{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:07:15Z","timestamp":1767625635726},"reference-count":73,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Ophthalmology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (<jats:styled-content style=\"fixed-case\">KCS<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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<jats:styled-content style=\"fixed-case\">KCS<\/jats:styled-content>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tear production in the sirolimus\u2010treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>1.17, 5.75;<jats:italic>P<\/jats:italic>= 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>1.95, 8.05;<jats:italic>P<\/jats:italic>= 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production &gt;4 mm\/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (<jats:italic>P<\/jats:italic>= 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle\u2010treatment. Side effects were not reported in any treated eyes with chronic<jats:styled-content style=\"fixed-case\">KCS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vop.12503","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T15:16:46Z","timestamp":1507043806000},"page":"255-263","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye"],"prefix":"10.1111","volume":"21","author":[{"given":"Ronald","family":"Spatola","sequence":"first","affiliation":[{"name":"660 Independence Parkway Virginia Beach VA 23455 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad","family":"Nadelstein","sequence":"additional","affiliation":[{"name":"660 Independence Parkway Virginia Beach VA 23455 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