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

TL;DR

Long-term use of ketorolac eye drops in cats can cause dry eye symptoms and damage to eye tissues, especially when preservatives are included.

Contribution

The study is the first to evaluate the effects of ketorolac formulations on feline ocular surface health over 15 days.

Findings

Both ketorolac formulations reduced tear production and goblet cell density in cats.

BACKT caused more meibomian gland loss and higher lipid peroxidation compared to FKT.

No significant corneal staining or hyperemia was observed in any group.

Abstract

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.

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.

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.

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.

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