Current Concepts in Corneal Neurotization

Neurotrophic keratopathy (NK) results from loss of trigeminal innervation to the cornea, disrupting epithelial integrity, tear film regulation, and ocular surface homeostasis. Conventional treatments address the surface consequences of denervation but do not restore sensory input. Corneal neurotization (CN) directly addresses this biological deficit by transferring healthy donor axons to the anesthetic cornea, re-establishing afferent innervation, and creating the conditions for epithelial maintenance and visual rehabilitation. Since Terzis first described direct surgical CN in 2009, the field has evolved considerably. Minimally invasive techniques using interpositional nerve grafts have broadened applicability to bilateral disease and patients without intact ipsilateral trigeminal sensation. Donor nerve selection follows a hierarchical algorithm based on the pattern of sensory loss, with ipsilateral trigeminal branches preferred, and the greater auricular nerve available when trigeminal sensation is absent. Both direct and indirect techniques achieve comparable improvements in epithelial healing, ocular surface metrics, and Mackie staging, though indirect CN via nerve grafting appears to yield superior sensory recovery. Acellular nerve allografts eliminate donor site morbidity but lack Schwann cells, and head-to-head comparisons with autografts remain lacking. Meta-analyses demonstrate statistically significant improvements in corneal sensation following CN, with the majority of patients also achieving gains in visual acuity. Younger age and congenital etiology are associated with greater sensory recovery, while older age and acquired etiology predict greater visual improvement, likely reflecting the confounding effects of amblyopia in pediatric cohorts. Keratoplasty post-CN can also be undertaken in eyes previously considered poor candidates, though surgery should be deferred for a year after CN and not until corneal sensation exceeds 30 mm with a stable ocular surface. The complication profile is low. Donor site sequelae are typically mild and self-limiting, and serious ocular complications are uncommon. Adjuvant neurotrophic therapy represents a potential future strategy for optimizing outcomes, with current evidence limited. Given the consistent efficacy and safety of CN across international centers, earlier referral of NK and intervention before visual loss and irreversible stromal injury should now be considered a central principle of NK management. A multi-institutional outcomes registry would strengthen the evidence base and guide future clinical decision-making.