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Observational Study
. 2025 Oct;263(10):2885-2892.
doi: 10.1007/s00417-025-06875-w. Epub 2025 Jun 16.

Intraocular inflammation following intravitreal injections of anti-vascular endothelial growth factor drugs

Ana Margarida Ferreira  1   2 , António Ferrão Mendes  3 , João Nuno Beato  3   4 , Ana Catarina Pedrosa  3   4 , Susana Penas  3   4 , Sónia Torres-Costa  3   4 , Cláudia Oliveira Ferreira  3   4 , Carolina Maia  3 , Manuel Falcão  3   4 , Ângela Carneiro  3   4
Affiliations
Observational Study

Intraocular inflammation following intravitreal injections of anti-vascular endothelial growth factor drugs

Ana Margarida Ferreira et al. Graefes Arch Clin Exp Ophthalmol. 2025 Oct.

Abstract

Purpose: To describe cases of infectious and non-infectious intraocular inflammation (NI-IOI) associated with intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) drugs in the largest tertiary center with the highest number of IVI in Portugal.

Methods: Prospective observational study including all patients diagnosed with infectious endophthalmitis (IE) or NI-IOI after IVI of different anti-VEGF drugs in a total of 83,145 IVI between 2018 and 2023. The most frequent indications for treatment were macular neovascularization or macular edema from different etiologies.

Results: Twenty-six eyes developed IE (mean incidence 0.031%) after IVI and 24 eyes were diagnosed with NI-IOI (mean incidence 0.028%), including anterior plus intermediate uveitis (n = 18), only vitritis (n = 4) and retinal vasculitis (n = 2). Regarding NI-IOI, eyes were under treatment with aflibercept (n = 12), bevacizumab (n = 11) and faricimab (n = 1). The most common initial presentation was a painless decrease in visual acuity (VA) at a mean of 8 days [1-20] after IVI in patients with NI-IOI versus red eye, pain and blurry vision, at a mean of 3 days [1-9] after IVI in the IE group. There was a significant improvement in VA between the NI-IOI diagnosis and final visits (35 ± 25 vs. 49 ± 24 ETDRS letters) in the NI-IOI group (p = 0.022), an improvement that occurred over a mean of almost 2 months. There were no significant differences between VA at the time of diagnosis and after treatment (25 ± 28 vs. 26 ± 25 ETDRS letters) in the IE group (p = 0.801).

Conclusion: NI-IOI represents an emergent treatment-related adverse event, that can be reversible when adequately managed, contrasting with the sight-threatening severe cases of IE. We emphasize the importance of maintaining active surveillance in patients under intravitreal therapy.

Keywords: Infectious endophthalmitis; Intraocular inflammation; Intravitreal therapy.

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Conflict of interest statement

Declarations. Compliance with ethical standards: The study was approved by the Institutional Ethics Review Board of Local Health Unit of São João, Porto, Portugal. The protocol conformed with the canons of the Declaration of Helsinki for research involving human participants, as well as the European Union’s General Data Protection Regulation. Informed consent was waived in view of the prospective nature of the study. This article was redacted according to the recommendations of The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Left eye retinal evaluation of a patient who developed an asymptomatic vasculitis after aflibercept IVI. Fundus photography presents retinal hemorrhages temporal to the macula and superior to the optic disc, as well as the presence of some hyalinized vessels in the temporal retina. Fluorescein angiography (both wide-field (6:35) and optic disc centered (2:33)) confirms the presence of retinal hemorrhages (fluorescence blockage), temporal ischemia and late staining of the optic disc
Fig. 2
Fig. 2
Best corrected visual acuity (in ETDRS letters) at the time of diagnosis of both IE and NI-IOI and after appropriate treatment, in both study groups (IE and NI-IOI)
See this image and copyright information in PMC

References

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