What the Research Says About the Mediterranean Diet and Age-Related Macular Degeneration

Editorial note: We only cite studies published in peer-reviewed journals. We summarize findings without overstating conclusions.

Published in the peer-reviewed journal Nutrients in March 2025, this systematic review and meta-analysis by researchers at the Ophthalmology Department of the Local Health Unit of São João and the Faculty of Medicine of the University of Porto (Portugal) synthesizes the available observational evidence on the relationship between adherence to the Mediterranean diet and the development or progression of age-related macular degeneration. Conducted in accordance with PRISMA guidelines and registered prospectively in the PROSPERO international register of systematic reviews, the study analyzed eight observational studies drawn from searches of three major academic databases. The full study is available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11944936/

Background: Why Diet Matters in AMD

Age-related macular degeneration (AMD) is a progressive disease of the macula — the central portion of the retina responsible for sharp, detailed vision — and a leading cause of irreversible vision impairment in older adults worldwide. Approximately 196 million people have AMD globally, a number projected to reach 288 million by 2040 as populations age. The disease proceeds through two advanced forms: geographic atrophy, marked by progressive loss of retinal tissue in a slow, expanding pattern, and neovascular AMD, characterized by abnormal blood vessel growth causing leakage, hemorrhage, and often rapid central vision loss.

AMD is multifactorial. Genetic predisposition, older age, and cigarette smoking are its strongest established risk factors. But diet has increasingly been recognized as a meaningful modifiable risk factor — one that individuals can act on, unlike their genes or their age. Among dietary patterns, the Mediterranean diet has attracted the most scientific attention in this context.

The rationale for this interest is mechanistic. AMD’s pathogenesis centers on two processes — chronic oxidative stress and inflammation — that progressively damage the retinal pigment epithelium and photoreceptors. The Mediterranean diet is rich in compounds that directly counteract both: antioxidants from vegetables and fruits; polyphenols from olive oil, red wine, and nuts; omega-3 fatty acids from fish; and carotenoids including lutein and zeaxanthin from leafy greens. The question the review addresses is whether the scientific evidence from real-world observational studies supports what the biology predicts: that eating this way actually reduces AMD risk and slows its progression.

What the Mediterranean Diet Is

For the purposes of this review, adherence to the Mediterranean diet was defined as consistent and substantial adherence to its core components: high consumption of fruits, vegetables, legumes, whole grains, nuts, and olive oil; moderate consumption of fish and poultry; low to moderate consumption of dairy products; low consumption of red meat and processed foods; and, in some cultural contexts, moderate red wine consumption with meals. Adherence was measured in most included studies using validated Mediterranean diet scoring systems that assign points based on how closely an individual’s reported dietary pattern matches these principles.

How the Review Was Conducted

The authors searched three major academic databases — MEDLINE (via PubMed), Web of Science, and SCOPUS — for observational studies examining the relationship between Mediterranean diet adherence and AMD outcomes. Studies were eligible if they included participants either at risk of AMD or already diagnosed with it, and measured the association between diet and either disease development (incidence in previously unaffected eyes) or disease progression (advancing to a more severe stage).

AMD staging used the AREDS classification system throughout: category 1 represents no AMD (no or minimal small drusen); progression was defined as the transition between or within AREDS categories toward more advanced disease.

After screening, eight studies met the eligibility criteria: two cross-sectional studies, three case-control studies, and three prospective cohort studies. Because these study designs answer different epidemiological questions and have different methodological strengths, the authors ran separate meta-analyses for each design type rather than combining all eight studies into a single pooled estimate. This was a sound methodological choice: cross-sectional studies capture a snapshot in time, case-control studies compare people with and without the disease, and prospective cohort studies follow participants forward from baseline — each design carries different implications for causation.

Statistical heterogeneity between studies was assessed using the I² statistic, where values closer to zero indicate that studies are finding consistent results and values above roughly 50% suggest meaningfully discordant findings. Publication bias — the tendency for studies with positive results to be published more readily than those with null findings — was evaluated through funnel plots.

The Results: Three Different Answers From Three Different Study Designs

Cross-Sectional Studies: No Significant Association Detected

Two cross-sectional studies were included, with a combined pooled odds ratio of 0.96 (95% CI: 0.83–1.11; p = 0.62; I² = 0%). This result was not statistically significant — there was no meaningful association between Mediterranean diet adherence and AMD in these studies. The I² of 0% indicates the two studies were highly consistent with each other.

However, the authors flag an important caveat: the weight distribution between the two studies in the meta-analysis was severely imbalanced. One study dominated the pooled estimate because of its much larger sample size, meaning the result was essentially driven by a single study. This limits the interpretability of the cross-sectional finding.

More fundamentally, cross-sectional studies have an inherent limitation when studying a chronic, slowly progressing disease like AMD: they measure diet and disease status at a single point in time, making it impossible to establish whether diet preceded the disease or whether people changed their eating habits after being diagnosed. This temporal ambiguity is a well-recognized weakness of cross-sectional data in nutritional epidemiology.

Case-Control Studies: A 34% Reduction in Odds of AMD

Three case-control studies — studies that compare the dietary patterns of people who have AMD with those who do not — told a more consistent and compelling story. The pooled odds ratio from the meta-analysis of these three studies was 0.66 (95% CI: 0.54–0.81; p < 0.0001; I² = 41.5%), representing a 34% reduction in the odds of AMD among people with high Mediterranean diet adherence compared to those with low adherence. This result was highly statistically significant.

Looking at the individual studies within this group provides useful texture. The Coimbra Eye Study (Nunes et al., 2018) found a 34% reduction in AMD prevalence among those with high MD adherence (OR = 0.73; 95% CI: 0.58–0.93). A separate Coimbra Eye Study report (Raimundo et al., 2018) reported a 37% reduction (OR = 0.63; 95% CI: 0.41–0.98). The most recent case-control study (Barreto et al., 2023) found the strongest effect: a 59% reduction in the odds of AMD among individuals with high Mediterranean diet adherence (OR = 0.41; 95% CI: 0.23–0.73). All three studies pointed in the same direction, and all three reached statistical significance individually.

The I² value of 41.5% indicates moderate heterogeneity — the studies were not entirely consistent in the size of their effect estimates, though they agreed on direction. A sensitivity analysis (“leave-one-out”) confirmed that no single study was unduly driving the overall result; removing any one study preserved the significant protective association.

Prospective Cohort Studies: A 23% Reduced Risk of AMD Progression

The three prospective cohort studies provide the most methodologically robust evidence of the three design types. By following participants forward in time from a baseline dietary assessment, prospective studies establish that diet preceded disease outcomes — a requirement for inferring a causal relationship that cross-sectional and case-control studies cannot fulfil.

The pooled hazard ratio from the meta-analysis of these three studies was 0.77 (95% CI: 0.67–0.88; p < 0.0001; I² = 0%). This represents a 23% reduced risk of AMD progression among people with higher Mediterranean diet adherence, again highly statistically significant. The I² of 0% is particularly noteworthy: it indicates essentially no heterogeneity — the three independent prospective studies found remarkably consistent results with each other.

The prospective cohort studies included in this analysis draw from well-established research populations. One was conducted within the AREDS (Age-Related Eye Disease Study) cohort, the landmark NIH study of 2,525 participants with AMD followed for 13 years, in which higher Mediterranean diet adherence was associated with reduced risk of progression to advanced AMD — with the protective effect being strongest in participants who did not carry the highest-risk CFH gene variant, suggesting a gene-diet interaction. Another included prospective cohort from the European Eye Study (EUREYE) examined two large European population cohorts and also found that higher Mediterranean diet adherence was associated with reduced incidence of advanced AMD. A third prospective study specifically examined the dry form of AMD (geographic atrophy) and found that closer Mediterranean diet adherence was associated with lower risk of progression, with fish intake identified as a particularly important contributor to the protective association.

Why Do the Results Differ by Study Design?

The divergence between the null cross-sectional results and the positive case-control and prospective results is not surprising to nutritional epidemiologists and deserves some explanation for a general audience.

Cross-sectional studies are the weakest design for establishing dietary associations with chronic disease because they cannot determine whether the dietary pattern came before or after the disease. AMD is a slowly progressive condition that often exists in early or intermediate stages for years before it becomes symptomatic or is formally diagnosed. By the time a cross-sectional study captures someone’s diet and disease status simultaneously, the person may have already changed their diet in response to a diagnosis, concerns about their vision, or advice from a healthcare provider — a phenomenon called reverse causation. This would bias the result toward the null (obscuring any real protective effect), because the people with AMD might be eating just as healthily as those without it precisely because they were told to after their diagnosis.

Case-control and prospective designs are better positioned to avoid this problem, though they are not immune to all forms of bias. Prospective studies are generally considered the gold standard among observational designs because the diet is measured before the disease outcomes occur, eliminating reverse causation entirely.

The authors note that the consistent finding across both case-control and prospective designs — two different methodological approaches pointing to the same conclusion — strengthens confidence in the association.

Why the Mediterranean Diet May Protect the Retina: The Biological Mechanisms

The review situates its numerical findings within a well-established biological framework. AMD’s two driving pathological processes — oxidative stress and chronic inflammation — are precisely the processes that the Mediterranean diet’s key components are known to counteract.

Omega-3 polyunsaturated fatty acids (primarily from fish) exert anti-inflammatory effects by competing with omega-6 arachidonic acid for the enzymes that produce inflammatory signaling molecules. DHA is also a structural component of photoreceptor cell membranes, suggesting a direct architectural role in retinal health beyond anti-inflammation.

Lutein and zeaxanthin, abundant in the leafy green vegetables central to the Mediterranean diet, accumulate selectively in the macula, where they function as both an optical blue-light filter and direct antioxidants. Their relationship to AMD protection has been covered in detail elsewhere on this site; suffice to say that they are among the most biologically plausible dietary protective factors for AMD specifically.

Polyphenols from olive oil, fruits, vegetables, nuts, and wine have documented anti-inflammatory and antioxidant properties through multiple molecular pathways, including suppression of the NF-κB inflammatory signaling pathway and activation of cellular antioxidant defense systems.

Vitamins C and E from fruits and vegetables contribute to antioxidant defense, and the AREDS trials established that antioxidant supplementation reduces AMD progression — lending further plausibility to the idea that diets naturally rich in these compounds would have similar effects.

The Mediterranean diet operates through all these pathways simultaneously, as a coherent package rather than as isolated nutrients — which is one reason why it may be more effective than supplementation with any single component.

The Genetic Interaction: Not Everyone Responds the Same Way

One of the more nuanced findings from the prospective cohort literature included in this review concerns gene-diet interactions. The AREDS-based prospective study found that the protective effect of Mediterranean diet adherence was significantly reduced in participants who carried two copies of the highest-risk CFH gene variant (the CC genotype of Y402H), suggesting that genetic predisposition can partially override the dietary benefit. Participants with one or no copies of the risk allele showed a clearer protective effect from higher diet adherence.

This interaction has practical implications: while the Mediterranean diet appears protective on average across the population, individuals with the highest genetic AMD risk — particularly those with two copies of CFH risk variants — may receive less dietary protection and should discuss additional monitoring or preventive strategies with their eye care provider.

Strengths, Limitations, and What This Evidence Can and Cannot Tell Us

The review is admirably transparent about its limitations. Eight studies is a small evidence base for a meta-analysis, and the authors explicitly acknowledge this. All included studies were observational in design — none was a randomized controlled trial, the gold standard for establishing causation. Even prospective cohort studies, the strongest design available here, can be confounded by factors the researchers did not measure. People who adhere closely to the Mediterranean diet may also exercise more, smoke less, have higher incomes, and have better access to healthcare — all factors independently associated with better health outcomes, including potentially lower AMD progression.

Dietary assessment in all included studies relied on self-reported questionnaires (food frequency questionnaires or similar tools), which are subject to recall bias and measurement error. The definition of “high adherence” to the Mediterranean diet varied between studies, using different validated scoring systems, which contributes to the heterogeneity observed in the case-control meta-analysis.

Despite these limitations, the authors make a reasonable case that the consistent direction of effect across multiple study types, from different research groups, in different countries (Portugal, France, Ireland, the United States, Greece), using different dietary assessment methods, increases confidence that the association reflects something real rather than methodological artifact. The I² of 0% in the prospective cohort analysis — perfect consistency across three independent studies — is particularly reassuring.

The practical recommendation from the review is clear: Mediterranean diet adherence may have a meaningful protective role in AMD management, and the evidence is sufficient to support dietary counseling toward this pattern for people at risk of or already diagnosed with AMD. The authors call for larger, well-controlled prospective studies with standardized dietary assessment tools to confirm and quantify this effect more precisely.

Summary of Key Takeaways

• This 2025 systematic review and meta-analysis synthesized eight observational studies examining Mediterranean diet adherence and AMD outcomes, using separate meta-analyses for each study design type.
• Cross-sectional studies found no significant association (OR = 0.96), likely due to methodological limitations including the inability to establish whether diet preceded disease and a highly imbalanced weight distribution between studies.
• Case-control studies — which compare diet between people with and without AMD — showed a 34% reduction in the odds of AMD among high versus low Mediterranean diet adherents (OR = 0.66; p < 0.0001), with consistent findings across all three individual studies, including one showing a 59% reduction.
• Prospective cohort studies — which follow participants forward from baseline — showed a 23% reduced risk of AMD progression among higher Mediterranean diet adherents (HR = 0.77; p < 0.0001), with zero statistical heterogeneity across three independent cohorts, including populations from the AREDS trial and European cohorts.
• The protective effect appears to be mediated through the diet’s combined antioxidant and anti-inflammatory properties: omega-3 fatty acids, lutein and zeaxanthin, polyphenols, and vitamins C and E all contribute through complementary mechanisms.
• Gene-diet interactions appear to modify the benefit: individuals with the highest-risk CFH genetic variants may receive less dietary protection and warrant additional clinical attention.
• All included studies were observational; confounding and reverse causation cannot be fully excluded. The authors call for larger prospective studies with standardized dietary assessments to strengthen the evidence base.
• Despite these limitations, the consistency of findings across designs, countries, and research groups supports dietary counseling toward Mediterranean eating patterns for people at risk of or diagnosed with AMD.

Source: Marques-Couto P, Coelho-Costa I, Ferreira-da-Silva R, Andrade JP, Carneiro Â. Mediterranean Diet on Development and Progression of Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Observational Studies. Nutrients. 2025 Mar 15;17(6):1037. doi: 10.3390/nu17061037. Full text available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11944936/