{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:44:06Z","timestamp":1792140246887,"version":"4.4.0"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Immune-mediated inflammatory disorders of the ocular surface and anterior segment frequently require sustained immunosuppression, yet prolonged topical corticosteroid use carries the risk of glaucoma, cataract, and infection. Tacrolimus, a macrolide calcineurin inhibitor, has emerged as a steroid-sparing alternative for T-cell-mediated ocular disease. This review summarizes the mechanism of action, ocular pharmacology, clinical applications, and safety profile of topical tacrolimus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Narrative synthesis of the peer-reviewed literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Tacrolimus binds the immunophilin FK506-binding protein 12; the resulting complex inhibits the phosphatase calcineurin, preventing dephosphorylation and nuclear translocation of the nuclear factor of activated T-cells (NFAT) and thereby suppressing transcription of interleukin-2 and a broad program of pro-inflammatory cytokines. The downstream result is reduced activation across the Th1, Th2, and Th17 lineages, diminished T-follicular helper and B-cell responses, stabilization of mast cells and eosinophils, and anti-angiogenic effects. Compounded topical formulations (typically 0.01%\u20130.1%) penetrate the cornea and reach therapeutic aqueous concentrations. Topical tacrolimus has shown efficacy in vernal and atopic keratoconjunctivitis, anterior uveitis, scleritis, ocular graft-versus-host disease, cicatrizing conjunctivitis, Thygeson superficial punctate keratitis, autoimmune polyglandular syndrome-1-associated keratitis, and corneal graft rejection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Topical tacrolimus is an effective steroid-sparing immunomodulator for a broad spectrum of T-cell-mediated ocular disease, with a favorable safety profile notable for the absence of steroid-related rises in intraocular pressure or cataractogenesis. Standardized formulations and prospective comparative trials remain priorities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261497924","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:38:24Z","timestamp":1791963504000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Topical Tacrolimus in Ocular Disease: A Narrative Review of Mechanism of Action and Therapeutic Applications"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2953-2188","authenticated-orcid":false,"given":"Hashem","family":"Abu Serhan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Abu Al-Burak","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University, London, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lameece","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Medical Intern, Faculty of Medicine, Alexandria University, Alexandria, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-0669","authenticated-orcid":false,"given":"Samir","family":"Shoughy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Doctor Samir Eye Clinic, Alexandria, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_3_1_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40662-017-0072-z"},{"key":"e_1_3_1_3_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.1249"},{"key":"e_1_3_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90111-J"},{"key":"e_1_3_1_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/11587010-000000000-00000"},{"key":"e_1_3_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90124-h"},{"key":"e_1_3_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1632"},{"key":"e_1_3_1_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15569527.2025.2485139"},{"key":"e_1_3_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1567-5769(01)00059-5"},{"key":"e_1_3_1_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132710"},{"key":"e_1_3_1_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031465"},{"key":"e_1_3_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.5"},{"key":"e_1_3_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2010.08.033"},{"key":"e_1_3_1_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01184"},{"key":"e_1_3_1_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12614216"},{"key":"e_1_3_1_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2017-311473"},{"key":"e_1_3_1_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2010.516620"},{"key":"e_1_3_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.10.019"},{"key":"e_1_3_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.02.044"},{"key":"e_1_3_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoc.2019.100582"},{"key":"e_1_3_1_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2008.0125"},{"key":"e_1_3_1_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S99157"},{"key":"e_1_3_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2013.08.007"},{"key":"e_1_3_1_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2013-304453"},{"key":"e_1_3_1_25_1","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.11-OA-0349"},{"key":"e_1_3_1_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2009.0087"},{"key":"e_1_3_1_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2011.75"},{"key":"e_1_3_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaapos.2018.09.010"},{"key":"e_1_3_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.10.065"},{"key":"e_1_3_1_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-9-34"},{"key":"e_1_3_1_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)90156-2"},{"key":"e_1_3_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.07.025"},{"key":"e_1_3_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2012.12.009"},{"key":"e_1_3_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2014.11.035"},{"key":"e_1_3_1_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002224"},{"key":"e_1_3_1_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-309808"},{"key":"e_1_3_1_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2006.097428"},{"key":"e_1_3_1_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2004.00006.x"}],"container-title":["Journal 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