Neurotrophic keratitis: inflammatory pathogenesis and novel therapies

Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management.

Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging.

Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.