{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:53:53Z","timestamp":1793328833648,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: To investigate the association of meibomian gland dysfunction (MGD) and ocular surface exposure with tear film instability in untreated thyroid eye disease (TED) patients. Methods: A cross-sectional study of TED patients from September 2020 to September 2022 was conducted. Ocular surface parameters included ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive tear break-up time (NITBUT), partial blinking rate, lipid layer thickness (LLT), meibomian gland dropout (meiboscore), Schirmer\u2019s test, and corneal punctate epithelial erosions (PEE). Ocular surface exposure was assessed by the margin reflex distances of the upper and lower eyelid (MRD1 and MRD2), the amount of exophthalmos, lateral flare, and lagophthalmos. Results: In total, 152 eyes from 76 TED patients (64 females and 12 males, age 42.99 \u00b1 12.28 years) and 93 eyes from 61 healthy controls (51 females and 10 males, age 43.52 \u00b1 17.93 years) were examined. Compared with control eyes, TED eyes had higher OSDI, TMH, LLT, and PEE; shorter NITBUT; and worse meiboscore (all p &lt; 0.05). They also had larger amounts of exophthalmos, longer MRD1, more lateral flare, and lagophthalmos. Multivariate analysis identified an association of the tear film instability with lagophthalmos (\u03b2 = \u22121.13, 95%CI: \u22122.08, \u22120.18) and severe MGD in the lower eyelid (\u03b2 = \u22125.01, 95%CI = \u22127.59, \u22122.43). Conclusions: Dry eye in TED is mainly manifested as evaporative dry eye disease. Severe lower eyelid MGD and worse lagophthalmos were significantly associated with tear film instability in treatment-naive TED patients.<\/jats:p>","DOI":"10.3390\/jcm12093066","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T02:31:05Z","timestamp":1682303465000},"page":"3066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ocular Surface Changes in Treatment-Naive Thyroid Eye Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Xulin","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-2060","authenticated-orcid":false,"given":"Kenneth Ka Hei","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatema Mohamed Ali Abdulla","family":"Aljufairi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Ophthalmology, Salmaniya Medical Complex, Government Hospitals, Manama 435, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-6280","authenticated-orcid":false,"given":"Wanxue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-4274","authenticated-orcid":false,"given":"Zhichao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanson Yiu Man","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Statistics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Statistics, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4407-6907","authenticated-orcid":false,"given":"Clement Chee Yung","family":"Tham","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Pui","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-1323","authenticated-orcid":false,"given":"Kelvin Kam Lung","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"G43","DOI":"10.1530\/EJE-21-0479","article-title":"The 2021 European Group on Graves\u2019 orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves\u2019 orbitopathy","volume":"185","author":"Bartalena","year":"2021","journal-title":"Eur. J. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1001\/jamaophthalmol.2022.1002","article-title":"Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark","volume":"140","author":"Boulakh","year":"2022","journal-title":"JAMA Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.4103\/ijo.IJO_2228_21","article-title":"Triamcinolone acetonide injection in the treatment of upper eyelid retraction in Graves\u2019 ophthalmopathy evaluated by 3.0 Tesla magnetic resonance imaging","volume":"70","author":"Duan","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.4103\/ijo.IJO_3217_21","article-title":"Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management","volume":"70","author":"Yu","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S2213-8587(21)00056-5","article-title":"Teprotumumab for patients with active thyroid eye disease: A pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials","volume":"9","author":"Kahaly","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wu, H., Luo, B., Wang, Q., Zhao, Y., Yuan, G., Liu, P., Zhai, L., Lv, W., and Zhang, J. (2022). Functional and Morphological Brain Alterations in Dysthyroid Optic Neuropathy: A Combined Resting-State fMRI and Voxel-Based Morphometry Study. J. Magn. Reson. Imaging JMRI.","DOI":"10.1002\/jmri.28534"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1210\/clinem\/dgac230","article-title":"Measuring Health-Related Quality of Life in Thyroid Eye Disease","volume":"107","author":"Sharma","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/ICO.0000000000002753","article-title":"Impact of Graves Disease on Ocular Surface and Corneal Epithelial Thickness in Patients with and without Graves Orbitopathy","volume":"41","author":"Carreira","year":"2022","journal-title":"Cornea"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3109\/02713683.2010.526285","article-title":"Ocular surface and dry eye in Graves\u2019 disease","volume":"36","author":"Takmaz","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/sj.eye.6703101","article-title":"Prevalence of dry eye among adult Chinese in the Beijing Eye Study","volume":"23","author":"Jie","year":"2009","journal-title":"Eye"},{"key":"ref_11","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":"ref_12","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jtos.2017.05.001","article-title":"TFOS DEWS II Diagnostic Methodology report","volume":"15","author":"Wolffsohn","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_13","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":"ref_14","doi-asserted-by":"crossref","first-page":"100842","DOI":"10.1016\/j.preteyeres.2020.100842","article-title":"Advances in the diagnosis and treatment of dry eye","volume":"78","author":"Kojima","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Netto, A.R.T., Hurst, J., Bartz-Schmidt, K.U., and Schnichels, S. (2022). Porcine Corneas Incubated at Low Humidity Present Characteristic Features Found in Dry Eye Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094567"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101770","DOI":"10.1016\/j.clae.2022.101770","article-title":"Estimates of dry eye disease in Saudi Arabia based on a short questionnaire of prevalence, symptoms, and risk factors: The Twaiq Mountain Eye Study I","volume":"46","author":"Alkhaldi","year":"2022","journal-title":"Contact Lens Anterior Eye J. Br. Contact Lens Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jtos.2022.02.001","article-title":"Ocular surface disease in thyroid eye disease: A narrative review","volume":"24","author":"Rana","year":"2022","journal-title":"Ocul. Surf."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kim, S.E., Yang, H.J., and Yang, S.W. (2020). Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-019-1301-0"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.survophthal.2019.08.007","article-title":"Management of meibomian gland dysfunction: A review","volume":"65","author":"Sabeti","year":"2020","journal-title":"Surv. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/S0002-9394(14)72787-4","article-title":"Diagnostic criteria for Graves\u2019 ophthalmopathy","volume":"119","author":"Bartley","year":"1995","journal-title":"Am. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Paik, J.S., Han, K., Yang, S.W., Park, Y., Na, K., Cho, W., Jung, S.K., and Kim, S. (2020). Blepharoptosis among Korean adults: Age-related prevalence and threshold age for evaluation. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-020-01350-y"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1038\/s41433-018-0022-6","article-title":"Change in eyelid parameters after orbital decompression in thyroid-associated orbitopathy","volume":"32","author":"Park","year":"2018","journal-title":"Eye"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8630","DOI":"10.1167\/iovs.11-8027","article-title":"Rasch analysis of the Ocular Surface Disease Index (OSDI)","volume":"52","author":"Dougherty","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1097\/ICO.0b013e3182a7f3e1","article-title":"Evaluation of lipid layer thickness measurement of the tear film as a diagnostic tool for Meibomian gland dysfunction","volume":"32","author":"Finis","year":"2013","journal-title":"Cornea"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.ophtha.2007.06.031","article-title":"Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population","volume":"115","author":"Arita","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.clae.2020.02.011","article-title":"Introducing a novel in vivo method to access visual performance during dewetting process of contact lens surface","volume":"43","author":"Kolbe","year":"2020","journal-title":"Contact Lens Anterior Eye J. Br. Contact Lens Assoc."},{"key":"ref_27","first-page":"809","article-title":"Effects of Lycium barbarum (goji berry) on dry eye disease in rats","volume":"17","author":"Chien","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jcjo.2015.05.012","article-title":"Meibomian gland dysfunction in Graves\u2019 orbitopathy","volume":"50","author":"Kim","year":"2015","journal-title":"Can. J. Ophthalmol. J. Can. D\u2019ophtalmologie"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/08820538.2021.1937662","article-title":"Evaluation of Meibomian Gland Loss and Ocular Surface Changes in Patients with Mild and Moderate-to-Severe Graves\u2019 Ophthalmopathy","volume":"37","year":"2022","journal-title":"Semin. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ijrobp.2019.07.015","article-title":"Prospective Assessment of Patient-Reported Dry Eye Syndrome after Whole Brain Radiation","volume":"105","author":"Wang","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Takahashi, Y., Vaidya, A., and Kakizaki, H. (2022). Changes in Dry Eye Status after Steroid Pulse and Orbital Radiation Therapies in Active Thyroid Eye Disease. J. Clin. Med., 11.","DOI":"10.3390\/jcm11133604"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1367-0484(01)00005-4","article-title":"The tear (lacrimal) meniscus height in human eyes: A useful clinical measure or an unusable variable sign?","volume":"25","author":"Doughty","year":"2002","journal-title":"Contact Lens Anterior Eye J. Br. Contact Lens Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1167\/iovs.14-16313","article-title":"The Effects of Increasing Ocular Surface Stimulation on Blinking and Tear Secretion","volume":"56","author":"Wu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1167\/iovs.13-13780","article-title":"The effects of increasing ocular surface stimulation on blinking and sensation","volume":"55","author":"Wu","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.5114\/pjr.2019.84096","article-title":"Assessment of lacrimal glands in thyroid eye disease with diffusion-weighted magnetic resonance imaging","volume":"84","author":"Razek","year":"2019","journal-title":"Pol. J. Radiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Inoue, S., Kawashima, M., Arita, R., Kozaki, A., and Tsubota, K. (2020). Investigation of Meibomian Gland Function and Dry Eye Disease in Patients with Graves\u2019 Ophthalmopathy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092814"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jcjo.2017.11.006","article-title":"Functional and structural evaluation of the meibomian gland using a LipiView interferometer in thyroid eye disease","volume":"53","author":"Park","year":"2018","journal-title":"Can. J. Ophthalmol. J. Can. D\u2019ophtalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/ICO.0000000000000092","article-title":"Comparison of meibomian gland loss and expressed meibum grade between the upper and lower eyelids in patients with obstructive meibomian gland dysfunction","volume":"33","author":"Eom","year":"2014","journal-title":"Cornea"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wang, C.Y., Ho, R.W., Fang, P.C., Yu, H.J., Chien, C.C., Hsiao, C.C., and Kuo, M.T. (2018). The function and morphology of Meibomian glands in patients with thyroid eye disease: A preliminary study. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0763-9"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1167\/iovs.10-6997b","article-title":"The international workshop on meibomian gland dysfunction: Report of the definition and classification subcommittee","volume":"52","author":"Nelson","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","first-page":"327","article-title":"Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease","volume":"24","author":"Farid","year":"2016","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.4103\/ijo.IJO_3017_21","article-title":"Lagophthalmos: An etiological lookout to frame the decision for management","volume":"70","author":"Rita","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ophtha.2010.04.037","article-title":"Blink lagophthalmos and dry eye keratopathy in patients with non-facial palsy: Clinical features and management with upper eyelid loading","volume":"118","author":"Patel","year":"2011","journal-title":"Ophthalmology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3066\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:50Z","timestamp":1760124110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,23]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12093066"],"URL":"https:\/\/doi.org\/10.3390\/jcm12093066","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,23]]}}}