Abstract
PurposeTo investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects.DesignProspective, interventional case series.MethodsIn this study, 6 healthy subjects were administered ripasudil 0.4% in the right eye twice daily for 1 week. Morphological changes and corneal endothelial cell density were examined by noncontact and contact specular microscopy. Central corneal thickness and corneal volume of 5 mm-diameter area of center cornea were analyzed by Pentacam Scheimpflug topography. All the above measurements were conducted in both eyes before administration, 1.5 and 6 hours after the initial administration on day 0; and in the same manner after the final administration on day 7.ResultsBy noncontact specular microscopy, indistinct cell borders with pseudo guttae were observed, but by contact specular microscopy, morphological changes of corneal endothelial cells were mild and pseudo guttae was not observed after single and repeated administration of ripasudil in all subjects. These changes resolved prior to the next administration, and corneal endothelial cell density, central corneal thickness and corneal volume were not changed throughout the study period.ConclusionTransient morphological changes of corneal endothelial cells such as indistinct cell borders with pseudo guttae were observed by noncontact specular microscopy in healthy subjects after ripasudil administration. Corneal edema was not observed and corneal endothelial cell density did not decrease after 1 week repetitive administration. These morphological changes were reversible and corneal endothelial cell morphology returned to normal prior to the next administration.Trial RegistrationJAPIC Clinical Trials Information 142705
Highlights
Rho-associated, coiled-coil containing protein kinase (ROCK), serine/threonine kinase is involved in diverse physiological functions, such as cytoskeletal rearrangement related to cell shape, smooth muscle contraction, and gene expression [1,2]
Transient morphological changes of corneal endothelial cells such as indistinct cell borders with pseudo guttae were observed by noncontact specular microscopy in healthy subjects after ripasudil administration
Corneal edema was not observed and corneal endothelial cell density did not decrease after 1 week repetitive administration
Summary
Rho-associated, coiled-coil containing protein kinase (ROCK), serine/threonine kinase is involved in diverse physiological functions, such as cytoskeletal rearrangement related to cell shape, smooth muscle contraction, and gene expression [1,2]. By focusing on these physiological functions, many researchers are investigating clinical applications for ROCK inhibitors [3,4,5,6]. Some selective ROCK inhibitors are used in clinical practice, for example, fasudil and ripasudil are therapeutic agents for cerebral vasospasm and glaucoma, respectively. Attention has been focused on the effect of ROCK inhibitor on corneal endothelial cells (CECs). Okumura et al reported that the selective ROCK inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate CECs in culture [12]. The positive effect of Y-27632 eye drops in treating patients with central corneal edema due to Fuchs corneal endothelial dystrophy was reported [5,13,16]
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