Association Between Neurotrophic Keratitis and Limbal Stem Cell Deficiency

Area of Science:

• Ophthalmology
• Corneal Biology
• Immunology

Background:

• Neurotrophic keratitis (NK) is characterized by corneal nerve damage, limbal stem cell deficiency, and immune dysregulation.
• Understanding the interplay between these factors is crucial for developing effective treatments.

Purpose of the Study:

• To investigate corneal nerve, immune cell, and limbal epithelial stem cell (LESC) changes in NK patients.
• To analyze correlations between these parameters and clinical manifestations.
• To monitor long-term corneal changes in NK patients treated with recombinant human nerve growth factor (rhNGF).

Main Methods:

• Cross-sectional study with an interventional case series involving 54 NK patients and 57 healthy controls.
• In vivo confocal microscopy (IVCM) assessed subbasal nerve fiber parameters, LESC density, and dendritic cell (DC) status.
• Longitudinal data collected at baseline, 4, 8 weeks, and 2-year follow-up for rhNGF-treated patients.

Main Results:

• NK patients exhibited significantly reduced corneal nerve fiber density, length, and branch density compared to controls.
• LESC density was lower, while DC density and activation were higher in NK patients.
• Corneal nerve fiber density positively correlated with LESC density and negatively with fluorescein staining scores and DC density. rhNGF treatment improved LESC and DC parameters within 4 weeks, with nerve regeneration evident by 8 weeks and significant recovery by 2 years.

Conclusions:

• NK involves corneal nerve damage, LESC deficiency, and immune activation, with interconnected alterations.
• rhNGF treatment initiates corneal recovery by enhancing the limbal microenvironment and modulating immune responses, fostering nerve regeneration and epithelial repair.