A research consortium based in Europe believes the three subgroups of geographic atrophy (GA) it identified could provide new insights into disease pathogenesis. The three subgroups differed mostly by their genotype, with atrophy location and drusen type the two most relevant phenotypic features.

The researchers assessed 196 eyes of GA patients 50 years and older for the presence of the following fundus features on color fundus photography: large soft drusen, reticular pseudodrusen (RPD), refractile drusen, hyperpigmentation, location of atrophy (foveal vs. extrafoveal) and multifocal lesions. The analysis also included genotypes of 33 single nucleotide polymorphisms previously associated with the complement, lipid metabolism or extracellular matrix pathways and ARMS2, and the researchers then calculated genetic risk scores (GRS) for each of those three pathways.

In subgroup 1, with a high complement GRS, analyses showed a high proportion of large soft drusen (≥125μm) and foveal atrophy. Subgroup 2 was less consistent with variable results, including generally low to moderate values for all GRS, foveal atrophy and few drusen (any type). Subgroup 3 presented a high ARMS2 and extracellular matrix GRS, RPD and extrafoveal atrophy.

The researchers noted that the patterns observed for subgroups 1 and 3 were the most consistent results of this study. Subgroup 2 cases may be more heterogeneous or have mixed characteristics and may have been more difficult to differentiate with this approach. Nevertheless, the researchers believe their results could contribute to research strategies for therapies targeting specific disease pathways for different subgroups.

Biarnés M, Colijn JM, Sousa J, et al. Genotype and phenotype-based subgroups in geographic atrophy secondary to age-related macular degeneration. The EYE-RISK Consortium. Ophthalmol Retina. May 3, 2020. [Epub ahead of print].