{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:07Z","timestamp":1785432367200,"version":"3.56.0"},"reference-count":98,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lucian Blaga University of Sibiu (Knowledge Transfer Center) & Hasso Plattner Foundation","award":["LBUS-HPI-ERG-2023-05"],"award-info":[{"award-number":["LBUS-HPI-ERG-2023-05"]}]},{"award":["LBUS-HPI-ERG-2023-05"],"award-info":[{"award-number":["LBUS-HPI-ERG-2023-05"]}],"id":[{"id":"https:\/\/ror.org\/026gdz537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The corneal endothelium maintains corneal transparency through its barrier function and active pumping mechanism that regulates stromal hydration. Limited regenerative capacity makes these cells vulnerable to progressive cell loss. Although local ocular factors are well known, recent data suggest that numerous systemic diseases may contribute to endothelial dysfunction and reduce endothelial reserve before the onset of clinically apparent corneal pathology. The purpose of this narrative review is to synthesize current evidence on the impact of systemic diseases on corneal endothelial health and to highlight the underlying mechanisms and clinical implications. Methods: A narrative literature review was conducted using the PubMed, MEDLINE, and Google Scholar databases for articles published between January 2000 and December 2025. Observational studies, case series, and review articles that evaluated structural or functional changes in the corneal endothelium in association with systemic diseases were included. Results: Reviewed literature shows that several categories of systemic diseases are associated with signs of corneal endothelial stress. These changes include decreased endothelial cell density, increased cell size variability, reduced hexagonality, and, in some cases, increased central corneal thickness. Metabolic, cardiovascular, renal, autoimmune, and hypoxic conditions, as well as extracellular matrix disorders and aging, show consistent associations with these changes. Conclusions: Systemic diseases can compromise corneal endothelial integrity and reduce functional reserve even in the absence of clinically evident corneal pathology. Recognition of these associations underscores the importance of evaluating the patient\u2019s systemic context, including a detailed medical history and corneal endothelial analysis, particularly before intraocular surgery.<\/jats:p>","DOI":"10.3390\/jcm15083013","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:02:33Z","timestamp":1776261753000},"page":"3013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Cornea: Systemic Diseases and Their Impact on Endothelial Health\u2014A Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-3683","authenticated-orcid":false,"given":"Maria-Emilia","family":"Cerghedean-Florea","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-3549","authenticated-orcid":false,"given":"Cosmin Adrian","family":"Teodoru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hora\u021biu","family":"Dura","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-8515","authenticated-orcid":false,"given":"Mihai Dan","family":"Roman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3739-0562","authenticated-orcid":false,"given":"Adrian","family":"Ha\u0219egan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-1585","authenticated-orcid":false,"given":"Adrian","family":"Boicean","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0821","authenticated-orcid":false,"given":"Mihaela Laura","family":"Vic\u0103","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Institute of Legal Medicine, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-6319","authenticated-orcid":false,"given":"Horia","family":"Stanca","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"T\u0103n\u0103sescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550024 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","first-page":"40","article-title":"Limbal stem cells in review","volume":"4","author":"Ebrahimi","year":"2009","journal-title":"J. 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