Purpose: This retrospective longitudinal study investigates the long-term efficacy of topical recombinant human nerve growth factor (Cenegermin 0.002%) in treating neurotrophic keratopathy (NK) stages 1-3 by correlating multimodal imaging with clinical endpoints up to 12 months post-treatment.

Methods: We conducted a retrospective review of NK patients treated with an 8-week course of Cenegermin with a minimum of 3-month post-treatment follow-up. Corneal sensation (Cochet-Bonnet esthesiometry), tear MMP-9 assay, slit lamp photography, and in vivo confocal microscopy (IVCM, HRT 3 RCM, Heidelberg, Germany) were acquired at baseline, 4, 8, 12 weeks, 6 months, and 1 year after treatment initiation. IVCM images were analyzed for epithelial cell density, corneal nerve parameters (density, reflectivity, tortuosity), and dendritic cell density using ImageJ software (NIH, Bethesda, MD).

Results: Twenty-eight eyes of 28 patients were analyzed (stage 1 = 13, stage 2 = 13, and stage 3 = 2). Of 15 eyes with epithelial defects at baseline, 93.3% healed after an average 49 ± 26 days. Mean epithelial cell density improved from 2495 ± 1464 to 3339 ± 1127 cells/mm² (p=0.004) in the wing layer and from 3203 ± 2500 to 5687 ± 2557 cells/mm² (p<0.0001) in the basal layer at 12 months. Mean corneal sensation improved from 2.29 ± 1.53cm to 3.92 ± 1.43cm (p=0.003), correlating with increased corneal nerve density (0.0467 ± 0.1126 to 0.6451 ± 0.7325 mm/mm², p<0.0001) at 1-year follow-up.

Conclusions: Recombinant human nerve growth factor (Cenergermin 0.002%) has clinical efficacy in corneal epithelial healing in eyes with neurotrophic keratitis (NK). This study demonstrates the long-lasting effect of rhNGF on the structural and functional improvement of the corneal epithelium and corneal nerves in NK-affected eyes.