{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:12:29Z","timestamp":1782745949847,"version":"3.54.5"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Various preparations of tacrolimus have been implemented for patients with vernal keratoconjunctivitis (VKC). However, there is a lack of evidence regarding the safety and effectiveness of different dosages and forms of tacrolimus for patients with VKC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The present systematic review and meta-analysis evaluated the safety and effectiveness of various dosages and forms of tacrolimus for patients with VKC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The literature review was performed through 12 databases on 15 June 2024. All clinical studies comparing the outcomes of different dosages and tacrolimus preparations for VKC were included. Subgroup analysis was performed based on the dosages and formulations of tacrolimus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The present meta-analysis included 17 articles, encompassing 832 patients with VKC. Of them, 421 patients received tacrolimus, while 411 patients were in the control group. Of the treated patients with tacrolimus, 66 were treated with tacrolimus ophthalmic suspension 0.1%, and 62 were treated with tacrolimus 0.1% ointment. Furthermore, 293 patients were treated with tacrolimus 0.03% ointment. There was a statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.02) difference between tacrolimus and the control group regarding the mean score for objective signs with SMD of \u22120.70 (95%CI:\u22121.28, \u22120.13). A statistically significant difference (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) was observed between the tacrolimus ophthalmic suspension 0.1% and the control group with an SMD of \u22121.09 (95%CI:\u22121.59, \u22120.59). There was a significantly lower total subjective symptom score among patients treated with tacrolimus with an SMD of \u22120.86 (95%CI:\u22121.44, 0.28) and a probability value of 0.004. A statistically significant lower risk of treatment-related adverse events was revealed among patients treated with tacrolimus 0.03% ointment (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0002) with an RR of 0.16.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tacrolimus is an effective and safe therapeutic intervention for patients with VKC. It remarkably reduced the total score for objective signs and total subjective symptom score of VKC, with a relatively lower risk of treatment-related adverse events. The improvement of clinical manifestations was significantly associated with tacrolimus ophthalmic suspension 0.1%, while tacrolimus 0.03% ointment was associated with the lowest risk of treatment-related adverse events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1542440","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T05:28:57Z","timestamp":1753853337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The impact of tacrolimus therapy on the outcomes of vernal keratoconjunctivitis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Reem","family":"AlHuthail","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU)","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"658","DOI":"10.3390\/ph14070658","article-title":"Immunopharmacology in vernal keratoconjunctivitis: current and future perspectives","volume":"14","author":"Chigbu","year":"2021","journal-title":"Pharm"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e2021517","DOI":"10.23750\/abm.v92iS7.12419","article-title":"Vernal keratoconjunctivitis: state of art and update on treatment","volume":"92","author":"Brindisi","year":"2021","journal-title":"Acta Bio Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.jtos.2019.07.004","article-title":"Adult vernal keratoconjunctivitis: clinical and biochemical profile of a rare disease","volume":"17","author":"Di Zazzo","year":"2019","journal-title":"Ocul Surf"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.ajo.2012.11.018","article-title":"Vernal keratoconjunctivitis-like disease in adults","volume":"155","author":"Leonardi","year":"2013","journal-title":"Am J of Ophthalmol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3390\/life11101012","article-title":"Understanding vernal keratoconjunctivitis: beyond allergic mechanisms","volume":"11","author":"Sacchetti","year":"2021","journal-title":"Life"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"882240","DOI":"10.3389\/fmed.2022.882240","article-title":"Diagnosis, management, and treatment of vernal keratoconjunctivitis in Asia: recommendations from the Management of Vernal Keratoconjunctivitis in Asia expert working group","volume":"9","author":"Mehta","year":"2022","journal-title":"Front Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1097\/ACI.0000000000000672","article-title":"Adult vernal keratoconjunctivitis","volume":"20","author":"Di Zazzo","year":"2020","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1755-3768.2011.02272.x","article-title":"Management of seasonal allergic conjunctivitis: guide to therapy","volume":"90","author":"Bielory","year":"2012","journal-title":"Acta Ophthalmol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"145","DOI":"10.36351\/pjo.v31i1.145","article-title":"To assess the efficacy and safety of tacrolimus skin cream, 0.03% in moderate to severe vernal keratoconjunctivitis","volume":"31","author":"Irfan","year":"2015","journal-title":"Pak J of Ophthalmol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.survophthal.2023.10.008","article-title":"Management of vernal keratoconjunctivitis: navigating a changing treatment landscape","volume":"69","author":"Ali","year":"2023","journal-title":"Survey Ophthalmol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2165\/11587010-000000000-00000","article-title":"Tacrolimus in the treatment of ocular diseases","volume":"25","author":"Zhai","year":"2011","journal-title":"BioDrugs"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"165","DOI":"10.5114\/pdia.2013.35619","article-title":"Topical calcineurin inhibitors in dermatology. 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