{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:51:14Z","timestamp":1784332274185,"version":"3.55.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007332","name":"Autism Research Institute","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>An increasing body of evidence supports the role of altered sensory processing in autism spectrum disorder (ASD) and attention-deficit\/hyperactivity disorder (ADHD). This exploratory study undertook corneal confocal microscopy (CCM) to assess for differences in corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) in relation to ASD severity in children with ASD+ADHD (n\u2009=\u200921), ASD (n\u2009=\u20096) and healthy controls (HC) (n\u2009=\u200915). CNBD was significantly lower in children with ASD+ADHD (P\u2009=\u20090.002) and ASD (P\u2009&lt;\u20090.001) and CNFL was significantly lower in children with ASD (P\u2009=\u20090.02) compared to HC. However, CNFD (mean difference\u2009=\u20092.28, 95% CI [\u22125.84, 10.40], P\u2009&gt;\u20090.99) CNBD (mean difference\u2009=\u200914.1, 95% CI [\u22128.22, 36.4], p\u2009=\u20090.37) and CNFL (mean difference\u2009=\u20092.46, 95% CI [\u22122.28, 7.20], p\u2009=\u20090.61) did not differ between ASD+ADHD and ASD. CNFD (P\u2009=\u20090.876), CNBD (P\u2009=\u20090.405) and CNFL (P\u2009=\u20090.606) did not correlate with the severity of ASD. Corneal confocal microscopy reveals sensory nerve degeneration in children with ASD+ADHD and ASD alone compared to controls. Larger studies integrating CCM with sensory and cognitive assessment are required to determine the utility of CCM as a clinical screening strategy for neurodegneration in ASD, ADHD and ASD-ADHD combined.<\/jats:p>","DOI":"10.1371\/journal.pone.0342439","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T18:30:06Z","timestamp":1771871406000},"page":"e0342439","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Children with autism spectrum disorder and attention deficit hyperactivity disorder have evidence of sensory nerve degeneration"],"prefix":"10.1371","volume":"21","author":[{"given":"Hoda","family":"Gad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulla","family":"AlObaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeeha","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba 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McCracken","year":"2023","journal-title":"Brain Sci"},{"issue":"16","key":"pone.0342439.ref025","doi-asserted-by":"crossref","first-page":"4645","DOI":"10.1002\/hbm.24727","article-title":"Stepwise functional connectivity reveals altered sensory-multimodal integration in medication-na\u00efve adults with attention deficit hyperactivity disorder","volume":"40","author":"C Pretus","year":"2019","journal-title":"Hum Brain Mapp"},{"issue":"1","key":"pone.0342439.ref026","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s10803-022-05798-3","article-title":"Transdiagnostic Patterns of Sensory Processing in Autism and ADHD","volume":"54","author":"NE Scheerer","year":"2024","journal-title":"J Autism Dev Disord"},{"issue":"4","key":"pone.0342439.ref027","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1590\/bjpt-rbf.2014.0043","article-title":"Sensory processing abilities of children with ADHD","volume":"18","author":"VT Shimizu","year":"2014","journal-title":"Braz J Phys Ther"},{"key":"pone.0342439.ref028","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.comppsych.2017.10.008","article-title":"The relationship between ADHD traits and sensory sensitivity in the general population","volume":"80","author":"M Panagiotidi","year":"2018","journal-title":"Compr Psychiatry"},{"issue":"10","key":"pone.0342439.ref029","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/j.freeradbiomed.2012.03.011","article-title":"Oxidative stress-related biomarkers in autism: systematic review and meta-analyses","volume":"52","author":"A Frustaci","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"pone.0342439.ref030","unstructured":"Autismspeaks. 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