Corneal Nerve Injury and Regeneration: Mechanisms, Clinical Consequences, and Emerging Therapeutic Strategies

Abstract The cornea is among the most densely innervated tissues in the body and depends on intact sensory and autonomic innervation to maintain epithelial integrity, tear film homeostasis, and ocular surface defense. Corneal nerve injury may occur after surgery, infection, inflammation, trauma, or systemic disease and can lead to reduced corneal sensitivity, impaired epithelial healing, dry eye, neuropathic pain, and neurotrophic keratopathy. Effective management requires both treatment of the underlying cause and restoration of a microenvironment permissive for reinnervation. This review examines the mechanisms underlying corneal nerve injury and repair, with emphasis on therapeutic strategies relevant to clinical translation. These include anti-inflammatory and immunomodulatory agents, growth factors and cytokines, blood-derived products, extracellular matrix-based therapies, stem cell- and secretome-based approaches, surgical neurotization, and physical stimulation modalities. We also highlight emerging challenges in the field, including the gap between structural nerve regeneration and functional recovery, limitations in clinical evidence, and barriers to therapeutic accessibility and implementation.