Rock Inhibitors

Inhibition of the Rho-kinase (ROCK) signalling pathway has widespread effects on cellular behaviour. In the cornea, ROCK inhibitors promote the integrity of the epithelial layer and limbal stem cells and regeneration of the endothelium layer. Clinical studies have demonstrated successful regeneration of the endothelium using ROCK inhibitors without a corneal graft in patients with corneal endothelial decompensation. Moreover, ROCK inhibitors have inhibitory effects on angiogenesis and prevent corneal neovascularization—a critical risk factor for allograft rejection. In a significant proportion of patients, intraocular pressure increases in the post-keratoplasty period negatively affecting graft survival and nerve fibre layer health. Thus, ROCK inhibitors may promote graft survival and visual outcome through multiple means. Worldwide, there are two approved ROCK inhibitors for usage in patients with ocular hypertension and glaucoma. Generally, ROCK inhibitors are considered safe, but a significant percentage of patients using eye drops containing ROCK inhibitors experience local adverse side-effects, such as blepharitis and conjunctival hyperaemia. Newer, more selective ROCK inhibitors are being developed and may have a better ocular tolerability profile. This chapter will describe the ROCK signalling pathway and discuss clinical applications and future perspectives with special reference to the cornea, and to a lesser extent, glaucoma.