{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:51:33Z","timestamp":1777909893813,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"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"],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet\u2013Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      confocal microscopy images before and 3 months after treatment were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.01). The mean squamous metaplasia grade also showed a significant improvement (1.2\u2009\u00b1\u20090.1\u2009\u2192\u20090.3\u2009\u00b1\u20090.1) 3 months after treatment (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.004). There were similar significant improvements in the mean corneal epithelial cell density (660.1\u2009\u00b1\u200962.6\u2009\u2192\u20091015.5\u2009\u00b1\u200943.5 cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.002) and nucleocytoplasmic ratios (0.1\u2009\u00b1\u20090.0\u2009\u2192\u20090.2\u2009\u00b1\u20090.0) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.0042) after treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Topical use of 2% rebamipide for 3 months was associated with improvements in ocular surface differentiation due to changes of mucosal functions at the cellular level. These alterations may explain objective and subjective improvements in dry eye disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2018.0130","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T11:12:00Z","timestamp":1561979520000},"page":"350-358","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease"],"prefix":"10.1177","volume":"35","author":[{"given":"Cem","family":"Simsek","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"Dogru","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Shinzawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seika","family":"Den","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Iseda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Shibasaki","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Shimazaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.008"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2011.0147"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000126436.25751.fb"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2013.834939"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13128"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2011.0142"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2013.11.010"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2013.838557"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S54511"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-23213"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-005-2800-9"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1984.01040030851031"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(84)34251-8"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0069"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3181ba0cb2"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2015.1009636"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.06.052"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.12.022"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e3181819f0a"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006324-200308000-00009"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1985.tb01584.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(85)33967-2"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-198801000-00012"},{"key":"e_1_3_4_25_2","first-page":"2457","article-title":"The application of in vivo laser scanning confocal microscopy as a tool of conjunctival in vivo cytology in the diagnosis of dry eye ocular surface disease","volume":"16","author":"Kojima T.","year":"2010","unstructured":"Kojima T., , Matsumoto Y., , Dogru M., , and Tsubota K. The application of in vivo laser scanning confocal microscopy as a tool of conjunctival in vivo cytology in the diagnosis of dry eye ocular surface disease. Mol Vis, 16:2457, 2010.","journal-title":"Mol Vis"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0818"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.09.019"},{"key":"e_1_3_4_28_2","first-page":"211","article-title":"Lid-wiper epitheliopathy and dry-eye symptoms in contact lens wearers1","volume":"28","author":"Korb D.R.","year":"2002","unstructured":"Korb D.R., , Greiner J.V., , Herman J.P., et al. Lid-wiper epitheliopathy and dry-eye symptoms in contact lens wearers1. Eye Contact Lens, 28:211\u2013216, 2002.","journal-title":"Eye Contact Lens"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e318188896b"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.18.s1.20.x"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-010-0221-5"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICL.0000000000000558"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0883"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2256"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/112067210301300201"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(88)33009-5"},{"key":"e_1_3_4_37_2","first-page":"563","article-title":"Immune profile of squamous metaplasia development in autoimmune regulator-deficient dry eye","volume":"15","author":"Chen Y.T.","year":"2009","unstructured":"Chen Y.T., , Li S., , Nikulina K., , Porco T., , Gallup M., , and McNamara N. Immune profile of squamous metaplasia development in autoimmune regulator-deficient dry eye. Mol Vis, 15:563\u2013576, 2009.","journal-title":"Mol Vis"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4677"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1983.01040020286025"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(84)90186-7"},{"key":"e_1_3_4_41_2","first-page":"1004","article-title":"Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome","volume":"43","author":"Argueso P.","year":"2002","unstructured":"Argueso P., , Balaram M., , Spurr-Michaud S., , Keutmann H.T., , Dana M.R., , and Gipson I.K. Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci, 43:1004\u20131011, 2002.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00165940"}],"container-title":["Journal of Ocular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jop.2018.0130","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2018.0130","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2018.0130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:42:56Z","timestamp":1777646576000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jop.2018.0130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,7,1]]}},"alternative-id":["10.1089\/jop.2018.0130"],"URL":"https:\/\/doi.org\/10.1089\/jop.2018.0130","relation":{},"ISSN":["1080-7683","1557-7732"],"issn-type":[{"value":"1080-7683","type":"print"},{"value":"1557-7732","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}