{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:38:07Z","timestamp":1777617487874,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Santen Pharmaceutical Asia Pte. Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Purpose: To profile tear cytokine changes in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) patients after instillation of daily topical cyclosporine-A 0.1% cationic emulsion. Methods: Participants in a longitudinal study were given cyclosporine eyedrops daily from 3 to 5 weeks before and 3 months, 6 months, and 12 months post-HSCT. The outcomes included tear cytokine concentration assayed by the Proximity Extension Assay O-linked target 96 platform. The patients were divided into two groups: Group 1 (n = 8 conjunctival CD4 cells responding to cyclosporine) and Group 2 (n = 5 conjunctival CD4 cells not suppressed after cyclosporine, where patients were non-compliant with cyclosporine). All participants had a standardized clinical examination, including meibomian gland evaluation and tear breakup times. Results: The levels of 38 cytokines\/chemokines showed significant changes (p &lt; 0.05) over time, and in many, the elevation was marked at one year. These include gamma-interferon, CXCL9, CCL3, and CCL4 (all p &lt; 0.0001). For gamma-interferon, there was significant interaction between group and time at 1 year (p = 0.022), where the cytokine was significantly suppressed in Group 1. Four other cytokines showed significant group and time interaction at 1 year: FGF23, FGF5, LIFR, and Enrage (all p &lt; 0.05). All patients had either withdrawal or a reduction in systemic immunomodulation between 6 months and 1 year. We found several cytokines to be associated with changes in tear osmolarity or symptom scores. Conclusions: HSCT induces significant elevation of 38 tear cytokines\/chemokines even without the occurrence of ocular graft-versus-host disease when systemic immunosuppression is reduced within the first year. Topical daily cyclosporine eyedrops can reduce some pro-inflammatory tear cytokines.<\/jats:p>","DOI":"10.3390\/ijms26125915","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T03:05:27Z","timestamp":1750388727000},"page":"5915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tear Cytokine Changes up to One Year After Allogeneic Hematopoietic Stem Cell Transplant: Effect of Daily Topical Cyclosporine-A 0.1% Emulsion"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3986-6552","authenticated-orcid":false,"given":"Louis","family":"Tong","sequence":"first","affiliation":[{"name":"Corneal and External Eye Disease Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road Discovery Tower Level 6, The Academia, Singapore 169856, Singapore"},{"name":"Eye-Academic Clinical Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr., Singapore 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Corneal and External Eye Disease Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road Discovery Tower Level 6, The Academia, Singapore 169856, Singapore"},{"name":"Eye-Academic Clinical Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon Wan Jie","family":"Yeo","sequence":"additional","affiliation":[{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road Discovery Tower Level 6, The Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road Discovery Tower Level 6, The Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle Xin Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road Discovery Tower Level 6, The Academia, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeh Ching","family":"Linn","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aloysius","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-083X","authenticated-orcid":false,"given":"Hein","family":"Than","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey Kim Siang","family":"Quek","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Ying Khee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7194-2845","authenticated-orcid":false,"given":"Francesca Lorraine Wei Inng","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Lim","sequence":"additional","affiliation":[{"name":"Corneal and External Eye Disease Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Eye-Academic Clinical Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jtos.2018.04.001","article-title":"Ocular chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in an Italian referral center","volume":"16","author":"Berchicci","year":"2018","journal-title":"Ocul. 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