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. 2023 Oct;12(5):2397-2408.
doi: 10.1007/s40123-023-00741-w. Epub 2023 Jun 13.

Real-World Frequency and Management of Ocular Adverse Events in Eyes with Neovascular Age-Related Macular Degeneration Treated with Brolucizumab

Ryan Zubricky  1 , Jasmyne McCoy  2 , Richard Donkor  2 , David G Miller  2 , Nina Sonbolian  3 , Andrew Heaney  3 , Ver Bilano  3 , Helene Karcher  3 , Joseph M Coney  4
Affiliations

Real-World Frequency and Management of Ocular Adverse Events in Eyes with Neovascular Age-Related Macular Degeneration Treated with Brolucizumab

Ryan Zubricky et al. Ophthalmol Ther. 2023 Oct.

Abstract

Introduction: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice.

Methods: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics.

Results: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3-6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes.

Conclusions: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited.

Keywords: Brolucizumab; Intraocular inflammation; Neovascular age-related macular degeneration; Retinal vascular occlusion; Retinal vasculitis; nAMD.

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Conflict of interest statement

Nina Sonbolian, Andrew Heaney, Ver Bilano, and Helene Karcher are Novartis employees and Helene Karcher is a Novartis shareholder. David G. Miller reports consultancy fees and Speakers’ Bureau honoraria from Regeneron Pharmaceuticals. Joseph M. Coney has received grants from Alimera Sciences, Allergan/Abbvie, Apellis, Genentech, MacTel, National Eye Institute, Novartis, Regeneron, and RegenexBio, consulting fees from Alimera Sciences, Apellis, and RegenexBio, and honoraria from Alimera Sciences, Allergan/Abbvie, Apellis, Genentech, Novartis, Regeneron, and RegenexBio.

Figures

Fig. 1
Fig. 1
A Brolucizumab injection distribution in eyes with and without IOI-related AEs. B Time from the first brolucizumab injection until the IOI-related AE (dark grey bars) or end of follow-up (light grey bars). Percentages are presented above bars, and the absolute numbers of eyes in each category are presented at bar base. AE, adverse event; IOI, intraocular inflammation
Fig. 2
Fig. 2
VA at 3 months or 6 months (whichever is the higher VA of the two) after resolution/stability of an IOI-related AE compared with the last VA measurement prior to the AE. *AE unresolved at the last visit before the end of the study period, so no 3- or 6-month VA measurement was available for one eye. AE, adverse event; IOI, intraocular inflammation
Fig. 3
Fig. 3
Images from case 1, an 86-year old female with AE occurring 160 days after initiating brolucizumab. A OCT image on the day of switch to brolucizumab, B OCT on the day of fourth and last brolucizumab injection, C, D OCT 1-day post-surgery, E–H OCT 1-week post-surgery, I OCT 6-weeks post-surgery, and J OCT 12-weeks post-surgery
See this image and copyright information in PMC

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