Real-world efficacy of higher-dose aflibercept in pro-re-nata dosing without loading phases: A cost-effective approach for resource-limited settings

Background: Aflibercept therapy for chronic macular diseases mandates loading dose phases followed by fixed intervals, placing a heavy and often prohibitive treatment burden on elderly patients in resource-limited settings. We evaluated the real-world efficacy of higher-dose aflibercept (4 mg/0.1 mL) versus standard dose (2 mg/0.05 mL) using immediate modified pro-re-nata (PRN) dosing without loading phases, with specific focus on burden reduction while maintaining therapeutic outcomes. Methods: This retrospective comparative study included 194 eyes (101 receiving 4 mg/0.1 mL, 93 receiving 2 mg/0.05 mL) with diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion treated with immediate modified PRN aflibercept between October 2023 and September 2024. The primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcomes assessed injection intervals, visit frequency, caregiver accompaniment, time commitments, and safety. Results: The mean baseline BCVA was 0.55 ± 0.18 logMAR (4 mg group) and 0.54 ± 0.17 logMAR (2 mg group). At final follow-up, both groups achieved comparable improvement: 0.45 ± 0.15 logMAR (4 mg) versus 0.47 ± 0.16 logMAR (2 mg), with no significant difference between groups ( P = 0.23). The mean CMT reduction was 85.2 ± 45.8 μm (4 mg) versus 86.6 ± 48.2 μm (2 mg), P = 0.82. The 4 mg group recorded 22.6% fewer annual visits (4.8 versus 6.2, P < 0.001), translating to 8.52 fewer hours per patient per year. No safety concerns emerged with higher-dose extraction. Conclusion: Higher-dose aflibercept with immediate modified PRN dosing achieves visual and anatomical outcomes comparable to standard dosing, with a 22.6% reduction in annual visit frequency. This approach addresses practical barriers to care in elderly populations requiring long-term anti-VEGF therapy in resource-limited settings.