Objective:

To investigate the relationship between neurotrophic keratitis (NK), limbal stem cell deficiency (LSCD), and immune dysregulation, highlighting its clinical significance.

Key Findings:

• Profound corneal nerve loss and marked depletion of LESCs across all limbal quadrants were observed in NK patients, indicating a systemic issue.
• NK patients exhibited increased DC density and activation, indicating chronic inflammation that may contribute to epithelial failure.
• Corneal nerve fiber density positively correlated with LESC density and negatively with fluorescein staining and DC density, suggesting a complex interplay.
• Recombinant human nerve growth factor (rhNGF) treatment led to early increases in LESC density and reductions in DC activation, followed by nerve regeneration, indicating a potential therapeutic pathway.

Interpretation:

NK is a complex, multisystem ocular surface disease involving a neuro-stem cell-immune axis, rather than solely a neurogenic disorder, with significant implications for treatment.

Limitations:

• The study's sample size may limit the generalizability of findings, particularly in diverse populations.
• Long-term effects of rhNGF on nerve and LESC parameters did not fully normalize, suggesting ongoing challenges in treatment.

Conclusion:

Management of NK should include assessment of limbal health and inflammation, alongside corneal sensation and epithelial integrity, to improve patient outcomes.