{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:51:23Z","timestamp":1792065083895,"version":"4.4.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"vor","delay-in-days":276,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R1-05991"],"award-info":[{"award-number":["R1-05991"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW) and the German Federal Ministry of Health"},{"name":"Canadian Diabetes Association Operating Grant","award":["OG-3-3123-BP"],"award-info":[{"award-number":["OG-3-3123-BP"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["NIH 1ULTR001067"],"award-info":[{"award-number":["NIH 1ULTR001067"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DK064814"],"award-info":[{"award-number":["R01-DK064814"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008871","name":"JDRF International","doi-asserted-by":"crossref","award":["17-2008-1032"],"award-info":[{"award-number":["17-2008-1032"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008871","name":"JDRF International","doi-asserted-by":"crossref","award":["17-2008-715"],"award-info":[{"award-number":["17-2008-715"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008871","name":"JDRF International","doi-asserted-by":"crossref","award":["27-2008- 362"],"award-info":[{"award-number":["27-2008- 362"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JDRF International -Scholar","award":["R106784"],"award-info":[{"award-number":["R106784"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>There was a significant linear age-dependent decrease in CNFD (\u22120.164 no.\/mm2 per year for men, P &amp;lt; 0.01, and \u22120.161 no.\/mm2 per year for women, P &amp;lt; 0.01). There was no change with age in CNBD (0.192 no.\/mm2 per year for men, P = 0.26, and \u22120.050 no.\/mm2 per year for women, P = 0.78). CNFL decreased in men (\u22120.045 mm\/mm2 per year, P = 0.07) and women (\u22120.060 mm\/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P &amp;lt; 0.01) and women (0.046 per year, P &amp;lt; 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc14-2311","type":"journal-article","created":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T03:48:48Z","timestamp":1422589728000},"page":"838-843","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":193,"title":["Normative Values for Corneal Nerve Morphology Assessed Using Corneal Confocal Microscopy: A Multinational Normative Data Set"],"prefix":"10.2337","volume":"38","author":[{"given":"Mitra","family":"Tavakoli","sequence":"first","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Ferdousi","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis N.","family":"Petropoulos","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Morris","sequence":"additional","affiliation":[{"name":"Medical Statistics Unit, University of Manchester and University Hospital of South Manchester, Manchester, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Zhivov","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Rostock, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, D\u00fcsseldorf, Germany"},{"name":"Department of Endocrinology and Diabetology, University Hospital, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00e8le","family":"Pacaud","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital, Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Romanchuk","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital, Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif E.","family":"Lovblom","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Bril","sequence":"additional","affiliation":[{"name":"Division of Neurology, University Health Network, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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