{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:25:03Z","timestamp":1786955103891,"version":"build-2736575974"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Biomark&amp;#65533;Insights"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Neurodegeneration in the cornea, particularly in diabetic patients, is an emerging area of research that highlights the potential of tear fluid as a source of biomarkers. Neurofilaments light chain (Nf-L), which are structural proteins found in neurons, have been identified as promising candidates for early biomarkers of neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study investigates the correlation Nf-L levels in tears and corneal in vivo confocal microscopy (IVCM) parameters in patients with diabetes mellitus without retinopathy with the aim of associating Nf-L level with corneal neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Case-control observational study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We enrolled 20 patients with diabetes mellitus type 2 (DM) and 20 healthy controls (HC): we studied the levels of Nf-L in serum and tears, and we looked for a correlation with the parameters detected on IVCM, including corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD) and corneal nerve branching density (CNBD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Serum Nf-L levels showed no difference between DM (mean\u2009\u00b1\u2009SD 14.00\u2009\u00b1\u20092.18\u2009pg\/mL) and HC (mean\u2009\u00b1\u2009SD 15.18\u2009\u00b1\u20092.28\u2009pg\/mL). Instead we detected a significant increase in Nf-L levels in DM tears (right eye mean\u2009\u00b1\u2009SD\u2009321.23\u2009\u00b1\u2009192.40\u2009pg\/mL; left eye mean\u2009\u00b1\u2009SD\u2009277.90\u2009\u00b1\u2009254.23\u2009pg\/mL) compared to HC (right eye mean\u2009\u00b1\u2009SD\u200925.80\u2009\u00b1\u200922.0\u2009pg\/mL; left eye mean\u2009\u00b1\u2009SD\u200927.96\u2009\u00b1\u200920.21\u2009pg\/mL). Furthermore, a negative correlation was evident between Nf-L levels and IVCM parameters: CNFL\/Nf-L\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      \u2212.4234\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u2009.001; CNFD\/Nf-L \u2212.4959\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u2009.001; CNBD\/Nf-L\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      \u2212.5310\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u2009.0005.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our findings indicate that Nf-L levels are significantly elevated in the tears of DM patients and that high Nf-L levels correlate with lower corneal IVCM parameters, suggesting that tears Nf-L could be a reliable biomarker for early corneal neurodegeneration in diabetes without retinopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11772719251368696","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:15:51Z","timestamp":1786691751000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurofilaments in Tears as Early Biomarkers of Corneal Neurodegeneration in Diabetes Without Retinopathy"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-3961","authenticated-orcid":false,"given":"Vincenzo","family":"Macaione","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Polito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni W.","family":"Oliverio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Aragona","sequence":"additional","affiliation":[{"name":"IRCSS San Raffaele Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa I.","family":"Postorino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2615-436X","authenticated-orcid":false,"given":"Maura","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Palino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u2019hammed","family":"Aguennouz","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Aragona","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, University of Messina, 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