Corneal nerve loss is related to the severity of painful diabetic neuropathy

A. Kalteniece, M. Ferdousi, S. Azmi, S.U. Khan, A. Worthington, A. Marshall, C.G. Faber, G. Lauria, A.J.M. Boulton, H. Soran, R.A. Malik*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background and purpose Previously it has been shown that patients with painful diabetic neuropathy (PDN) have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of PDN. Methods Participants with diabetic neuropathy (n = 118) and healthy controls (n = 38) underwent clinical and neurological evaluation, quantitative sensory testing, nerve conduction testing and corneal confocal microscopy and were categorized into those with no (n = 43), mild (n = 34) and moderate-to-severe (n = 41) neuropathic pain. Results Corneal nerve fibre density (p = 0.003), corneal nerve fibre length (p < 0.0001) and cold perception threshold (p < 0.0001) were lower and warm perception threshold was higher (p = 0.002) in patients with more severe pain, but there was no significant difference in the neuropathy disability score (p = 0.5), vibration perception threshold (p = 0.5), sural nerve conduction velocity (p = 0.3) and amplitude (p = 0.7), corneal nerve branch density (p = 0.06) and deep breathing heart rate variability (p = 0.08) between patients with differing severity of PDN. The visual analogue scale correlated significantly with corneal nerve fibre density (r = -0.3, p = 0.0002), corneal nerve branch density (r = -0.3, p = 0.001) and corneal nerve fibre length (r = -0.4, p < 0.0001). Receiver operating curve analysis showed that corneal nerve fibre density had an area under the curve of 0.78 with a sensitivity of 0.73 and specificity of 0.72 for the diagnosis of PDN. Conclusions Corneal confocal microscopy reveals increasing corneal nerve fibre loss with increasing severity of neuropathic pain and a good diagnostic outcome for identifying patients with PDN.
Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalEuropean Journal of Neurology
Issue number1
Early online date13 Oct 2021
Publication statusPublished - Jan 2022


  • cornea
  • corneal confocal microscopy
  • corneal nerve
  • neuropathic pain
  • painful diabetic neuropathy

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