A non-invasive imaging technique demonstrated that, after eight weeks of treatment, Oxervate eye drops repaired cornea nerve fibers, which are damaged in people with neurotrophic keratitis (NK), according to a study that reported these results for the first time.
All patients, who were moderately or severely affected, achieved complete healing of the cornea surface and improved tear secretion and corneal sensitivity, the study found.
The study, “In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Recombinant Nerve Growth Factor for Neurotrophic Keratopathy,” was published in the American Journal of Ophthalmology.
Oxervate (cenegermin), developed by Dompé, is a recombinant or lab-made form of the human protein nerve growth factor (NGF), approved in the U.S. and some European countries for people with neurotrophic keratitis.
NGF, which occurs naturally in the eye, plays an essential role in the growth and survival of nerve cells by promoting tear secretion and wound healing in the cornea — the transparent protective outer layer of the eye.
Administered as eye drops, Oxervate — which is structurally identical to the natural form of NGF — is the first medical intervention aimed at restoring corneal nerves damaged in NK.
Now, researchers based at the University of Chieti-Pescara, in Italy, sought to directly investigate the impact of Oxervate treatment on corneal nerve fibers. The case-controlled study (NCT04293549) involved 18 people with moderate or severe NK who did not respond to other medical treatments.
The team used a non-invasive imaging technique called in vivo confocal microscopy (IVCM), which allowed for the “direct and real-time evaluation” of corneal nerves following Oxervate treatment.
A total of nine women and nine men, ranging in age from 50 to 83, were enrolled. All had been treated for at least four weeks with lubricants, topical antibiotics, and therapeutic contact lenses, without success. A group of 20 healthy people (controls) matched for age and sex was included as a comparison.
The patients were treated with one drop of 20 mg/mL Oxervate six times daily in the affected eye for eight weeks.
Additional tests evaluated changes to the outer (epithelium) and inner (stroma) layer of the cornea, tear film secretion, and cornea sensitivity. All tests were conducted at the beginning of the study (baseline) and after four and eight weeks of treatment.
After four weeks of Oxervate, complete corneal epithelial healing was achieved in 15 of 18 patients, and in all patients at eight weeks. Overall, tear film secretion significantly increased at week eight compared with the trial’s start.
Corneal sensitivity at the start of the study was significantly lower in patients treated with Oxervate compared with the healthy participants. Notably, after eight weeks of treatment, there was a significant increase in corneal sensation in three of four areas tested.
The IVCM analysis revealed a significant increase in nerve fiber density at the interface between the corneal epithelium and the stroma (subbasal) at weeks four and eight of treatment.
At the study’s start, the average nerve fiber density in patients was 945.0 micrometers per square millimeter (microm/mm2) compared with 5,312.5 microm/mm2 in healthy controls. After four weeks of treatment, the nerve fiber density expanded to 2,002.4 microm/mm2, and was 2,500.5 microm/mm2 at eight weeks.
After eight weeks of treatment, the average number of nerve branches significantly increased from 2.5 at baseline to 6.0, and the diameter of nerve fibers significantly increased from an average of 3.3 micrometers to 6.8 micrometers.
Despite the regeneration of nerve fibers in the treated patients, their nerve fiber density, number of branches, and the diameter of nerve fibers were still less than the control group after treatment.
“Topical treatment with [Oxervate] was effective in promoting complete corneal healing of persistent epithelial defects and corneal ulcers in patients with NK,” the researchers wrote.
“This was associated with an improvement of corneal sensitivity and an increase of sub-basal nerve density, diameter, and number of nerve branches, indicating improvement in structure and function of corneal nerves,” they concluded.