Injection Intervals Extended in nAMD Eyes with Switch to Brolucizumab


Real-world data suggest nAMD eyes can extend injection intervals by switching to brolucizumab from other anti-VEGF therapies, while maintaining vision and reducing CMT.

Joseph M. Coney, MD

Joseph M. Coney, MD

Eyes with neovascular age-related macular degeneration (nAMD) on anti-vascular endothelial growth factor (anti-VEGF) therapy can prolong injection intervals with a switch to brolucizumab, according to new real-world research.1

The findings suggest mean visual acuity (VA) was maintained 12 months after switching to brolucizumab from other anti-VEGFs and central macular thickness (CMT) was reduced by a mean of 35 µm with its use.

“It is notable that these results were obtained in real-world eyes with a particularly high burden of disease,” wrote corresponding author Joseph M. Coney, MD, Retina Associates of Cleveland Inc. “In general, these patients were switched to brolucizumab because of an incomplete response to prior anti-VEGF agents and/or their treatment interval could not be extended without increasing nAMD disease activity.”1

Prior results from the pivotal HAWK and HARRIER studies indicate brolucizumab provided similar vision gains and superior reduction in CMT compared with aflibercept, with most brolucizumab-treated patients remaining on a 12-week dosing interval at week 48. Both VA gains and anatomical improvements achieved with the agent were sustained at week 96.

Injection intervals remain a complicated factor in treatment compliance and treatment burden, as frequent intravitreal injections can be burdensome for both patients and physicians, while undertreatment can put the patient at risk of avoidable vision loss. Dosing regimens, including treat-and-extend, can balance disease control and reduce overall injection burden.

Coney and colleagues performed a retrospective real-world study of patients with nAMD treated with brolucizumab 6 mg between October 2019 and November 2021 at their practice in Cleveland, Ohio. A 12-month brolucizumab cohort included all nAMD eyes switched to brolucizumab from other anti-VEGFs, had at least 12 months of follow-up after the first injection, and had received ≥3 brolucizumab injections and no other anti-VEGF agent within the first 12 months after switching to brolucizumab. An 18-month brolucizumab sub-cohort was then derived from the 12-month brolucizumab cohort.

Investigators collected and analyzed baseline VA, injection intervals, and CMT at the time of the first brolucizumab injection and after 12 and 18 months of follow-up and reported changes relative to baseline measurements. Safety data were additionally collected, including all intraocular inflammation (IOI) events.

Overall, 482 eyes from 414 patients received ≥1 brolucizumab injection during the study period. Additionally, 174 eyes received ≥3 brolucizumab injections with ≥12 months of follow-up and 95 eyes received ≥3 brolucizumab injections with ≥18 months of follow-up.

Results suggest the average vision across the cohort remained stable at 12 months of brolucizumab treatment after switching, with the cohort undergoing a mean change from baseline of –1.1 ETDRS letters (95% confidence interval [CI], –3.7 to 1.6; P - .42). The study reported similar results for the change in VA in the 18-month brolucizumab cohort.Pre-switch injection intervals or baseline VA were reported to have no notable effect.

At 12 months after switching to brolucizumab, injection intervals were extended from baseline by 26.9 days, according to the data. Eyes with pre-switch injection intervals <8 weeks had their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥8 weeks. Data from 18 months suggest injection intervals were extended by 36.3 days compared to baseline.

The mean CMT was lowered by –35.2 µm compared to the pre-switch CMT (P <.0001) 12 months after switching to brolucizumab, with comparable reductions (–38.9 µm) observed in the 18-month brolucizumab cohort. Safety data show IOI-related adverse events were reported in 4.6% of brolucizumab eyes.

"Any treatment decision to switch a patient with nAMD to brolucizumab needs to be based on an individual beneft-risk assessment due to the associated risk of IOI-related AEs," Coney wrote.1


1. Coney, J.M., Zubricky, R., Sinha, S.B. et al. Switching to brolucizumab: injection intervals and visual, anatomical and safety outcomes at 12 and 18 months in real-world eyes with neovascular age-related macular degeneration. Int J Retin Vitr 9, 8 (2023).

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