Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

Shaishav Dhage, Maryam Ferdousi, Safwaan Adam, Jan Hoong Ho, Alise Kalteniece, Shazli Azmi, Uazman Alam, Georgios Ponirakis, Ioannis Petropoulos, Andrew J. Atkinson, Andrew Marshall, Maria Jeziorska, Handrean Soran, Rayaz A. Malik

Research output: Contribution to journalArticlepeer-review


Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.

Original languageEnglish
Article number1859
JournalScientific Reports
Issue number1
Publication statusPublished - 21 Jan 2021


  • Adult
  • Aged
  • Analysis of Variance
  • Body Mass Index
  • Cholesterol, LDL/blood
  • Cornea/pathology
  • Diabetes Mellitus, Type 1/blood
  • Diabetes Mellitus, Type 2/blood
  • Diabetic Neuropathies/blood
  • Disease Progression
  • Glycated Hemoglobin A/metabolism
  • Humans
  • Microscopy, Confocal/methods
  • Middle Aged
  • Nerve Fibers/pathology


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