{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:10:30Z","timestamp":1778130630842,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to evaluate tear cytokine and chemokine profiles in keratoconus (KC) and to assess their association with long-term tomographic outcomes after corneal collagen cross-linking (CXL). In this cross-sectional observational study, 30 KC eyes and nine healthy controls were enrolled. KC severity was graded using the modified Amsler\u2013Krumeich classification. Tear samples were collected and analyzed using multiplex bead-based immunoassays (LEGENDplex\u2122) for cytokines, chemokines, and TGF-\u03b21. Patients were followed for five years after CXL. Treatment response was categorized according to corneal flattening (&lt;1 D, 1\u20133 D, &gt;3 D). Individual cytokine levels showed no major differences between the KC and controls, although IL-6 and MCP-1 tended to be higher in the KC group. However, IP 10 and IL-17 were higher in controls (p &lt; 0.05). In contrast, multiple pro-\/anti-inflammatory ratios (TNF\/TGF-\u03b21, IL-17\/IL-10, MCP-1\/IL-10, IL-6\/IL-10, IL-8\/TGF-\u03b21, MCP-1\/TGF-\u03b21, IL-6\/TGF-\u03b21, and IL-8\/IL-10) were significantly elevated in the KC group (p &lt; 0.05), indicating immune imbalance. After five years, all treated eyes remained stable or flattened. Lower baseline MCP-1 and IL-8 levels correlated with greater postoperative corneal flattening (p &lt; 0.05). Keratoconus is characterized by disturbed tear immune homeostasis rather than isolated cytokine elevation. Lower preoperative inflammatory activity may predict a more favorable biomechanical response to CXL, supporting the potential role of tear cytokine profiling in patient stratification and prognostication.<\/jats:p>","DOI":"10.3390\/ijms27093768","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"3768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Pro- and Anti-Inflammatory Cytokine Profile in Keratoconus as a Predictor of Five-Year Corneal Cross-Linking Outcomes"],"prefix":"10.3390","volume":"27","author":[{"given":"Tiana","family":"Petrovic","sequence":"first","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Stanojlovic","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-8322","authenticated-orcid":false,"given":"Sanja","family":"Petrovic Pajic","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-2588","authenticated-orcid":false,"given":"Borivoje","family":"Savic","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-3615","authenticated-orcid":false,"given":"Tanja","family":"Kalezic","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada","family":"Avram","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, University Hospital Fo\u010da, 73300 Fo\u010da, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Sobot","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8315-8869","authenticated-orcid":false,"given":"Marko","family":"Svetel","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Jeremic Kaplarevic","sequence":"additional","affiliation":[{"name":"Clinic for Eye Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-1738","authenticated-orcid":false,"given":"Vladimir","family":"Perovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: An updated review","volume":"45","author":"Carracedo","year":"2022","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/ICO.0000000000003585","article-title":"The Pathophysiology of Keratoconus","volume":"44","author":"Vought","year":"2025","journal-title":"Cornea"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e303","DOI":"10.1111\/j.1755-3768.2011.02369.x","article-title":"Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus","volume":"90","author":"Balasubramanian","year":"2012","journal-title":"Acta Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20891","DOI":"10.1038\/s41598-021-99805-9","article-title":"Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile","volume":"11","author":"Nair","year":"2021","journal-title":"Sci. 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