Persistent corneal epithelial defects: an updated review of literature

Abstract Background: Persistent corneal epithelial defects (PCEDs) represent a significant clinical challenge characterized by the failure of the corneal epithelium to heal within the normal period, leading to potential sight-threatening complications. These defects arise from a variety of underlying etiologies, including limbal stem cell deficiency, neurotrophic keratopathy, dry eye syndrome, and systemic diseases such as diabetes mellitus. Despite advances in ophthalmic care, PCEDs remain difficult to treat due to diverse pathophysiological mechanisms and variable response to conventional therapies. Recent developments in growth factor therapies, biological treatments, surgical techniques, and regenerative medicine have expanded therapeutic options but necessitate comprehensive review to guide clinical practice. Methods: A comprehensive narrative review was conducted through a systematic search of major electronic databases including PubMed/MEDLINE, Embase, Scopus, and Google Scholar. The search incorporated keywords and Medical Subject Headings related to “persistent corneal epithelial defects”, “corneal epithelial healing”, “limbal stem cell deficiency”, “neurotrophic keratopathy”, “amniotic membrane transplantation”, and “emerging treatments”. Peer-reviewed original studies, clinical trials, reviews, and meta-analyses published between ۱ January ۲۰۰۰ and ۳۱ March ۲۰۲۵ were included. Articles were critically appraised and selected according to their relevance, methodological quality, and contribution to understanding PCED pathophysiology, diagnosis, and treatment advancements. Results: The review delineates the anatomy and physiological roles of the corneal epithelium, highlighting mechanisms that lead to epithelial defect persistence, including impaired basement membrane integrity, stem cell deficiency, inflammation, and neurotrophic factors. Clinical presentation and diagnostic modalities such as fluorescein staining and advanced imaging techniques are discussed. Standard management with lubricants, therapeutic contact lenses, infection control, and autologous serum eye drops is described, alongside medical therapies targeting epithelial regeneration, including recombinant human nerve growth factor and platelet-rich plasma. Surgical interventions like amniotic membrane transplantation and novel regenerative approaches involving stem cell therapy and corneal neurotization show promising results in refractory cases. Emerging molecular therapies and bioengineered drug delivery systems represent the forefront of innovation in PCED treatment. Conclusion: PCEDs pose complex therapeutic challenges necessitating a multifaceted treatment approach. Advances in molecular, cellular, and surgical therapies have substantially expanded management options and improved healing outcomes. However, continued research into personalized therapies, optimization of delivery methods, and long-term safety is essential. This review provides a comprehensive synthesis of current knowledge and emerging trends to inform clinicians and researchers in the effective management of PCEDs, ultimately aiming to preserve vision and enhance quality of life. Future research should focus on minimally invasive sustained-release therapies, biomarker-guided personalized interventions, and combination approaches targeting epithelium, inflammation, and nerves. Keywords: corneal epithelium persistent corneal epithelial defects neurotrophic keratopathy limbal stem cell limbal stem cell deficiency corneal disease wound healings amniotic membrane stem cell transplantations