{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:40:23Z","timestamp":1791463223295,"version":"4.3.4"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019081","name":"Aerie Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Ocular Surface"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.jtos.2022.08.003","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T22:03:39Z","timestamp":1660341819000},"page":"166-173","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"special_numbering":"C","title":["A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)"],"prefix":"10.1016","volume":"26","author":[{"given":"David L.","family":"Wirta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Senchyna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber E.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene B.","family":"McLaurin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W.","family":"Ousler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Hollander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtos.2022.08.003_bib1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib3","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/eye.2016.186","article-title":"Depression and anxiety in dry eye disease: a systematic review and meta-analysis","volume":"30","author":"Wan","year":"2016","journal-title":"Eye"},{"key":"10.1016\/j.jtos.2022.08.003_bib4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12886-018-0919-7","article-title":"Dry eye symptoms and impact on vision-related function across International Task Force guidelines severity levels in the United States","volume":"18","author":"Barber","year":"2018","journal-title":"BMC Ophthalmol"},{"key":"10.1016\/j.jtos.2022.08.003_bib5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ajo.2013.12.023","article-title":"Dry eye in the Beaver Dam Offspring Study: prevalence, risk factors, and health-related quality of life","volume":"157","author":"Paulsen","year":"2014","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jtos.2022.08.003_bib6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jtos.2021.10.007","article-title":"The vision-related burden of dry eye","volume":"23","author":"Morthen","year":"2022","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib7","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1136\/bjophthalmol-2013-304619","article-title":"ODISSEY European Consensus Group members. Diagnosing the severity of dry eye: a clear and practical algorithm","volume":"98","author":"Baudouin","year":"2014","journal-title":"Br J Ophthalmol"},{"issue":"Suppl 1","key":"10.1016\/j.jtos.2022.08.003_bib8","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1136\/bjo.2009.168849","article-title":"Emerging treatment paradigms of ocular surface disease: proceedings of the Ocular Surface Workshop","volume":"94","author":"Rolando","year":"2010","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.jtos.2022.08.003_bib9","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","volume":"5","year":"2007","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II epidemiology report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40135-013-0009-1","article-title":"Dry eye disease: impact on quality of life and vision","volume":"1","author":"Uchino","year":"2013","journal-title":"Curr Ophthalmol Rep"},{"key":"10.1016\/j.jtos.2022.08.003_bib12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3390\/jcm11010108","article-title":"New perspectives in the pathophysiology and treatment of pain in patients with dry eye disease","volume":"11","author":"Giannaccare","year":"2021","journal-title":"J Clin Med"},{"key":"10.1016\/j.jtos.2022.08.003_bib13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s40135-015-0073-9","article-title":"What causes eye pain?","volume":"3","author":"Belmonte","year":"2015","journal-title":"Curr Ophthalmol Rep"},{"key":"10.1016\/j.jtos.2022.08.003_bib14","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib15","first-page":"1","article-title":"ONSET-2 Study Group. Efficacy and safety of OC-01 (varenicline solution) nasal spray on signs and symptoms of dry eye disease: the ONSET-2 phase 3 randomized trial","author":"Wirta","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2022.08.003_bib16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1021\/cn100102c","article-title":"Chemosensory properties of the trigeminal system","volume":"2","author":"Viana","year":"2011","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.jtos.2022.08.003_bib17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12886-017-0495-2","article-title":"A novel TRPM8 agonist relieves dry eye discomfort","volume":"17","author":"Yang","year":"2017","journal-title":"BMC Ophthalmol"},{"key":"10.1016\/j.jtos.2022.08.003_bib18","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3390\/ph11040125","article-title":"TRPM8 channels and dry eye","volume":"11","author":"Yang","year":"2018","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.jtos.2022.08.003_bib19","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.neuron.2007.02.024","article-title":"TRPM8 is required for cold sensation in mice","volume":"54","author":"Dhaka","year":"2007","journal-title":"Neuron"},{"key":"10.1016\/j.jtos.2022.08.003_bib20","first-page":"48","article-title":"Cool opportunities to modulate nociception","volume":"20","author":"Abelson","year":"2013","journal-title":"Rev Ophthalmol"},{"key":"10.1016\/j.jtos.2022.08.003_bib21","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.jtos.2022.08.003_bib22","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1542-0124(12)70196-9","article-title":"Methodologies for the study of ocular surface disease","volume":"3","author":"Ousler","year":"2005","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejphar.2013.03.003","article-title":"Targeting TRP channels for pain relief","volume":"716","author":"Brederson","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.jtos.2022.08.003_bib24","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.cub.2006.07.061","article-title":"Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain","volume":"16","author":"Proudfoot","year":"2006","journal-title":"Curr Biol"},{"key":"10.1016\/j.jtos.2022.08.003_bib25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jtos.2017.10.001","article-title":"Neuropathic pain and dry eye","volume":"16","author":"Galor","year":"2018","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib26","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jtos.2020.07.008","article-title":"Capsaicin-induced pain sensitivity in short tear break-up time dry eye","volume":"18","author":"Kaido","year":"2020","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib27","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jtos.2019.12.004","article-title":"Ocular pain response to treatment in dry eye patients","volume":"18","author":"Siedlecki","year":"2020","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jtos.2020.10.004","article-title":"Pain sensitivity and autonomic nervous system parameters as predictors of dry eye symptoms after LASIK","volume":"19","author":"Levitt","year":"2021","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2022.08.003_bib29","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3390\/jcm10020250","article-title":"Topical TRPM8 agonist for relieving neuropathic ocular pain in patients with dry eye: a pilot study","volume":"10","author":"Yoon","year":"2021","journal-title":"J Clin Med"}],"container-title":["The Ocular Surface"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1542012422000751?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1542012422000751?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:48:37Z","timestamp":1761540517000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1542012422000751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":29,"alternative-id":["S1542012422000751"],"URL":"https:\/\/doi.org\/10.1016\/j.jtos.2022.08.003","relation":{},"ISSN":["1542-0124"],"issn-type":[{"value":"1542-0124","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)","name":"articletitle","label":"Article Title"},{"value":"The Ocular Surface","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtos.2022.08.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}