Adherence to the Mediterranean Diet and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2.

PURPOSE: To determine whether closer adherence to a Mediterranean diet (and its individual components) was associated with altered risk of progression to late age-related macular degeneration (AMD) and large drusen. Additional objectives were to assess interactions with AMD genotype. DESIGN: Retrospective analysis of 2 controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2. PARTICIPANTS: Eyes with no late AMD at baseline in AREDS participants (n = 4255) and AREDS2 participants (n = 3611): total of 13 204 eyes (7756 participants). Mean age was 71 years (standard deviation, 6.6); 56.5% were female. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late AMD. The modified Alternative Mediterranean Diet Index (aMedi) score was calculated for each participant from food frequency questionnaires. MAIN OUTCOME MEASURES: Progression to late AMD, geographic atrophy (GA), and neovascular AMD; progression to large drusen. RESULTS: Over a median follow-up of 10.2 years, of the 13 204 eyes, 34.0% progressed to late AMD. Hazard ratios (HRs) for progression in aMedi tertile 3 versus 1 were 0.78 (95% confidence interval [CI], 0.71-0.85, P < 0.0001) for late AMD, 0.71 (0.63-0.80, P < 0.0001) for GA, and 0.84 (0.75-0.95, P = 0.005) for neovascular AMD. For fish consumption, HRs for late AMD in quartile 4 versus 1 were 0.69 (0.58-0.82, P < 0.0001; AREDS) and 0.92 (0.78-1.07, P = 0.28; AREDS2). In AREDS, both aMedi and its fish component interacted with CFH rs10922109 for late AMD (P = 0.01 and P = 0.0005, respectively); higher aMedi and fish intake were each associated with decreased risk only in participants with protective alleles. In separate analyses (n = 5029 eyes of 3026 AREDS participants), the HR for progression to large drusen in aMedi tertile 3 versus 1 was 0.79 (0.68-0.93, P = 0.004). CONCLUSIONS: Closer adherence to a Mediterranean-type diet was associated with lower risk of progression to late AMD and to large drusen. The signal was greater for GA than neovascular AMD. Fish intake contributed to this protective association. CFH genotype strongly influenced these relationships. These findings may help inform evidence-based dietary recommendations.

Dietary zinc intake is associated with macular fluid in neovascular age-related macular degeneration.

IMPORTANCE: Numerous dietary factors have been shown to reduce progression from early to late age-related macular degeneration (AMD), however, little is known on their impact in patients diagnosed with late-stage disease. BACKGROUND: To determine whether a dietary intake high in antioxidants and zinc, fruits, vegetables and fish is associated with favourable clinical outcomes in patients with neovascular AMD (nAMD) undergoing anti-vascular endothelial growth factor therapy. DESIGN: Cross-sectional study carried out at a private ophthalmology clinic. PARTICIPANTS: Five hundred forty-seven participants with nAMD. METHODS: Diet was determined using a validated food frequency questionnaire. Presence of intra-retinal and sub-retinal fluid (IRF, SRF), pigment epithelial detachment and central macular thickness (CMT) were recorded from ocular coherence tomography images. MAIN OUTCOME MEASURES: Fluid presence, mean CMT and visual acuity. RESULTS: Participants with daily zinc intake below (n = 91) vs above (n = 333) 8.1 mg had greater odds of SRF being present, multivariable-adjusted odds ratio (OR) of 0.56 (95% CI 0.36-0.96). This association was stronger in persons with at least 6 months of treatment, OR of 0.32 (95% CI 0.14-0.75). In the entire cohort, participants in the lowest or first quartile compared to those in the upper three quartiles of zinc intake combined had significantly greater mean CMT (254.81 µm vs 232.15 µm, respectively, multivariable-adjusted P = .03). CONCLUSIONS AND RELEVANCE: Low dietary zinc intake was associated with a greater likelihood of SRF presence, particularly in those treated for at least 6 months, and increased macular thickness in treated eyes with nAMD.

Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration.

Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

PURPOSE: In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. METHODS: The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. RESULTS: After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (ß = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. CONCLUSION: In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA.

Dietary Intakes of Eicosapentaenoic Acid and Docosahexaenoic Acid and Risk of Age-Related Macular Degeneration.

PURPOSE: To evaluate the associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the intermediate and advanced stages of age-related macular degeneration (AMD). DESIGN: Prospective cohort study. PARTICIPANTS: We followed 75 889 women from the Nurses' Health Study and 38 961 men from the Health Professionals Follow-Up Study who were at least 50 years old, from 1984 to 2012 and 1986 to 2010, respectively. Cohort participants are mostly white (≥95%). METHODS: We assessed dietary intake by a validated food frequency questionnaire (FFQ) at baseline and every 4 years. We calculated cumulative average intakes of EPA and DHA from FFQs and also computed predicted erythrocyte and plasma scores directly from food intake using regression models. Cox proportional hazards models were used to compute the associations with AMD outcomes. MAIN OUTCOME MEASURES: We confirmed 1589 incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse, owing primarily to AMD, by medical record review. RESULTS: For intermediate AMD, the pooled hazard ratio (HR) between the 2 cohorts for DHA comparing the extreme quintiles of intake was 0.78 (95% confidence interval [CI], 0.66-0.92; P trend, 0.008) and for EPA + DHA was 0.83 (95% CI, 0.71-0.98; P trend, 0.03). The pooled HR for fatty fish, comparing ≥5 servings per week to almost never, was 0.61 (95% CI, 0.46-0.81; P trend, <0.001). For advanced AMD, the pooled HR for DHA was 1.01 (95% CI, 0.84-1.21; P trend, 0.75) and for fatty fish was 0.80 (95% CI, 0.59-1.08; P trend, 0.11). Secondary analyses using predicted erythrocyte and plasma scores of EPA and DHA yielded slightly stronger inverse associations for intermediate AMD and similar results for advanced AMD. CONCLUSIONS: Higher intakes of EPA and DHA may prevent or delay the occurrence of visually significant intermediate AMD. However, the totality of current evidence for EPA and DHA and advanced AMD is discordant, though there was no association with advanced AMD in the present study.