{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:16:08Z","timestamp":1790172968383,"version":"4.1.0"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p>Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.<\/jats:p>","DOI":"10.3389\/fpain.2021.725363","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:50:22Z","timestamp":1629366622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology"],"prefix":"10.3389","volume":"2","author":[{"given":"Ioannis N.","family":"Petropoulos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulfidan","family":"Bitirgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Ferdousi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alise","family":"Kalteniece","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazli","family":"Azmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"D'Onofrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze Hway","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Ponirakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda","family":"Gad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacob E.","family":"Mohammadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gosal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monty","family":"Silverdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Handrean","family":"Soran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayaz A.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/cxo.12887","article-title":"Corneal confocal microscopy: ready for prime time","volume":"103","author":"Petropoulos","year":"2020","journal-title":"Clin Exp Optomet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1097\/OPX.0b013e31824ee8c9","article-title":"Optimal image sample size for corneal nerve morphometry","volume":"89","author":"Vagenas","year":"2012","journal-title":"Optomet Vis Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"5801","DOI":"10.1167\/iovs.15-17434","article-title":"Comparison of standard versus wide-field composite images of the corneal subbasal layer by in vivo confocal microscopy","volume":"56","author":"Kheirkhah","year":"2015","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1167\/iovs.14-15919","article-title":"The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy","volume":"56","author":"Petropoulos","year":"2015","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1167\/tvst.9.9.43","article-title":"The utility of corneal nerve fractal dimension analysis in peripheral neuropathies of different etiology","volume":"9","author":"Petropoulos","year":"2020","journal-title":"Transl Vis Sci Technol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1167\/iovs.13-13787","article-title":"Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy","volume":"55","author":"Petropoulos","year":"2014","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00125-019-05023-4","article-title":"An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study","volume":"63","author":"Williams","year":"2020","journal-title":"Diabetologia."},{"key":"B8","doi-asserted-by":"publisher","first-page":"103666","DOI":"10.1016\/j.compbiomed.2020.103666","article-title":"Computational methods for automated analysis of corneal nerve images: lessons learned from retinal fundus image analysis","volume":"119","author":"Salahuddin","year":"2020","journal-title":"Comp Biol Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00125-003-1086-8","article-title":"Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients","volume":"46","author":"Malik","year":"2003","journal-title":"Diabetologia."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.2337\/db07-0285","article-title":"Surrogate markers of small fiber damage in human diabetic neuropathy","volume":"56","author":"Quattrini","year":"2007","journal-title":"Diabetes."},{"key":"B11","doi-asserted-by":"publisher","first-page":"dc142422","DOI":"10.2337\/dc14-2422","article-title":"Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density","volume":"38","author":"Chen","year":"2015","journal-title":"Diabetes Care."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0180175","DOI":"10.1371\/journal.pone.0180175","article-title":"Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy","volume":"12","author":"Alam","year":"2017","journal-title":"PLoS ONE."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00125-018-4653-8","article-title":"Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study","volume":"61","author":"Perkins","year":"2018","journal-title":"Diabetologia"},{"key":"B14","doi-asserted-by":"publisher","first-page":"838","DOI":"10.2337\/dc14-2311","article-title":"Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set","volume":"38","author":"Tavakoli","year":"2015","journal-title":"Diabetes Care."},{"key":"B15","doi-asserted-by":"publisher","first-page":"150","DOI":"10.2337\/figshare.13020023.v1","article-title":"Diagnosis of neuropathy and risk factors for corneal nerve loss in type 1 and type 2 diabetes: a corneal confocal microscopy study","volume":"44","author":"Ferdousi","year":"2020","journal-title":"Diabetes Care."},{"key":"B16","doi-asserted-by":"publisher","first-page":"8758","DOI":"10.1038\/s41598-019-45116-z","article-title":"Early corneal nerve fibre damage and increased Langerhans cell density in children with type 1 diabetes mellitus","volume":"9","author":"Ferdousi","year":"2019","journal-title":"Sci Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1111\/jdi.13313","article-title":"Corneal nerve loss in children with type 1 diabetes mellitus without retinopathy or microalbuminuria","volume":"11","author":"Gad","year":"2020","journal-title":"J Diabetes Investig."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0123517","DOI":"10.1371\/journal.pone.0123517","article-title":"Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria","volume":"10","author":"Petropoulos","year":"2015","journal-title":"PLoS ONE."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.2337\/dc14-0279","article-title":"Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance","volume":"37","author":"Asghar","year":"2014","journal-title":"Diabetes Care."},{"key":"B20","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/aos.14359","article-title":"Reduced corneal nerve fibre length in prediabetes and type 2 diabetes: The Maastricht Study","volume":"98","author":"De Clerck","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.2337\/db13-1819","article-title":"Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes","volume":"63","author":"Ziegler","year":"2014","journal-title":"Diabetes."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1038\/s41598-020-60422-7","article-title":"Corneal confocal microscopy detects small nerve fibre damage in patients with painful diabetic neuropathy","volume":"10","author":"Kalteniece","year":"2020","journal-title":"Sci Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.1038\/s41598-018-21643-z","article-title":"Greater corneal nerve loss at the inferior whorl is related to the presence of diabetic neuropathy and painful diabetic neuropathy","volume":"8","author":"Kalteniece","year":"2018","journal-title":"Sci Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/dme.12583","article-title":"In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes","volume":"32","author":"Maddaloni","year":"2015","journal-title":"Diabet Med."},{"key":"B25","first-page":"2851","article-title":"[Early diagnosis of diabetic autonomic neuropathy by corneal confocal microscopy]","volume":"95","author":"Wang","year":"2015","journal-title":"Zhonghua Yi Xue Za zhi."},{"key":"B26","doi-asserted-by":"publisher","first-page":"6069730","DOI":"10.1155\/2017\/6069730","article-title":"The preferential impairment of pupil constriction stimulated by blue light in patients with type 2 diabetes without autonomic neuropathy","volume":"2017","author":"Ishibashi","year":"2017","journal-title":"J Diabetes Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5060","DOI":"10.1167\/iovs.15-16711","article-title":"In vivo confocal microscopy of corneal nerves: an ocular biomarker for peripheral and cardiac autonomic neuropathy in type 1 diabetes mellitus","volume":"56","author":"Misra","year":"2015","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1002\/mus.24553","article-title":"Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy","volume":"52","author":"Tavakoli","year":"2015","journal-title":"Muscle Nerve."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1007\/s00125-017-4245-z","article-title":"Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study","volume":"60","author":"Azmi","year":"2017","journal-title":"Diabetologia."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e3263","DOI":"10.1002\/dmrr.3263","article-title":"Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes","volume":"36","author":"Dhage","year":"2020","journal-title":"Diabetes Metab Res Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"dc142114","DOI":"10.2337\/dc14-2114","article-title":"Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes","volume":"38","author":"Pritchard","year":"2015","journal-title":"Diabetes Care."},{"key":"B32","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.jcjd.2015.02.006","article-title":"In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis","volume":"39","author":"Lovblom","year":"2015","journal-title":"Can J Diabetes."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.2337\/dc19-0951","article-title":"Rapid corneal nerve fiber loss: a marker of diabetic neuropathy onset and progression","volume":"43","author":"Lewis","year":"2020","journal-title":"Diabetes Care."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1016\/j.jdiacomp.2016.07.004","article-title":"A rapid decline in corneal small fibers and occurrence of foot ulceration and Charcot foot","volume":"30","author":"Dehghani","year":"2016","journal-title":"J Diabetes Comp."},{"key":"B35","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1001\/archneurol.2010.17","article-title":"Chemotherapy-associated peripheral sensory neuropathy assessed using in vivo corneal confocal microscopy","volume":"67","author":"Ferrari","year":"2010","journal-title":"Arch Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e0139394","DOI":"10.1371\/journal.pone.0139394","article-title":"Corneal confocal microscopy detects small fibre neuropathy in patients with upper gastrointestinal cancer and nerve regeneration in chemotherapy induced peripheral neuropathy","volume":"10","author":"Ferdousi","year":"2015","journal-title":"PLoS ONE."},{"key":"B37","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/jns.12413","article-title":"Oxaliplatin- and docetaxel-induced polyneuropathy: clinical and neurophysiological characteristics","volume":"25","author":"Bennedsgaard","year":"2020","journal-title":"J Periph Nerv Syst."},{"key":"B38","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1167\/tvst.10.1.24","article-title":"A cross-sectional study of sub-basal corneal nerve reduction following neurotoxic chemotherapy","volume":"10","author":"Chiang","year":"2021","journal-title":"Transl Vis Sci Technol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3389\/fneur.2018.00204","article-title":"In vivo confocal microscopic evaluation of corneal nerve fibers and dendritic cells in patients with Behcet's disease","volume":"9","author":"Bitirgen","year":"2018","journal-title":"Front Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1111\/jns.12098","article-title":"Corneal confocal microscopy detects small fiber damage in chronic inflammatory demyelinating polyneuropathy (CIDP)","volume":"19","author":"Schneider","year":"2014","journal-title":"J Periph Nerv Syst."},{"key":"B41","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/acn3.275","article-title":"Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy","volume":"3","author":"Stettner","year":"2016","journal-title":"Ann Clin Transl Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12974-021-02130-1","article-title":"Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy","volume":"18","author":"Fleischer","year":"2021","journal-title":"J Neuroinflamm."},{"key":"B43","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1001\/jamaophthalmol.2017.1703","article-title":"Use of corneal confocal microscopy to evaluate small nerve fibers in patients with human immunodeficiency virus","volume":"135","author":"Kemp","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1167\/iovs.17-23342","article-title":"Corneal nerve fractal dimension: a novel corneal nerve metric for the diagnosis of diabetic sensorimotor polyneuropathy","volume":"59","author":"Chen","year":"2018","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1212\/WNL.0000000000010988","article-title":"Idiopathic distal sensory polyneuropathy: ACTTION diagnostic criteria","volume":"95","author":"Freeman","year":"2020","journal-title":"Neurology."},{"key":"B46","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.expneurol.2009.08.033","article-title":"Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy","volume":"223","author":"Tavakoli","year":"2010","journal-title":"Exp Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/17562864211004318","article-title":"Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study","volume":"14","author":"Egenolf","year":"2021","journal-title":"Ther Adv Neurol Disord."},{"key":"B48","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1002\/mus.23377","article-title":"Corneal confocal microscopy detects small-fiber neuropathy in Charcot\u2013Marie\u2013Tooth disease type 1A patients","volume":"46","author":"Tavakoli","year":"2012","journal-title":"Muscle Nerve."},{"key":"B49","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1152\/jn.00667.2015","article-title":"Rare human nerve growth factor-beta mutation reveals relationship between C-afferent density and acute pain evaluation","volume":"116","author":"Perini","year":"2016","journal-title":"J Neurophysiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1002\/ana.25355","article-title":"Corneal confocal microscopy: neurologic disease biomarker in Friedreich ataxia","volume":"84","author":"Pagovich","year":"2018","journal-title":"Ann Neurol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/mus.26687","article-title":"Evidence of small-fiber neuropathy in neurofibromatosis type 1","volume":"60","author":"Barnett","year":"2019","journal-title":"Muscle Nerve."},{"key":"B52","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1007\/s00415-017-8708-4","article-title":"Transthyretin familial amyloid polyneuropathy: an update","volume":"265","author":"Plante-Bordeneuve","year":"2018","journal-title":"J Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1212\/WNL.0000000000004016","article-title":"Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy","volume":"88","author":"Masuda","year":"2017","journal-title":"Neurology."},{"key":"B54","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jns.2018.08.031","article-title":"Kind and distribution of cutaneous sensation loss in hereditary transthyretin amyloidosis with polyneuropathy","volume":"394","author":"Pinto","year":"2018","journal-title":"J Neurol Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1159\/000446538","article-title":"Confocal cornea microscopy detects involvement of corneal nerve fibers in a patient with light-chain amyloid neuropathy caused by multiple myeloma: a case report","volume":"8","author":"Sturm","year":"2016","journal-title":"Case Rep Neurol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1001\/jamaophthalmol.2016.1889","article-title":"Potential role of in vivo confocal microscopy for imaging corneal nerves in transthyretin familial amyloid polyneuropathy","volume":"134","author":"Rousseau","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1111\/ene.14563","article-title":"Corneal sub-basal whorl-like nerve plexus: a landmark for early and follow-up evaluation in transthyretin familial amyloid polyneuropathy","volume":"28","author":"Zhang","year":"2020","journal-title":"Eur J Neurol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2326409816661351","DOI":"10.1177\/2326409816661351","article-title":"Small fiber neuropathy in Fabry disease: a review of pathophysiology and treatment","volume":"4","author":"Politei","year":"2016","journal-title":"J Inborn Errors Metab Screen."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1097\/j.pain.0000000000002152","article-title":"Fabry disease pain: patient and preclinical parallels.","volume":"162","author":"Burand","year":"2021","journal-title":"Pain."},{"key":"B60","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/mus.21383","article-title":"Corneal confocal microscopy: a novel noninvasive means to diagnose neuropathy in patients with Fabry disease","volume":"40","author":"Tavakoli","year":"2009","journal-title":"Muscle Nerve."},{"key":"B61","doi-asserted-by":"publisher","first-page":"12244","DOI":"10.1038\/s41598-018-30688-z","article-title":"Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease","volume":"8","author":"Bitirgen","year":"2018","journal-title":"Sci Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1210\/jc.2018-00671","article-title":"The LDIFLARE and CCM methods demonstrate early nerve fibre abnormalities in untreated hypothyroidism: a prospective study","volume":"103","author":"Sharma","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"key":"B63","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.semarthrit.2015.03.003","article-title":"Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy","volume":"45","author":"Ramirez","year":"2015","journal-title":"Semin Arthrit Rheumat."},{"key":"B64","doi-asserted-by":"publisher","first-page":"23573","DOI":"10.1038\/srep23573","article-title":"Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia","volume":"6","author":"Oudejans","year":"2016","journal-title":"Sci Rep."},{"key":"B65","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/ICO.0000000000001447","article-title":"Ocular surface alterations in the context of corneal in vivo confocal microscopic characteristics in patients with fibromyalgia","volume":"37","author":"Turan","year":"2018","journal-title":"Cornea."},{"key":"B66","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/ana.25565","article-title":"Reduction of skin innervation is associated with a severe fibromyalgia phenotype","volume":"86","author":"Evdokimov","year":"2019","journal-title":"Ann Neurol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"108631","DOI":"10.1016\/j.diabres.2020.108631","article-title":"Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection","volume":"172","author":"Odriozola","year":"2020","journal-title":"Diabetes Res Clin Pract."},{"key":"B68","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.ijid.2020.11.146","article-title":"Nerve conduction study and electromyography findings in patients recovering from Covid-19 - case report","volume":"103","author":"Daia","year":"2021","journal-title":"Int J Infect Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.neucli.2021.01.003","article-title":"Sudomotor dysfunction in patients recovered from COVID-19","volume":"51","author":"Hinduja","year":"2021","journal-title":"Clin Neurophysiol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"e11452","DOI":"10.7759\/cureus.11452","article-title":"Peripheral neuropathy as a complication of SARS-Cov-2","volume":"12","author":"Bureau","year":"2020","journal-title":"Cureus."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1016\/j.clinph.2020.09.017","article-title":"Neuromuscular involvement in COVID-19 critically ill patients","volume":"131","author":"Caba\u00f1es-Mart\u00ednez","year":"2020","journal-title":"Clin Neurophysiol."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2021-319450","article-title":"Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID","author":"Bitirgen","year":"2021","journal-title":"Br J Ophthalmol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.neurol.2020.06.015","article-title":"Chronic pain in Parkinson's disease: clinical and pathophysiological aspects","volume":"177","author":"Marques","year":"2020","journal-title":"Rev Neurol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1755-3768.2014.2433.x","article-title":"Peripheral neuropathy in Parkinson disease: an in vivo confocal microscopy study","author":"Anjos","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1016\/j.parkreldis.2015.10.019","article-title":"Small fiber neuropathy in Parkinson's disease: a clinical, pathological and corneal confocal microscopy study","volume":"21","author":"Kass-Iliyya","year":"2015","journal-title":"Parkinson Relat Disord."},{"key":"B76","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.parkreldis.2016.04.033","article-title":"Evidence for small fiber neuropathy in early Parkinson's disease","volume":"28","author":"Podgorny","year":"2016","journal-title":"Parkinson Relat Disord."},{"key":"B77","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jocn.2017.02.033","article-title":"Corneal nerve microstructure in Parkinson's disease","volume":"39","author":"Misra","year":"2017","journal-title":"J Clin Neurosci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1097\/ICO.0000000000001517","article-title":"Early corneal innervation and trigeminal alterations in Parkinson disease: a pilot study","volume":"37","author":"Arrigo","year":"2018","journal-title":"Cornea."},{"key":"B79","doi-asserted-by":"publisher","first-page":"191","DOI":"10.17116\/oftalma2020136052191","article-title":"[Changes in corneal nerves fibers in the early stages of Parkinson's disease according to in vivo confocal microscopy (preliminary report)]","volume":"136","author":"Avetisov","year":"2020","journal-title":"Vestnik Oftalmol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"20147","DOI":"10.1038\/s41598-020-76768-x","article-title":"Corneal confocal microscopy detects small fibre neurodegeneration in Parkinson's disease using automated analysis","volume":"10","author":"Lim","year":"2020","journal-title":"Sci Rep."},{"key":"B81","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3760\/cma.j.cn112137-20200614-01851","article-title":"[Measurement of corneal nerve fiber parameters in patients with Parkinson's disease]","volume":"101","author":"Che","year":"2021","journal-title":"Zhonghua yi xue za zhi."},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28602","article-title":"Corneal confocal microscopy identifies Parkinson's disease with more rapid motor progression","author":"Lim","year":"2021","journal-title":"Mov Disord."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2021.05.003","article-title":"Pain intensity and pain interference in people with progressive multiple sclerosis compared to people with relapsing-remitting multiple sclerosis","author":"Knowles","year":"2021","journal-title":"Arch Phys Med Rehabil."},{"key":"B84","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s00482-021-00554-5","article-title":"[Pain in multiple sclerosis and neuromyelitis optica spectrum disorders]","volume":"35","author":"Pellkofer","year":"2021","journal-title":"Schmerz."},{"key":"B85","volume-title":"Lhermitte Sign. StatPearls.","author":"Teoli","year":"2021"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnab103","article-title":"Central neuropathic pain in multiple sclerosis is associated with impaired innocuous thermal pathways and neuronal hyperexcitability","author":"Rivel","year":"2021","journal-title":"Pain Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1097\/j.pain.0000000000002164","article-title":"Brainstem trigeminal fiber microstructural abnormalities are associated with treatment response across subtypes of trigeminal neuralgia","volume":"162","author":"Tohyama","year":"2021","journal-title":"Pain."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1177\/1352458516677590","article-title":"Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density","volume":"23","author":"Mikolajczak","year":"2017","journal-title":"Multiple Scler J."},{"key":"B89","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1001\/jamaophthalmol.2017.1590","article-title":"Use of corneal confocal microscopy to detect corneal nerve loss and increased dendritic cells in patients with multiple sclerosis","volume":"135","author":"Bitirgen","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"3677","DOI":"10.1167\/iovs.17-22050","article-title":"Corneal confocal microscopy: an imaging endpoint for axonal degeneration in multiple sclerosis","volume":"58","author":"Petropoulos","year":"2017","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1167\/tvst.10.4.30","article-title":"Abnormal dynamic pupillometry relates to neurologic disability and retinal axonal loss in patients with multiple sclerosis","volume":"10","author":"Bitirgen","year":"2021","journal-title":"Transl Vis Sci Technol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1167\/tvst.10.4.19","article-title":"Corneal immune cells are increased in patients with multiple sclerosis","volume":"10","author":"Khan","year":"2021","journal-title":"Transl Vis Sci Technol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1167\/tvst.9.13.37","article-title":"Progressive loss of corneal and retinal nerve fibers in patients with multiple sclerosis: a 2-year follow-up study","volume":"9","author":"Bitirgen","year":"2020","journal-title":"Transl Vis Sci Technol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.21037\/apm-20-864","article-title":"Pain characteristics in amyotrophic lateral sclerosis patients and its impact on quality of life: a prospective observational study in a northern city of China","volume":"10","author":"Kong","year":"2021","journal-title":"Ann Palliat Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neurol.2017.11.009","article-title":"Clinical features of pain in amyotrophic lateral sclerosis: a clinical challenge","volume":"175","author":"Delpont","year":"2019","journal-title":"Rev Neurol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3389\/fnagi.2014.00278","article-title":"Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis","volume":"6","author":"Ferrari","year":"2014","journal-title":"Front Aging Neurosci."},{"key":"B97","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s40263-021-00791-3","article-title":"Pharmacotherapy to manage central post-stroke pain","volume":"35","author":"Choi","year":"2021","journal-title":"CNS Drugs."},{"key":"B98","doi-asserted-by":"publisher","first-page":"e22611","DOI":"10.1097\/MD.0000000000022611","article-title":"Nonpharmacological therapies for central poststroke pain: a systematic review","volume":"99","author":"Xu","year":"2020","journal-title":"Medicine."},{"key":"B99","doi-asserted-by":"publisher","first-page":"e0213319","DOI":"10.1371\/journal.pone.0213319","article-title":"Corneal nerve and endothelial cell damage in patients with transient ischemic attack and minor ischemic stroke","volume":"14","author":"Gad","year":"2019","journal-title":"PLoS ONE."},{"key":"B100","doi-asserted-by":"publisher","first-page":"17333","DOI":"10.1038\/s41598-018-35298-3","article-title":"Corneal confocal microscopy detects a reduction in corneal endothelial cells and nerve fibres in patients with acute ischemic stroke","volume":"8","author":"Khan","year":"2018","journal-title":"Sci Rep."},{"key":"B101","doi-asserted-by":"publisher","first-page":"e0231987","DOI":"10.1371\/journal.pone.0231987","article-title":"Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke","volume":"15","author":"Khan","year":"2020","journal-title":"PLoS ONE."},{"key":"B102","doi-asserted-by":"publisher","first-page":"104543","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104543","article-title":"Cornea: a window to white matter changes in stroke; corneal confocal microscopy a surrogate marker for the presence and severity of white matter hyperintensities in ischemic stroke","volume":"29","author":"Kamran","year":"2020","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B103","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.jamda.2016.12.078","article-title":"Prevalence of pain in nursing home residents: the role of dementia stage and dementia subtypes","volume":"18","author":"van Kooten","year":"2017","journal-title":"J Am Med Direct Assoc."},{"key":"B104","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s40263-016-0342-7","article-title":"Identifying and managing pain in people with Alzheimer's disease and other types of dementia: a systematic review","volume":"30","author":"Husebo","year":"2016","journal-title":"CNS Drugs."},{"key":"B105","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.1167\/iovs.18-24694","article-title":"Ocular biomarkers of Alzheimer's disease: the role of anterior eye and potential future directions","volume":"59","author":"Dehghani","year":"2018","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/acn3.746","article-title":"Association of corneal nerve fiber measures with cognitive function in dementia","volume":"6","author":"Ponirakis","year":"2019","journal-title":"Ann Clin Transl Neurol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.3233\/JAD-200678","article-title":"Corneal nerve and brain imaging in mild cognitive impairment and dementia","volume":"77","author":"Al-Janahi","year":"2020","journal-title":"J Alzheimers Dis."},{"key":"B108","doi-asserted-by":"publisher","first-page":"105273","DOI":"10.1016\/j.nbd.2021.105273","article-title":"Tau associated peripheral and central neurodegeneration: identification of an early imaging marker for tauopathy","volume":"151","author":"Marquez","year":"2021","journal-title":"Neurobiol Dis."},{"key":"B109","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1111\/head.12547","article-title":"Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye","volume":"55","author":"Kinard","year":"2015","journal-title":"Headache."},{"key":"B110","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1097\/ICO.0000000000001403","article-title":"Subbasal nerve plexus changes in chronic migraine","volume":"37","author":"Shetty","year":"2018","journal-title":"Cornea."},{"key":"B111","doi-asserted-by":"publisher","first-page":"661","DOI":"10.3389\/fneur.2020.00661","article-title":"Corneal confocal microscopy demonstrates corneal nerve loss in patients with trigeminal neuralgia","volume":"11","author":"Lee","year":"2020","journal-title":"Front Neurol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"337","DOI":"10.11607\/ofph.2338","article-title":"Corneal confocal microscopy detects small-fiber neuropathy in burning mouth syndrome: a cross-sectional study","volume":"33","author":"O'Neill","year":"2019","journal-title":"J Oral Fac Pain Headache."},{"key":"B113","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.2337\/dc07-0870","article-title":"Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes","volume":"30","author":"Mehra","year":"2007","journal-title":"Diabetes Care."},{"key":"B114","doi-asserted-by":"publisher","first-page":"254","DOI":"10.2337\/db12-0574","article-title":"Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation","volume":"62","author":"Tavakoli","year":"2013","journal-title":"Diabetes."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1007\/s00125-019-4897-y","article-title":"Early nerve fibre regeneration in individuals with type 1 diabetes after simultaneous pancreas and kidney transplantation","volume":"62","author":"Azmi","year":"2019","journal-title":"Diabetologia."},{"key":"B116","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s11695-020-05052-8","article-title":"Improvements in diabetic neuropathy and nephropathy after bariatric surgery: a prospective cohort study","volume":"31","author":"Adam","year":"2020","journal-title":"Obesity Surg."},{"key":"B117","doi-asserted-by":"publisher","first-page":"334","DOI":"10.2119\/molmed.2013.00122","article-title":"ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density","volume":"19","author":"Dahan","year":"2013","journal-title":"Mol Med."},{"key":"B118","doi-asserted-by":"publisher","first-page":"BIO52","DOI":"10.1167\/iovs.16-21291","article-title":"Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain","volume":"58","author":"Culver","year":"2017","journal-title":"Investig Ophthalmol Vis Sci."},{"key":"B119","doi-asserted-by":"publisher","first-page":"658","DOI":"10.2119\/molmed.2014.00215","article-title":"ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes","volume":"20","author":"Brines","year":"2014","journal-title":"Mol Med."},{"key":"B120","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1212\/WNL.0000000000004033","article-title":"Effect of omega-3 supplementation on neuropathy in type 1 diabetes: a 12-month pilot trial","volume":"88","author":"Lewis","year":"2017","journal-title":"Neurology."},{"key":"B121","doi-asserted-by":"publisher","first-page":"107798","DOI":"10.1016\/j.jdiacomp.2020.107798","article-title":"Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes","volume":"35","author":"Lewis","year":"2021","journal-title":"J Diabetes Comp."},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0136","article-title":"Investigating the neuroprotective effect of oral omega-3 fatty acid supplementation in type 1 diabetes (nPROOFS1): a randomized placebo-controlled trial","author":"Britten-Jones","year":"2021","journal-title":"Diabetes"},{"key":"B123","doi-asserted-by":"publisher","first-page":"e001420","DOI":"10.1136\/bmjdrc-2020-001420","article-title":"Effect of treatment with exenatide and pioglitazone or basal-bolus insulin on diabetic neuropathy: a substudy of the Qatar Study","volume":"8","author":"Ponirakis","year":"2020","journal-title":"BMJ Open Diabetes Res Care."},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13582","article-title":"Insulin resistance limits corneal nerve regeneration in patients with Type 2 diabetes undergoing intensive glycemic control","author":"Ponirakis","year":"2021","journal-title":"J Diabetes Investig."},{"key":"B125","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/jdi.13544","article-title":"Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control","volume":"127","author":"Ponirakis","year":"2021","journal-title":"J Diabetes Investig."},{"key":"B126","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/bs.irn.2016.03.008","article-title":"Wherefore art thou, o treatment for diabetic neuropathy?","volume":"127","author":"Malik","year":"2016","journal-title":"Int Rev Neurobiol."}],"container-title":["Frontiers in Pain Research"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2021.725363\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:50:26Z","timestamp":1629366626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2021.725363\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":126,"alternative-id":["10.3389\/fpain.2021.725363"],"URL":"https:\/\/doi.org\/10.3389\/fpain.2021.725363","relation":{},"ISSN":["2673-561X"],"issn-type":[{"value":"2673-561X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]},"article-number":"725363"}}