“Ἐν τροφῇ φαρμακεῖη ἄριστον, ἐν τροφῇ φαρμακεῖη φλαῦρον.”

“In food, excellent medicine can be found; in food, harmful medicine can be found.” (Hippocrates, De Alimento )

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss among older adults in high-income countries and represents a growing global public health challenge as populations age. Although effective treatments exist for neovascular AMD, management options to slow progression to advanced disease remain very limited. For example, no therapies are available to slow progression from early to intermediate AMD, or from intermediate disease to geographic atrophy (GA) ( Figure 1 ). Therefore, there is increasing focus on modifiable lifestyle factors that may alter the trajectory of AMD. Cigarette smoking is the most clearly established modifiable risk factor for AMD, and smoking cessation should be strongly advised for patients with AMD or those at risk. ^, Alongside smoking cessation, diet has emerged as one of the most promising areas for intervention.

Simplified diagram of the protective associations of the Mediterranean diet and AREDS2 formulation supplements at different stages of age-related macular degeneration.

Across medicine, the concept of “food as medicine” has achieved renewed prominence. ^,,, For example, a recent simulation study found that economic incentives for healthier foods could generate substantial health gains and be highly cost-effective. Cardiologists emphasize predominantly plant-based and non-ultraprocessed diets for cardiovascular risk reduction, oncologists increasingly evaluate how dietary patterns influence cancer prevention and survival, and neurologists are investigating nutritional strategies to support cognitive health and decrease the risk of neurodegenerative diseases, particularly dementia. ^,,, Ophthalmology is no exception. Dietary modification is a non-invasive, scalable intervention that empowers patients to protect their own visual health, typically with broader systemic health and longevity benefits. In the context of AMD, mounting epidemiologic and clinical evidence indicates that what patients eat may meaningfully influence both early disease development and the rate of disease progression.

Much of the evidence synthesized in this perspective comes from the Age-Related Eye Disease Studies (AREDS and AREDS2), which followed large numbers of individuals in the United States with a wide range of AMD severity over many years. ^, These studies collected detailed information on dietary intake, tracked disease progression with reading center grading and treatment history, and included randomized assignment to different micronutrient formulations, to provide rich, prospective, longitudinal datasets. Additional insights come from other major epidemiologic and cohort studies in both Europe and North America that have evaluated the Mediterranean diet in relation to AMD. This perspective is therefore informed by a substantial body of evidence, though it does not aim to be an exhaustive review of all studies in the field. Our understanding in this area remains incomplete. For example, approaches such as caloric restriction, intermittent fasting, and modulation of the intestinal microbiome might be relevant to AMD, but current evidence appears insufficient to be translated into specific clinical guidance.

Among dietary patterns evaluated in aging and chronic disease, the Mediterranean diet has attracted particular attention for its consistently robust associations with favorable health outcomes. Interest in the Mediterranean diet arose following the observation that people living on Crete had remarkably low rates of coronary artery disease mortality. This led to the first characterization and definitions of the Mediterranean diet, based on the eating habits observed in olive-growing regions bordering the Mediterranean Sea. In general, the diet is defined not by strict rules but by a balance of whole, minimally processed foods ( Figure 2 ). Its core features include high intake of vegetables, whole fruits, legumes, nuts, and whole grains; liberal use of extra-virgin olive oil; moderate consumption of fish and other sources of omega-3 fatty acids; low to moderate intake of dairy products; low intake of red and processed meats; and minimal consumption of refined sugars and highly processed foods. ^,,, Moderate wine intake with food is included in some traditional definitions, though this component is often excluded or de-emphasized in clinical guidance, especially now that the World Health Organization has determined that there is no safe level of alcohol consumption.

The Mediterranean diet pyramid. Updated version (2008) developed by Oldways Preservation and Exchange Trust in collaboration with the World Health Organization and the Harvard T.H. Chan School of Public Health. At the base of the pyramid are the core foods eaten at almost every meal, namely plant foods including vegetables, fruits, nuts, whole grains, olive oil, and spices. Water is the main beverage for everyone. For individuals who choose to consume alcohol, it is consumed in moderation and typically with a meal. Moving upward is seafood, which is eaten at least twice a week. Moving further up are foods eaten on a daily to weekly basis, including eggs, poultry, and dairy products (yogurt and traditional cheese). At the top of the pyramid are foods consumed less frequently, such as red meat, processed meat products, and sweets, which are eaten no more than a few times a month.

Although the Mediterranean diet currently has the strongest evidence base in AMD, its potentially protective features are unlikely to be unique to Mediterranean cuisines or cultures. Other traditional dietary patterns that emphasize plant foods, minimal processing, and regular fish intake may provide similar benefits. Accordingly, patients from diverse regions and cultural backgrounds do not necessarily need to adopt the Mediterranean diet in all its specific features; instead, they can apply the same principles within their own traditional dietary patterns. Consistent with this view, previous studies have reported protective associations for an Asian dietary pattern and for a Japanese dietary pattern characterized by varied staple foods. ^,, In this way, the Mediterranean diet may be best understood as an evidence-based template rather than a uniquely Mediterranean prescription.

One highly validated method to quantify an individual’s diet relative to the Mediterranean diet pattern is the Alternative Mediterranean Diet Index (aMED). ^, The alternative index is a modified version of the original Mediterranean Diet Score ; it was adapted for populations outside the Mediterranean region, especially those in the United States, by refining the food group definitions. Individuals are scored on their intake of the following nine components: whole fruits, vegetables, whole grains, nuts, legumes, red meat, fish, monounsaturated fatty acid to saturated fatty acid ratio (MUFA: SFA), and alcohol. For most of the components, higher intake represents higher adherence to the Mediterranean diet. However, red meat is scored the opposite way, with lower intake representing higher adherence, while alcohol is considered in a binary way, with intake within the specified interval representing higher adherence and intake outside the interval representing lower adherence.

We and others have modified the aMED to provide a more granular index by scoring each component in quartiles (separately for men and women), leading to a score range of 8-36, with 36 representing perfect adherence to the aMED and 8 representing the opposite. ^, For a health outcome of interest (e.g., progression to late AMD), individuals can be considered in tertiles of the aMED. Tertile 3 would be the third of the study population with the most Mediterranean diet, while tertile 1 would be the third with the least Mediterranean diet.

Mechanistically, a Mediterranean diet confers advantages through several pathways relevant to AMD. ^,, It is rich in antioxidants, carotenoids, and polyphenols that may protect the retina from oxidative damage, a central process in AMD pathophysiology. It features favorable lipid and fatty acid profiles that may support retinal pigment epithelium and photoreceptor function. Its emphasis on plant-based foods and reduced intake of saturated fats may help modulate systemic inflammation and vascular health. This aligns with the growing body of epidemiologic data demonstrating that individuals who adhere more closely to a Mediterranean diet experience slower progression from early to intermediate AMD, decreased risk of progression to advanced disease, and even slower GA progression.

These data, combined with the results of clinical trials evaluating micronutrient supplements, can equip physicians with the information needed to answer a straightforward and practical question asked by their patients with AMD: “What, exactly, should I eat?” This perspective article aims to synthesize current evidence and translate it into clear, actionable guidance for physicians and patients. By examining the relationships between dietary patterns, their specific components, and AMD progression across disease stages, we hope to clarify the role of diet in AMD management and highlight how nutritional strategies can complement existing therapeutic options, including oral micronutrient supplements.

INTERMEDIATE AMD

Diet

Of the AREDS and AREDS2 participants without late AMD in at least one eye, individuals whose diet was closer to a Mediterranean pattern were very significantly less likely to progress to late AMD. ^, Eyes without late AMD were 23% less likely to develop late AMD over time, for participants in aMED tertile 3 vs 1 (following adjustment as described above). Again, a dose-response association was present. This was also true for AREDS and AREDS2 analyzed independently and in analyses that included adjustment for the randomized supplement assignments. Interestingly, the level of decreased risk was greater for progression to GA than to neovascular AMD, at 29% vs 16%, respectively. This strongly suggests that patients with intermediate AMD should adopt a Mediterranean diet. Lowering an individual’s risk of progression to GA is particularly important, since treatment options are limited for atrophic as opposed to neovascular AMD.

It is helpful to know whether one or several components of the aMED may be especially important in driving the protective association with late AMD. Indeed, statistical analyses that aim to isolate the contribution of each component show this is the case. In the AREDS, the strongest protective association by far was for fish intake. Eyes of participants in quartile 4 vs 1 for fish intake had 31% decreased risk of progression to late AMD (following adjustment for the factors described above). Protective associations were present for both GA and neovascular AMD, and a consistent dose-response association was present, suggesting that patients may benefit from even moderate fish intake. Importantly, the association could not be explained by lower red meat intake in those with higher fish intake. The next strongest associations included a protective association for vegetable intake (23% decreased risk) and a harmful association for red meat intake (20% increased risk).

Multiple systematic reviews and meta-analyses involving both European and North American study populations have confirmed that high adherence to a Mediterranean diet is associated with decreased risk of progression to late AMD. ^,, Similar observations were made in individual studies, including EYE-RISK (combining population-based data from the Rotterdam I and Alienor studies, in Europe) and analyses of the AREDS dataset by another research group. Interestingly, cross-sectional analyses of the Alienor study in France demonstrated that regular use of olive oil, an important component of the Mediterranean diet, was associated with decreased risk of late AMD.

Taken together, these results strongly suggest that patients with intermediate AMD should adopt a Mediterranean diet, with a strong emphasis on high fish intake and a moderate emphasis on high vegetable intake and low red meat intake. The numbers of servings of each food type required for the optimum quartile are shown in Table 1 . For example, in the AREDS, the median number for quartile 4 of fish intake was 3-4 medium-sized servings per week. The equivalent values were ∼25 servings for quartile 4 of vegetable intake and ∼1 serving for quartile 1 of red meat intake.

Importantly, a Mediterranean diet appears to be protective even in individuals with a high genetic risk of AMD, consistent with the idea of “eating away your risk”. AREDS analyses have suggested that a Mediterranean diet was protective against progression to late AMD even in those with a higher AMD genetic risk score, though it appears that a Mediterranean diet and high fish intake are each more strongly protective against progression to late AMD in those with protective alleles at CFH . ^,, For example, recent AREDS analyses found that, even in individuals with a high genetic risk of late AMD, a healthy lifestyle (comprising not smoking, having a body mass index below 25, avoiding high calorie intake, and having higher intake of green leafy vegetables and fish) conferred a 3-to-5-fold decreased risk of progression to late AMD, compared to an unhealthy lifestyle. Analyses of cross-sectional European data reported that a favorable lifestyle (including a healthy diet and not smoking) was associated with decreased risk of late AMD at all levels of genetic risk, but particularly in those with the highest genetic risk scores. Even for progression at non-advanced stages (i.e., increasing maximum drusen size), it appears that a Mediterranean diet may be protective, irrespective of AMD genetic risk levels.

Supplements

The AREDS2 formulation of oral micronutrient supplements is recommended by the American Academy of Ophthalmology for patients with intermediate or advanced AMD in one or both eyes. Specifically, they identify patients with intermediate AMD or GA in one or both eyes and patients with neovascular AMD in one eye. In the AREDS, the combination of antioxidants (vitamin C, vitamin E, and beta-carotene) and zinc (with copper) decreased the risk of progression to advanced AMD, for participants in categories 3 and 4, with an odds ratio of 0.66. Interestingly, this appears to have been driven principally by decreased risk of neovascular AMD rather than GA: the odds ratios were 0.62 (statistically significant) for neovascular AMD and 1.08 (not statistically significant) for moderate GA.

In the AREDS2, where all participants were also assigned the AREDS supplements, the addition of lutein/zeaxanthin led to significantly lower risk of progression to advanced AMD, in secondary analyses, with a hazard ratio of 0.90. ^, The decreased risk appeared stronger for neovascular AMD than for central GA. In addition, a comparison of lutein/zeaxanthin vs beta-carotene showed, in secondary analyses, that the replacement of beta-carotene with lutein/zeaxanthin led to lower risk of advanced AMD and an improved safety profile. Thus, in individuals with intermediate AMD or GA in at least one eye, or neovascular AMD in one eye only, the AREDS2 oral supplement (containing vitamin C, vitamin E, zinc, copper, and lutein/zeaxanthin) decreases the risk of progression to advanced AMD, particularly neovascular AMD. The ingredients and dosages comprising the AREDS2 formulation are shown in Table 2 .

Table 2

Ingredients and Doses of the Age-Related Eye Disease Study (AREDS) and AREDS2 Supplement Components

Supplement component	AREDS	AREDS2
Vitamin C	500 mg	500 mg
Vitamin E	400 IU	400 IU
Beta-Carotene	15 mg	0
Zinc oxide	80 mg	80 mg *
Copper	2 mg	2 mg
Lutein	0	10 mg
Zeaxanthin	0	2 mg

Only gold members can continue reading. Log In or Register to continue

Share this:

• X
• Facebook

Related

Related posts:

1. The Multimodal Imaging in Uveitis Virtual Special Issue
2. Association Between PDE-5 Inhibitor Therapy and the Hazard of Open-Angle Glaucoma
3. Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients With Type 2 Diabetes and Diabetic Retinopathy
4. Altitude-Specific IOP Risks After Vitrectomy With Gas Tamponade: Modeling and Travel Guidance Based on Calculated Elevation Profiles

Stay updated, free articles. Join our Telegram channel

Join