Journal
OPHTHALMOLOGY
Volume 126, Issue 11, Pages 1541-1548Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ophtha.2019.06.004
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Funding
- Intramural Research Program of the National Eye Institute, National Institutes of Health, Bethesda, Maryland [EY000546, HHS-N-260-2005-00007-C, NO1-EY-5-0007, NOI-EY-0-2127]
- Office of Dietary Supplements, National Center for Complementary and Alternative Medicine
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute of Neurological Disorders and Stroke
- Intramural Research Program of the National Eye Institute [EY000546]
- Nederlandse Oogonderzoek Stichting
- Dr. P. Binkhorst Stichting
- Stichting Dondersfonds
- Prins Bernhard Cultuurfonds
- Stichting A.F. Deutman Oogheelkunde Researchfonds
- AREDS1
- AREDS2
- NATIONAL EYE INSTITUTE [ZIAEY000546] Funding Source: NIH RePORTER
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Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of beta-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and b-carotene, were assessed for genotype interaction. Main Outcome Measures: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age +/- standard deviation, 72.1 +/- 7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 x 10(-5) and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD). Published by Elsevier on behalf of the American Academy of Ophthalmology
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