Systematic Literature Review on the Effect of Cenegermin on Corneal Sensation and Innervation in Patients with Neurotrophic Keratopathy

PURPOSE: Neurotrophic keratopathy (NK) results from trigeminal nerve impairment, leading to loss of corneal sensation (CS), epithelial breakdown, and in advanced stages, stromal ulceration or perforation. Cenegermin, a recombinant human nerve growth factor, is the first and only FDA-approved therapy for NK, although existing studies are limited by small sample sizes. This systematic literature review evaluated cenegermin's effects on CS and corneal innervation (CI) in patients with NK. METHODS: English-language studies published between August 2018 and June 2024 measuring CS or CI after cenegermin treatment for NK were identified through PubMed and Embase. For studies reporting quantitative data, sample size-based weighting was applied to each study's reported or derived mean change. Weighted means were calculated by NK stage or overall, where applicable. RESULTS: A total of 25 studies met the inclusion criteria. The pooled mean age was 61.8 years (range: 2-93 years). Most included patients with stage II (moderate; 19 studies) and stage III (severe; 17 studies) NK. Across 8 studies reporting quantitative CS outcomes and 3 studies reporting quantitative CI outcomes, the weighted mean improvement from baseline to 8 weeks post-treatment was 116.5% for CS (range: 78.3%-259.3%) and 64.5% for CI (range: 39.1%-188.9%). CONCLUSION: An 8-week course of cenegermin led to improvements in CS and CI in patients with NK, with greater relative gains observed among those patients with more severe disease. While study design heterogeneity and small sample sizes may limit the generalizability of these findings, the data support cenegermin's role in promoting corneal nerve regeneration.