Comparing Phenotype of Subretinal Drusenoid Deposits in Age Related Macular Degeneration (AMD) with ARMS2 Risk Alleles versus High Risk Vascular Disease

Abstract

Purpose : Subretinal drusenoid deposits (SDD) are currently considered a morphological change to the retina commonly associated with AMD. An association has been made with ARMS2 rs10490924 gene polymorphism and the presence of SDD in AMD. 1 The presence of SDD have also been linked to the high risk vascular diseases (HRVD) of carotid artery stenosis, cardiac valve defect, and cardiac pump defect, possibly due to hypoperfusion of the choroid. 2 These groups have never been compared and our goal is to detect possible phenotype differences to better understand the mechanism and improve management.

Methods : Volume spectral-domain optical coherence tomography (SD-OCT) scans, health history questionnaire, genetic testing and serum samples containing lipid values were obtained for 61 subjects with SDD. Images were categorized into atrophic vs exudative and early vs advanced. We compared 2 subgroups: 1) subjects homozygous for ARMS2 risk alleles (TT) and 2) subjects with HRVD without homozygous ARMS2 risk alleles. Univariate statistics used were chi square for categorical variables and two-tailed t-test for continuous variables.

Results : Of the 61 subjects with SDD, 11 were in ARMS2 group and 24 in HRVD group. Age of presentation for subjects in ARMS2 group was 78.1 yo vs. HRVD group was 83.4 yo (p=0.033). Exudative AMD was found in 3/11 (27%) of ARMS2 group and 0/24 (0%) of HRVD group (p=0.007); geographic atrophy was found in 5/11 (45%) of ARMS2 group vs 7/24 (29%) of HRVD group (p=0.34). Advanced AMD in 8/11 (73%) in ARMS2 Group and 7/24 (29%) in HRVD group (p=0.016). There were no statistically significant differences in subfoveal choroidal thickness (CTh), health history questionnaire and serum lipid levels between the groups.

Conclusions : Our small study suggests that ARMS2 Homozygous risk allele carriers have a different disease profile than SDD phenotype non-carriers. These risk allele carriers develop a more aggressive phenotype at a younger age with exudative AMD and advanced AMD being more common in this group. This suggests subjects with ARMS2 associated SDD have a different natural history and prognosis than those with systemic vasculopathy associated SDD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.