Two-dose aflibercept 8 mg versus three-dose aflibercept 2 mg loading for treatment-naïve neovascular age-related macular degeneration.

Shirakami, Mai; Miyata, Manabu; Hata, Masayuki; Ooto, Sotaro; Tamura, Hiroshi; Otsuka, Ai; Tsukui, Lin; Ueda-Arakawa, Naoko et al. · PLoS One · 2026

retrospective_cohort · Level III

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Abstract

This retrospective study compared the short-term efficacy of a two-dose intravitreal aflibercept (IVA) 8-mg loading regimen (2024-2025) with a conventional three-dose IVA 2-mg regimen (2013-2014) for treatment-naïve neovascular age-related macular degeneration (nAMD). Using 1:1 propensity score matching for age, sex, nAMD subtype, and baseline visual acuity, we evaluated 31 eyes per group. The primary endpoint was the proportion of eyes achieving a fluid-free center subfield one month after completing the respective loading phase (at 2 and 3 months from baseline, respectively). The fluid-free proportion was numerically higher in the 8-mg group (90.3%; 95% confidence interval [CI], 74.2-98.0%) than in the 2-mg group (80.6%; 95% CI, 62.5-92.5%); however, the difference was not statistically significant (P = 0.28). Both regimens yielded significant reductions in central retinal thickness, central choroidal thickness, and pigment epithelial detachment height, with no significant between-group differences. Within the 8-mg group, baseline intraretinal fluid strongly correlated with one-month visual acuity (r = 0.61, P < 0.001). These exploratory findings suggest that a reduced two-dose aflibercept 8-mg loading regimen provided short-term anatomical outcomes that did not differ significantly from the standard three-dose 2-mg regimen. This shortened loading phase potentially reduces the initial treatment burden. Further prospective studies should validate these preliminary outcomes.

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