{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:21:24Z","timestamp":1790742084978,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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":[[2022,4]]},"DOI":"10.1016\/j.jtos.2021.12.007","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T17:58:42Z","timestamp":1639591122000},"page":"15-21","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"special_numbering":"C","title":["A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study"],"prefix":"10.1016","volume":"24","author":[{"given":"Hugo","family":"Quiroz-Mercado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everardo","family":"Hernandez-Quintela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuei Hsun","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Nau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtos.2021.12.007_bib1","doi-asserted-by":"crossref","first-page":"9271","DOI":"10.3390\/ijms21239271","article-title":"Defining dry eye from a clinical perspective","volume":"21","author":"Tsubota","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jtos.2021.12.007_bib2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ajo.2017.06.033","article-title":"Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older","volume":"182","author":"Farrand","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib3","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ophtha.2015.10.011","article-title":"Long-term natural history of dry eye disease from the patient's perspective","volume":"123","author":"Lienert","year":"2016","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2021.12.007_bib5","first-page":"704946","article-title":"A comprehensive review on dry eye disease: diagnosis, medical management, recent developments, and future challenges","volume":"2015","author":"Phadatare","year":"2015","journal-title":"Adv Pharm"},{"key":"10.1016\/j.jtos.2021.12.007_bib6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2147\/OPTH.S228838","article-title":"Managing dry eye disease and facilitating realistic patient expectations: a review and appraisal of current therapies","volume":"14","author":"Shen Lee","year":"2020","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib7","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/j.ophtha.2005.05.013","article-title":"Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years","volume":"112","author":"Barber","year":"2005","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib9","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ophtha.2013.09.015","article-title":"Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study","volume":"121","author":"Sheppard","year":"2014","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib10","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/j.ophtha.2015.08.001","article-title":"Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study","volume":"122","author":"Tauber","year":"2015","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.2147\/TCRM.S49754","article-title":"Health claims database study of cyclosporine ophthalmic emulsion treatment patterns in dry eye patients","volume":"9","author":"Stonecipher","year":"2013","journal-title":"Ther Clin Risk Manag"},{"key":"10.1016\/j.jtos.2021.12.007_bib12","article-title":"Comparing the needs and preferences of patients with moderate and severe dry eye symptoms across four countries","volume":"4","author":"Messmer","year":"2019","journal-title":"BMJ Open Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib13","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.2021.12.007_bib14","doi-asserted-by":"crossref","first-page":"C942","DOI":"10.1152\/ajpcell.00275.2015","article-title":"Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjogren's Syndrome","volume":"310","author":"Meng","year":"2016","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.jtos.2021.12.007_bib15","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1242\/jcs.122242","article-title":"Polymeric immunoglobulin receptor traffics through two distinct apically targeted pathways in primary lacrimal gland acinar cells","volume":"126","author":"Xu","year":"2013","journal-title":"J Cell Sci"},{"key":"10.1016\/j.jtos.2021.12.007_bib16","doi-asserted-by":"crossref","first-page":"C507","DOI":"10.1152\/ajpcell.00355.2010","article-title":"Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland","volume":"301","author":"Chiang","year":"2011","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.jtos.2021.12.007_bib17","doi-asserted-by":"crossref","first-page":"C13","DOI":"10.1152\/ajpcell.00330.2007","article-title":"The class V myosin motor, myosin 5c, localizes to mature secretory vesicles and facilitates exocytosis in lacrimal acini","volume":"295","author":"Marchelletta","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.jtos.2021.12.007_bib18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.preteyeres.2009.04.003","article-title":"Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases","volume":"28","author":"Dartt","year":"2009","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.jtos.2021.12.007_bib19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/aos.13844","article-title":"Role of corneal nerves in ocular surface homeostasis and disease","volume":"97","author":"Labetoulle","year":"2019","journal-title":"Acta Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib20","article-title":"A phase 2b randomized trial to evaluate the safety and efficacy of a nicotinic acetylcholine receptor agonist nasal spray on the signs and symptoms of dry eye disease (ONSET-1)","author":"Wirta","year":"2021","journal-title":"Cornea"},{"key":"10.1016\/j.jtos.2021.12.007_bib21","article-title":"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":"Opthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib22","author":"Sealed Envelope Ltd"},{"key":"10.1016\/j.jtos.2021.12.007_bib23","doi-asserted-by":"crossref","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"Pflugfelder","year":"2020","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.jtos.2021.12.007_bib24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3341\/kjo.2011.25.6.369","article-title":"Cyclosporine 0.05% ophthalmic emulsion for dry eye in Korea: a prospective, multicenter, open-label, surveillance study","volume":"25","author":"Byun","year":"2011","journal-title":"Korean J Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib25","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1136\/bjophthalmol-2015-306930","article-title":"Long-term outcome after topical ciclosporin in severe dry eye disease with a 10-year follow-up","volume":"100","author":"Straub","year":"2016","journal-title":"Br J Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3341\/kjo.2018.0116","article-title":"Efficacy of topical cyclosporine nanoemulsion 0.05% compared with topical cyclosporine emulsion 0.05% and diquafosol 3% in dry eye","volume":"33","author":"Park","year":"2019","journal-title":"Korean J Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib27","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.2147\/OPTH.S175065","article-title":"A phase II\/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease","volume":"12","author":"Tauber","year":"2018","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib28","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.jtos.2021.12.007_bib29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ophtha.2016.09.025","article-title":"Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3)","volume":"124","author":"Holland","year":"2017","journal-title":"Ophthalmology"},{"key":"10.1016\/j.jtos.2021.12.007_bib30","doi-asserted-by":"crossref","first-page":"481","DOI":"10.2147\/OPTH.S228070","article-title":"A review of topical cyclosporine a formulations\u2014a disease-modifying agent for keratoconjunctivitis sicca","volume":"14","author":"Jerkins","year":"2020","journal-title":"Clin Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib31","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3390\/pharmaceutics11090460","article-title":"Advanced formulation approaches for ocular drug delivery: state-of-the-art and recent patents","volume":"11","author":"Souto","year":"2019","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.jtos.2021.12.007_bib32","first-page":"2694","article-title":"In vivo confocal microscopy demonstrates intranasal neurostimulation-induced goblet cell alterations in patients with dry eye disease","volume":"58","author":"Dieckmann","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.jtos.2021.12.007_bib33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ajo.2017.03.002","article-title":"Randomized controlled crossover trial comparing the impact of sham or intranasal tear neurostimulation on conjunctival goblet cell degranulation","volume":"177","author":"Gumus","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.jtos.2021.12.007_bib34","first-page":"2673","article-title":"Effect of intranasal neurostimulation on tear protein content in patient with dry eye","volume":"58","author":"Woodward","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.jtos.2021.12.007_bib35","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1542-0124(12)70296-3","article-title":"Basal, reflex, and psycho-emotional tears","volume":"7","author":"Murabe","year":"2009","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jtos.2021.12.007_bib36","doi-asserted-by":"crossref","first-page":"7542929","DOI":"10.1155\/2016\/7542929","article-title":"Review: the lacrimal gland and its role in dry eye","volume":"2016","author":"Conrady","year":"2016","journal-title":"J Ophthalmol"}],"container-title":["The Ocular Surface"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1542012421001464?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1542012421001464?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:45:02Z","timestamp":1761540302000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1542012421001464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":35,"alternative-id":["S1542012421001464"],"URL":"https:\/\/doi.org\/10.1016\/j.jtos.2021.12.007","relation":{},"ISSN":["1542-0124"],"issn-type":[{"value":"1542-0124","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study","name":"articletitle","label":"Article Title"},{"value":"The Ocular Surface","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtos.2021.12.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}