Abstract
PURPOSE To investigate whether time to peak best-corrected visual acuity (BCVA) was predictive of magnitude of BCVA changes at study end in patients with neovascular age-related macular degeneration (nAMD) who received ranibizumab and assess whether patient baseline characteristics and on-study events were predictive of time to peak BCVA. DESIGN Exploratory analysis of data from HARBOR (ClinicalTrials.gov identifier, NCT00891735). PARTICIPANTS Treatment-naïve patients 50 years of age or older with subfoveal nAMD. METHODS Data by ranibizumab dose were pooled; data by dosing schedule (pro re nata [PRN] and monthly) were evaluated separately. Time to peak BCVA was the monthly evaluation at which the patient's greatest gain in Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline was achieved. Early peakers achieved peak BCVA between day 7 and month 6; late peakers achieved peak BCVA between months 7 and 12, months 13 and 18, and months 19 and 24. Variables evaluated for effect of time to peak BCVA included baseline demographic and clinical characteristics, presence of persistent subretinal fluid (SRF) or intraretinal fluid (IRF), and on-study events (atrophy status, fibrosis, retinal pigment epithelium tears). MAIN OUTCOME MEASURES Time to peak BCVA and its predictive value for magnitude of BCVA changes and BCVA at month 24 (study end). RESULTS Most patients reached peak BCVA after more than 6 months of treatment: 64% in the PRN group (301/474) and 70% in the monthly groups (327/469). Thirty-six percent and 30% of patients, respectively, peaked early, and 64% and 70%, respectively, peaked late. At month 24, early peakers on average lost vision (PRN, -1.6 ETDRS letters; monthly, -1.9 ETDRS letters). By contrast, late peakers achieved significantly better vision gains from baseline (PRN, 8.5-17.7 ETDRS letters; monthly, 10.1-18.7 ETDRS letters). No differences were found in patient characteristics, persistent SRF or IRF, or on-study events to account for the observed different outcomes between early and late peakers. CONCLUSIONS In most treatment-naïve patients with nAMD, vision gains were achieved at a slower rate (>6 months), and a slower response was associated with better vision outcomes after 24 months of ranibizumab. These findings suggest that continued treatment may result in greater vision improvements when consistent anti-vascular endothelial growth factor therapy is maintained over a longer period.
