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. 2017 Jul 18;12(7):e0180175.
doi: 10.1371/journal.pone.0180175. eCollection 2017.

Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy

Uazman Alam  1   2 , Maria Jeziorska  2 , Ioannis N Petropoulos  2 , Omar Asghar  2 , Hassan Fadavi  2 , Georgios Ponirakis  3 , Andrew Marshall  2 , Mitra Tavakoli  2   4 , Andrew J M Boulton  2 , Nathan Efron  5 , Rayaz A Malik  2   3
Affiliations

Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy

Uazman Alam et al. PLoS One. .

Abstract

Objectives: Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against a range of established measures of nerve damage in patients with diabetic neuropathy.

Methods: In this cross sectional study, thirty subjects with Type 1 diabetes without neuropathy (T1DM), thirty one T1DM subjects with neuropathy (DSPN) and twenty seven non-diabetic healthy control subjects underwent detailed assessment of neuropathic symptoms and neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy and corneal confocal microscopy (CCM).

Results: Subjects with DSPN were older (C vs T1DM vs DSPN: 41.0±14.9 vs 38.8±12.5 vs 53.3±11.9, P = 0.0002), had a longer duration of diabetes (P<0.0001), lower eGFR (P = 0.006) and higher albumin-creatinine ratio (P = 0.03) with no significant difference for HbA1c, BMI, lipids and blood pressure. Patients with DSPN were representative of subjects with diabetic neuropathy with clinical signs and symptoms of neuropathy and greater neuropathy deficits quantified by QST, electrophysiology, intra-epidermal nerve fibre density and CCM. Corneal nerve fibre density (CNFD) (Spearman's Rho = 0.60 P<0.0001) and IENFD (Spearman's Rho = 0.56 P<0.0001) were comparable when correlated with peroneal nerve conduction velocity. For the diagnosis of diabetic neuropathy the sensitivity for CNFD was 0.77 and specificity was 0.79 with an area under the ROC curve of 0.81. IENFD had a diagnostic sensitivity of 0.61, specificity of 0.80 and area under the ROC curve of 0.73.

Conclusions: CCM is a valid accurate non-invasive method to identify small nerve fibre pathology and is able to diagnose DPN.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
A, B & C. Skin biopsy images of IENF in C, T1DM and DSPN.Red arrows point to intra-epidermal nerve fibres.
Fig 2
Fig 2
A, B & C. CCM images in C, T1DM and DSPN. Red arrows show corneal nerve branches and yellow arrows show corneal nerve fibres.
Fig 3
Fig 3. Receiver-operated characteristic (ROC) curves, based on the analysis of CNFD and IENFD in T1DM without DSPN versus with DSPN.
Black line represents CNFD and red line represents IENFD.
See this image and copyright information in PMC

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