{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T17:07:07Z","timestamp":1779988027959,"version":"3.53.1"},"reference-count":156,"publisher":"Wiley","issue":"S291","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006286","name":"Kongelig Hofbuntmager Aage Bangs Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ENGLISH SUMMARY<\/jats:title>\n                  <jats:p>Atopic keratoconjunctivitis (AKC) is a severe ocular surface disease (OSD) that significantly affects patients' quality of life and can lead to blindness. AKC is associated with atopic dermatitis (AD), a common chronic inflammatory skin disease affecting both children and adults. This thesis investigates the prevalence, clinical features and underlying mechanisms of OSD and AKC in AD patients, aiming to improve the understanding and management of these conditions.<\/jats:p>\n                  <jats:p>Two distinct questionnaire studies were conducted to assess the association of OSD symptoms in AD patients within the general population (I) and to identify risk factors associated with OSD in AD patients (II). To further explore AKC, a cohort of AD patients with and without AKC was established. This cohort underwent clinical examinations and tear fluid analyses to characterize the clinical phenotype and cytokine profiles associated with AKC (III). Complementary in\u00a0vitro studies on conjunctival goblet cells (GCs) were also conducted. These experiments explored the effects of key cytokines involved in AD (interleukin (IL)\u201013, IL\u20104 and interferon\u2010gamma (IFN\u2010\u03b3)) on GC proliferation and mucin production. The findings aimed to provide insights into the roles of these cytokines in GC function, which is important for maintaining ocular surface homeostasis (IV).<\/jats:p>\n                  <jats:p>In a study involving 57\u2009464 participants, OSD symptoms were found to be associated with both current AD (adjusted odds ratio (aOR): 1.16) and previous AD (aOR: 1.19), revealing a significantly higher occurrence of symptoms among individuals with AD (I). Among 7044\u2009AD patients, the prevalence of current conjunctivitis was 12.7%, while the lifetime prevalence was 66.6% (II). Additionally, the prevalence of OSD was associated with AD severity and the occurrence of atopic comorbidities (II). Moderate\u2013severe AKC was linked to higher levels of IL\u20104, IL\u201013 and IFN\u2010\u03b3 in the tear fluid, as well as more severe AD, and higher occurrence of atopic comorbidities (III). Studies of GC cultures revealed contrasting effects of IL\u201013, IL\u20104 and IFN\u2010\u03b3, with IL\u201013 and IL\u20104 promoting GC proliferation and increasing mucin messenger ribonucleic acid (mRNA) expression (IV).<\/jats:p>\n                  <jats:p>The findings presented in this thesis highlight the strong association between AD and OSD, showing that the risk of OSD is increased by the cumulative burden of AD. Furthermore, the results reveal that increased AKC severity is linked to altered cytokine levels in the tear fluid, specifically elevated levels of IL\u201013, IL\u20104 and IFN\u2010\u03b3. Additionally, IL\u201013, IL\u20104 and IFN\u2010\u03b3 demonstrate opposing effects on conjunctival GC function, suggesting these cytokines play essential roles in modulating ocular surface integrity in AKC. This research contributes to the growing understanding of the link between AD and OSD, identifying potential biomarkers and therapeutic targets for improved management of AKC.<\/jats:p>","DOI":"10.1111\/aos.70165","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T16:59:36Z","timestamp":1779987576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ocular surface disease in atopic dermatitis"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-4980","authenticated-orcid":false,"given":"Pernille May","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Copenhagen University Hospital \u2014 Rigshospitalet\u2010Glostrup  Glostrup Denmark"},{"name":"Eye Translational Research Unit (EyeTRU), Department of Drug Design and Pharmacology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/cea.14127","article-title":"Ocular surface disease is common in moderate\u2010to\u2010severe atopic dermatitis patients","volume":"52","author":"Achten R.E.","year":"2022","journal-title":"Clinical and Experimental Allergy"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/bjd.17869","article-title":"Conjunctivitis in dupilumab clinical trials","volume":"181","author":"Akinlade B.","year":"2019","journal-title":"British Journal of Dermatology"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jtos.2019.12.006","article-title":"Immune\u2014goblet cell interaction in the conjunctiva","volume":"18","author":"Alam J.","year":"2020","journal-title":"The Ocular Surface"},{"key":"e_1_2_14_5_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/jdv.15424","article-title":"Demographics, healthcare utilization and drug use in children and adults with atopic dermatitis in Denmark: a population\u2010based cross\u2010sectional study","volume":"33","author":"Andersen Y.M.F.","year":"2019","journal-title":"Journal of the European Academy of Dermatology and Venereology"},{"key":"e_1_2_14_6_1","first-page":"21","article-title":"The origin of keratopathy in chronic allergic eye disease: a histopathological study","volume":"7","author":"Bacon A.S.","year":"1993","journal-title":"Eye"},{"key":"e_1_2_14_7_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18050978","article-title":"Goblet cells contribute to ocular surface immune tolerance\u2014implications for dry eye disease","volume":"18","author":"Barbosa F.L.","year":"2017","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_14_8_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1167\/tvst.9.3.29","article-title":"Dupilumab\u2010associated mucin deficiency (DAMD)","volume":"9","author":"Barnett B.P.","year":"2020","journal-title":"Translational Vision Science & Technology"},{"key":"e_1_2_14_9_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jtos.2013.07.003","article-title":"Role of hyperosmolarity in the pathogenesis and Management of dry eye Disease: proceedings of the OCEAN group meeting","volume":"11","author":"Baudouin C.","year":"2013","journal-title":"The Ocular Surface"},{"key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1136\/bjophthalmol-2013-304619","article-title":"Diagnosing the severity of dry eye: a clear and practical algorithm","volume":"98","author":"Baudouin C.","year":"2014","journal-title":"British Journal of Ophthalmology"},{"key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.preteyeres.2018.11.007","article-title":"Reconsidering the central role of mucins in dry eye and ocular surface diseases","volume":"71","author":"Baudouin C.","year":"2019","journal-title":"Progress in Retinal and Eye Research"},{"key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.jaci.2007.08.067","article-title":"Toward a major risk factor for atopic eczema: meta\u2010analysis of filaggrin polymorphism data","volume":"120","author":"Baurecht H.","year":"2007","journal-title":"The Journal of Allergy and Clinical Immunology"},{"key":"e_1_2_14_13_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s40257-019-00455-5","article-title":"Ocular Co\u2010morbidities of atopic dermatitis. 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