ARMS2/HTRA1 genotype linked to faster geographic atrophy enlargement
The presence of ARMS2/HTRA1 risk alleles is strongly associated with faster enlargement of geographic atrophy (GA), according to a study. However, this relationship is highly dependent on the initial size of the GA area.
The post hoc analysis of the Age-Related Eye Disease Study 2 (AREDS2) clinical trial included 546 eyes from 406 participants with GA, with a mean age of 73.8 years. Researchers measured GA area using color fundus photographs during annual visits.
The results showed that eyes with ARMS2 risk alleles exhibited considerably faster GA enlargement compared to those without these alleles (P < 0.0001). Specifically, the enlargement rates were 0.224 mm/year, 0.298, and 0.317 for 0-2 risk alleles, respectively.
However, in eyes with a small GA area (<1.9 mm²), the enlargement was significantly accelerated with ARMS2 risk alleles (P < 0.0001), measuring 0.193 mm/year compared to 0.304 for 0 versus 1-2 risk alleles.
In eyes with moderately small (1.9-3.8 mm²) or medium/large (≥3.8 mm²) GA area, the presence of ARMS2 risk alleles did not lead to significantly faster enlargement (P = 0.66 and P = 0.70, respectively). Similarly, ARMS2 genotype did not significantly influence progression to multifocal GA.
Although ARMS2 risk alleles were associated with faster GA enlargement in non-multifocal GA (P = 0.001), the study found no significant association with progression to multifocal GA. The hazard ratios for 1 and 2 risk alleles were 1.03 and 1.12, respectively.
Agrón E, Domalpally A, Cukras CA, et al; AREDS2 Research Group. Critical Dependence on Area in Relationship between ARMS2/HTRA1 Genotype and Faster Geographic Atrophy Enlargement: AREDS2 Report 33. Ophthalmology. 2023;S0161-6420(23)00670-X. doi: 10.1016/j.ophtha.2023.09.013. Epub ahead of print. PMID: 37717737.