Neurotrophic keratopathy

Prog Retin Eye Res. 2018 Sep;66:107-131. doi: 10.1016/j.preteyeres.2018.04.003. Epub 2018 Apr 23.


Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.

Keywords: Keratitis; Matrix regenerating agents; Nerve growth factor; Neurotrophic keratopathy; Trigeminal neve diseases.

Publication types

  • Review

MeSH terms

  • Contact Lenses
  • Cornea / physiopathology*
  • Corneal Diseases / physiopathology*
  • Corneal Diseases / therapy
  • Epithelium, Corneal / pathology
  • Humans
  • Keratitis / physiopathology
  • Ophthalmic Solutions / therapeutic use
  • Trigeminal Nerve Diseases / physiopathology*


  • Ophthalmic Solutions