{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T13:04:25Z","timestamp":1787403865998,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Ophthalmology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Evaluate the efficacy of a therapeutic approach combining tacrolimus and hyaluronate\u2010based lubricant for the management of evaporative dry eye disease (EDED) in dogs, compared to hyaluronate monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010four client\u2010owned dogs with EDED were randomly assigned to three groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918 each): Group 1 received 0.03% tacrolimus and 0.3% hyaluronate twice daily; Group 2 received 0.3% hyaluronate four times daily; and Group 3 received 0.3% hyaluronate twice daily. Blink rate, clinical scoring, corneal esthesiometry, Schirmer tear test, tear film breakup time (TFBUT), punctate fluorescein staining, lissamine green staining, and owner\u2010reported symptoms were assessed at baseline, 15, and 45\u2009days after initiating therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Group 1 showed the most significant improvements, with TFBUT increasing by +57% by Day 15 and\u2009+\u200993% by Day 45, accompanied by notable reductions in ocular discharge and conjunctival hyperemia. Most ocular changes and owner\u2010reported symptoms improved more rapidly and with greater amplitude in Group 1. Although Groups 2 and 3 also improved, changes were less pronounced despite the higher dosing frequency in Group 2. Neither corneal sensitivity nor corneal changes (fibrosis, neovascularization, pigmentation, and edema) showed significant variation in any group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dogs receiving combined tacrolimus and hyaluronate treatment showed faster and more pronounced improvements in both objective and subjective assessments of ocular health. These findings underscore the importance of addressing both the immunologic aspects and tear film instability associated with EDED, particularly in cases where inflammation plays a significant role. Future studies should directly evaluate tacrolimus monotherapy and explore different tacrolimus formulations and vehicles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/vop.70042","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T01:18:11Z","timestamp":1756257491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tacrolimus and Hyaluronate Therapy Enhance Tear Film Stability in Canine Evaporative Dry Eye Disease"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-0127","authenticated-orcid":false,"given":"Lionel","family":"Sebbag","sequence":"first","affiliation":[{"name":"Koret School of Veterinary Medicine The Hebrew University of Jerusalem  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirlene F.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Zootechny Federal University of Bahia, UFBA  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-6841","authenticated-orcid":false,"given":"Arianne P.","family":"Ori\u00e1","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Zootechny Federal University of Bahia, UFBA  Salvador 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