To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy.Design: Multicenter, randomized, double-masked, vehicle-controlled trial.Participants: Patients with neurotrophic persistent epithelial defect with or without stromal thinning. Methods: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 mg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. Main Outcome Measures: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8.Results: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (þ40.4%; 95% confidence interval [CI], 14.2%e66.6%; P ¼ 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (þ48.6%; 95% CI, 24.0%e73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermintreated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient.Conclusions: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.

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The overall incidence of fungal infection following penetrating keratoplasty is low, but all cases in our study were associated with positive rim cultures. Whether prophylactic antifungal therapy would be of any benefit in the presence of a positive corneoscleral rim culture has not yet been determined.

Our experience with fungal keratitis in the northeastern United States appears to be different than those reported from other areas of the United States. Serologic positivity for HIV and chronic ocular surface disease were the most common associated risk factors followed by trauma, herpes simplex keratitis, and contact lens use. Candida species predominated, whereas filamentous fungi were uncommon.