Initial Functional and Anatomical Outcomes of High-dose Aflibercept 8 mg in Exudative Neovascular Age-related Macular Degeneration

Abstract

Purpose: To evaluate the short-term outcomes of patients with exudative neovascular age-related macular degeneration (nAMD) treated with high-dose aflibercept (HDA) 8.0 mg, focusing on anatomical and functional changes, as well as the feasibility of extending treatment intervals in a clinical practice setting.

Design: Retrospective, noncomparative cohort study.

Subjects: Two hundred nineteen eyes from 184 patients with nAMD who received ≥3 HDAs between August 2023 and October 2024.

Methods: Patients included in this study were either treatment-naïve or had been previously treated with other anti-VEGF agents. Clinical outcomes, including best-corrected visual acuity (BCVA) and macular OCT parameters, were evaluated at baseline and after each HDA.

Main outcome measures: The primary outcome was the proportion of eyes able to sustain an 8 ± 1-week or longer treatment interval without anatomical deterioration. The secondary outcomes included anatomical and functional changes.

Results: The average follow-up time was 22.9 ± 4.9 weeks; 209 eyes (95.4%) were previously treated, and 10 eyes (4.6%) were treatment-naïve. After the first 3 injections, 206 eyes (94.1%) received a fourth HDA, and 70 eyes (31.9%) received a fifth HDA. One hundred two eyes (46.6%) of the total cohort with an interval shorter than 8 weeks after 3 initial injections had persistent macular fluid; 24 eyes (11.0%) were switched to another anti-VEGF agent. Overall, the mean BCVA was 61.9 ± 21.7 ETDRS letters at baseline and 61.7 ± 22.6 at the final visit, with no statistically significant difference observed (P = 0.934). Central subfield thickness and pigment epithelial detachment height remained stable. Significant reductions were observed in subretinal (54.3%-41.1%, P = 0.006) and intraretinal fluid (53.9%-39.3%, P = 0.002). Among previously treated eyes, the mean preswitch treatment interval was 5.8 ± 2.5 weeks and increased to 7.4 ± 2.2 weeks after the 3 initial injections (P < 0.0001).

Conclusions: High-dose aflibercept demonstrated stable BCVA and significant reductions in macular fluid during the follow-up period. A considerable proportion of patients were unable to extend treatment intervals to ≥8 weeks due to persistent macular fluid. These findings suggest that HDA maintains functional stability while improving anatomic outcomes, though challenges in managing chronic nAMD in a clinical-practice setting may limit the ability to extend treatment intervals.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Aflibercept; Age-related macular degeneration; Choroidal neovascularization; VEGF.