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

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


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.

MeSH terms

  • Adult
  • Cornea / diagnostic imaging*
  • Cornea / pathology
  • Cross-Sectional Studies
  • Diabetic Neuropathies / diagnostic imaging*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology
  • Epidermis / innervation*
  • Female
  • Humans
  • Male
  • Microscopy, Confocal*
  • Middle Aged
  • Nerve Fibers / pathology*
  • ROC Curve
  • Temperature
  • Touch Perception
  • Vibration