Aflibercept 8 mg May Cause More Intraocular Inflammation Than Reported

A recent retrospective case series examining the incidence of intraocular inflammation (IOI) after intravitreal injection of aflibercept 8 mg has indicated that IOI may be more frequent than previously reported.

Aflibercept is a commonly used anti-vascular endothelial growth factor (anti-VEGF) injection for treating fluid accumulation in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Anti-VEGF treatments are widely considered the gold standard for the treatment of retinal disorders, as alternative methods such as laser photocoagulation have been associated with poor visual outcomes and adverse effect risks.2

However, despite the comparative safety of anti-VEGF injections, adverse events (AEs) and complications still may arise in rare cases. While some conditions, including subconjunctival hemorrhage, are considered mild, others are associated with vision loss and may require surgery, such as retinal detachment or vitreous hemorrhage. This, coupled with the relative newness of aflibercept 8 mg outside of clinical settings, led investigators to undergo this study.1

“While publications of inflammatory events associated with anti-VEGF agents have been more frequently reported with faricimab, to our knowledge only a few case reports of occurrences with aflibercept, 8 mg, exist,” wrote Karoline E. Binder, MD, department of ophthalmology, TUM School of Medicine and Health, Technical University of Munich, and colleagues. “Because of the recent approval of this agent, it is important to identify whether intraocular inflammation also occurs after injections with aflibercept, 8 mg, in clinical practice setting.”1

Binder and colleagues evaluated IOI incidence in patients receiving aflibercept 8 mg injections from March to October 2024. All participants exhibited signs of macular exudation secondary to nAMD or DME, which had been previously treated with anti-VEGF agents. Switching to aflibercept 8 mg was related to persistent retinal fluid or a lack of extension in retreatment intervals. There were no exclusion criteria.1

A total of 41 patients were treated during this period for exudative maculopathy (nAMD: 23 patients, 56%) or DME (18 patients, 44%. 27 patients (66%) were male. A total of 136 aflibercept 8 mg injections were administered (nAMD: 81 injections, 60%; DME: 55 injections, 40%).1

No case of infectious IOI was detected over the observation period, but 5 patients exhibited sterile IOI. Sterile IOI incidence was 3.7% per injection (95% CI, 1.6%-8.3%) and 12% per patient (95% CI, 5.3%-25.5%). Of these patients, 4 were returned to the clinic with ocular symptoms and 1 was treated by their local ophthalmologist. Symptoms included blurred vision or floaters (n = 4) and mild ocular pain (n = 2).1

Four of the patients with IOI had prior exposure to aflibercept 8 mg before the inflammation occurred, and only 1 developed inflammation after the first dose. All 5 were treated with local anti-inflammatory therapy – topical or subconjunctival corticosteroids. Notably, no reduction of best-corrected visual acuity (BCVA) was observed after AEs receded.1

Investigators note that, while noninfectious IOIs have been reported for aflibercept 2 mg, the incidence per injection is stated to be very low, ranging from .004%-.37%. Additionally, clinical approval studies for aflibercept 8 mg indicate a similarly low incidence of sterile IOI, highlighting a drug safety profile roughly consistent with aflibercept 2 mg in nAMD or DME.1

Binder and colleagues suggested that the discrepancies between inflammation in clinical trials and the findings of this study may have been a result of rigorous follow-up of ≤4 days after injection that this study utilized.1

Regardless of the discrepancies, however, the team points out that clinical practice setting noninfectious IOI after aflibercept 8 mg may be substantially more than previously reported.1

“Whether this higher incidence stems from patient-, medication-, or delivery-specific mechanisms or a combination currently remains unclear,” wrote Binder and colleagues. “Further trials with a larger study population and exact documentation of shipping, storage, and application modalities will be needed to identify specific risk factors.”1

References

1. JAMA Ophthalmology. Noninfectious Intraocular Inflammation after Intravitreal Aflibercept. JAMA Ophthalmology. May 1, 2025. Accessed April 30, 2025. https://media.jamanetwork.com/wp-content/handlers/downloader.php?a=114956

2. Lanzetta P, Loewenstein A; Vision Academy Steering Committee. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases. Graefes Arch Clin Exp Ophthalmol. 2017;255(7):1259-1273. doi:10.1007/s00417-017-3647-4