A higher-than-expected percentage of real-world patients developed signs of sterile intraocular inflammation within 1 to 3 days of injection with high-dose aflibercept, according to the results of a new study.
In a retrospective case series conducted at the Technical University of Munich, researchers reviewed the medical records of 41 patients who received aflibercept, 8 mg, between March and October 2024. Among the cohort, 23 patients (56%) were treated for neovascular age-related macular degeneration.
Patients had prior treatment with other antivascular endothelial growth factor agents, including aflibercept, 2 mg, ranibizumab, and faricimab. A total of 136 injections were administered: 81 for nAMD and 55 for diabetic macular edema.
Five patients (12%) developed signs of sterile intraocular inflammation (IOI) within 3 days of injection (per-injection incidence rate = 3.7%, 95% confidence interval = 1.6%–8.3%). Notably, only one of these cases occurred after a first-time injection; the rest occurred after multiple prior injections of aflibercept, 8 mg (1, 4, or 8 previous doses).
Symptoms included blurred vision or floaters (n = 4), and mild ocular pain (n = 2). Slitlamp examinations confirmed anterior chamber and vitreous cells in all cases, without signs of infectious endophthalmitis such as hypopyon or fibrin. Vision loss was transient, and no patients experienced a persistent decline in best-corrected visual acuity (BCVA).
The researchers described two patient cases specifically:
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Patient 1: A 73-year-old male with bilateral nAMD experienced BCVA reduction from 20/40 to 20/63, which resolved within 3 days after topical corticosteroid treatment.
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Patient 3: A 74-year-old male reported vision loss from 20/50 to 20/100 post injection. Fluorescein angiography ruled out vasculitis, and vision returned to baseline following steroid therapy.
Treatment protocols included topical corticosteroids and antibiotics for all patients and additional systemic corticosteroids for two patients. No patients required surgical intervention. Following recovery, patients were transitioned back to aflibercept, 2 mg, without recurrence of IOI.
The findings contrast with data from controlled trials. In the CANDELA, PHOTON, and PULSAR trials, IOI incidences ranged from 0% to 1% for aflibercept, 8 mg.
"A potential explanation for the discrepancies between reported rates of inflammation in clinical trials and our findings might be the rigorous follow-up within 4 days after injection that has been established in most German ophthalmic practices. Mild, self-limiting symptoms in the first weeks after injection may have been overlooked in the approval studies, with the first scheduled follow-up taking place after 4 weeks," explained Karoline E. Binder, MD, and colleagues.
They also discussed plausible mechanisms for the observed sterile IOI:
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Some patients may be predisposed to developing inflammation because of underlying autoimmune conditions or a baseline presence of antidrug antibodies. The antibodies have been reported in approximately 3% of patients.
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Aflibercept’s Fc region may interact with intraretinal Fc receptors and potentially form immune complexes that trigger inflammation—particularly at the higher molar dose of the 8 mg formulation.
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Injection-related variables such as silicon oil contamination from syringes or protein aggregation during shipping may provoke immunogenic responses. Freeze-thaw cycles and syringe design are implicated.
Larger studies with “exact documentation of shipping, storage, and application modalities will be needed to identify specific risk factors," noted Dr. Binder and colleagues.
“While the observed IOI can be considered mild and resolved under corticosteroid therapy, careful evaluation of patient-associated risk factors and a thorough patient education are warranted during treatment with aflibercept, 8 mg," they concluded.
A full list of author disclosures can be found in the published research.
Source: JAMA Ophthalmology
