Determinants of Epithelial Healing Time and Cumulative Risk-Factor Burden in Eyes with Delayed Corneal Epithelialization After Routine Keratoplasty.

Abstract

Background: Delayed epithelialization is a common complication after keratoplasty that can compromise graft survival and increase the economic burden.

Purpose: To identify donor and recipient factors linked to extended epithelial healing time in eyes with delayed epithelialization after routine penetrating and lamellar keratoplasty.

Methods: This retrospective cohort study included eyes undergoing penetrating or lamellar keratoplasty that developed delayed epithelialization, defined as complete epithelial closure occurring ≥8 days postoperatively. Recipient, donor, surgical, and postoperative variables were analyzed. Multivariable linear regression was used to quantify the effect of predictors on epithelial healing time (days). Time to epithelial closure was additionally analyzed using Kaplan-Meier estimates and Cox proportional hazards regression. A cumulative risk-factor burden model was constructed based on independent predictors.

Results: A total of 146 eyes were included. In multivariable analysis, three independent predictors of prolonged epithelial healing were identified: recipient vernal keratoconjunctivitis (VKC) (β = +9.51 days, p < 0.001), female donor sex (β = +2.13 days, p = 0.030), and donor history of chemotherapy or radiotherapy (β = +3.28 days, p = 0.013). Cox regression confirmed slower epithelial healing associated with VKC (HR 0.38), female donor sex (HR 0.65), and donor chemotherapy/radiotherapy exposure (HR 0.64). Kaplan-Meier analysis demonstrated progressively delayed epithelial closure with increasing risk-factor burden (log-rank p < 0.001), with median healing times of approximately 10, 12, and 16 days for patients with 0, 1, and ≥2 risk factors, respectively.

Conclusion: VKC, female donor sex, and donor history of chemotherapy or radiotherapy were independently associated with prolonged epithelial healing time in this single-center cohort of eyes that already exhibited delayed epithelialization after routine keratoplasty. The cumulative risk-factor burden model showed a stepwise association with slower epithelial closure; however, these findings are exploratory and require prospective external validation before integration into donor allocation strategies or routine clinical protocols.