Corneal endothelial dysfunction treatments: Recent advances in non-invasive treatment strategies

The corneal endothelium plays an essential role in the maintenance of a healthy vision. However, in contrast to epithelial cells with high proliferation rates and a turnover lifespan of six to seven days that allows maintenance of constant cell density and high control of cell adhesion, human corneal endothelial cells (HCECs) do not normally proliferate. Therefore, loss of HCECs density over time leads to corneal transparency loss, and the development of corneal edema, bullous keratopathy and other eye diseases. Developments for repairing HCECs are continuously searched for and are evolving around possible topical drug applications as well as emerging strategies such as CRISPR-Cas9 gene editing, antisense oligonucleotides (ASOs) and nanotechnological concepts. Here, the state-of-the-art treatment strategies for corneal endothelial diseases (e.g. Fuch's endothelial corneal dystrophy (FECD), corneal edema, bullous keratopathy) will be outlined with a special focus on where topical applications have shown positive therapeutic outcomes. • Most molecules cannot efficiently penetrate through corneal multilayer structures. • Corneal endothelial disorders are rarely treated using topical non-invasive therapy. • Number of chemicals were successfully used as topical treatment of corneal edema. • Gene therapy could modulate corneal endothelial diseases, but not via topical rote. • Nanoparticles can increase corneal permeability and drug efficiency.