{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:32:51Z","timestamp":1788877971458,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870624"],"award-info":[{"award-number":["81870624"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171013"],"award-info":[{"award-number":["82171013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017599","name":"Science and Technology Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2022C03173"],"award-info":[{"award-number":["2022C03173"]}],"id":[{"id":"10.13039\/501100017599","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Investigate the correlation and agreement between the results of semiautomated and fully automated quantitative analysis of the corneal sub-basal nerve plexus (SNP) in patients with dry eye disease (DED) with ocular pain using <jats:italic>in vivo<\/jats:italic> confocal microscopy (IVCM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 50 voluntary participants were enrolled in this study, i.e., 25 DED patients with ocular pain and 25 healthy controls. Each patient underwent an evaluation of ocular symptoms that utilized: the Ocular Surface Disease Index (OSDI), the Ocular Pain Assessment Survey (OPAS), the tear film breakup time (TBUT) test, the Schirmer test, corneal staining, and IVCM. Five SNP images of the cornea of each eye were selected and analyzed using a semiautomated analysis software (NeuronJ) and a fully automated method (ACCMetrics) to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The intraclass correlation coefficient (ICC) of the CNFD (0.460 [0.382\u20130.532], <jats:italic>p<\/jats:italic> &amp;lt; 0.001), CNBD (0.608 [0.545\u20130.665], <jats:italic>p<\/jats:italic> &amp;lt; 0.001), and CNFL (0.851 [0.822\u20130.875], <jats:italic>p<\/jats:italic> &amp;lt; 0.001) represents the repeatability and consistency of measurements by the NeuronJ and ACCMetrics software. The CNFL values (r = 0.881, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) obtained using the two methods have extremely high correlation, and similarly, the CNFD values (r = 0.669, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and CNBD values (r = 0.703, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) are highly correlated. The CNFL had the biggest area under the curve (AUC; 0.747 [0.700\u20130.793], <jats:italic>p<\/jats:italic> &amp;lt; 0.001) when using ACCMetrics. In DED patients with ocular pain, the mean CNFD values for semiautomated and fully automated quantization were 23.5 \u00b1 8.1 and 23.8 \u00b1 8.6 n\/mm<jats:sup>2<\/jats:sup>; the mean CNBD values were 46.0 \u00b1 21.3, 35.7 \u00b1 23.3 n\/mm<jats:sup>2<\/jats:sup>; and the mean CNFL values were 19.3 \u00b1 4.3 and 15.2 \u00b1 3.8 mm\/mm<jats:sup>2<\/jats:sup>, which were significantly lower than healthy subjects (<jats:italic>p<\/jats:italic> &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>There is a significant correlation between the measurements obtained via ACCMetrics and NeuronJ, especially for CNFL, which can be considered as the primary indicator in the diagnosis of DED with ocular pain. The SNP of the disease was significantly lower than that of healthy subjects.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.831307","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T05:36:35Z","timestamp":1644557795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Semiautomated and Automated Quantitative Analysis of Corneal Sub-Basal Nerves in Patients With DED With Ocular Pain Using IVCM"],"prefix":"10.3389","volume":"9","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ajo.2017.06.033","article-title":"Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older","volume":"182","author":"Farrand","year":"2017","journal-title":"Am J Ophthalmol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/NHH.0000000000000652","article-title":"Dry eye disease: prevalence, assessment, and management","volume":"36","author":"Rouen","year":"2018","journal-title":"Home Healthc Now."},{"key":"B3","doi-asserted-by":"publisher","first-page":"020503","DOI":"10.7189\/jogh.08.020503","article-title":"Variations of dry eye disease prevalence by age, sex and geographic characteristics in China: a systematic review and meta-analysis","volume":"8","author":"Song","year":"2018","journal-title":"J Global Health."},{"key":"B4","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf."},{"key":"B5","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul Surf."},{"key":"B6","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1007\/s00417-018-04225-7","article-title":"In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system. 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