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

Jordan K. Roberts Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Jessica M. Meekins Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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James K. Roush Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Amy J. Rankin Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Abstract

OBJECTIVE

To investigate the effects of short-term and prolonged topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity (CS) in ophthalmologically normal cats.

ANIMALS

12 healthy adult domestic shorthair cats.

PROCEDURES

In the first of 2 study phases, each cat received 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.03% flurbiprofen sodium, and saline (0.9% NaCl; control) solutions (1 drop [0.05 mL]/eye, q 5 min for 5 treatments) in a randomized order with a 2-day washout period between treatments. For each cat, an esthesiometer was used to measure CS before treatment initiation (baseline) and at 15, 30, 45, and 60 minutes after the last dose. There was a 2-day washout period between phases. The second phase was similar to the first, except each treatment was administered at a dosage of 1 drop/eye, twice daily for 5 days and CS was measured before treatment initiation and at 15 minutes and 24 and 48 hours after the last dose. The Friedman test was used to evaluate change in CS over time.

RESULTS

None of the 4 treatments had a significant effect on CS over time in either study phase.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that neither short-term nor prolonged topical instillation of 3 NSAID ophthalmic solutions had any effect on the CS of healthy cats. Given potential differences in cyclooxygenase expression between healthy and diseased eyes, further investigation of the effects of topical NSAID instillation in the eyes of cats with ocular surface inflammation is warranted.

Abstract

OBJECTIVE

To investigate the effects of short-term and prolonged topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity (CS) in ophthalmologically normal cats.

ANIMALS

12 healthy adult domestic shorthair cats.

PROCEDURES

In the first of 2 study phases, each cat received 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.03% flurbiprofen sodium, and saline (0.9% NaCl; control) solutions (1 drop [0.05 mL]/eye, q 5 min for 5 treatments) in a randomized order with a 2-day washout period between treatments. For each cat, an esthesiometer was used to measure CS before treatment initiation (baseline) and at 15, 30, 45, and 60 minutes after the last dose. There was a 2-day washout period between phases. The second phase was similar to the first, except each treatment was administered at a dosage of 1 drop/eye, twice daily for 5 days and CS was measured before treatment initiation and at 15 minutes and 24 and 48 hours after the last dose. The Friedman test was used to evaluate change in CS over time.

RESULTS

None of the 4 treatments had a significant effect on CS over time in either study phase.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that neither short-term nor prolonged topical instillation of 3 NSAID ophthalmic solutions had any effect on the CS of healthy cats. Given potential differences in cyclooxygenase expression between healthy and diseased eyes, further investigation of the effects of topical NSAID instillation in the eyes of cats with ocular surface inflammation is warranted.

Supplementary Materials

    • Supplementary Figure S1 (PDF 212 kb)

Contributor Notes

Address correspondence to Dr. Meekins (jslack@vet.k-state.edu).
  • 1.

    Chan-Ling T. Sensitivity and neural organization of the cat cornea. Invest Ophthalmol Vis Sci 1989;30:1075 1082.

  • 2.

    Nasisse MP, Guy JS, Davidson MG, et al. Experimental ocular herpesvirus infection in the cat. Sites of virus replication, clinical features and effects of corticosteroid administration. Invest Ophthalmol Vis Sci 1989;30:1758 1768.

    • Search Google Scholar
    • Export Citation
  • 3.

    Maggs DJ. Update on pathogenesis, diagnosis, and treatment of feline herpesvirus type 1. Clin Tech Small Anim Pract 2005;20:94 101.

  • 4.

    Gould D. Feline herpesvirus-1: ocular manifestations, diagnosis and treatment options. J Feline Med Surg 2011;13:333 346.

  • 5.

    Haesaert SP. Drugs and recurrent ocular herpes. Am J Optom Physiol Opt 1986;63:223 228.

  • 6.

    Hendricks RL, Barfknecht CF, Schoenwald RD, et al. The effect of flurbiprofen on herpes simplex virus type 1 stromal keratitis in mice. Invest Ophthalmol Vis Sci 1990;31:1503 1511.

    • Search Google Scholar
    • Export Citation
  • 7.

    Barba KR, Samy A, Lai C, et al. Effect of topical anti-inflammatory drugs on corneal and limbal wound healing. J Cataract Refract Surg 2000;26:893 897.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Chen X, Gallar J, Belmonte C. Reduction by antiinflammatory drugs of the response of corneal sensory nerve fibers to chemical irritation. Invest Ophthalmol Vis Sci 1997;38:1944 1953.

    • Search Google Scholar
    • Export Citation
  • 9.

    Aragona P, Stilo A, Ferreri F, et al. Effects of the topical treatment with NSAIDs on corneal sensitivity and ocular surface of Sjögren's syndrome patients. Eye (Lond) 2005;19:535 539.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Szerenyi K, Sorken K, Garbus JJ, et al. Decrease in normal human corneal sensitivity with topical diclofenac sodium. Am J Ophthalmol 1994;118:312 315.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Giuliano EA. Nonsteroidal anti-inflammatory drugs in veterinary ophthalmology. Vet Clin North Am Small Anim Pract 2004;34:707 723.

  • 12.

    Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf 2002;25:233 250.

  • 13.

    Gaynes BI, Onyekwuluje A. Topical ophthalmic NSAIDs: a discussion with focus on nepafenac ophthalmic suspension. Clin Ophthalmol 2008;2:355 368.

  • 14.

    Sun R, Gimbel HV. Effects of topical ketorolac and diclofenac on normal corneal sensation. J Refract Surg 1997;13:158 161.

  • 15.

    Narváez J, Kroll P, Guzek JP. Effect of topical diclofenac and ketorolac on patient discomfort and corneal sensitivity. J Refract Surg 2002;18:145 148.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Surv Ophthalmol 2010;55:108 133.

  • 17.

    Ahuja M, Dhake AS, Sharma SK, et al. Topical ocular delivery of NSAIDs. AAPS J 2008;10:229 241.

  • 18.

    Radi ZA, Render JA. The pathophysiologic role of cyclo-oxygenases in the eye. J Ocul Pharmacol Ther 2008;24:141 151.

  • 19.

    Sellers RS, Silverman L, Khan KN. Cyclooxygenase-2 expression in the cornea of dogs with keratitis. Vet Pathol 2004;41:116 121.

  • 20.

    Sim ZH, Pinard CL, Plattner BL, et al. Cyclooxygenase-2 expression in the eyes of cats with and without uveitis. Am J Vet Res 2018;79:90 97.

  • 21.

    Aragona P, Tripodi G, Spinella R, et al. The effects of the topical administration of non-steroidal anti-inflammatory drugs on corneal epithelium and corneal sensitivity in normal subjects. Eye (Lond) 2000;14:206 210.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Acosta MC, Berenguer-Ruiz L, García-Galvez A, et al. Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs. Invest Ophthalmol Vis Sci 2005;46:282 286.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Hsu KK, Pinard CL, Johnson RJ, et al. Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats. Am J Vet Res 2015;76:253 265.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1988;35:244 285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Tang-Liu DD, Liu SS, Weinkam RJ. Ocular and systemic bio-availability of ophthalmic flurbiprofen. J Pharmacokinet Biopharm 1984;12:611 626.

  • 26.

    Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997;53:139 188.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Blocker T, Van Der Woerdt A. A comparison of corneal sensitivity between brachycephalic and domestic short-haired cats. Vet Ophthalmol 2001;4:127 130.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Lum E, Murphy PJ. Effects of ambient humidity on the Cochet-Bonnet aesthesiometer. Eye (Lond) 2018;32:1644 1651.

  • 29.

    Cantarella RA, de Oliveira JK, Dorbandt DM, et al. Effects of topical flurbiprofen sodium, diclofenac sodium, ketorolac tromethamine and benzalkonium chloride on corneal sensitivity in normal dogs. Open Vet J 2017;7:254 260.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Seitz B, Sorken K, LaBree LD, et al. Corneal sensitivity and burning sensation. Comparing topical ketorolac and diclofenac. Arch Ophthalmol 1996;114:921 924.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Singer DD, Kennedy J, Wittpenn JR. Topical NSAIDs effect on corneal sensitivity. Cornea 2015;34:541 543.

  • 32.

    Binder DR, Herring IP. Duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in clinically normal cats. Am J Vet Res 2006;67:1780 1782.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Dorbandt DM, Labelle AL, Mitchell MA, et al. The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs. Vet Ophthalmol 2017;20:160 170.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Kulkarni PS, Fleisher L, Srinivasan BD. The synthesis of cyclooxygenase products in ocular tissues of various species. Curr Eye Res 1984;3:447 452.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Waterbury LD, Silliman D, Jolas T. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin 2006;22:1133 1140.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Masferrer JL, Kulkarni PS. Cyclooxygenase-2 inhibitors: a new approach to the therapy of ocular inflammation. Surv Ophthalmol 1997;41(suppl 2):S35–S40.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Hendrix DV, Ward DA, Barnhill MA. Effects of anti-inflammatory drugs and preservatives on morphologic characteristics and migration of canine corneal epithelial cells in tissue culture. Vet Ophthalmol 2002;5:127 135.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Court MH. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Vet Clin North Am Small Anim Pract 2013;43:1039 1054.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Lanuza R, Rankin AJ, KuKanich B, et al. Evaluation of systemic absorption and renal effects of topical ophthalmic flurbiprofen and diclofenac in healthy cats. Vet Ophthalmol 2016;19(suppl 1):24 29.

    • Crossref
    • Search Google Scholar
    • Export Citation

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