Corneal Fibrosis: Mechanistic Networks, Stage-Dependent Therapeutic Windows, and Regenerative Strategies.

Abstract

Corneal fibrosis is a dysregulated wound-healing response in which epithelial and basement membrane failure, limbal dysfunction, unresolved inflammation, persistent myofibroblasts, vascular amplification, and extracellular matrix disorganisation impair corneal transparency and vision. Although transforming growth factor-β is central, persistence reflects interconnected epithelial, stromal, immune, vascular, and mechanobiological networks. This review frames fibrosis as a stage-dependent continuum from early fibrotic commitment through active stromal remodelling to established structural scar and evaluates interventions according to their most plausible biological window. Anti-inflammatory and pathway-directed treatments are considered primarily as preventive or active-stage interventions, whereas limbal restoration, mesenchymal stromal cell- and extracellular vesicle-based approaches, amniotic membrane-derived interventions, bioengineered constructs, and keratoplasty address surface stabilisation, regeneration, or structural replacement. Current evidence supports prevention and modulation of early or active fibrosis more strongly than pharmacological reversal of mature scar and remains dominated by preclinical studies and small clinical datasets. Translation will require stage- and phenotype-matched models, objective structural and optical endpoints, biologically informed patient stratification, and clear separation of prevention, suppression of active remodelling, regenerative stabilisation, and true scar reversal.