Neurotrophic keratitis (NK) is a degenerative corneal disease resulting from the partial or total impairment of trigeminal innervation.1 The underlying cause is often unknown, symptoms are often absent, and most cases are identified based on a loss of corneal sensation. However, trauma to the trigeminal nerve could result in impairment.
Treatment of NK is often complicated because interventions are targeted to symptomatic relief. The recent availability of approaches that stimulate regeneration of the trigeminal nerve may offer a new paradigm for treatment.2-3 This is a case involving the successful treatment of NK that was refractory to conventional treatments in a young patient affected by a diffuse midline glioma.
Presentation
A 7-year-old male child was referred to our cornea service with a diagnosis of NK in the left eye (Figure 1). On examination, the right eye was within normal limits, whereas the left eye showed decreased corneal sensitivity, absent corneal reflex, mild ptosis, and decreased tear production. The medical record indicated a recent diagnosis of pediatric glioma. Symptom reports included frontal headaches, enlarged stride, and slurred speech. One month prior to the development of the NK, he underwent a brainstem biopsy, which revealed a diffuse midline glioma with the H3K27M mutation. He underwent chemotherapy and radiotherapy to treat the brain tumor located in the pons region.
Figure 1. Neurotrophic keratitis in a 7-year-old male child.
Treatment
To treat the NK, we initially started with preservative-free artificial tears, a therapeutic contact lens, and levofloxacin 0.5% eye drops 3 times a day. Subsequently, we administered topical autologous serum at a concentration of 40%, 6 times a day for 6 weeks, but there was no improvement in the condition. After receiving approval from the Italian Medicines Agency for pediatric use in this case, we switched to cenegermin-bkbj ophthalmic solution 0.002% (Oxervate; Dompé), which was administered 6 times a day for 8 weeks. Complete reepithelialization was achieved within 3 weeks of starting this treatment (Figure 2).
Figure 2. Complete reepithelialization was achieved within 3 weeks of starting Oxervate.
Summary and Discussion
In this young patient, the pathophysiology of the NK could be explained by the tumor’s infiltration into the cerebellopontine angle, with the resulting impairment manifesting as corneal denervation. The lack of treatment response to palliative measures and efforts to protect and regrow the cornea are perhaps not surprising. Although each measure is a reasonable option to achieve symptomatic relief and/or to attempt repair, none directly address the underlying anatomy. Until recently, treatment approaches for NK have been limited by the absence of treatments targeting the underlying cause.
In this case, corneal denervation resulted in decreased cell metabolism and impaired epithelial mitosis. Cenegermin was effective in restoring corneal integrity. Early diagnosis and prompt management of pediatric NK are mandatory to prevent corneal complications such as perforation and amblyopia. By stimulating nerve regeneration, recombinant human nerve growth factor promotes corneal healing, and may eventually lead to a new standard of care for pediatric patients affected by NK.
1. Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191-197.
2. Bonzano C, Olivari S, Cutolo C.A., et al. Recombinant Human Nerve Growth Factor (Cenegermin)-Driven Corneal Wound Healing Process: An Evidence-Based Analysis. Front Pharmacol. 2022;12:760507.
3. Mastropasqua L, Lanzini M, Dua HS et al. In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Recombinant Nerve Growth Factor for Neurotrophic Keratopathy. Am J Ophthalmol. 2020;217:278-286.
