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Marc Biarnes Perez, Johanna Colijn, Jose Sousa, Lucia Ferraro, Míriam Garcia, Timo Verzijden, Magda A. Meester, Cecile Delcourt, Caroline Klaver, Anneke Den Hollander, Imre Lengyel, Tunde Peto, Jordi Monés; Genotype-phenotype correlation in geographic atrophy secondary to age-related macular degeneration. The EYE-RISK Consortium. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3520.
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© ARVO (1962-2015); The Authors (2016-present)
Geographic atrophy (GA) is the advanced form of dry age-related macular degeneration and is considered a single disease entity. We performed a retrospective analysis using the EYE-RISK database to determine whether there are subgroups in GA based on their fundus features (phenotype) and genotype.
Individuals (196 eyes of 196 patients) aged 50 years or older with pure GA from the EYE-RISK database (132 from the Rotterdam Study, Rotterdam; 43 from ALIENOR, Bordeaux; and 21 from GAIN, Barcelona) were graded on color fundus photography for the presence of each of the following fundus features: large soft drusen, reticular pseudodrusen (RPD), refractile drusen, hyperpigmentation, location of atrophy (foveal vs extrafoveal) and multifocal lesions. Thirty-two single nucleotide polymorphisms previously assigned to the complement pathway, lipid metabolism or the extracellular matrix (ECM) pathways were determined, and genetic risk scores (GRS) for each of these three pathways were calculated; the ARMS2 polymorphism (rs3750846) was also included. An agglomerative hierarchical cluster analysis (with the Calinski-Harabasz metric to determine the optimal number of clusters) was used to identify subgroups of participants with similar fundus features and pathway-based GRS. Comparison of fundus features and GRS between the resulting subgroups was made using Fisher’s exact test or Kruskal-Wallis. K-means clustering was also conducted to compare its results with those of the hierarchical method.
Hierarchical cluster analyses identified three subgroups of GA: Group 1, characterized by large soft drusen, foveal atrophy and high complement and lipid metabolism-based GRS; Group 2, with foveal atrophy and few drusen of any type, was characterized by low GRS; and Group 3, with RPD, extrafoveal atrophy and a high ECM-based GRS. Hierarchical and k-means clustering methods classified 87.2% of the eyes in the same categories.
We identified three subgroups in GA that differed in the presence of RPD, location of atrophy, large soft drusen load and pathway-based GRS. These results may foster research aimed at identification of distinct disease pathways in GA.
This is a 2020 ARVO Annual Meeting abstract.
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