Fifteen-day topical ketorolac tromethamine, with and without benzalkonium chloride, alters tear function, goblet cell density, and meibomian gland integrity in healthy cats

Vet World Vol.19 January-2026 Article - 22

Research Article

Veterinary World, 19(1): 310-323

https://doi.org/10.14202/vetworld.2026.310-323

Bruna Carvalho Silveira¹, Alexandre Pinto Ribeiro², Matheus Anthony Mendes¹, Maria Gabriela de Mendonça Mazetti², Douglas Lisboa Ramalho³, Anderson Oliveira Souza⁴, Nathalia de Assis Pereira¹, and Nataliê Ecker¹

1. Postgraduate Program in Veterinary Science, Faculty of Veterinary Medicine, Federal University of Mato Grosso, Fernando Correa da Costa Avenue, 2367, Boa Esperança, Cuiabá, 78.060-900, Mato Grosso, Brazil.

2. Faculty of Veterinary Medicine, Federal University of Mato Grosso, Fernando Correa da Costa Avenue, 2367, Boa Esperança, Cuiabá, 78.060-900, Mato Grosso, Brazil.

3. Postgraduate Program in Health Sciences, Faculty of Chemistry, Federal University of Mato Grosso, Fernando Correa da Costa Avenue, 2367, Boa Esperança, Cuiabá, 78.060-900, Mato Grosso, Brazil.

4. Faculty of Chemistry, Federal University of Mato Grosso, Fernando Correa da Costa Avenue, 2367, Boa Esperança, Cuiabá, 78.060-900, Mato Grosso, Brazil.

Background and Aim: Topical nonsteroidal anti-inflammatory drugs are commonly used in feline ophthalmology, especially for long-term management of uveitis after cataract surgery. However, there is very limited data on how they affect the feline ocular surface, particularly the conjunctival tissue, goblet cell density (GCD), meibomian glands (MGs), and oxidative stress. This study assessed whether 15-day, thrice-daily application of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride (BAC)–preserved ketorolac tromethamine (BACKT) influences ocular surface disease scores, tear film parameters, GCD, MG morphology, matrix metalloproteinase-9 (MMP-9), and oxidative stress biomarkers (OSB) in healthy cats.

Materials and Methods: A prospective, randomized, double-masked, crossover design was used with 13 healthy cats. Each cat received FKT in one eye and BACKT in the other eye every 8 h for 15 days, followed by a 3-week washout period and reversal of treatment. A separate control group (CG; n=13) received topical saline. Clinical assessments included conjunctival hyperemia, blepharospasm, Schirmer tear test (STT), tear film break-up time (TFBT), lissamine green, and fluorescein staining. Meibography was used to quantify MG loss. Conjunctival biopsies obtained at baseline and day 15 were analyzed for GCD, MMP-9, superoxide dismutase, catalase, reduced glutathione, and malondialdehyde levels.

Results: No groups showed corneoconjunctival staining or conjunctival hyperemia at any point. Mild blepharospasm developed in 3 out of 13 FKT-treated eyes and 9 out of 13 BACKT-treated eyes (p = 0.003). STT values significantly decreased from baseline to day 15 in both FKT and BACKT groups (p < 0.05). TFBT decreased significantly only in FKT-treated eyes (p = 0.009), although BACKT showed a similar, non-significant trend. MG loss increased significantly only in BACKT-treated eyes (p = 0.04). GCD decreased markedly in both FKT (p = 0.0003) and BACKT (p < 0.0001) groups and was lower than CG at day 15. OSB remained largely unchanged, except for higher MDA levels in BACKT-treated eyes compared with CG (p = 0.04). MMP-9 expression did not differ within or between groups.

Conclusion: Both ketorolac formulations reduced STT, TFBT, and GCD, supporting the development of a qualitative dry eye state in healthy cats. BACKT resulted in greater ocular discomfort, increased MG loss, and higher lipid peroxidation, indicating BAC-related cytotoxicity. Caution is advised when prescribing prolonged topical ketorolac, and concurrent ocular lubrication is recommended.

Keywords: benzalkonium chloride, feline ophthalmology, goblet cell density, Ketorolac tromethamine, matrix metalloproteinase-9, meibomian gland loss, ocular surface disease, oxidative stress biomarkers, Schirmer tear test, tear film break-up time.

How to cite this article: Silveira BC, Ribeiro AP, Mendes MA, Mazetti MGM, Ramalho DL, Souza AO, Pereira NA, Ecker N. Fifteen-day topical ketorolac tromethamine, with and without benzalkonium chloride, alters tear function, goblet cell density, and meibomian gland integrity in healthy cats. Vet World. 2026; 19(1): 310–323.

Received: 19-07-2025 Accepted: 24-11-2025 Published online: 25-01-2026

Corresponding author: Alexandre Pinto Ribeiro E-mail: alexandre.aleribs@gmail.com

DOI: 10.14202/vetworld.2026.310-323

Copyright: Silveira, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.