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Corneal Confocal Microscopy

A novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

  1. Mitra Tavakoli, PHD1,
  2. Cristian Quattrini, MD, PHD1,
  3. Caroline Abbott, PHD1,
  4. Panagiotis Kallinikos, PHD1,
  5. Andrew Marshall, MD2,
  6. Joanne Finnigan, BSC2,
  7. Philip Morgan, PHD3,
  8. Nathan Efron, PHD4,
  9. Andrew J.M. Boulton, MD1 and
  10. Rayaz A. Malik, MD, PHD1
  1. 1Division of Cardiovascular Medicine, University of Manchester and Central Manchester Foundation Trust, Manchester, U.K.;
  2. 2Department of Neurophysiology, Central Manchester Foundation Trust, Manchester, U.K.;
  3. 3Eurolens Research Group, University of Manchester, Manchester, U.K.;
  4. 4Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
  1. Corresponding author: Rayaz A. Malik, rayaz.a.malik{at}man.ac.uk.

Abstract

OBJECTIVE The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.

RESEARCH DESIGN AND METHODS A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).

RESULTS Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74).

CONCLUSIONS CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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This Article

  1. Diabetes Care August 2010 vol. 33 no. 8 1792-1797
  1. All Versions of this Article:
    1. dc10-0253v1
    2. 33/8/1792 most recent
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