Sustained biweekly aflibercept for refractory neovascular age-related macular degeneration

Purpose: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). Methods: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. Results: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (−31.9 µ m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 µ m compared with week 14. By week 52, improvements in BCVA and CST were lost. Conclusion: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.