Abstract
Introduction Corneal persistent epithelial defects (PEDs) represent a significant clinical challenge due to their multifactorial etiology and their potential to progress to severe complications. Early recognition and effective medical management of PEDs are essential to prevent worsening up to corneal blindness.Areas covered A comprehensive search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov was performed, focusing on established treatments as well as novel therapies targeting neurotrophic dysfunction, inflammation, and extracellular-matrix dysregulation. This review synthesizes current and emerging medical therapies for PEDs, emphasizing mechanisms of action and available clinical evidence, finally offering a coherent, evidence-based strategy.Expert opinion Effective management of PEDs requires a stepwise, mechanism-driven approach that starts with addressing underlying ocular and systemic contributors. While traditional supportive treatments remain foundational, biologically active agents are increasingly crucial for refractory cases. Emerging pathway-specific therapies such as lufepirsen, RGN-259, neurotrophic peptides, growth factors, matrix regenerating peptides, and regenerative secretome-based formulations offer promising targeted strategies, though high-quality evidence remains limited. Future progress will depend on identification of biomarkers guiding therapy selection and robust clinical trials to validate emerging agents and support more personalized treatment algorithms.