{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:06:07Z","timestamp":1791644767866,"version":"4.3.4"},"reference-count":43,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Research and Biotechnology Division of St. Luke\u2019s Medical Center-Quezon City","award":["SL-19208"],"award-info":[{"award-number":["SL-19208"]}]},{"name":"Santen Pharmaceutical Co., Ltd.","award":["Not Applicable"],"award-info":[{"award-number":["Not Applicable"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyze the effect of 3% diquafosol sodium ophthalmic solution on tear film proinflammatory cytokine levels, ocular symptoms, and tear film stability in patients with dry eye disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was an open-label, noncomparative, single-cohort, interventional, proof-of-concept study among patients with dry eye disease who were administered diquafosol eye drops six times a day for 4 weeks. Pretreatment and posttreatment tear samples were collected, and ocular surface disease index scores and fluorescein tear break-up time were measured. Interferon-gamma, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels were measured in the tear samples using a cytokine magnetic bead panel. Independent associations of cytokine responses with sex, age, tear break-up time, and ocular surface disease index were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-one eyes (n\u2009=\u200931) in 31 patients with dry eye disease were included. At baseline, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were detected in all samples, whereas interleukin-1 beta was detected in 3% (1\/31) of the samples. Baseline concentrations of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma decreased by \u226525% in 58%, 51.6%, and 45.1% of the eyes, respectively, reaching significance for tumor necrosis factor-alpha (W\u2009=\u2009101, z\u2009=\u20092.694, p\u2009=\u20090.006, two-tailed) and interleukin-6 (W\u2009=\u2009134, z\u2009=\u20092.224, p\u2009=\u20090.026, two-tailed). The tear break-up time (from 3.95 to 4.65\u2009s; p\u2009=\u20090.013) and ocular surface disease index scores (from 20.57 to 13.85; p\u2009=\u20090.005) significantly improved following treatment. Individual responses were found to be independent of age, sex, eye laterality, pretreatment tear break-up time, and ocular surface disease index scores based on the multivariate logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Diquafosol reduced the levels of proinflammatory cytokines in the tears of patients with dry eye disease after 4 weeks of treatment, suggesting their possible role in modulating ocular surface inflammation. Larger prospective studies are recommended to validate these results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605251387924","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T03:34:05Z","timestamp":1762486445000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["The effect of diquafosol on tear film inflammatory markers in patients with dry eye: A noncomparative, open-label, proof-of-concept study"],"prefix":"10.1177","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-223X","authenticated-orcid":false,"given":"Raymund V","family":"Tanchuling","sequence":"first","affiliation":[{"name":"Eye Institute, St. Luke\u2019s Medical Center, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Vivian C","family":"Tan","sequence":"additional","affiliation":[{"name":"Eye Institute, St. Luke\u2019s Medical Center, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Nelson C","family":"Regalado","sequence":"additional","affiliation":[{"name":"Eye Institute, St. Luke\u2019s Medical Center, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Lim Bon Siong","sequence":"additional","affiliation":[{"name":"Eye Institute, St. Luke\u2019s Medical Center, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-067007"},{"key":"e_1_3_7_3_2","first-page":"29","article-title":"Prevalence of dry eye disease in an urban community","volume":"40","author":"Panggat K","year":"2015","unstructured":"Panggat K, Covar R, Lim-Bon-Siong R. Prevalence of dry eye disease in an urban community. Philipp J Ophthalmol 2015; 40: 29\u201335.","journal-title":"Philipp J Ophthalmol"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2016.09.003"},{"key":"e_1_3_7_5_2","article-title":"Utilizing the immune system to combat dry eye disease","volume":"16","author":"Whitley WO.","year":"2024","unstructured":"Whitley WO. Utilizing the immune system to combat dry eye disease. Optom Times 2024; 16.","journal-title":"Optom Times"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31818c69ef"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-9417"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.07.010"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093111"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.02.009"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S69486"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0409-7"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22925"},{"key":"e_1_3_7_14_2","first-page":"929","article-title":"The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice","volume":"20","author":"Kojima T","year":"2014","unstructured":"Kojima T, Dogru M, Ibrahim OM, et\u00a0al. The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice. Mol Vis 2014; 20: 929\u2013938.","journal-title":"Mol Vis"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2228192"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-63784-4"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01188-x"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/APO.0000000000000493"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.11.008"},{"key":"e_1_3_7_20_2","first-page":"65","article-title":"Cross-cultural adaptation and reliability of a Filipino dry eye screening questionnaire","volume":"43","author":"Dal Roa-Lingad RM","year":"2018","unstructured":"Dal Roa-Lingad RM, Lim-Bon-Siong R. Cross-cultural adaptation and reliability of a Filipino dry eye screening questionnaire. Philipp J Ophthalmol 2018; 43: 65\u201371.","journal-title":"Philipp J Ophthalmol"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.3341\/kjo.1988.2.2.69"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31803dcda2"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2008.08.032"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3181a16578"},{"key":"e_1_3_7_25_2","first-page":"862","article-title":"Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease","volume":"16","author":"Enr\u00edquez-de-Salamanca A","year":"2010","unstructured":"Enr\u00edquez-de-Salamanca A, Castellanos E, Stern ME, et\u00a0al. Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease. Mol Vis 2010; 16: 862\u2013873.","journal-title":"Mol Vis"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.40.11.10607"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.3341\/kjo.2019.0046"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0069"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-017-0693-1"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1364"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000150445"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-51241-1"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2018.0005"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000429"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-023-06083-4"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2014-306084"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1130117"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/cxo.12521"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49159-0"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-022-02584-z"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13397"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2021.0083"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2023.0098"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40123-023-00784-z"}],"container-title":["Journal of International Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605251387924","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03000605251387924","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605251387924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:51:13Z","timestamp":1777459873000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03000605251387924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1177\/03000605251387924"],"URL":"https:\/\/doi.org\/10.1177\/03000605251387924","relation":{},"ISSN":["0300-0605","1473-2300"],"issn-type":[{"value":"0300-0605","type":"print"},{"value":"1473-2300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"article-number":"03000605251387924"}}