Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs

Abstract

To evaluate corneal sensitivity by using the Cochet-Bonnet® esthesiometer in normal canine eyes at different time points following instillation of three different topical non-steroidal anti-inflammatory drugs (flurbiprofen sodium 0.03%, diclofenac sodium 0.1% and ketorolac tromethamine 0.5%) and benzalkonium chloride 0.01%. Six healthy mixed breed dogs from the same litter were used in two different stages. First, one drop of flurbiprofen sodium 0.03% and diclofenac sodium 0.1% in each eye; second, one drop of ketorolac tromethamine 0.5% and benzalkonium chloride 0.01% in each eye. Baseline esthesiometry was obtained before eye drop application and every 15 minutes thereafter until a total of 105 minutes of evaluation time. A one-week interval was allowed between the two treatment phases. Statistical analysis was used to compare means according to time of evaluation and drug used. Diclofenac sodium 0.1% decreased corneal sensitivity at 75 and 90 minutes (P > 0.015) with possible interference on neuronal nociceptive activity and analgesic effect while ketorolac tromethamine 0.5% did not show any variation for esthesiometry means along the evaluation. Flurbiprofen sodium 0.03% resulted in increased esthesiometry values 30 minutes after instillation (P > 0.013), increasing corneal sensitivity and possibly producing a greater irritant corneal effect over its analgesic properties. Benzalkonium chloride 0.01% significantly increased corneal sensitivity at 15 minutes of evaluation (P > 0.001), most likely resulting from its irritating effect. Esthesiometry did not allow a definite conclusion over the analgesic effect of the NSAIDs tested; however it was effective in detecting fluctuations in corneal sensitivity.

Effects of topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity in ophthalmologically normal cats

“…findings were contrary to results of similar studies involving dogs 29 and humans 9,10,14,15,21,30,31 that suggest topical instillation of diclofenac, ketorolac, and flurbiprofen induces corneal analgesia. For the cats of the present study, the median CTT at baseline for both the immediate-dosing and prolonged-dosing phases was lower than the CTT for cats of other studies 1,23,27,32 but was considered within the recommended reference interval owing to the large variation in the CTTs reported for the cats of those studies.…”

“…The findings of the present study were similar to the results of another study 33 in which neither 0.1% diclofenac sodium nor 0.03% flurbiprofen sodium had any effect on the CS of ophthalmologically normal dogs following administration of multiple drops over a short duration or twice-daily dosing for 30 days. In a study 29 of ophthalmologically normal nonbrachycephalic dogs, topical instillation of 0.1% diclofenac sodium resulted in a decrease in CS at 75 and 90 minutes after administration, whereas topical instillation of 0.03% flurbiprofen sodium resulted in an increase in CS between 15 and 30 minutes after administration and topical instillation of 0.5% ketorolac tromethamine had no effect on CS. Conversely, in ophthalmologically normal human subjects, repeated topical instillation of many NSAIDs including 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.3% nepafenac, and 0.07% bromfenac consistently causes immediate and transient decreases in CS.…”

“…Another limitation was the lack of a true control group. Although physiologic saline solution served as a control, a more appropriate control treatment would have been an ophthalmic solution that contained a preservative because results of another study 29 indicate that preservatives within ophthalmic solutions can significantly affect CS. The selection of a control solution containing only 1 preservative would have been complicated because all 3 of the commercially available topical NSAIDs evaluated in this study contained different preservatives.…”

Decreased corneal subbasal nerve fiber length and density in diabetic dogs with cataracts using in vivo confocal microscopy

“…Additionally, comparisons to the CSNP of clinically normal and diabetic dogs without cataracts would be enlightening but our study was limited in scope due to the enrollment of client‐owned pets presenting to the CUHA ophthalmology service for ophthalmic disease processes. Finally, two of the diabetic dogs and three of the non‐diabetic dogs were prescribed diclofenac ophthalmic solution once or twice daily prior to IVCM and esthesiometry, which has been reported to decrease corneal sensitivity at 75 and 90 min after administration 44 . However, diclofenac was demonstrated to not have any significant effect on corneal sensitivity by 105 minutes after administration; 44 by the time of IVCM and esthesiometry testing, these dogs had not received diclofenac for greater than 24 h. Another study reports no decrease in corneal sensitivity after receiving diclofenac ophthalmic solution topically twice daily for 30 days compared to control dogs 45 .…”

Once-Daily Topical Phosphosulindac Is Efficacious in the Treatment of Dry Eye Disease: Studies in Rabbit Models of Its Main Clinical Subtypes

“…Corneal sensitivity was measured with the Cochet–Bonnet Esthesiometer (Luneau, France) in a quiet examination room and without anesthesia. 19 For esthesiometry, 8 , 20 , 21 each rabbit was placed in a restraining bag 16 h after the last dose of PS and before any sedation. The nylon filament was applied to the central cornea, its most sensitive area.…”