Influence of Genotype on Severity of Exudative Age-Related Macular Degeneration

Abstract

Purpose: : Major genetic risk factors have recently been identified for age-related macular degeneration (AMD) including the ARMS2/LOC387715 and CFH at-risk polymorphisms. Our purpose was to establish correlations between genotypes and both phenotype and severity of AMD.

Methods: : In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n=264): double homozygous for wild-type alleles (group 1, n=49), homozygous for the at-risk allele of the ARMS2/LOC387715 only (group 2, n=57), homozygous for the at-risk allele of the CFH only (group 3, n=106), and double homozygous for the at-risk alleles (group 4, n=52). The phenotypic classification of exudative AMD was based on fluorescein angiography. Criteria for severity of the disease were best corrected VA of 0.1 or worse, a fibrovascular lesion, and involvement of both eyes.

Results: : Mean age at presentation was lower in group 4 than in group 1 (p<0.014). Classic CNV were more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (p<0.026). Patients in group 4 had more often bilateral CNV and fibrovascular scars than patients in group 1 (p<0.001 and p<0.0031 respectively), and had a lower visual acuity (VA) in the first affected eye than patients in group 1 (p<0.02). Patients in group 2 presented with worse visual acuity than patients in group 3 (p<0.003).

Conclusions: : This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at risk alleles (group 4) had an increased risk of being affected with a severe form of AMD at an earlier age.

Keywords: age-related macular degeneration • choroid: neovascularization • genetics