{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:43:20Z","timestamp":1775267000834,"version":"3.50.1"},"reference-count":49,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"He Eye Specialist Hospital, Shenyang, China","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,1,30]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The lipid layer of the tear film is critical to maintaining the integrity of the tear film and absence in the tear film lipid layer (TFLL) is one of the main causes of evaporative dry eye (EDE) in dry eye disease patients, resulting in excessive evaporation (so-called hyperevaporative dry eye). This study protocol will be designed to assess and compare the effects of intense pulsed light (IPL), heated eye mask (HEM), vectored thermal pulsation system (VTPS) and eyelid massage device (EMD) for improving signs and symptoms of EDE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Patients with EDE will be randomly divided into IPL, HEM, VTPS and EMD groups and will be followed up for 6\u2009weeks. The primary outcome measure will be non-invasive tear breakup time (NITBUT). The secondary outcome measures will include, TFLL score, meibomian gland quality and expressibility change from baseline conjunctivocorneal staining with fluorescein and lissamine, tear meniscus height, conjunctival hyperaemia (redness score) and ocular surface disease index questionnaire. Additionally, adverse events will be monitored and documented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval number: IRB(2023)K019.01. The findings will be shared regardless of the effect\u2019s direction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05923528\">NCT05923528<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-078727","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:40:50Z","timestamp":1708994450000},"page":"e078727","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of non-pharmaceutical treatments for evaporative dry eye: a randomised controlled study protocol"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05923528","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jiayan","family":"Chen","sequence":"first","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghao","family":"Qin","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sile","family":"Yu","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"},{"name":"He University, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Moore","sequence":"additional","affiliation":[{"name":"Cathedral Eye Clinic, Belfast, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0848-827X","authenticated-orcid":false,"given":"Emmanuel Eric","family":"Pazo","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingru","family":"He","sequence":"additional","affiliation":[{"name":"He Eye Specialist Hospital, Shenyang, Liaoning, China"},{"name":"He University, Shenyang, Liaoning, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"2025120521451424000_14.2.e078727.1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6997c"},{"key":"2025120521451424000_14.2.e078727.2","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8091439","article-title":"Dry eye disease: emerging approaches to disease analysis and therapy","volume":"8","author":"Heidari","year":"2019","journal-title":"J Clin Med"},{"key":"2025120521451424000_14.2.e078727.3","doi-asserted-by":"crossref","first-page":"101499","DOI":"10.1016\/j.clae.2021.101499","article-title":"Tear film Interferometry assessment after intense pulsed light in dry eye disease: a randomized, single masked, sham-controlled study","volume":"45","author":"Song","year":"2022","journal-title":"Cont Lens Anterior Eye"},{"key":"2025120521451424000_14.2.e078727.4","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/01.ico.0000208822.70732.25","article-title":"Efficacy of a new warm moist air device on tear functions of patients with simple Meibomian gland dysfunction","volume":"25","author":"Matsumoto","year":"2006","journal-title":"Cornea"},{"key":"2025120521451424000_14.2.e078727.5","first-page":"189","article-title":"Comparison between heated eye mask and intense pulsed light treatment for contact lens-related dry eye","volume":"40","author":"Xu","year":"2022","journal-title":"Photobiomodul Photomed Laser Surg"},{"key":"2025120521451424000_14.2.e078727.6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40123-021-00418-2","article-title":"Management of post-LASIK dry eye with intense pulsed light in combination with 0.1% sodium hyaluronate and heated eye mask","volume":"11","author":"Wu","year":"2022","journal-title":"Ophthalmol Ther"},{"key":"2025120521451424000_14.2.e078727.7","doi-asserted-by":"publisher","DOI":"10.1097\/01.ICL.0000060998.20142.8D"},{"key":"2025120521451424000_14.2.e078727.8","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.clae.2019.07.008","article-title":"Randomised trial of the clinical utility of an eyelid massage device for the management of Meibomian gland dysfunction","volume":"42","author":"Wang","year":"2019","journal-title":"Cont Lens Anterior Eye"},{"key":"2025120521451424000_14.2.e078727.9","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.10145"},{"key":"2025120521451424000_14.2.e078727.10","doi-asserted-by":"crossref","first-page":"101449","DOI":"10.1016\/j.clae.2021.101449","article-title":"Treatment of contact lens related dry eye with intense pulsed light","volume":"45","author":"Yang","year":"2022","journal-title":"Cont Lens Anterior Eye"},{"key":"2025120521451424000_14.2.e078727.11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40123-021-00418-2","article-title":"Management of post-LASIK dry eye with intense pulsed light in combination with 0.1% sodium Hyaluronate and heated eye mask","volume":"11","author":"Wu","year":"2022","journal-title":"Ophthalmol Ther"},{"key":"2025120521451424000_14.2.e078727.12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajo.2017.08.021","article-title":"Analysis of cytokine levels in tears and clinical correlations after intense pulsed light treating meibomian gland dysfunction","volume":"183","author":"Liu","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.13","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000028166","article-title":"Factors influencing the clinical outcomes of intense pulsed light for Meibomian gland dysfunction","volume":"100","author":"Chen","year":"2021","journal-title":"Medicine (Baltimore)"},{"key":"2025120521451424000_14.2.e078727.14","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/02713683.2017.1406525","article-title":"Changes in the meibomian gland after exposure to intense pulsed light in Meibomian gland dysfunction (MGD) patients","volume":"43","author":"Yin","year":"2018","journal-title":"Curr Eye Res"},{"key":"2025120521451424000_14.2.e078727.15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1089\/pho.2010.2867","article-title":"Effects of intense pulsed light on the biological properties and ultrastructure of skin Dermal fibroblasts: potential roles in photoaging","volume":"29","author":"Cao","year":"2011","journal-title":"Photomed Laser Surg"},{"key":"2025120521451424000_14.2.e078727.16","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/lsm.23183","article-title":"Beneficial effect of intense pulsed light on the wound healing in diabetic rats","volume":"52","author":"Jeng","year":"2020","journal-title":"Lasers Surg Med"},{"key":"2025120521451424000_14.2.e078727.17","first-page":"444","article-title":"Subjective quality of vision in evaporative dry eye patients after intense pulsed light","volume":"38","author":"Fan","year":"2020","journal-title":"Photobiomodul Photomed Laser Surg"},{"key":"2025120521451424000_14.2.e078727.18","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s40123-023-00649-5","article-title":"Managing severe evaporative dry eye with intense pulsed light therapy","volume":"12","author":"Qin","year":"2023","journal-title":"Ophthalmol Ther"},{"key":"2025120521451424000_14.2.e078727.19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.clae.2019.09.005","article-title":"Effect of the bruder moist heat eye compress on contact lens discomfort in contact lens wearers: an open-label randomized clinical trial","volume":"42","author":"Tichenor","year":"2019","journal-title":"Cont Lens Anterior Eye"},{"key":"2025120521451424000_14.2.e078727.20","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6514"},{"key":"2025120521451424000_14.2.e078727.21","doi-asserted-by":"crossref","first-page":"8396503","DOI":"10.1155\/2021\/8396503","article-title":"Screening evaporative dry eyes severity using an infrared image","volume":"2021","author":"Zhang","year":"2021","journal-title":"J Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.22","unstructured":"Borchman D , Foulks G , Yappert M , et al . Spectroscopic evaluation of human tear lipids. Elsevier,"},{"key":"2025120521451424000_14.2.e078727.23","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1631\/jzus.B1900091","article-title":"Eyelid margin cleaning using deep cleaning device for the treatment of Meibomian gland dysfunction-associated dry eye: a preliminary investigation","volume":"20","author":"Xie","year":"2019","journal-title":"J Zhejiang Univ Sci B"},{"key":"2025120521451424000_14.2.e078727.24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3109\/02713683.2010.509529","article-title":"A novel thermodynamic treatment for Meibomian gland dysfunction","volume":"36","author":"Friedland","year":"2011","journal-title":"Current Eye Research"},{"key":"2025120521451424000_14.2.e078727.25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00417-021-05363-1","article-title":"Efficacy and safety of a Vectored thermal pulsation system (Lipiflow\u00ae) in the treatment of meibomian gland dysfunction: a systematic review and meta-analysis","volume":"260","author":"Hu","year":"2022","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.26","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"2025120521451424000_14.2.e078727.27","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1007\/s10792-021-01802-4","article-title":"Repeatability of non-invasive keratograph break-up time measurements obtained using Oculus Keratograph 5m","volume":"41","author":"Garc\u00eda-Marqu\u00e9s","year":"2021","journal-title":"Int Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.28","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1007\/s10792-022-02287-5","article-title":"Preoperative dry eyes disease in cataract patients with deficient tear break up time: evaluation of OSDI questionnaire, its Subcategories and Keratograph 5m device results","volume":"42","author":"Fydanaki","year":"2022","journal-title":"Int Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2010.07.019"},{"key":"2025120521451424000_14.2.e078727.30","doi-asserted-by":"publisher","DOI":"10.1364\/JOSAA.23.002097"},{"key":"2025120521451424000_14.2.e078727.31","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5359-5_50"},{"key":"2025120521451424000_14.2.e078727.32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ajo.2016.06.025","article-title":"Development of definitive and reliable grading scales for meibomian gland dysfunction","volume":"169","author":"Arita","year":"2016","journal-title":"Am J Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.33","doi-asserted-by":"crossref","first-page":"834","DOI":"10.18240\/ijo.2021.06.07","article-title":"Reliability of Chinese web-based ocular surface disease index questionnaire in dry eye patients: a randomized, crossover study","volume":"14","author":"Zhang","year":"2021","journal-title":"Int J Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.34","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.jtos.2019.08.008","article-title":"The development and evaluation of the new ocular surface disease Index-6","volume":"17","author":"Pult","year":"2019","journal-title":"Ocul Surf"},{"key":"2025120521451424000_14.2.e078727.35","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8027"},{"key":"2025120521451424000_14.2.e078727.36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jtos.2016.09.003","article-title":"New perspectives on dry eye definition and diagnosis: a consensus report by the Asia dry eye society","volume":"15","author":"Tsubota","year":"2017","journal-title":"Ocul Surf"},{"key":"2025120521451424000_14.2.e078727.37","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jfo.2018.03.007","article-title":"Assessment of ocular redness measurements obtained with keratograph 5m and correlation with subjective grading scales","volume":"41","author":"P\u00e9rez-Bartolom\u00e9","year":"2018","journal-title":"J Fr Ophtalmol"},{"key":"2025120521451424000_14.2.e078727.38","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e3180339f6e"},{"key":"2025120521451424000_14.2.e078727.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2010.10.033"},{"key":"2025120521451424000_14.2.e078727.40","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-0484(99)80025-3"},{"key":"2025120521451424000_14.2.e078727.41","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2023-073055","article-title":"Protocol for a parallel assignment prospective, randomised, comparative trial to evaluate the safety and efficacy of intense pulsed light (IPL) combined with 3% Diquafosol (DQS) ophthalmic solution in dry eye syndrome","volume":"13","author":"Chen","year":"2023","journal-title":"BMJ Open"},{"key":"2025120521451424000_14.2.e078727.42","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-052488","article-title":"Clinical efficacy of Diquafosol sodium 3% versus Hyaluronic acid 0.1% in patients with dry eye disease after cataract surgery: a protocol for a single-centre, randomised controlled trial","volume":"12","author":"Miura","year":"2022","journal-title":"BMJ Open"},{"key":"2025120521451424000_14.2.e078727.43","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.clae.2017.09.001","article-title":"Drugs \u2013 do we need them? Applications of non-pharmaceutical therapy in anterior eye disease: a review","volume":"40","author":"Mandal","year":"2017","journal-title":"Cont Lens Anterior Eye"},{"key":"2025120521451424000_14.2.e078727.44","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6997g"},{"key":"2025120521451424000_14.2.e078727.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2011.03.003"},{"key":"2025120521451424000_14.2.e078727.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2011.03.003"},{"key":"2025120521451424000_14.2.e078727.47","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318239aaea"},{"key":"2025120521451424000_14.2.e078727.48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00417-021-05363-1","article-title":"Efficacy and safety of a Vectored thermal pulsation system (Lipiflow\u00ae) in the treatment of Meibomian gland dysfunction: a systematic review and meta-analysis","volume":"260","author":"Hu","year":"2022","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2025120521451424000_14.2.e078727.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.clae.2007.07.008"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-078727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T05:45:25Z","timestamp":1764999925000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-078727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,26]]},"published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1136\/bmjopen-2023-078727"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-078727","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]}}}