryam Zekavat; Pirro G Hysi; Seang Mei Saw; Qiao Fan; Yih-Chung Tham; Chen-Wei Pan; Ching-Yu Cheng

doi:10.1016/j.ajo.2024.08.041

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

Am J Ophthalmol. 2024 Dec:268:368-377. doi: 10.1016/j.ajo.2024.08.041. Epub 2024 Sep 5.

Authors

Affiliations

¹ From the Singapore Eye Research Institute, Singapore National Eye Centre (C.C.X., M.Y., Z.D.S., C.C., S.M.S., Y.-C.T., C.-Y.C.), Singapore.
² Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Y.-C.T., C.-Y.C.), Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Z.D.S., S.M.S., Y.-C.T., C.-Y.C.), Singapore.
³ School of Public Health, Suzhou Medical College of Soochow University (X.-X.D., C.-W.P.), Suzhou, China.
⁴ From the Singapore Eye Research Institute, Singapore National Eye Centre (C.C.X., M.Y., Z.D.S., C.C., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Z.D.S., S.M.S., Y.-C.T., C.-Y.C.), Singapore.
⁵ Division of Research, Kaiser Permanente Northern California (C.J., H.C.), Pleasanton, CA, USA.
⁶ Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., S.M.Z.), Boston, MA, USA; Program in Medical and Population Genetics, Broad institute of MiT and Harvard (N.Z., S.M.Z.), Cambridge, MA, USA.
⁷ Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., S.M.Z.), Boston, MA, USA; Program in Medical and Population Genetics, Broad institute of MiT and Harvard (N.Z., S.M.Z.), Cambridge, MA, USA; Cardiovascular Research Center, Massachusetts General hospital, Harvard Medical School (S.M.Z.), Boston, MA, USA.
⁸ King's College London, Section of Ophthalmology, School of Life Course Sciences (P.G.H.), London, United Kingdom; King's College London, Department of Twin Research and Genetic Epidemiology (P.G.H.), London, United Kingdom; University College London, GOSH Institute of Child Health (P.G.H.), London, United Kingdom.
⁹ From the Singapore Eye Research Institute, Singapore National Eye Centre (C.C.X., M.Y., Z.D.S., C.C., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Z.D.S., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Saw Swee Hock School of Public Health, National University of Singapore (S.M.S.), Singapore.
¹⁰ Centre for Quantitative Medicine, Duke-NUS Medical School (Q.F.), Singapore.
¹¹ From the Singapore Eye Research Institute, Singapore National Eye Centre (C.C.X., M.Y., Z.D.S., C.C., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Y.-C.T., C.-Y.C.), Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Z.D.S., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School (Y.-C.T., C.-Y.C.), Singapore.
¹² From the Singapore Eye Research Institute, Singapore National Eye Centre (C.C.X., M.Y., Z.D.S., C.C., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Y.-C.T., C.-Y.C.), Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore (H.L., Z.D.S., S.M.S., Y.-C.T., C.-Y.C.), Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School (Y.-C.T., C.-Y.C.), Singapore. Electronic address: chingyu.cheng@nus.edu.sg.

PMID: 39244001
PMCID: PMC11606739 (available on 2025-12-01)
DOI: 10.1016/j.ajo.2024.08.041

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.

MeSH terms

Adult
Axial Length, Eye
Choroid / pathology
Fatty Acids, Omega-3*
Female
Genome-Wide Association Study
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Myopia* / physiopathology
Myopia* / prevention & control
Polymorphism, Single Nucleotide
Protective Factors
Refraction, Ocular* / physiology

Substances

Fatty Acids, Omega-3

Abstract

MeSH terms

Substances

Grants and funding