title: Morphological Changes of Human Corneal Endothelial Cells after Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Administration: A Prospective Open-Label Clinical Study.
abstract: OBJECTIVE
  To investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  JAPIC Clinical Trials Information 142705.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan; Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Koizumi
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan; Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.affiliation: Kowa Company, Ltd, Nagoya, Aichi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Suganami
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D004728:Endothelium, Corneal / Q000187:drug effects*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000009:adverse effects* / Q000494:pharmacology; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D007546:Isoquinolines; C584679:K-115; D009883:Ophthalmic Solutions; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D054460:rho-Associated Kinases