{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:17:56Z","timestamp":1772137076602,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Dry eye disease (DED) is a multifactorial ocular surface disease that markedly diminishes quality of life. Although diabetes mellitus is well-known for its retinal consequences, anterior segment symptoms including dry eye disease are often overlooked. Chronic hyperglycemia causes metabolic, neurovascular, and immunological changes that undermine tear film stability, corneal innervation, and ocular surface integrity. This review seeks to consolidate existing knowledge regarding the concealed impacts of diabetes on ocular surface homeostasis, highlighting processes, diagnostic difficulties, and treatment prospects. Materials and Methods: A narrative review of the literature was performed by searching PubMed for publications from January 2020 to July 2025 using the terms \u201cdiabetic dry eye,\u201d \u201chyperglycemia AND ocular surface,\u201d \u201ctear proteomics AND diabetes,\u201d \u201ccorneal nerves AND diabetes,\u201d and \u201cneurotrophic keratitis.\u201d Eligible studies were experimental research, clinical trials, and translational investigations concerning tear film function, corneal neuropathy, inflammatory indicators, or lacrimal gland dysfunction in diabetes. The exclusion criteria were non-English language, lack of primary data, and inadequate methodological description. Results: Hyperglycemia compromises lacrimal gland functionality, modifies lipid secretion from Meibomian glands, and diminishes corneal nerve density, resulting in neurotrophic deficits. Inflammatory cytokines and oxidative stress compromise epithelial integrity, but proteome alterations in tears serve as sensitive indicators of disease. Diagnosis is impeded by corneal hypoesthesia, resulting in a disconnection between symptoms and findings. Progress in imaging, proteomics, and artificial intelligence may facilitate earlier detection and improved risk assessment. Novel therapeutics, such as neurotrophic drugs, antioxidants, and customized anti-inflammatory approaches, show promise but remain under clinical evaluation. Conclusions: Diabetes-related dry eye disease is a multifaceted and underappreciated condition influenced by systemic metabolic dysfunction. The ocular surface may act as an initial indicator for systemic disease load. Narrative synthesis emphasizes the necessity for customized diagnostic instruments, individualized treatment approaches, and collaborative management. Reconceptualizing diabetic dry eye disease within the context of systemic metabolic care presents prospects for precision medicine strategies that enhance both ocular and systemic results.<\/jats:p>","DOI":"10.3390\/medicina61111992","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"1992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Beyond the Surface: Revealing the Concealed Effects of Hyperglycemia on Ocular Surface Homeostasis and Dry Eye Disease"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2969-8610","authenticated-orcid":false,"given":"Matteo","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6710-2460","authenticated-orcid":false,"given":"Federico","family":"Visalli","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8361","authenticated-orcid":false,"given":"Mutali","family":"Musa","sequence":"additional","affiliation":[{"name":"Department of Optometry, University of Benin, Benin 300283, Nigeria"},{"name":"Department of Ophthalmology, Africa Eye Laser Center Ltd., Benin 300211, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-0786","authenticated-orcid":false,"given":"Rosa","family":"Giglio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Tognetto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Eye Center \u201cG.B. Morgagni-DSV\u201d, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Imperial College Ophthalmic Research Group [ICORG] Unit, Imperial College, London NW1 5QH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6807-9455","authenticated-orcid":false,"given":"Francesco","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Eye Center \u201cG.B. Morgagni-DSV\u201d, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Britten-Jones, A.C., Wang, M.T.M., Samuels, I., Jennings, C., Stapleton, F., and Craig, J.P. (2024). Epidemiology and Risk Factors of Dry Eye Disease: Considerations for Clinical Management. Medicina, 60.","DOI":"10.3390\/medicina60091458"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.12998\/wjcc.v11.i16.3736","article-title":"Diabetes more than retinopathy, it\u2019s effect on the anterior segment of eye","volume":"11","author":"Morya","year":"2023","journal-title":"World J. Clin. Cases"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Yang, L., Wang, Q., Li, Y., Wei, C., and Xie, L. (2022). Mechanistic investigations of diabetic ocular surface diseases. Front. 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