{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T08:38:38Z","timestamp":1782549518529,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Adverum Biotechnologies"},{"name":"Department of Genetic Medicine, Weill Cornell Medical College"},{"name":"Parker B. Francis Fellowship"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by mutations in the gene encoding for the mitochondrial protein frataxin, is characterized by ataxia and gait instability, immobility, and eventual death. We evaluated corneal confocal microscopy (CCM) quantification of corneal nerve morphology as a novel, noninvasive, in vivo quantitative imaging biomarker for the severity of neurological manifestations in FRDA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Corneal nerve fiber density, branch density, and fiber length were quantified in individuals with FRDA (n\u2009=\u200923) and healthy age\u2010matched controls (n\u2009=\u200914). All individuals underwent genetic testing and a detailed neurological assessment with the Scale for the Assessment and Rating of Ataxia (SARA) and Friedreich's Ataxia Rating Scale (FARS). A subset of individuals with FRDA who were ambulatory underwent quantitative gait assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCM demonstrated a significant reduction in nerve fiber density and length in FRDA compared to healthy controls. Importantly, CCM parameters correlated with genotype, SARA and FARS neurological scales, and linear regression modeling of CCM nerve parameter\u2013generated equations that predict the neurologic severity of FRDA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Together, the data suggest that CCM quantification of corneal nerve morphology is a rapid, sensitive imaging biomarker for quantifying the severity of neurologic disease in individuals with FRDA. Ann Neurol 2018;84:893\u2013904<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25355","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T04:41:13Z","timestamp":1538973673000},"page":"893-904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Corneal confocal microscopy: Neurologic disease biomarker in Friedreich ataxia"],"prefix":"10.1002","volume":"84","author":[{"given":"Odelya E.","family":"Pagovich","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Neurology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe Z.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College  New York NY"},{"name":"Department of Biological Statistics and Computational Biology Cornell University  Ithaca NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis N.","family":"Petropoulos","sequence":"additional","affiliation":[{"name":"Department of Medicine Weill Cornell Medicine\u2010Qatar  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buntitar","family":"Lertsuwanroj","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Ciralsky","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilard","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Mezey","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College  New York NY"},{"name":"Department of Biological Statistics and Computational Biology Cornell University  Ithaca NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayaz A.","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Medicine Weill Cornell Medicine\u2010Qatar  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/104.3.589"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5254.1423"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.03.012"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448230"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.05.023"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt.15.73"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27353"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000156802.15466.79"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000218155.46739.90"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219042.60538.92"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0675-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1086-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0285"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23377"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21383"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.1703"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139394"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183040"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gaitpost.2017.03.019"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2011.05.016"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2016.2573642"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v027.i05"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.332"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/951081"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200105000-00008"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13787"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2016.1889"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.275"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23107-w"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21643-z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.07.004"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2114"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0870"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0574"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00215"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21291"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004033"},{"key":"e_1_2_8_39_1","first-page":"1","article-title":"Medical and surgical treatments for tinnitus: the efficacy of combined treatment with sulodexide and melatonin","volume":"59","author":"Ferrari G","year":"2015","journal-title":"J Neurosurg Sci"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.10.019"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.1590"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018289"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22050"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30287-3"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12318"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.25355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T07:05:39Z","timestamp":1694329539000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/ana.25355"],"URL":"https:\/\/doi.org\/10.1002\/ana.25355","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12]]},"assertion":[{"value":"2018-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}