Long-term macular atrophy growth in neovascular age-related macular degeneration: influential factors and role of genetic variants

Abstract

Objectives: This retrospective cohort study aimed to assess the long-term growth and associated risk factors of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) compounds.

Methods: Two hundred and six patients initiating anti-VEGF therapy were followed for 8 years using a treat-and-extend protocol. The study analysed correlations between MA growth (by square root transformation measured in infrared images) and clinical parameters, and genetic variants for AMD in the complement and lipid pathways and the ARMS2 gene.

Results: Seventy-six patients (n = 92 eyes) were included, with a mean age of 73.9 ± 7.9 years. Eyes received an average of 7.1 ± 3.2 anti-VEGF injections per year. The prevalence of MA increased from 28.3% at baseline to 78.3% at 8 years, exhibiting an average annual growth rate of 0.25 ± 0.22 mm. Correlations were found between MA growth and size, and number of atrophic foci at baseline, and the common ARMS2 variant. Eyes with subretinal fluid (SRF) at baseline showed less foveal atrophy at 8 years compared to those with IRF or both IRF and SRF. No correlation was observed between MA growth and genetic variants in the complement and lipid pathways.

Conclusion: Most eyes with nAMD under 8 years of anti-VEGF therapy developed MA, with significant growth. Correlations with baseline MA characteristics and the ARMS2 variant were identified. Further investigation is needed to understand the potential role of complement as a therapeutic target for preventing macular atrophy in nAMD-affected eyes.

Fig. 1. Delineation of atrophic foci using image analysis.

a IR and SD-OCT images with color enhancement were analyzed using ImageJ to identify atrophic areas, which are highlighted in yellow. b Progression of atrophic foci from baseline to 8 years is depicted, illustrating the growth of the affected regions. The table on the right summarizes the measured MA foci and the corresponding area of each focus.

Fig. 2

Survival curve to the development of MA in nAMD eyes from baseline.

Fig. 3. Macular Atrophy (MA) development and foveal atrophy risk based on baseline features.

a Example of MA development after 8 years of follow-up in area that had macula neovascularization at baseline. The arrow indicates point the original MNV. b Percentage of eyes that developed foveal atrophy based on location of macula fluid at baseline. According to the analysis of SD-OCT. Groups compared by Fisher exact test.