Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration

Stephen R Kaufman; Pradeepa Yoganathan; Kent W Small; Deepam Rusia; Sophia I Pachydaki; Stephen M Conti; Robert E Wenz; Mark A Gersman; Fadi S Shaya; Rafal Kustra

doi:10.1177/2474126420941713

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration

J Vitreoretin Dis. 2020 Aug 19;5(1):46-52. doi: 10.1177/2474126420941713. eCollection 2021 Jan-Feb.

Authors

Affiliations

¹ Vitreo-Retinal Consultants, Canton, OH, USA.
² Kresge Eye Institute, Wayne State University, Detroit, MI, USA.
³ Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada.
⁴ Laurel Eye Clinic, Brookville, PA, USA.
⁵ Macula and Retina Institute, Glendale, CA, USA.
⁶ Dana Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Abstract

Purpose: This work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD).

Methods: We conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk alleles. Physicians, who were blind to patients' GTGs, obtained patients' AREDS-F use history. The facility performing genetic analysis was blind to the AREDS-F use history. We used logistic analysis to estimate the interaction coefficient between AREDS-F use and GTG 2 vs GTG 3 in a general-population model.

Results: The odds ratio of numbers of patients reporting prior AREDS-F use to nonuse for GTG 2 vs GTG 3 was 4.18 (P = .001). Logistic regression, correcting for nongenetic risk factors, gave an estimate of the β for interaction of AREDS-F with genotype of 1.57 (P = .001). This estimates a corrected odds ratio associated with the effect of interaction of 4.81 between those in GTG 2 compared with those in GTG 3.

Conclusions: Our data indicate an interaction between GTGs and AREDS-F use that is consistent in size and direction with previously published reports, which had found that using AREDS-F supplements significantly increases the risk of nvAMD for some users and significantly protects other users.

Keywords: complement factor H; dry AMD (nonneovascular); genetics; wet AMD (neovascular).