Subclinical Effects of Anti-VEGF Therapies for Neovascular AMD

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A new Japanese study¹ evaluated the subclinical effects of anti-vascular endothelial growth factor (VEGF) therapies for neovascular age-relatedmacular degeneration (AMD) and reported that brolucizumab (Beovu, Novartis) may cause transient retinal disturbances undetectable during general ophthalmologic examinations that affect the implicit electroretinography (ERG) times, according to first author Hisashi Matsubara, MD. He is from theDepartment of Ophthalmology, Mie University Graduate School of Medicine, Mie, Japan.

Clinical studies of brolucizumab have reported intraocular inflammation (IOI) and retinal vascular occlusion,^2-4 and those studies have spawned a growing interest in determining the cause of the IOI after intravitreal injections of anti-VEGF agents.

In light of those reports, the investigators wanted to determine if subclinical changes in the blood–aqueous barrier and the retinal physiology developed after anti-VEGF treatments with aflibercept (Eylea, Regeneron), brolucizumab, and or faricimab (Vabysmo, Roche), anti-VEGF drugs that are commonly used to treat neovascular AMD.

To that end, they evaluated the anterior chamber based on the aqueous flare value (AFV) and the retina by flicker ERG after the initial intravitreal injections of the 3 drugs. The AFV and flicker ERGs were determined before and 2 and 4 weeks after the injections in 14 eyes of 14 patients for each drug.

Adverse events

The investigators found that no patients had IOI after the injections, but the AFV increased significantly in the aflibercept and faricimab groups; the increase in the latter was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The authors commented that aflibercept and faricimab are high-molecular-mass formulations, and the increases did not likely result from inflammation induced by intravitreal injection of these drugs.

In the brolucizumab group, the implicit time was prolonged significantly but unchanged in the other 2 groups. Brolucizumab has a lower molecular mass than the other 2 study drugs and can be administered in higher molar doses, causing the implicit times of the flicker ERGs to be transiently prolonged. This effect, they believe, may have been due to changes in the retinal circulation by the potent VEGF suppressive effect of brolucizumab.

The investigators concluded, “Both the AFV and implicit time changes are subclinical reactions that are undetectable by general ophthalmologic examinations. Further research is required to assess the changes in AFV and ERG after the administration of anti-VEGF agents for neovascular AMD.”

References

1. Mitsubara H, Nagashima R, Chujo S, et al. Subclinical ocular changes after intravitreal injections of different anti-VEGF agents for neovascular age-related macular degeneration. J Clin Med. 2023;12:7401; https://doi.org/10.3390/jcm12237401

2. Monés J, Srivastava SK, Jaffe GJ, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology. 2021;128:1050–1059.

3. Saito M, Kobori H, Nozuki N, et al. A case of intraocular inflammation after intravitreal brolucizumab injection monitored by laser flare-cell photometer. Am J Ophthalmol Case Rep. 2022;28:101727.

4. Kataoka K, Horiguchi E, Kawano K, et al. Three cases of brolucizumab-associated retinal vasculitis treated with systemic and local steroid therapy. Jpn J Ophthalmol. 2021;65: 199–207.