Nerve Growth Factor Treatment May Initiate Corneal Recovery in Neurotrophic Keratitis

Reduced LESC density in all quadrants in NK was observed in this study, with corneal nerve parameters positively correlating with central basal epithelial cells and LESC densities. By year two of rhNGF treatment, NK patients showed significant recovery in LESCs density, dendritic cell density, activation and fluorescein staining scores, the latter showing improvements after only four weeks. Photo: Paul Karpecki, OD. Click image to enlarge. It’s been hypothesized that recombinant human neurotrophic growth factor (rhNGF; cenegermin, Dompé), the only approved topical therapy for neurotrophic keratitis (NK), may also enhance the function of limbal epithelial stem cells (LESCs) and dendritic cells. To investigate further, researchers analyzed correlations among changes in corneal nerves, immune cells and LESCs in NK patients vs. healthy subjects. Additionally, they monitored long-term corneal changes in NK patients receiving rhNGF. The data revealed that short-term treatment with rhNGF may initiate corneal recovery by first improving the limbal microenvironment and modulating immune responses, thereby promoting a regenerative feedback loop that supports sustained nerve regeneration and epithelial repair. The findings were reported earlier this month in American Journal of Ophthalmology.A total of 54 NK patients (55 eyes) and 57 healthy controls (59 eyes) were enrolled. In vivo confocal microscopy (IVCM) was performed to evaluate subbasal nerve fiber parameters, density of LESCs in different directions and dendritic cell status. In the rhNGF-treated subgroup (seven eyes of seven patients), longitudinal changes in these parameters were recorded at baseline, four weeks, eight weeks and two years. According to the researchers, for the first time, these findings reveal concurrent impairments in neural, immune and stem cell functions at the cellular level in NK patients. “These microstructural deficits are consistent with clinical manifestations and demonstrate unique patterns of LESC distribution in NK,” the authors wrote in their paper. “Our study provides the first in vivo evidence that rhNGF promotes not only nerve regeneration, but may also enhance corneal epithelial healing through dendritic cell suppression and LESC restoration.”Although no significant changes in corneal nerves were observed at week four, a reduction in fluorescein staining scores, increased LESC density and decreased total and activated dendritic cell densities were evident. “These early effects may facilitate epithelial repair, reduce nerve exposure and enhance endogenous NGF secretion, thereby alleviating inflammation and creating a favorable environment for nerve regeneration,” the authors explained in their paper.By week eight, gradual nerve recovery became apparent, which may have promoted LESC proliferation and survival and helped restore immune balance. Previous studies using IVCM showed that patients with complete LSCD secondary to ocular graft-vs.-host disease exhibit significantly reduced corneal sensitivity. These reports also showed that moderate-to-severe LSCD is frequently associated with NK and decreased corneal sensation, which correlates with the finding that LSCD severity and subbasal nerve loss precede the clinical detection of NK.“Our study supports these findings and extends them by quantitatively demonstrating reduced LESC density in all quadrants in NK, with corneal nerve parameters (e.g., corneal nerve fiber density, corneal nerve branch density) positively correlated with central basal epithelial cell and LESC densities,” the authors explained in their paper. “Notably,” they continued, “quadrant-specific corneal staining scores are more strongly correlated with LESC density than with nerve parameters, suggesting that in patients with persistent epithelial defects, monitoring and restoring LESC function may be especially critical.”The authors speculate that the long-term effects of NGF are attributed to several mechanisms. “Although many patients exhibited markedly reduced or even absent central subbasal nerve parameters at baseline, IVCM revealed residual stromal nerve fibers in the paracentral regions, which may have provided a foundation for subbasal nerve regeneration after treatment,” the authors explained. “Second, NGF facilitates earlier epithelial recovery and rapidly establishes a more favorable environment for nerve regeneration.”Because NGF also exerts direct neurotrophic and growth-promoting effects, it may help maintain limbal stem cell stability and promote the early formation of a positive regenerative cycle. However, these findings also indicated that although a single course of NGF treatment resulted in higher nerve density, nerve length and LESC density at two years compared with baseline, these parameters remained lower than those of healthy controls. “This suggests that NGF provides partial and sustained therapeutic benefit for centrally mediated NK, but does not achieve complete restoration,” the authors concluded. Click here for the journal source. Yan Y, Yang Z, Deng Q, et al. Association between neurotrophic keratitis and limbal stem cell deficiency. Am J Ophthalmol. January 18, 2026. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.