We present a novel case of a neurotrophic keratopathy associated inflammatory hypopyon that resolved after initiation of therapy with cenegermin (Oxervate; Dompe, Milan, Italy), a recombinant human nerve growth factor (rhNGF). This finding illustrates the potential of cenegermin in advanced inflammatory neurotrophic disease.
A 60-year-old female with a history of herpes zoster keratitis was evaluated in our clinic for stage 2 neurotrophic keratopathy. One month later, she presented emergently with a large epithelial defect, infiltrate, and hypopyon. Three separate sets of corneal cultures returned negative. She was treated with oral antivirals and aggressive topical antibiotics with no clinical improvement. Given the presumed diagnosis of stage 3 neurotrophic keratopathy with a sterile hypopyon, she was started on cenegermin 6 times daily for 8 weeks in the absence of a corticosteroid. By 2 weeks after starting cenegermin, the epithelial defect, infiltrate, and hypopyon sizes had improved. Within 4 weeks of starting cenegermin, the hypopyon had clinically resolved. The patient was subsequently started on topical corticosteroid drops for the last 4 weeks of cenegermin therapy. Examination at the conclusion of 8 weeks of cenegermin treatment revealed a closed epithelium and minimal scar. Best-corrected visual acuity with contact lens overrefraction was 20/70. Over the course of 7 months of continued follow-up, the cornea remained epithelialized without recurrent corneal infiltration or hypopyon.
Conclusions and importance
While cenegermin has been previously shown to be an effective treatment for neurotrophic keratopathy associated epithelial defects, resolution of a neurotrophic keratopathy associated inflammatory hypopyon with cenegermin is novel.
The cornea has the greatest innervation density of any tissue in the human body, and corneal nerves play a key role in epithelial cell proliferation, migration, adhesion, and differentiation through the release of various neuropeptides. The corneal epithelium, in return, releases neurotrophic molecules that stimulate nerve survival. As a result, damage to corneal nerves results in deteriorating trophic properties and subsequent epithelial breakdown. This condition is known as neurotrophic keratopathy. Common causes of neurotrophic keratopathy include herpetic disease, chemical injuries, trauma, prior corneal surgery, and chronic topical medications. Neurotrophic keratopathy is typically classified into three stages: early epithelial breakdown (stage 1), persistent epithelial defects (stage 2), and corneal ulceration (stage 3). Stage 3 disease may be complicated by progression to corneal perforation, and rarely a sterile hypopyon may be present in the anterior chamber.
Cenegermin is a recombinant human nerve growth factor (rhNGF), and under the tradename Oxervate (Dompe, Milan, Italy) was approved for the treatment of neurotrophic keratopathy in 2018 in the United States. The REPARO II trial evaluated safety and efficacy in 156 patients randomized to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. In this study, the cenegermin groups demonstrated a significantly higher proportion of complete epithelial healing compared to placebo both at 4 and 8 weeks with an excellent safety profile.
In this case report, we present the case of neurotrophic keratopathy associated hypopyon that resolved after treatment with cenegermin in the absence of a corticosteroid. This novel finding demonstrates the potential of cenegermin in advanced inflammatory neurotrophic disease.
A 60-year-old female presented for evaluation of occasional redness and blurry vision in the right eye. She denied any medical history or systemic medications. Her past ocular history was notable for herpes zoster keratitis two years prior to presentation with resulting neurotrophic keratopathy. On initial evaluation, her best-corrected visual acuity (BCVA) was 20/30 in the right eye and 20/20 in the left eye. Intraocular pressure (IOP) was 20 mmHg in the right eye. Examination of the right cornea demonstrated a chronic non-healing epithelial defect and early stromal haze. She had decreased corneal sensation demonstrated using a cotton-tipped applicator. The patient was using loteprednol twice a week, preservative free tears 4–6 times daily, and valacyclovir 500 mg daily. At this visit, options were discussed including cenegermin for stage 2 neurotrophic keratopathy, which the patient wished to further consider prior to initiating.
Approximately 1 month after her initial evaluation, the patient presented to the emergency room with cloudy vision, photophobia, and aching in the right eye. Her visual acuity was counting fingers and IOP was 10 mmHg. Examination demonstrated 2+ conjunctival injection, and corneal evaluation revealed a 3.0 × 6.5 mm epi defect with a 2.4 × 4.6 mm underlying infiltrate. The inferior aspect of the infiltrate was associated with approximately 50% thinning and surrounding edema was present. Two additional <0.5 mm nasal infiltrates were also noted. A 1.6 mm hypopyon was also present ( Fig. 1 ). Corneal cultures were taken, and the patient was started on fortified cefazolin and tobramycin hourly, cyclopentolate twice daily, erythromycin ointment four times daily, and valacyclovir 1 g three times daily. Corticosteroids were discontinued due to the large epithelial defect and possible underlying infection.