Real-world unmet needs in the management of poorly responsive neovascular age-related macular degeneration in Europe: data from the FRB! Registry

Purpose: To evaluate the proportion, predictors and outcomes of neovascular age-related macular degeneration (nAMD) patients treated with a high burden of vascular endothelial growth factor (VEGF) inhibitor injections (IVT) after two years in routine clinical practice.

Design: Retrospective analysis of data from a prospectively designed observational outcomes registry, Fight Retinal Blindness! project, of patients treated in European centers.

Participants: Treatment-naïve eyes (one eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed three treatment burden groups defined by the mean interval of the three closest injections to the 24-month visit: (1) those with a high treatment burden had injection intervals ≤ 42 days, (2) those with a low treatment burden had injection intervals between 43 and 83 days and those with tolerable treatment burden had injection intervals between 84 and 365 days.

Methods: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high treatment burden.

Main outcome measures: The proportion of patients that experienced a high treatment burden at 2 years and its predictors.

Results: We identified 2,038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (Q1, Q3) of 13 (10, 17) injections. The proportion of patients with a high treatment burden was 25% (516 patients) at 2 years. Younger patients (Odds ratio (OR), 0.97; 95%CI, 0.96-0.99; P<0.01) were more likely to have high treatment burden, while eyes with type 3 CNV at baseline were significantly less likely (OR, 0.26; 95%CI, 0.13-0.52; P<0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95%CI, 1.34-11.01; P=0.01) and persistent active intraretinal (OR, 1.56; 95%CI, 1.18-2.06; P<0.01) or subretinal fluid only (OR, 2.21; 95%CI, 1.52-3.21; P<0.01) after the loading phase had a higher risk of high treatment burden at 2 years. Conclusions: High treatment burden is common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40 percent discontinuing treatment within 2 years. Keywords: Age-related macular degeneration; VEGF inhibitor; anti-VEGF; real-world; routine clinical practice; treatment burden; unmet need.