{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:16:42Z","timestamp":1774948602217,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability.<\/jats:p>","DOI":"10.3390\/cells15070622","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Cellular Effects of Therapies for Thyroid Eye Disease on Ocular Surface and Adnexal Homeostasis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-2906","authenticated-orcid":false,"given":"Monika","family":"Sarnat-Kucharczyk","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical Sciences, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Ophthalmology, Professor K. Gibi\u0144ski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-1803","authenticated-orcid":false,"given":"Wojciech","family":"Lubo\u0144","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical Sciences, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Ophthalmology, Professor K. Gibi\u0144ski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-3460","authenticated-orcid":false,"given":"Dorota","family":"Wygl\u0119dowska-Promie\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical Sciences, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Ophthalmology, Professor K. Gibi\u0144ski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-955X","authenticated-orcid":false,"given":"Adrian","family":"Sm\u0119dowski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical Sciences, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Ophthalmology, Professor K. Gibi\u0144ski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Pediatric Ophthalmology, Faculty of Medical Sciences, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"GlaucoTech Co., Ltd., 40-282 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","first-page":"25158414251393119","article-title":"Evaluation of Clinical and Ocular Surface Changes in Thyroid Eye Disease: Impact of Treatment and Risk Factors","volume":"17","author":"Arslan","year":"2025","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kulbay, M., Tanya, S.M., Tuli, N., Dahoud, J., Dahoud, A., Alsaleh, F., Arthurs, B., and El-Hadad, C. (2024). A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches. Int. J. 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