Retinal Function, Risk Genotypes and Response to Nanosecond Laser Therapy in Intermediate AMD: A Pilot Study

Purpose: To investigate whether the major age-related macular degeneration (AMD) risk variants, Complement Factor H (CFH rs1061170, T/C) and Age-Related Maculopathy Susceptibility 2 (ARMS2 rs10490924, G/T), are associated with differences in full-field electroretinographic (ERG) function among patients with intermediate AMD (iAMD), and to evaluate whether retinal functional responses to subthreshold nanosecond laser (2RT^®) therapy are influenced by these genetic variants. Methods: This retrospective observational study included 23 iAMD patients who underwent genotyping for rs1061170 and rs10490924 and subthreshold nanosecond laser treatment (2RT^®). For each genetic variant, patients were stratified into those with the risk allele and those with the corresponding wild-type genotype. Full-field ERG measurements were obtained at baseline and at 1 and 3 months after 2RT^® treatment. Twenty-six age-matched healthy subjects served as controls for the electrophysiological comparisons. Results: Patients with the CFH risk allele showed lower photopic b-wave amplitudes than CFH WT/negative patients overall (group effect: p = 0.0431, partial η² = 0.1809), whereas no corresponding group effect was observed for ARMS2 genotypes (p = 0.6805). Following 2RT treatment, mixed rod-cone amplitude showed a significant effect of time (Greenhouse-Geisser-corrected p = 0.0355), with mean amplitudes increasing at 1 month and remaining above baseline at 3 months. Photopic b-wave amplitude also changed significantly over time in both the CFH (p = 0.0370) and ARMS2 (p = 0.0342) stratifications. No significant genotype-by-time interactions were found, indicating that no genotype-dependent difference was detected in the functional response to 2RT according to CFH or ARMS2 genotype. PhNR amplitude and peak time showed no significant group or time effects. Conclusions: The CFH risk allele was associated with lower photopic b-wave amplitudes, whereas no corresponding difference was observed for ARMS2 genotypes. Following 2RT treatment, mixed rod-cone and photopic b-wave amplitudes showed significant changes over the 3-month follow-up, with no significant genotype-by-time interactions. These preliminary findings provide no evidence that the functional response to 2RT differs according to CFH or ARMS2 genotypes and require confirmation in larger controlled studies.