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There remain, however, major limitations to the method, hindering its widespread clinical use. Finding the same exact area of the central cornea to standardize image acquisition is difficult without a reference point. Alternatively, creating wide-area mosaics of the SBNP is resource-intensive and has not yet been developed for routine clinical use. Here, we investigated whether IVCM analysis of the corneal SBNP in a predetermined, anatomically standardized region of interest (ROI) could be applied as an equivalent substitution for wide-area SBNP mosaic generation and analysis. Furthermore, we investigated nerve patterns outside the central corneal region for a possible relationship to type 2 diabetes mellitus status using a publicly available dataset. We found that corneal nerve fibre length density (CNFL) based on the ROI underestimated the mosaic-based CNFL by an average of 34% in 90% of cases (150 eyes), and did not exhibit a significant reduction with diabetes, as seen in the full SBNP. Outside the central cornea, nerve orientation differed depending on the anatomic region (left, central or right superior plexus, P\u2009&lt;\u20090.001). Moreover, in long-term type 2 diabetes mellitus (\u2265\u200910\u00a0years, 28 subjects), nerve density in the left superior sector of the SBNP was decreased (P\u2009&lt;\u20090.001) while that in the central superior SBNP increased (P\u2009=\u20090.01) relative to 35 age-matched healthy subjects with normal glucose tolerance. These results indicate that subbasal nerve degeneration in type 2 diabetes mellitus can vary according to anatomic location, and regions with potential diagnostic value outside the central SBNP may warrant further investigation.<\/jats:p>","DOI":"10.1038\/s41598-020-67737-5","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T10:40:20Z","timestamp":1593600020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Region of interest and directional analysis of subbasal nerves in wide-area corneal nerve plexus mosaics in type 2 diabetes mellitus"],"prefix":"10.1038","volume":"10","author":[{"given":"Reza A.","family":"Badian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor Paaske","family":"Utheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Lagali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"67737_CR1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","volume":"37","author":"DW DelMonte","year":"2011","unstructured":"DelMonte, D. 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