The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye

Vet Ophthalmol. 2018 May;21(3):255-263. doi: 10.1111/vop.12503. Epub 2017 Oct 3.

Abstract

Purpose: To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS).

Methods: Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment.

Results: Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS.

Conclusion: Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted.

Keywords: aqueous; canine; dry eye; rapamycin; sirolimus; topical.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Dog Diseases / drug therapy*
  • Dogs
  • Female
  • Keratoconjunctivitis Sicca / drug therapy
  • Keratoconjunctivitis Sicca / veterinary*
  • Male
  • Ophthalmic Solutions / therapeutic use*
  • Sirolimus / pharmacology*
  • Tears / drug effects*

Substances

  • Ophthalmic Solutions
  • Sirolimus