Mediterranean diet linked to slower AMD progression across stages

Closer adherence to a Mediterranean-style diet is associated with slower progression of age-related macular degeneration (AMD) at early, intermediate, and advanced stages, according to a clinical perspective published in the American Journal of Ophthalmology.¹ The authors, led by Tiarnan D. L. Keenan, MD, PhD, of the National Eye Institute, concluded that the dietary components most strongly linked to slower disease vary by stage, and that diet should be viewed as a complement to, not a substitute for, AREDS2 supplementation.¹

The publication is a focused literature review rather than a new trial. Its conclusions rest largely on post hoc analyses of the Age-Related Eye Disease Study (AREDS) and AREDS2 cohorts, together with epidemiologic studies from Europe and North America, so the findings describe associations rather than demonstrating that dietary change prevents progression.¹

Evidence by disease stage

Early AMD

In AREDS, participants with the highest adherence to the alternative Mediterranean Diet Index (aMedi) had a lower risk of progressing to large drusen than those with the lowest adherence (hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), based on 5029 eyes of 3026 participants.² The review found no evidence supporting oral micronutrient supplements for patients with early AMD.¹

Intermediate AMD

The primary analysis of 13,204 eyes of 7756 AREDS and AREDS2 participants, followed for a median of 10.2 years, reported HRs for the highest vs lowest aMedi tertile of 0.78 (95% CI, 0.71-0.85) for late AMD, 0.71 (95% CI, 0.63-0.80) for geographic atrophy (GA), and 0.84 (95% CI, 0.75-0.95) for neovascular AMD.² The association was stronger for GA than for neovascular disease.²

Fish was the individual component with the strongest association. In AREDS, the highest vs lowest quartile of fish intake was associated with a lower risk of late AMD (HR, 0.69; 95% CI, 0.58-0.82), although the corresponding estimate in AREDS2 was not statistically significant (HR, 0.92; 95% CI, 0.78-1.07).² Participants in the highest AREDS fish-intake group ate a median of about 3 to 4 medium servings per week.¹ Higher vegetable intake and lower red meat intake were also associated with lower risk, and the authors noted dose-response relationships, suggesting that partial dietary improvement may carry benefit.¹

Geographic atrophy

In an AREDS2 post hoc analysis of 1155 eyes of 850 participants with GA, followed for a mean of 3.1 years, mean GA enlargement was 0.256 mm/y in the highest aMedi tertile vs 0.298 mm/y in the lowest.³ Of the 9 aMedi components, slower enlargement was associated with higher whole fruit intake, lower red meat intake, moderate alcohol intake, and a higher ratio of monounsaturated to saturated fat; fish intake was not significantly associated with enlargement rate.³ A later analysis of both cohorts found that a higher aMedi score was also associated with slower progression toward the fovea in AREDS and with slower visual acuity decline in AREDS2 eyes with noncentral GA.⁴ The review reported roughly 30% slower foveal progression with higher adherence and 40% to 50% slower progression in the highest vegetable intake groups.¹

Clinical context

AMD was projected to affect 196 million people worldwide in 2020, rising to 288 million by 2040.⁵ For GA, the 2 approved therapies require repeated intravitreal injection and offer modest efficacy, which has sustained interest in low-risk oral or lifestyle approaches.⁶

AREDS2 established the current supplement formulation, substituting lutein (10 mg) and zeaxanthin (2 mg) for beta carotene after more lung cancers were observed among former smokers in the beta carotene group.⁷ The formulation is recommended for patients with intermediate AMD or advanced AMD in at least 1 eye.¹ In a post hoc analysis, AREDS2 supplements slowed extrafoveal GA progression toward the fovea by approximately 55% over about 3 years.^6,8 The review authors noted that supplementation appears to reduce neovascular AMD risk preferentially, whereas Mediterranean diet adherence shows a stronger relationship with GA, and they framed the 2 approaches as complementary.¹

Interpretation and limitations

The underlying data come from food frequency questionnaires collected within supplement trials, and dietary patterns correlate with other health behaviors, which limits causal inference despite adjustment for confounders. The fish association was not consistent across cohorts, and in AREDS the protective associations of aMedi and fish intake were seen only in participants carrying protective alleles at CFH rs10922109.² Findings on foveal progression have also varied: the earlier AREDS2 report found no association between aMedi and progression to central involvement among eyes with noncentral GA, whereas the later analysis reported slower proximity-based progression in AREDS.^3,4 The supplement effect on foveal progression likewise comes from post hoc analyses, and the review authors stated that it requires confirmation in a prospective trial.¹

For clinicians, the review supports stage-specific dietary counseling: fish, vegetables, and less red meat for patients with intermediate AMD, and fruit, vegetables, less red meat, and avoidance of heavy alcohol use for patients with GA, alongside AREDS2 supplementation where indicated.¹

References

1. Keenan TDL, Hébert M, Chew EY, Johnson MW. What should patients with age-related macular degeneration eat? Am J Ophthalmol. 2026;288:12-21. doi:10.1016/j.ajo.2026.04.003. https://doi.org/10.1016/j.ajo.2026.04.003

2. Keenan TD, Agrón E, Mares J, et al. Adherence to the Mediterranean diet and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology. 2020;127(11):1515-1528. doi:10.1016/j.ophtha.2020.04.030. https://pubmed.ncbi.nlm.nih.gov/32348832/

3. Agrón E, Mares J, Chew EY, Keenan TDL; AREDS2 Research Group. Adherence to a Mediterranean diet and geographic atrophy enlargement rate: Age-Related Eye Disease Study 2 report 29. Ophthalmol Retina. 2022. PMID: 35381392. https://pmc.ncbi.nlm.nih.gov/articles/PMC9464676

4. Agrón E, Vance E, Domalpally A, Chew EY, Keenan TDL. Relationships between diet and geographic atrophy progression in the Age-Related Eye Diseases Studies 1 and 2. Nutrients. 2025;17(5):771. doi:10.3390/nu17050771. https://doi.org/10.3390/nu17050771

5. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e116. doi:10.1016/S2214-109X(13)70145-1. https://pubmed.ncbi.nlm.nih.gov/25104651/

6. Keenan TDL, Agrón E, Keane PA, Domalpally A, Chew EY; AREDS and AREDS2 Research Groups. Oral antioxidant and lutein/zeaxanthin supplements slow geographic atrophy progression to the fovea in age-related macular degeneration. Ophthalmology. 2025;132(1):14-29. doi:10.1016/j.ophtha.2024.07.014. https://doi.org/10.1016/j.ophtha.2024.07.014

7. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015. doi:10.1001/jama.2013.4997. https://pubmed.ncbi.nlm.nih.gov/23644932/

8. National Eye Institute. Supplements slow disease progression during late stage of "dry" age-related macular degeneration. News release. Accessed October 28, 2026. https://www.nei.nih.gov/about/news-and-events/news/supplements-slow-disease-progression-during-late-stage-dry-age-related-macular-degeneration