Purpose: To compare long-term visual outcomes in patients with neovascular age-related macular degeneration (AMD) who
received frequent vs infrequent antivascular endothelial growth factor injections. Methods: This retrospective case series included treatment-naïve patients with AMD receiving either frequent injections (≤ 6-week intervals) or infrequent injections (≥ 10-week intervals). Best-available visual acuity (VA) and anatomic outcomes were assessed at the initial visit, 52 weeks, 104 weeks, and final visit. Results: A total of 151 eyes were studied over a mean follow-up of 42.6 months: 81 eyes (54%) in the frequent group and 70 eyes (46%) in the infrequent group. Baseline central foveal thickness (CFT) was higher in the frequent group (320 µm vs 265 µm; P = .002). Though CFT improved in both groups, it remained higher in the frequent group at 52 weeks (230 µm vs 185 µm; P = .004), 104 weeks (203 µm vs 173 µm; P = .004), and final visit (197 µm vs 165 µm; P = .015). The frequent group showed more subretinal and intraretinal fluid at all times. Baseline logMAR VA was 0.63 and 0.84 in the frequent and infrequent groups, respectively (P = .10). Visual improvement was similar between groups at 52 weeks (0.21 vs 0.22 logMAR; P = .916), 104 weeks (0.21 vs 0.18 logMAR; P = .714), and final visit (0.1 vs 0.05 logMAR; P = .510). Poor baseline VA (P < .001) and geographic atrophy (P = .025) were associated with worse outcomes. Conclusions: Over 4 years, despite higher CFT and more fluid, frequent injections showed similar visual improvement to infrequent injections. Baseline vision was the strongest predictor of final outcomes, regardless of injection frequency.