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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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