Despite the genetic complexity of AMD, the risk alleles that predispose a patient to the condition don’t seem to play a role in supplementation.1,2 A new post-hoc analysis of Age-Related Eye Disease Study 2 (AREDS2) patients revealed that genotypes at the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes did not significantly modify the response to any of the AREDS2 supplements.

The 1,684 AREDS2 participants with bilateral large drusen or late AMD in one eye were randomly assigned to lutein/zeaxanthin, omega-3 fatty acids, both or placebo, and most also received the AREDS supplements. The secondary randomization assessed modified AREDS supplements in four treatment arms: lower zinc dosage, omission of beta-carotene, both or no modification. For genotype interaction, researchers assessed the main treatment effects, as well as the direct comparison between lutein/zeaxanthin and beta-carotene.

To evaluate the progression to late AMD, researchers obtained fundus photographs at baseline and annual study visits, as well as history of treatment for late AMD from study visits and six-month interim telephone calls. The study followed participants (mean age 72.1, 58.5% female) for a median of five years.

Researchers found that the ARMS2 risk allele was significantly associated with progression to late AMD and neovascular AMD but not with geographic atrophy (GA). Also, the CFH risk allele was not associated with AMD progression. They concluded that the two risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD, including GA and neovascular AMD.

1. Hampton BM, Kovach JL, Schwartz SG. Pharmacogenetics and nutritional supplementation in age-related macular degeneration. Clin Ophthalmol. 2015; (9):873-876.

2. Van Asten F, Chiu CH, Agrón E, et al. No CFH/ARMS2 interaction with omega-3 fatty acids, low vs high zinc, or beta-carotene vs. lutein/zeaxanthin on progression of age-related macular degeneration in the Age-Related Eye Disease Study 2 Age-Related Eye Disease Study 2 (AREDS2) Report No. 18. Ophthalmology. June 12, 2019. [Epub ahead of print].