@article {1483619,
	title = {Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {14-26},
	abstract = {PURPOSE: 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 μg/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 (\&lt;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\&nbsp;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 (+40.4\%; 95\% confidence interval [CI], 14.2\%-66.6\%; P\&nbsp;= 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 (+48.6\%; 95\% CI, 24.0\%-73.1\%; P \&lt; 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated 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.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.08.020},
	author = {Pflugfelder, Stephen C and Massaro-Giordano, Mina and Perez, Victor L and Hamrah, Pedram and Deng, Sophie X and Espandar, Ladan and Foster, C Stephen and Affeldt, John and Seedor, John A and Afshari, Natalie A and Chao, Wendy and Allegretti, Marcello and Mantelli, Flavio and Dana, Reza}
}
