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  • Genotype and Phenotype of Geography Atrophy Subgroups

    By Jean Shaw
    Selected By: Andrew P. Schachat, MD

    Journal Highlights

    Ophthalmology Retina, December 2020

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    Biarnés et al. set out to examine whether subgroups of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) can be defined by their geno­type and phenotype. They identified three GA subgroups that differed mostly by genotype; atrophy location and drusen type were the most relevant phenotypic features.

    For this retrospective analysis, the researchers evaluated 188 eyes of 188 patients. The mean age of the partici­pants was 82.4 years (range, 56.9-97), and 121 (61.7%) were female.

    Participants were graded for the presence of six fundus features: large soft drusen, reticular pseudodrusen, refractile drusen, hyperpigmentation, location of atrophy, and multifocal lesions. Genetic risk scores (GRSs) were based on five major risk alleles—and if this genetic information was available for a participant, the person’s GRS was calculated for three different pathways previously associated with AMD: the complement pathway, lipid metabo­lism, and extracellular matrix remod­eling. The researchers used hierarchical cluster analysis to identify subgroups; they then determined the discrimina­tive ability of genotype, phenotype, or both for each subgroup.

    Three GA subgroups were identified:

    • Subgroup 1 (n = 115; 61.2%) was characterized by a high median GRS for the complement pathway. A high median GRS was found for the lipid pathway, and participants were more likely to have foveal atrophy and large soft drusen.
    • Subgroup 2 (n = 21; 11.2%) had low to moderate values for all GRSs, less foveal atrophy, and few drusen of any type.
    • Subgroup 3 (n = 52; 27.7%) had the highest GRSs for extracellular matrix remodeling and the ARMS2 gene, and participants were more likely to have reticular pseudodrusen and extrafoveal lesions. 

    These subgroups may provide new insights into GA pathogenesis and could contribute to developing therapies that target subgroup-specif­ic disease pathways, the authors said. (Also see related commentary by Tiarnán Keenan, MD, PhD, in the same issue.)

    The original article can be found here.