The ARMS2 A69S Variant and Bilateral Advanced Age-Related Macular Degeneration

Abstract

 

Purpose:

 

To identify genotype-phenotype correlations with respect to bilateral advanced age-related macular degeneration (AMD), including geographic atrophy (GA) or choroidal neovascularization (CNV).

 

Methods:

 

A retrospective, observational case series of 1003 patients with advanced AMD in at least one eye: 173 patients with GA in at least one eye and 830 patients with CNV in at least one eye. Patients underwent clinical examination and fundus photography. The images were subsequently graded using a modified grading system adapted from the Age-Related Eye Disease Study. Genetic analysis was performed to identify genotypes at four AMD-associated variants (ARMS2 A69S, CFH Y402H, C3 R102G, and CFB R32Q) in these patients. Logistic regression models were used to examine the effect of each variant on developing bilateral advanced AMD (GA or CNV), adjusting for age, sex, and smoking history.

 

Results:

 

There were no statistically significant relationships between clinical findings and genotypes at CFH, C3, and CFB. The genotype at ARMS2 correlated with bilateral advanced AMD (GA or CNV) using a variety of comparisons: unilateral GA versus bilateral GA (p=0.08), unilateral CNV versus bilateral advanced AMD (p=9.0 x 10^-8), unilateral advanced AMD versus bilateral advanced AMD (p=5.9 x 10^-8), and unilateral advanced AMD versus bilateral CNV (p=6.4 x 10^-9). The effect of ARMS2 on development of bilateral advanced AMD was not modified by smoking history.

 

Conclusions:

 

In this series, in patients with GA or CNV in at least one eye, the ARMS2 A69S substitution strongly associated with GA or CNV in the fellow eye. The ARMS2 A69S substitution may serve as a marker for progression to bilateral advanced AMD (GA or CNV) in individuals with unilateral advanced AMD.

 

Keywords: age-related macular degeneration • genetics • gene screening