Now, you may be wondering why someone focused on emergency medicine would be spotlighting an eye drop for neurotrophic keratitis. The answer is because I first heard of the drug years ago while performing med reconciliations in the emergency department. Diving down the rabbit hole, I couldn’t ignore how cool it was.
Image: Corneal ulceration as a result of neurotrophic keratitis
Naturally, this disease process leads to progressive damage of the lens of the eye and can produce visual blurriness and certain degrees of vision loss. Though it sounds scary, neurotrophic keratitis is quite rare, with an incidence of anywhere from 1-5/10,000 people, making it an orphan disease.
Now, back to my med reconciliation story. I was interviewing a patient who stated that he was receiving eye drops “from Italy” to “regrow my cornea.” Of course, I was intrigued but also skeptical since people can say some pretty odd things when they’re in the hospital. Sure enough, with a bit of googling, I came across cenegermin, which was originally produced by an Italian company and only became approved by the FDA as recent as 2018.
Cenegermin itself is a rhNGF (recombinant human nerve growth factor) which is identical to the nerve growth factor produced by your own body. This rhNGF performs the same function as your innate NGF produced by your own body: stimulate corneal epithelial cell growth, promote tear production via binding to lacrimal glands, and support reinnervation of the cornea itself. The last part I was particularly blown away by, since I don’t think of the ability to reinnervate portions of your body is something that’s particularly common. While NGF was discovered in the 1950s by Italian neurologist Rita Levi-Montalcini, Phase 1 trials did not begin on cenegermin itself until 2014, with the US Phase 2 trial coming via the REPARO trial.
The REPARO trial was utilized to assess efficacy and safety of cenegermin against placebo, as well as testing two dosing schemes of cenegermin against one another. To summarize, about 74% of active-treatment patients achieved corneal healing (74.5% in 10mcg/mL dose and 74.0% in 10mcg/mL dose) vs 43.1% in the placebo vehicle (plain eye drop) group at week 8. Additionally, corneal healing was maintained by >96% of treatment group patients at a 56 week follow-up. Notably, the control group who did achieve healing also had a similar rate of maintained healing, though the initial success with healing in the placebo group was much lower, as stated above.
Top images: Corneal ulceration lesions shown via fluorescein staining under cobalt blue light at baseline, week 4, week 6, and week 8 (notice decreasing size of green-staining lesion)
Bottom image: Least squares mean percentage change in lesion size from baseline through weeks 4 and 8.
Prior to the approval of Oxervate (cenegermin), outpatient maintenance care of stages 1 and 2 NK included combinations of lubricating applications of eye drops and ointments, soft contact lenses, outpatient procedures (amniotic membrane grafting, botulin induced ptosis, topical autologous serum application), and occasional application of topical antibiotics as needed for prevention of bacterial infections. Now, it seems that the outlook of this orphan disease has really turned a corner. Directions for Oxervate are the same for everybody: 1 drop to each affected eye, every 2 hours (6 times a day within a 12-hour period) for 8 weeks.
It should be noted that this breakthrough treatment comes at a hefty cost of $11,800 per week x 8 weeks = $94,400 per treatment. So, if you have NK and have either really good insurance or the ability to take out a second mortgage on your home, Oxervate is the breakthrough treatment you need in your life. Despite its drawbacks with cost, the technology behind it truly is fascinating and provides me with hope that many other degenerative nerve diseases may be able to find their cure in a not-so-distant future.
Sources (non-formatted because I’m a rebel):