High-Dose Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration Resistant to Standard-Dose Brolucizumab.

Introduction: The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD).

Methods: This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12 mg/0.1 ml) for over 12 months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6 mg/0.05 ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated.

Results: Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12 months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0 μm before high-dose treatment and 316.7 ± 18.5 μm at 12 months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4 weeks to 10.2 ± 2.2 weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8 weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed.

Conclusions: High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD.