Morphological Changes of Human Corneal Endothelial Cells after Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Administration: A Prospective Open-Label Clinical Study

PLoS One. 2015 Sep 14;10(9):e0136802. doi: 10.1371/journal.pone.0136802. eCollection 2015.

Abstract

Purpose: To investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects.

Design: Prospective, interventional case series.

Methods: In 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.

Results: By 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.

Conclusion: 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. These morphological changes were reversible and corneal endothelial cell morphology returned to normal prior to the next administration.

Trial registration: JAPIC Clinical Trials Information 142705.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Endothelium, Corneal / drug effects*
  • Female
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / adverse effects*
  • Isoquinolines / pharmacology
  • Male
  • Middle Aged
  • Ophthalmic Solutions / adverse effects*
  • Ophthalmic Solutions / pharmacology
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacology
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*
  • Sulfonamides / pharmacology
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Isoquinolines
  • K-115
  • Ophthalmic Solutions
  • Protein Kinase Inhibitors
  • Sulfonamides
  • rho-Associated Kinases

Grants and funding

This study was sponsored by Kowa Company, Ltd, Nagoya, Japan. The sponsor participated in design, study conduct, data collection, data management, data analysis, interpretation of the data of the study, and preparation, review, and approval of the manuscript.