Clinical Outcomes of Double-dose Aflibercept Treatment for Refractory Wet Age-related Macular Degeneration

Purpose: To evaluate the clinical outcomes and prognostic factors of double-dose aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD).Methods: We reviewed the medical records of nAMD patients treated with a double dose of aflibercept (4 mg/0.1 mL) due to an inadequate response to standard 8-weekly intravitreal injections of 2 mg/0.05 mL aflibercept. The assessment at week 8 after treatment included changes in subretinal/intraretinal fluid (SRF/IRF) and best-corrected visual acuity, with patients showing absence or reduction in SRF/IRF classified as the response group. Baseline factors influencing clinical outcomes were analyzed, including central macular thickness (CMT), central choroidal thickness (CCT), size of choroidal neovascularization (CNV), CNV subtype, and maximum height of SRF and IRF.Results: The study included 95 eyes of 95 subjects, with 61 eyes (64.2%) categorized as the response group following double-dose treatment. Responders exhibited thicker CCT (290.4 μm vs. 194.0 μm, <i>p</i> < 0.001), thinner CMT (251.2 μm vs 311.1 μm, <i>p</i> = 0.018), smaller CNV area (2.718 mm<sup>2</sup> vs. 3.964 mm<sup>2</sup>, <i>p</i> = 0.034), and a higher prevalence of type 1 CNV (85.2% vs. 58.8%, <i>p</i> = 0.011) compared to the non-response group. Multivariate binary logistic regression analysis identified thicker CCT (<i>p</i> < 0.001, r = 1.016), thinner CMT (<i>p</i> = 0.014, r = 0.988), smaller CNV area (<i>p</i> = 0.015, r = 0.662), and type 1 CNV (<i>p</i> = 0.001, r = 0.061) as factors associated with better anatomical outcomes.Conclusions: Double-dose aflibercept was effective in 64% of patients with refractory nAMD, suggesting it may be considered for those with small CNV areas, thinner CMT, and thicker CCT.