{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:55:21Z","timestamp":1788872121762,"version":"build-2803163510"},"reference-count":35,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aaojournal.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology"],"published-print":{"date-parts":[[2013,6]]},"DOI":"10.1016\/j.ophtha.2012.12.022","type":"journal-article","created":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T21:00:21Z","timestamp":1363122021000},"page":"1158-1165","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":132,"title":["A Randomized, Multicenter Phase 3 Study Comparing 2% Rebamipide (OPC-12759) with 0.1% Sodium Hyaluronate in the Treatment of Dry Eye"],"prefix":"10.1016","volume":"120","clinical-trial-number":[{"clinical-trial-number":"nct00885079","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Shigeru","family":"Kinoshita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Oshiden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Awamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Nakamichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Yokoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ophtha.2012.12.022_bib1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007)","volume":"5","year":"2007","journal-title":"Ocul Surf"},{"key":"10.1016\/j.ophtha.2012.12.022_bib2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3109\/08820538.2010.488568","article-title":"Dry eye disease","volume":"25","author":"de Pinho Tavares","year":"2010","journal-title":"Semin Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1358\/dnp.2008.21.3.1203413","article-title":"Therapeutic targets in dry eye syndrome","volume":"21","author":"Peral","year":"2008","journal-title":"Drug News Perspect"},{"key":"10.1016\/j.ophtha.2012.12.022_bib4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2147\/OPTH.S5555","article-title":"Etiology, prevalence, and treatment of dry eye disease","volume":"3","author":"Gayton","year":"2009","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/ICU.0b013e32833a8c15","article-title":"Impact of dry eye disease and treatment on quality of life","volume":"21","author":"Friedman","year":"2010","journal-title":"Curr Opin Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib6","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1167\/iovs.07-0770","article-title":"The ocular surface: the challenge to enable and protect vision: the Friedenwald lecture","volume":"48","author":"Gipson","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib7","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1136\/bjo.79.11.1007","article-title":"Sodium hyaluronate eyedrops in the treatment of dry eyes","volume":"79","author":"Shimmura","year":"1995","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib8","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1136\/bjo.86.8.879","article-title":"Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjogren's syndrome patients","volume":"86","author":"Aragona","year":"2002","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib9","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1136\/bjo.83.10.1121","article-title":"Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w\/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome","volume":"83","author":"Condon","year":"1999","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib10","series-title":"Preferred Practice Pattern Guidelines. Dry Eye Syndrome. Limited revision","year":"2011"},{"key":"10.1016\/j.ophtha.2012.12.022_bib11","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/00006324-199805000-00022","article-title":"Effects of lacrimal drainage occlusion with nondissolvable intracanalicular plugs on hydrogel contact lens wear","volume":"75","author":"Slusser","year":"1998","journal-title":"Optom Vis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib12","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.ajo.2008.05.016","article-title":"Advances in understanding and managing dry eye disease","volume":"146","author":"Lemp","year":"2008","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib13","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S1350-9462(96)00039-0","article-title":"Ocular mucins: purification, metabolism and functions","volume":"16","author":"Corfield","year":"1997","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ophtha.2012.12.022_bib14","first-page":"299","article-title":"Conjunctival goblet cell density in normal subjects and in dry eye syndromes","volume":"14","author":"Ralph","year":"1975","journal-title":"Invest Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib15","first-page":"2602","article-title":"Alteration of mucin in human conjunctival epithelia in dry eye","volume":"39","author":"Danjo","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib16","first-page":"1004","article-title":"Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome","volume":"43","author":"Argueso","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/978-1-4615-0717-8_52","article-title":"Mucin ophthalmic solution treatment of dry eye","volume":"506","author":"Shigemitsu","year":"2002","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib18","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1007\/s10620-008-0507-4","article-title":"Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test","volume":"54","author":"Iijima","year":"2009","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1586\/egh.10.25","article-title":"Rebamipide: a gastrointestinal protective drug with pleiotropic activities","volume":"4","author":"Naito","year":"2010","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0014-2999(87)90649-2","article-title":"Gastric mucosal protection by OPC-12759, a novel antiulcer compound, in the rat","volume":"142","author":"Yamasaki","year":"1987","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib21","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/01.ico.0000126436.25751.fb","article-title":"Rebamipide increases the amount of mucin-like substances on the conjunctiva and cornea in the N-acetylcysteine-treated in vivo model","volume":"23","author":"Urashima","year":"2004","journal-title":"Cornea"},{"key":"10.1016\/j.ophtha.2012.12.022_bib22","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1089\/jop.2011.0147","article-title":"Rebamipide increases mucin-like substance contents and periodic acid Schiff reagent-positive cells density in normal rabbits","volume":"28","author":"Urashima","year":"2012","journal-title":"J Ocul Pharmacol Ther"},{"key":"10.1016\/j.ophtha.2012.12.022_bib23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1089\/jop.2011.0142","article-title":"Rebamipide increases the mucin-like glycoprotein production in corneal epithelial cells","volume":"28","author":"Takeji","year":"2012","journal-title":"J Ocul Pharmacol Ther"},{"key":"10.1016\/j.ophtha.2012.12.022_bib24","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1016\/j.ophtha.2012.06.052","article-title":"Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study","volume":"119","author":"Kinoshita","year":"2012","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2012.12.022_bib25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2307\/2529712","article-title":"Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial","volume":"31","author":"Pocock","year":"1975","journal-title":"Biometrics"},{"key":"10.1016\/j.ophtha.2012.12.022_bib26","first-page":"221","article-title":"Report of the National Eye Institute\/Industry workshop on Clinical Trials in Dry Eyes","volume":"21","author":"Lemp","year":"1995","journal-title":"CLAO J"},{"key":"10.1016\/j.ophtha.2012.12.022_bib27","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1001\/archophthalmol.2009.103","article-title":"Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies","volume":"127","author":"Schaumberg","year":"2009","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S1542-0124(12)70082-4","article-title":"The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007)","volume":"5","year":"2007","journal-title":"Ocul Surf"},{"key":"10.1016\/j.ophtha.2012.12.022_bib29","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1038\/eye.2011.184","article-title":"Optimizing evaluation of lissamine green parameters for ocular surface staining","volume":"25","author":"Hamrah","year":"2011","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.ophtha.2012.12.022_bib30","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1167\/iovs.07-0635","article-title":"Dry eye diagnosis","volume":"49","author":"Khanal","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2012.12.022_bib31","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0161-6420(99)00176-1","article-title":"Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease","volume":"107","author":"Sall","year":"2000","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2012.12.022_bib32","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF00165940","article-title":"Morphological changes in ocular surface in dry eyes and other disorders by impression cytology","volume":"230","author":"Rivas","year":"1992","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"10.1016\/j.ophtha.2012.12.022_bib33","first-page":"402","article-title":"The effects of topical drugs and preservatives on the tears and corneal epithelium in dry eye","volume":"104","author":"Burstein","year":"1985","journal-title":"Trans Ophthalmol Soc U K"},{"key":"10.1016\/j.ophtha.2012.12.022_bib34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.preteyeres.2010.03.001","article-title":"Preservatives in eyedrops: the good, the bad and the ugly","volume":"29","author":"Baudouin","year":"2010","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ophtha.2012.12.022_bib35","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1185\/030079906X132640","article-title":"Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion","volume":"22","author":"Asbell","year":"2006","journal-title":"Curr Med Res Opin"}],"container-title":["Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642012012031?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642012012031?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T14:03:46Z","timestamp":1758981826000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161642012012031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["S0161642012012031"],"URL":"https:\/\/doi.org\/10.1016\/j.ophtha.2012.12.022","relation":{},"ISSN":["0161-6420"],"issn-type":[{"value":"0161-6420","type":"print"}],"subject":[],"published":{"date-parts":[[2013,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Randomized, Multicenter Phase 3 Study Comparing 2% Rebamipide (OPC-12759) with 0.1% Sodium Hyaluronate in the Treatment of Dry Eye","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ophtha.2012.12.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}