In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus

Graefes Arch Clin Exp Ophthalmol. 2010 Sep;248(9):1307-12. doi: 10.1007/s00417-010-1396-8. Epub 2010 May 21.


Background: Advanced diabetic keratopathy includes impaired corneal sensation, reduced tear secretion, conjunctival squamous metaplasia, and goblet cell loss, as well as susceptibility to corneal erosions and ulcerations. It is thought to be a form of generalized diabetic neuropathy. Early diagnosis of nerve fiber degeneration is essential to prevent further damage.

Methods: We examined the corneal innervation pattern of patients with diabetes mellitus type 1 and 2 of various durations by in vivo confocal microscopy, and correlated our findings to the severity of diabetic retinopathy, corneal sensation, peripheral diabetic neuropathy in the lower limb, and nephropathy.

Results: Nerve fiber length (NFL) was significantly different between patients without diabetic retinopathy and controls (p = 0.028). In patients with non-proliferative diabetic retinopathy (NPDR) and patients with proliferative diabetic retinopathy (PDR), nerve fiber parameters including density (NFD), NFL, and corneal nerve branching (NB) showed a difference with increasing significance compared to healthy persons. A history of nephropathy and/or peripheral neuropathy (all p < 0.001), decreased corneal sensation (all p < or = 0.03), and pathological vibration sensation (p < or = 0.04) were significantly associated with a decrease in NFD, NFL, and NB (except vibration sensation). Unexpectedly, diabetic patients with normal corneal and vibration sensation demonstrated significant changes in NFD (p = 0.005), NFL, and NB (both p = 0.001) compared to healthy volunteers with intact corneal and vibration sensation.

Conclusion: Confocal microscopy is a valuable tool for demonstrating subtle corneal nerve alterations in vivo. It is capable of demonstrating diabetic nerve fiber damage earlier than corneal sensation testing and vibration perception assessment in the lower limb.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Cornea / innervation*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetic Neuropathies / diagnosis*
  • Diabetic Neuropathies / etiology
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Male
  • Microscopy, Confocal*
  • Middle Aged
  • Nerve Fibers / pathology*
  • Ophthalmic Nerve / pathology*


  • Blood Glucose
  • Glycated Hemoglobin A