Defining Criteria for Choosing Corneal Neurotization in Neurotrophic Keratopathy: A Systematic Review Along with...

To identify and harmonize preoperative inclusion and exclusion criteria for corneal neurotization (CN) in neurotrophic keratopathy (NK), describe how consistently they are reported, and summarize practical, clinic-ready guidance for selection and follow-up.

Systematic review (PRISMA-2020; PROSPERO CRD420251117787) of human studies on CN for NK (databases searched July 18, 2025). Study-level eligibility criteria, disease stage, esthesiometry, chronicity thresholds, donor-nerve requirements, and stated exclusions were evaluated; risk of bias (ROBINS-I) and certainty (GRADE) were recorded.

Thirty-six studies (380 patients) were included; of these, 26 (72.2%) explicitly reported eligibility criteria. Most common inclusion criteria were refractory NK (92.3%), severe/objective corneal anaesthesia or Mackie III severity stage (69.2%), NK with intact donor territory (50.0%), and corneal epithelial instability (46.2%). Exclusion criteria were often not stated (76.9%); when present, they most often listed active infection/non-NK disease (38.5%), systemic unsuitability (34.6%), absent/abnormal donor nerve(s) (15.4%), and severe limbal stem cell deficiency (15.4%). Across studies, CN improved corneal protection and surface stability with sensory recovery over ~6-18 months and in vivo confocal microscopy evidence of nerve regrowth; visual acuity changes were variable. No randomized clinical trials were found; ROBINS-I was commonly moderate to serious, and overall certainty by GRADE was low.

This systematic review defined and harmonized preoperative inclusion and exclusion criteria for CN in NK. A minimum preoperative dataset, including disease stage, mapped corneal sensitivity, denervation timeline and etiology, donor-dermatome integrity, feasibility of tension-free coaptation, and ocular surface status, may guide referral timing, donor-feasibility-driven technique selection, and structured follow-up.