New therapeutic approaches in the treatment of diabetic keratopathy: a review

Clin Exp Ophthalmol. 2011 Apr;39(3):259-70. doi: 10.1111/j.1442-9071.2010.02435.x. Epub 2011 Apr 4.


The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Cornea / innervation
  • Corneal Diseases / drug therapy*
  • Diabetes Complications / drug therapy*
  • Epithelium, Corneal / physiology
  • Humans
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use
  • Nerve Growth Factors / pharmacology
  • Nerve Growth Factors / therapeutic use
  • Nicergoline / pharmacology
  • Nicergoline / therapeutic use
  • Trigeminal Ganglion / physiopathology
  • Wound Healing / drug effects


  • Insulin
  • Nerve Growth Factors
  • Naltrexone
  • Nicergoline