Background: Neovascular age-related macular degeneration (nAMD), a leading cause of irreversible blindness globally, develops in one eye and frequently is followed by nAMD in the fellow eye. Knowledge on second eye involvement largely comes from clinical trials in the 1980s through 1995, prior to anti-vascular endothelial growth factor trials and imaging advances with optical coherence tomography (OCT). It remains largely unknown if rates subsequently have changed.
Methods: We conducted a systematic review and meta-analysis of CNV and associated best corrected visual acuity (BCVA) in fellow eyes of clinical trial participants with nAMD in the first eye. We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ClinicalTrials.gov from January 1, 1995 through August 8, 2024, for randomized or non-randomized trials of FDA-approved nAMD therapies. We screened, extracted data, and assessed the risk of bias using standard methods.
Main Outcomes: CNV and associated BCVA in fellow eyes of patients treated for nAMD in the study eye. We also examined risk factors associated with CNV development.
Results: We identified 26,782 records, of which 18 trials (17 randomized and 1 non-randomized) with 5,994 participants met criteria. The cumulative incidence of CNV in fellow eyes varied by type of treatment and duration of follow-up, which ranged from 0.0% to 38.0% with ranibizumab, 1.0% to 24.0% with aflibercept, and 1.0% to 5.6% with brolucizumab. PDT and laser were associated with the highest incidence beyond 24 months. Only female sex (HR 1.31, 95% CI 1.06-1.63) is associated with a higher cumulative incidence of CNV in fellow eyes, while findings for age (adjusted hazard ratio [adjHR] 1.20, 95% CI 1.05-1.36), White race (23% incidence), subretinal fluid presence on OCT (21% incidence), systemic hypertension (P = .61), baseline BCVA in study eyes (P = .07), and central retinal thickness (CRT) (HR 1.08, 95% CI 1.01-1.16) were inconsistent or not statistically significant. No study reported on visual acuity outcomes and treatments in fellow eyes.
Conclusions: As noted prior to 1995, these data confirm the continued relatively high incidence of fellow eye CNV within 2 years of initiating therapy for CNV in the first eye, even in an era of anti-VEGF therapy and OCT, with little, if any, systemic risk factors
