Frequency and Characterization of Local Ocular Toxicity in Cats Treated With Topical Ophthalmic Cidofovir for Presumptive Feline Herpesvirus-1 Infection

Sep 29, 2026

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Objective: determine the frequency and clinical characteristics of local ocular adverse reactions to topical ophthalmic cidofovir in cats with presumptive feline herpesvirus-1 (FHV-1) keratoconjunctivitis. In a retrospective review (2021–2023), 140 cats received topical ophthalmic 0.5% cidofovir, and 6 (4.3%) developed suspected local ocular toxicity. The syndrome included persistent blepharospasm, discharge, conjunctival hyperemia, chemosis, and rapidly progressive conjunctival melanosis; repeat FHV-1 testing was negative. Mixed eosinophilic and neutrophilic inflammation with pigment-laden epithelial cells was seen, lesions resolved in ~3 weeks after discontinuation. Although uncommon, toxicity may mimic persistent FHV-1 infection; progressive melanosis suggests cidofovir toxicity and limiting treatment to ≤3 weeks may be advisable.

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Abstract

Introduction

Material and Methods

Study Design

Veterinary Ophthalmology ORIGINAL REPORT OPEN ACCESS Frequency and Characterization of Local Ocular Toxicity in Cats Treated With Topical Ophthalmic Cidofovir for Presumptive Feline Herpesvirus-1 Infection Eric C. Ledbetter | Amy J. Morgan Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA Correspondence: Eric C. Ledbetter ([ecl32@cornell.edu](ecl32@cornell.edu)) Received: 20 March 2025 | Revised: 16 June 2025 | Accepted: 25 June 2025 Keywords: antiviral | conjunctival melanosis | conjunctivitis | feline herpesvirus-1 | ocular toxicity ABSTRACT Objective: To determine the frequency and clinical characteristics of local ocular adverse reactions to topical ophthalmic cidofovir administration in cats with presumptive feline herpesvirus-1 (FHV-1) keratoconjunctivitis. Animal Studied: In total, 140 cats treated with cidofovir. Procedures: A retrospective search of electronic medical records was performed for cats treated with topical ophthalmic cidofovir and examined by the Cornell University Ophthalmology Service between 2021 and 2023. Signalment, clinical findings, and diagnostic assay results were recorded for cats that developed local ocular adverse reactions attributed to cidofovir administration. Results: During the 3-year study period, 140 cats were treated with topical ophthalmic 0.5% cidofovir solution, and 6 cats (4.3%) were suspected to have developed a local ocular toxic reaction to the medication. A distinct ocular toxicity clinical syndrome was observed that included persistent blepharospasm, ocular discharge, conjunctival hyperemia, chemosis, and rapidly progressive conjunctival melanosis. Repeat diagnostic evaluations for FHV-1 were negative in the cats, and conjunctival cytology revealed mixed eosinophilic and neutrophilic inflammation with epithelial cells heavily laden with pigment granules. Cats developing ocular toxicity were treated with cidofovir for a median of 32 (range: 23–62) days. Clinical ocular lesions resolved within approximately 3 weeks after discontinuing cidofovir in all cats. Conclusions and Clinical Relevance: Although uncommon, local ocular toxicity associated with cidofovir administration can develop in cats and may clinically mimic persistent FHV-1 infection. Progressive conjunctival melanosis is a suspected clinical marker of local ocular cidofovir toxicity in cats. When possible, restricting the duration of cidofovir administration to ≤3 weeks may be advisable. 1 | Introduction Feline herpesvirus-1 (FHV-1) is a ubiquitous infectious agent of domestic cats and a common etiology of ocular surface clinical disease [1] . Cytopathic ocular FHV-1 infections in cats are associated with blepharitis, conjunctivitis, and ulcerative keratitis [2] . Specific antiviral therapy is recommended in cats with ocular FHV-1 infections to reduce morbidity, improve comfort, hasten recovery, lessen environmental viral shedding, and to prevent the development of more serious negative clinical sequelae [3] . Cidofovir is a nucleoside analog of cytosine, a potent inhibitor of FHV-1 replication in vitro, and a common antiviral agent used to treat cats with clinical FHV-1 infections [4–7] . Cidofovir is an appealing topical antiviral agent due to the unusually long intracellular half-life of its metabolites. The ability to accumulate within epithelial cells and ocular tissues can This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2025 The Author(s). Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists. Veterinary Ophthalmology, 2026; 29:e70046 1 of 7 [https://doi.org/10.1111/vop.70046](https://doi.org/10.1111/vop.70046) resu

FAQs

How frequent is local ocular toxicity from topical ophthalmic cidofovir in cats with presumptive FHV-1 keratoconjunctivitis?

In the 2021–2023 retrospective review, 6 of 140 cats (4.3%) were suspected to develop local ocular toxicity associated with cidofovir.

What clinical signs characterize the local ocular toxicity syndrome?

A distinct syndrome was observed, including persistent blepharospasm, ocular discharge, conjunctival hyperemia, chemosis, and rapidly progressive conjunctival melanosis.

How were suspected cases evaluated for FHV-1 and what did cytology show?

Repeat diagnostic evaluations for FHV-1 were negative, and conjunctival cytology showed mixed eosinophilic and neutrophilic inflammation with epithelial cells heavily laden with pigment granules.

Sep 29, 2026

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