Pathogenesis and treatment: research progress on corneal endothelial decompensation

The corneal endothelium (CE) is essential for maintaining corneal transparency and physiological function. Corneal endothelial cells (CECs), which have limited regenerative capacity, undergo progressive loss due to aging, disease, surgical trauma, or injury, ultimately leading to endothelial dysfunction, corneal edema, and visual impairment. Corneal endothelial dysfunction (CED) remains a major cause of global visual morbidity. Recent advances in imaging and molecular biology have enhanced our understanding of CE pathogenesis and therapeutic interventions. Previous studies have elucidated the roles of oxidative stress and mitochondrial dysfunction in endothelial apoptosis and pump failure. Clinically, imaging innovations such as ultra-high-resolution optical coherence tomography and AI-assisted specular microscopy have markedly improved early detection of endothelial decompensation. Surgical outcomes have been optimized with the introduction of pre-Descemet endothelial keratoplasty and bioengineered endothelial grafts. Additionally, emerging regenerative therapies, including Rho kinase inhibitors (e.g., fasudil) and tissue-engineered corneal endothelial substitutes, have shown promising results. Moreover, genetic studies have identified pathogenic variants in several genes, which facilitate risk assessment and early diagnosis and pave the way for allele-specific therapies and personalized management strategies. Despite these advances, challenges remain in promoting CEC regeneration, ensuring long-term graft survival, and improving global access to these advanced treatments. This review integrates current insights into the etiology, molecular mechanisms, and therapeutic advances in CED, emphasizing key areas for future research and clinical application. • It systematically outlines the multifactorial etiology of corneal endothelial dysfunction, encompassing genetic predispositions, iatrogenic injuries, and environmental insults. • The review elaborates the core mechanisms driven by cellular stress pathways and apoptotic signaling, which lead to the irreversible loss of corneal endothelial cells. • A concise summary is provided on the transition from traditional corneal transplantation to emerging regenerative strategies, including ROCK inhibitors and cell-based therapies. • Future directions are proposed, focusing on deciphering molecular pathogenesis and advancing novel therapeutics for functional endothelial regeneration.