Macular Atrophy in Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

Abstract

Topic: Macular atrophy incidence in neovascular age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (VEGF) treatment.

Clinical relevance: Macular atrophy is a significant event that may occur in eyes with neovascular AMD treated with anti-VEGF therapy.

Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO, CRD42024474924). A comprehensive literature search of MEDLINE, EMBASE, and Web of Science was performed up to November 1, 2023. Randomized and non-randomized studies of treatment-naïve neovascular AMD patients reporting macular atrophy incidence at 24±3 months after anti-VEGF therapy were eligible for inclusion in this review. Two independent reviewers conducted screening, data extraction, and quality assessment. For randomized controlled trials, the Cochrane Risk of Bias 2 tool was employed, while non-randomized studies were evaluated using the ROBINS-I tool. Random-effects meta-analysis models were used for quantitative synthesis, accounting for study variability. Heterogeneity was assessed with the I² statistic, and publication bias by funnel plots and Egger's test. The primary outcome was the incidence of new macular atrophy at 24 months post-anti-VEGF therapy, with secondary outcomes at 12 months. Atrophy was diagnosed using color fundus photograph (CFP), fluorescein angiography (FA), fundus autofluorescence (FAF), optical coherence tomography (OCT), or multimodal imaging.

Results: Twenty-three studies met the inclusion criteria for qualitative analysis, with 11 included in the meta-analysis (N=3,013 eyes). The pooled 24-month incidence of macular atrophy was 29% (95% confidence interval [CI]:20%-38%,I²=93%). Subgroup analysis revealed incidence rates of 26% (95% CI:15%-37%,I²=88%) for 814 eyes with Type 1/2 macular neovascularization (MNV), 49% (95% CI:18%-80%,I²=92%) for Type 3 MNV (N=230 eyes), and 29% (95% CI:18%-40%,I²=96%) for all MNV types (N=2,131 eyes). The pooled 12-month incidence among 2,214 eyes was 11% (95% CI:4%-18%,I²=93%). The certainty of evidence regarding the incidence of macular atrophy after anti-VEGF treatment, as assessed by GRADE, was low.

Conclusions: While this meta-analysis has limitations, including a moderate risk of bias in non-randomized studies, inconsistencies in the results indicated by high heterogeneity, and imprecision due to the different imaging modalities used to diagnose macular atrophy, our results suggest that macular atrophy could be a common complication in neovascular AMD patients receiving anti-VEGF therapy.