Oxervate (cenegermin) eye drops healed corneal lesions and increased corneal sensitivity over the long term in cases of hard-to-treat neurotrophic keratitis (NK), according to a recent case series.
This increased sensitivity hints at the recovery of the nerves supplying the cornea, a hypothesis that deserves further investigation, the authors suggest.
The study, “Long-term restoration of corneal sensitivity in neurotrophic keratopathy after rhNGF treatment,” was published in the European Journal of Ophthalmology.
Oxervate, developed by Dompé, contains recombinant, or lab-made, human nerve growth factor (rhNGF). Nerve growth factor occurs naturally in the eyes, where it promotes the growth and survival of nerve cells by stimulating tear secretion and wound healing in the cornea — the eye’s transparent and protective outer layer.
To evaluate Oxervate’s long-term effects on corneal sensitivity, researchers at the Ophthalmology Operative Complex Unit of the University Campus Bio-Medico of Rome in Italy, evaluated three NK patients’ responses to the therapy over an eight-week treatment period and roughly 35 weeks of follow-up.
All patients had stage two (persistent epithelial effect) or three (corneal ulcer penetrating the epithelium) NK and a corneal lesion (wound) on one eye that was treated with Oxervate after not responding to one or more standard non-surgical treatments.
Each patient received these eye drops six times per day for eight weeks. Corneal sensitivity was evaluated with a Cochet-Bonnet aesthesiometer (CBA) before beginning treatment, then weekly during the course of treatment, and monthly thereafter.
The CBA consists of a small nylon filament that extends directly onto the cornea. As the filament is retracted, pressure increases until a patient feels the contact. Lower measurements indicate less sensitivity.
Best corrected visual acuity (BCVA) and Type I Schirmer test — a measure of tear secretion — were also used to assess each patient’s case.
The first patient was a 75-year-old man with a history of herpes simplex virus eye infections (HSV keratitis) and a corneal ulcer in his left eye. His corneal sensitivity was zero millimeters, according to the CBA, and the Shirmer test indicated reduced tear secretion.
The second patient was a 84-year-old woman with a previous diagnosis of HSV keratitis and a corneal ulcer in her right eye. Her corneal sensitivity was nearly absent and severely reduced tear secretion by Schirmer test.
The third patient was a 67-year-old man with a history of recurrent epithelial and stromal immune keratitis between January and October 2018. In November 2018, he developed a central corneal ulcer in his right eye with a corneal sensitivity of zero millimeters.
All patients had a BCVA of hand motion, indicating generally low visual acuity.
All three patients’ corneas completely healed after an average period of 47 days. All ulcers repaired within the eight-week treatment period. Measures of healing began between three and seven days after start of treatment.
These measures included the growth of epithelial cells from an ulcer’s margins to its center, the occurrence of mild to moderate redness of the vessels of the eye, mild pain, and sensitivity to light.
Corneal sensitivity returned to normal limits in the first and second patients, improving from 0 to a mean of 50 mm and from 0 to 52 mm, respectively). Corneal sensitivity improved from 0 to a mean of 12 mm in the third patient, which the researchers described as hypoesthesia, or reduced sensation.
The main side effect related to treatment was pain in the eyes. Other complaints included excessive tearing, light sensitivity, and pain and irritation of both the eye and eyelid. The investigators mentioned that these symptoms could reflect the restoration of corneal nerves.
All patients maintained stable, healed corneal epithelia over the entire follow-up period, which lasted for an average of 35 weeks.
“In conclusion,” the researchers wrote, “rhNGF has been proved beneficial in healing corneal ulcer, restoring corneal sensitivity and avoiding recurrences in this cases series of recalcitrant NK.”
They noted that Oxervate’s efficacy could be explained by a direct effect on corneal cells or by restoring the nerves that supply the cornea.
“Since no evidences of nerve regeneration with rhNFG treatment have been directly demonstrated, more studies are warranted to better understand the mechanisms of this novel therapy,” they concluded.