{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:52:47Z","timestamp":1789689167327,"version":"4.0.1"},"reference-count":230,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"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>Keratoconus (KC) is the most common ectatic corneal disease. In this review, the systemic aspects of the disease are discussed, including patient age, genetics, systemic inflammatory status and immune system dysregulation, atopy and eye rubbing, systemic metabolism, the metabolism of micronutrients (including vitamin D), and hormonal balance. The association between KC and metabolic diseases, collagen diseases, and psychiatric conditions is also considered. The evidence that is currently available strongly suggests a systemic predisposition toward KC. The understanding that KC may be the local manifestation of a systemic disease could allow earlier detection\/prevention and pave the way for research into new treatments addressing the pathogenetic foundations of KC, rather than limiting intervention to the corneal disease.<\/jats:p>","DOI":"10.3390\/jcm14134587","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"4587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Keratoconus: The Local Manifestation of a Systemic Disease?"],"prefix":"10.3390","volume":"14","author":[{"given":"Matteo","family":"Pederzolli","sequence":"first","affiliation":[{"name":"Eye Repair Lab, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Cornea and Ocular Surface Disease Service, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9595-1885","authenticated-orcid":false,"given":"Federico","family":"Procopio","sequence":"additional","affiliation":[{"name":"Cornea and Ocular Surface Disease Service, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Department of Ophthalmology, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Tombolini","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Marra","sequence":"additional","affiliation":[{"name":"Cornea and Ocular Surface Disease Service, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Department of Ophthalmology, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"De Micheli","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Ospedale Maggiore di Lodi, 21100 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-9682","authenticated-orcid":false,"given":"Francesco","family":"Bandello","sequence":"additional","affiliation":[{"name":"Cornea and Ocular Surface Disease Service, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Department of Ophthalmology, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6474-9908","authenticated-orcid":false,"given":"Giulio","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Eye Repair Lab, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Cornea and Ocular Surface Disease Service, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Department of Ophthalmology, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Ophthalmology Unit, Ospedale Maggiore di Lodi, 21100 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ali\u00f3, J.L. 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