First Clinical Use of Nerve Growth Factor (NGF) in Human Cornea
Nerve Growth Factor (NGF) was first used in the human cornea as a treatment in 2003 when it was applied to heal human corneal ulcers, as documented in the Archives Italiennes de Biologie. 1
Historical Development of NGF as a Corneal Therapy
NGF has a rich history in neuroscience since its discovery in the 1950s, but its application in ophthalmology came much later:
- Initially discovered for its action on the survival and differentiation of peripheral neurons 2
- First clinical application on human corneal ulcers was documented in 2003 1
- In this pioneering study, topical NGF was applied to corneal ulcers that were non-responsive to conventional treatments 1
- The treatment resulted in complete healing without side effects or relapse during follow-up 1
Mechanism of Action in Corneal Applications
NGF functions through multiple mechanisms that make it effective for corneal conditions:
- Promotes epithelial healing and prevents progression to corneal opacification 3
- Reduces allodynia and hyperalgesia through reduction of reactive astrocytosis and glial modulation 3
- Provides trophic support to corneal tissues 4
- Modulates immune reactions on the ocular surface 4
- Improves corneal sensitivity and tear film function 4
Evolution of NGF Therapy After Initial Use
Following the first clinical application, NGF therapy has expanded to treat various ocular conditions:
- Treatment of neurotrophic keratitis became a primary indication 4
- Applied to peripheral ulcerative keratopathy and dry eye conditions 4
- Used in cases of corneal surgery for improved healing 4
- Investigated for herpes virus corneal infections 4
- Studied for effects on ocular surface stem cell differentiation and proliferation 4
Current Status and Recognition
NGF has gained significant recognition in ophthalmology:
- Received orphan drug status within the last decade 5
- Now recognized by the American Academy of Ophthalmology for treating non-healing epithelial defects, particularly in neurotrophic keratopathy 3
- Considered a valuable alternative before resorting to more invasive procedures for delayed healing of corneal epithelial defects 3
Clinical Considerations and Limitations
Despite its therapeutic potential, there are important considerations:
- Limited availability and high cost may restrict widespread use 3
- Patient selection is critical, with best results seen in neurotrophic conditions 3
- Dosing protocols have evolved since initial applications
- NGF eye drops have demonstrated ability to target not only the cornea but also the optic nerve and brain, opening avenues for treating neurodegenerative diseases 6
NGF therapy represents a significant advancement in corneal treatment since its first human application in 2003, with continued research expanding its potential applications in ophthalmology and beyond.