title: Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density.
abstract: OBJECTIVE
  Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard.
  
  
  METHODS
  Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy.
  
  
  RESULTS
  Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14).
  
  
  CONCLUSIONS
  This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.
authors: Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester, U.K.
authors: Xin
authors: X
authors: Chen
authors: Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester, U.K.
authors: Jim
authors: J
authors: Graham
authors: Centre for Imaging Sciences, Institute of Population Health, University of Manchester, Manchester, U.K.
authors: Mohammad A
authors: MA
authors: Dabbah
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Ioannis N
authors: IN
authors: Petropoulos
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Georgios
authors: G
authors: Ponirakis
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Omar
authors: O
authors: Asghar
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Uazman
authors: U
authors: Alam
authors: Department of Clinical Neurophysiology, Central Manchester NHS Foundation Trust, Manchester, U.K.
authors: Andrew
authors: A
authors: Marshall
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Hassan
authors: H
authors: Fadavi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Maryam
authors: M
authors: Ferdousi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Shazli
authors: S
authors: Azmi
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Mitra
authors: M
authors: Tavakoli
authors: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors: Nathan
authors: N
authors: Efron
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Maria
authors: M
authors: Jeziorska
authors: Centre for Endocrinology and Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, Manchester, U.K. Division of Medicine, Weill Cornell Medical College in Qatar, Doha, Qatar ram2045@qatar-med.cornell.edu rayaz.a.malik@manchester.ac.uk.
authors: Rayaz A
authors: RA
authors: Malik
mesh_terms: D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D016022:Case-Control Studies; D003315:Cornea / Q000294:innervation / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000473:pathology* / Q000503:physiopathology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009412:Nerve Fibers / Q000473:pathology*; D009431:Neural Conduction / Q000502:physiology; D011115:Polyneuropathies / Q000473:pathology / Q000503:physiopathology; D012372:ROC Curve; D012867:Skin / Q000294:innervation / Q000473:pathology
chemical_list: D015415:Biomarkers