Asociación entre Queratitis Neurogénica y Deficiencia de Células Madre Limbales

To investigate changes in corneal nerves, immune cells, and limbal epithelial stem cells (LESCs) in neurotrophic keratitis (NK) patients, analyze correlations among these parameters and clinical manifestations, and monitor long-term corneal changes in NK patients receiving recombinant human nerve growth factor (rhNGF).

Cross-sectional study with an interventional case series.

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 LEBCs in different directions, dendritic cell (DC) status. Longitudinal changes in these parameters are recorded at baseline, weeks 4 and 8, and the 2-year follow-up in the rhNGF-treated subgroup (7 eyes of 7 patients). Correlation analyses are conducted among all parameters in NK group.

In patients with neurotrophic keratopathy (NK), corneal nerve fiber density (CNFD) (p < 0.01), nerve fiber length (CNFL) (p < 0.01), and nerve branch density (CNBD) (p < 0.01) are significantly less than healthy controls. Similarly, central BCD (p < 0.001) and peripheral LESCs density (p < 0.001) are markedly lower in NK group. In contrast, DCs density (p < 0.001), activation ratio (p < 0.001) of patients with NK are higher. 1. Correlation analyses reveal that CNFD is positively correlated with LESCs density (ρ= 0.46; p < 0.001), and negatively correlated with fluorescein staining scores (ρ=-0.46; p < 0.001) and DC density (ρ=-0.57; p < 0.001). LESCs density is negatively correlated with both fluorescein staining scores (ρ=-0.62; p < 0.001) and mean DC area (ρ=-0.44; p < 0.001), while fluorescein staining scores are positively correlated with DC density (ρ= 0.44; p < 0.001). 2. Compared with baseline, improvements in LESCs density, DC density, activation, and fluorescein staining scores become observed at 4 of rhNGF treatment, while nerve regeneration becomes detectable after 8 weeks and shows significant recovery by year 2.

This study demonstrates that patients with NK exhibit corneal nerve damage, limbal stem cell deficiency, and immune cell activation, with significant correlations observed among these alterations. 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.