Adherence to Mediterranean diet lowers risk of progression to late AMD, large drusen

Closer adherence to a Mediterranean-type diet appears to reduce the risk of progression to large drusen and to late age-related macular degeneration (AMD), with the signal being greater for geographic atrophy (GA) than neovascular AMD, as shown in a retrospective analysis of two controlled clinical trials cohorts, namely Age-Related Eye Disease Study (AREDS) and AREDS2.

Moreover, fish intake contributes to the protective association, while CFH genotype confers a robust impact on these relationships.

“The diet is less associated with decreased progression from intermediate to neovascular disease, but AREDS/AREDS2 [nutritional] supplements are beneficial here,” the researchers said. “Thus, diet and oral supplementation may play complementary roles, with a Mediterranean diet acting preferentially against atrophy and supplementation preferentially against neovascularization.”

A total of 13,204 eyes with no late AMD at baseline from 7,756 participants (mean age, 71 years; 56.5 percent female) in AREDS (n=4,255) and AREDS2 (n=3,611) were included in the analysis. Colour fundus photographs were collected at annual study visits and graded centrally for late AMD. Using food frequency questionnaires, the researchers calculated the modified Alternative Mediterranean Diet Index (aMedi) score.

Of the 13,204 eyes, 34.0 percent progressed to late AMD over a median follow-up of 10.2 years. Adherence to a Mediterranean diet lowered progression to late AMD (hazard ratio [HR] for aMedi tertile 3 vs 1: 0.78, 95 percent confidence interval [CI], 0.71–0.85; p<0.0001), GA (HR, 0.71, 95 percent CI, 0.63–0.80; p<0.0001), and neovascular AMD (HR, 0.84, 95 percent CI, 0.75–0.95; p=0.005). [Ophthalmology 2020;127:1515-1528]

Fish consumption was also associated with decreased progression to late AMD (AREDS: HR for quartile 4 vs 1, 0.69, 95 percent CI, 0.58–0.82; p<0.001; AREDS 2: HR, 0.92, 95 percent CI, 0.78–1.07; p=0.28).

In AREDS, both aMedi (p=0.01) and its fish component (p=0.0005) interacted with CFH rs10922109 for late AMD. Higher aMedi and fish intake independently reduced the risk of disease progression only in participants with protective alleles.

Separate analyses (n=5,029 eyes of 3,026 AREDS participants) showed an HR of 0.79 (95 percent CI, 0.68–0.93; p=0.004) for progression to large drusen in aMedi tertile 3 versus 1.

“As regards CFH status, adopting a Mediterranean diet with fish intake might be considered as exploiting protective alleles, rather than ‘eating away genetic risk’,” the researchers said. “However, in progression to large drusen and from intermediate AMD to GA, potential benefits appear less dependent on AMD genotype.”

These findings persisted with dose-response effects and were robust to sensitivity analyses, including construction of the aMedi by a different method used in earlier studies. [Circulation 2009;119:1093-1100; Am J Clin Nutr 2015;102:1196-1206]

The association of a lower risk of large drusen development with higher adherence was a novel and significant finding because there are no available interventions to reduce progression to this disease stage, apart from smoking cessation.

“Notably, this suggests that the Mediterranean diet may be protective both against late AMD (even at the intermediate AMD stage) and against intermediate disease itself,” the researchers said.

“Further research may uncover the mechanisms involved toward the generation of additional oral supplements. A randomized controlled trial of the Mediterranean diet on AMD progression would be essential, ideally encompassing a broad spectrum of disease severity, genotypes, and phenotypes,” they added.