A young boy with neurotrophic keratopathy (NK) caused by a rare congenital disorder was successfully treated with the topical nerve growth factor therapy Oxervate (cenegermin), a case study reports.
The treatment was well-tolerated, which represents a therapeutic option in managing congenital NK in children, the authors said.
The study, “A case report of pediatric neurotrophic keratopathy in pontine tegmental cap dysplasia treated with cenegermin eye drops,” was published in the journal Medicine.
Oxervate (developed by Dompé) is an eyedrop therapy designed to repair nerve damage in people with NK in which the active ingredient is recombinant human nerve growth factor (rhNGF). This protein helps maintain and heal nerves of the cornea by mimicking naturally-occurring NGF.
Oxervate is used to treat NK commonly caused by viral infections, eye injury, overuse of medications and contact lenses, and some surgical procedures.
However, few cases have been reported of people with NK caused by rare congenital disorders being treated with Oxervate.
Researchers based at the University of Pavia in Italy described the case of a 9-year-old boy affected by the rare congenital neurological disorder pontine tegmental cap dysplasia (PTCD) who was referred to the hospital for visual disturbances and redness of the left eye.
PTCD, with unknown cause, is a developmental disorder characterized by significant developmental delays, hearing deficits, uncontrolled movements (ataxia), language and speech disorders, heart malformations and facial paralysis, abnormalities of eye movements, and deficiency of the trigeminal nerve — the same nerve damaged in NK. So far, fewer than 50 cases of PTCD have been reported in the literature.
This boy, who had been managed at the institution, had a marked developmental delay, ataxia, hearing loss in both ears, and severe corneal hypoesthesia (deficits of the trigeminal nerve).
At assessment, his eye movements, facial expression, and eyelid closure during sleep were normal. Tests revealed damage to the cornea covering both eyes, and in the left eye there was an ulcer with stromal melting caused by the breakdown of the inner layer of the cornea called the stroma.
Amniotic membrane transplant to the eye surface was conducted five days later. Still, it did not prevent corneal melting, so one month laater his cornea was removed and replaced with donor tissue. After four months, his corneal ulcer was healed.
Over the next four years, both eyes were treated with artificial tears and antibiotic ointment as needed.
Then, at a routine follow-up visit, an examination found his right cornea was opaque (clouded), had new blood vessel growth in the stroma, and a loss of parts of the outer corneal layer. His left cornea showed signs of dryness and damage associated with his corneal hypoesthesia. Despite these findings, the boy did not complain of symptoms.
The boy was diagnosed with moderate NK in the right eye and mild NK in the left.
As he had undergone medication and surgical procedures for more than four years without signs of long-lasting effects, treatment with Oxervate was started, which became available at that time.
At the time of treatment, Oxervate was not approved for use in children in Italy; but permission was given by the Italian Medicines Agency.
Cenegermin at 20 micrograms/mL was administered to the eyes six times a day at two-hour intervals for eight weeks.
After four weeks of treatment, cloudiness in the right eye was slightly reduced, the surface of the cornea was smoother and more sensitive. At eight weeks, blood vessel growth was markedly reduced, the cloudiness had decreased significantly, and the cornea surface appeared normal. Treatment of the left eye also repaired corneal damage and sensitivity.
During the next six months, his cornea surface was normal, the cloudiness decreased in size and density, and only small blood vessels remained.
No local or systemic adverse side effects were reported in this patient who had multiple co-existing conditions.
“[Oxervate] was well-tolerated and may represent a valuable therapeutic option in the management of pediatric neurotrophic keratopathy,” the researchers wrote. “[More] studies may be needed to assess the long-term safety profile of topical hrNGF in this age group.”