Augmented Corneal Nerve Fiber Branching in Painful Compared With Painless Diabetic Neuropathy

J Clin Endocrinol Metab. 2019 Dec 1;104(12):6220-6228. doi: 10.1210/jc.2019-01072.


Context: The factors that determine the development of diabetic sensorimotor polyneuropathy (DSPN) as a painful or painless entity are unknown.

Objective: We hypothesized that corneal nerve pathology could be more pronounced in painful DSPN, indicating predominant small nerve fiber damage.

Design and methods: In this cross-sectional study, we assessed 53 patients with painful DSPN, 63 with painless DSPN, and 46 glucose-tolerant volunteers by corneal confocal microscopy (CCM), nerve conduction (NC), and quantitative sensory testing. DSPN was diagnosed according to modified Toronto Consensus criteria. A cutoff at 4 points on the 11-point rating scale was used to differentiate between painful and painless DSPN.

Results: After adjustment for age, sex, body mass index, and smoking, corneal nerve fiber density, corneal nerve fiber length, and corneal nerve branch density (CNBD) were reduced in both DSPN types compared with the control group (P < 0.05). Only CNBD differed between the groups; it was greater in patients with painful DSPN compared with those with painless DSPN [55.8 (SD, 29.9) vs 43.8 (SD, 28.3) branches/mm2; P < 0.05]. Several CCM measures were associated with NC and cold perception threshold in patients with painless DSPN (P < 0.05) but not those with painful DSPN.

Conclusion: Despite a similarly pronounced peripheral nerve dysfunction and corneal nerve fiber loss in patients with painful and painless DSPN, corneal nerve branching was enhanced in those with painful DSPN, pointing to some susceptibility of corneal nerve fibers toward regeneration in this entity, albeit possibly not to a sufficient degree.

Trial registration: NCT02243475 NCT01055093.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cornea / pathology*
  • Cross-Sectional Studies
  • Diabetic Neuropathies / complications*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microscopy, Confocal
  • Nerve Fibers / pathology*
  • Pain / diagnosis*
  • Pain / etiology
  • Peripheral Nervous System Diseases / diagnosis*
  • Peripheral Nervous System Diseases / etiology
  • Prognosis

Supplementary concepts

  • Neuropathy, Painful

Associated data