Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

Xin Chen, Jim Graham, Mohammad A. Dabbah, Ioannis N. Petropoulos, Georgios Ponirakis, Omar Asghar, Uazman Alam, Andrew Marshall, Hassan Fadavi, Maryam Ferdousi, Shazli Azmi, Mitra Tavakoli, Nathan Efron, Maria Jeziorska, Rayaz Malik

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73 Citations (Scopus)

Abstract

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. RESEARCH DESIGN AND 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 CCMand 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 CCMas a surrogate end point for DSPN.

Original languageEnglish
Pages (from-to)1138-1144
Number of pages7
JournalDiabetes Care
Volume38
Issue number6
DOIs
Publication statusPublished - 1 Jun 2015

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Diabetic Neuropathies
Nerve Fibers
Confocal Microscopy
Biomarkers
Type 1 Diabetes Mellitus
ROC Curve
Early Diagnosis
Guidelines
Biopsy
Skin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy : Comparing corneal confocal microscopy with intraepidermal nerve fiber density. / Chen, Xin; Graham, Jim; Dabbah, Mohammad A.; Petropoulos, Ioannis N.; Ponirakis, Georgios; Asghar, Omar; Alam, Uazman; Marshall, Andrew; Fadavi, Hassan; Ferdousi, Maryam; Azmi, Shazli; Tavakoli, Mitra; Efron, Nathan; Jeziorska, Maria; Malik, Rayaz.

In: Diabetes Care, Vol. 38, No. 6, 01.06.2015, p. 1138-1144.

Research output: Contribution to journalArticle

Chen, X, Graham, J, Dabbah, MA, Petropoulos, IN, Ponirakis, G, Asghar, O, Alam, U, Marshall, A, Fadavi, H, Ferdousi, M, Azmi, S, Tavakoli, M, Efron, N, Jeziorska, M & Malik, R 2015, 'Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density', Diabetes Care, vol. 38, no. 6, pp. 1138-1144. https://doi.org/10.2337/dc14-2422
Chen, Xin ; Graham, Jim ; Dabbah, Mohammad A. ; Petropoulos, Ioannis N. ; Ponirakis, Georgios ; Asghar, Omar ; Alam, Uazman ; Marshall, Andrew ; Fadavi, Hassan ; Ferdousi, Maryam ; Azmi, Shazli ; Tavakoli, Mitra ; Efron, Nathan ; Jeziorska, Maria ; Malik, Rayaz. / Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy : Comparing corneal confocal microscopy with intraepidermal nerve fiber density. In: Diabetes Care. 2015 ; Vol. 38, No. 6. pp. 1138-1144.
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AU - Petropoulos, Ioannis N.

AU - Ponirakis, Georgios

AU - Asghar, Omar

AU - Alam, Uazman

AU - Marshall, Andrew

AU - Fadavi, Hassan

AU - Ferdousi, Maryam

AU - Azmi, Shazli

AU - Tavakoli, Mitra

AU - Efron, Nathan

AU - Jeziorska, Maria

AU - Malik, Rayaz

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N2 - 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. RESEARCH DESIGN AND 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 CCMand 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 CCMas a surrogate end point for DSPN.

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