Switching to Brolucizumab May Improve Anatomical Outcomes in Eyes with Wet AMD

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Retrospective data suggest a treat-and-extend regimen using brolucizumab is effective for improving outcomes in eyes with exudative AMD refractory to aflibercept.

A treat-and-extend regimen with brolucizumab may be effective for improving anatomical outcomes in eyes with wet age-related macular degeneration (AMD) refractory to aflibercept for 12 months, according to new research.1

After switching to brolucizumab from aflibercept, the analysis revealed the treatment interval significantly extended from baseline to the last interval at 12 months; however, 26 eyes (43.3%) did not show any extension in the treatment interval at 12 months.

“Although we can select various vascular endothelial growth factor inhibitors (VEGF) with the advent of brolucizumab, we must recognize that treatment resistance concerns remain as well as safety concerns and we must work on how to treat these patients,” wrote Yoichi Sakurada, MD, PhD, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi.

Currently, VEGF inhibitors represent the standard of care for wet AMD, with approved therapies including ranibizumab, aflibercept, and brolucizumab. The phase 3 clinical trials of HAWK and HARRIER suggested intravitreal administration of 6.0 mg brolucizumab provided similar visual gains to and better morphological improvement than the intravitreal administration of 2.0 mg aflibercept. However, the therapy showed some safety concerns in the trials, including reports of intraocular inflammation (IOI), but investigators noted evidence is increasing on the incidence and prophylaxis of IOI.2

In the current analysis, the team analyzed the one-year efficacy of switching to intravitreal administration of 6.0 mg brolucizumab for wet AMD refractory to aflibercept, using a treat-and-extend regimen. A retrospective medical chart review was performed on consecutive patients with wet AMD treated with 6.0 mg brolucizumab, initiating a treat-and-extend regimen from September 2020 to June 2021.

Additional inclusion criteria included eyes with neovascular AMD or polypoidal choroidal vasculopathy (PCV), eyes showing exudation including subretinal fluid (SRF) or intraretinal fluid (IRF) despite regular intravitreal aflibercept injections ≤8-week intervals, and eyes that completed the follow-up of ≥12 months from switching. All patients had a treatment history of multiple regular aflibercept administration for ≥12 months and all eyes received intravitreal injection of brolucizumab at baseline.

The first visit (visit 1) was scheduled at the same interval between the last aflibercept injection and baseline. Then, the second visit (visit 2) was extended by 1 – 2 weeks based on the doctor’s discretion if there was no exudation, including subretinal fluid (SRF) and intraretinal fluid (IRF) on swept-source optical coherence tomography (OCT).

A total of 60 eyes from 56 patients were included in the study, with a mean age of 76.2 years and 51 male patients (85.0%). The patients had a mean of 30 aflibercept injections at regular 4–8-week (mean 7.6 weeks) intervals before switching to brolucizumab.

After switching to brolucizumab, the mean treatment interval at 12 months was found to be significantly longer than before the switch (7.6 ± 3.8 weeks at baseline and 12.1 ± 6.2 weeks at 12 months; P = 1.3 x 10-7). After the switch, patients received a mean of 6.15 ± 2.40 injections for 12 months, significantly fewer than during the 12 months prior to switching (6.87 ± 2.92 injections; P = .045).

The analysis revealed the mean logMAR best-corrected visual acuity (BCVA) was maintained from 0.44 ± 0.39 at baseline to 0.45 ± 0.43 at 12 months after switching (P = .72). To investigate the correlation between visual outcomes and changes in treatment intervals, investigators divided patients into 3 groups by length of the extended treatment interval: 0 weeks, 1 –3 weeks, and ≥4 weeks. They found no significant difference in mean BCVA from baseline to 12 months in each group.

Moreover, the mean central retinal thickness on SS-OCT was shown to significantly decrease from 313 ± 145 µm at baseline to 272 ± 165 µm at 12 months after switching (P = 3.6 x 10-3). In addition, the mean subfoveal choroidal thickness on SST also significantly decreased from 210 ± 93 µm at baseline to 193 ± 48 µm at visit 3 after switching (P = 1.0 x 10-3).

Investigators additionally found the number of patients showing exudation on SS-OCT before and after switching. At 12 months, the analysis showed 26 out of 60 eyes (43.3%) achieved a dry macula after switching. Among those remaining 34 eyes with exudation, 25 eyes showed SRF, 6 eyes showed IRF, and 3 eyes showed both.

In the study period, adverse events were observed in 12 eyes (20%), 7 of which showed mild posterior IOIs and 2 showed mild anterior chamber cells and keratic precipitates. Topical steroids were provided and resolved the IOIs. Intravitreal brolucizumab injections were discontinued and patients were switched to aflibercept again for the next visit.

Investigators indicated the study was limited by the small number of included participants and its retrospective design, suggesting “to validate the present conclusions, a longer duration study and/or a large-scale prospective study are needed.”


  1. Kikushima W, Sakurada Y, Fukuda Y, Matsubara M, Kotoda Y, Sugiyama A, Kashiwagi K. A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result. Pharmaceuticals. 2023; 16(4):562.
  2. Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: Ninety-Six-Week Outcomes from the Phase 3 Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration [published correction appears in Ophthalmology. 2022 May;129(5):593-596]. Ophthalmology. 2021;128(1):89-99. doi:10.1016/j.ophtha.2020.06.028