Faricimab-Associated Intraocular Inflammation with Features of Herpes Simplex Virus.

Abstract

Objective: Faricimab-associated intraocular inflammation (IOI) is an emerging concern. We aimed to investigate clinical features, management, and outcomes of severe IOI following faricimab therapy, with particular attention to cases displaying features consistent with herpes simplex virus (HSV) involvement.

Design: Single-center retrospective interventional case series.

Subjects: Five patients (five eyes) who developed severe IOI following intravitreal faricimab injection for neovascular age-related macular degeneration (nAMD, n=4) or diabetic macular edema (DME, n=1) between June 2023 and October 2024. The nAMD patients had received a mean of 17.75 ± 9.18 prior anti-VEGF injections (range 6-26 injections). The DME patient had previously received seven aflibercept injections and two dexamethasone implants. Prior to faricimab, three patients were being treated with aflibercept and two with ranibizumab biosimilar.

Methods: Medical records were reviewed for clinical features, treatment approaches, and outcomes. Cases were identified through systematic review of follow-up appointments and urgent care presentations. When clinically indicated, additional investigations including optical coherence tomography and fluorescein angiography were performed.

Main outcome measures: Best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber (AC) inflammation, presence of keratic precipitates (KPs), vitreous cells, signs of viral reactivation, and treatment response.

Results: The median number of faricimab injections before inflammation was 5 (range 3-13). Mean interval between injection and symptom onset was 16.8 days (range 1-35). All patients presented with AC inflammation and elevated IOP (mean 32.8 ± 4.15 mmHg, range 28-38 mmHg). All patients demonstrated features consistent with HSV keratouveitis, including dendritic ulcers, reduced corneal sensation, and granulomatous KPs. Treatment included topical or systemic steroids in all cases, with four patients (80%) receiving concurrent antiviral therapy. Median time to inflammation resolution was 15.5 days. Four patients (80%) did not recover baseline vision.

Conclusions: This case series identifies a previously unreported association between faricimab-associated IOI and features of viral reactivation. The temporal relationship including onset patterns suggestive of delayed hypersensitivity, alongside consistent HSV features and favourable antiviral response, suggests a possible mechanism linked to VEGF-A and Ang-2 mediated alterations in ocular immune surveillance. While further investigation is needed to establish causality, clinicians should consider viral mechanisms when evaluating and treating these cases.