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Morphological change and recovery of corneal endothelial cells after rho-associated protein kinase inhibitor eye-drop (ripasudil 0.4%) instillation
  1. Yuko Maruyama1,2,3,
  2. Yoko Ikeda1,4,
  3. Kazuhiko Mori1,
  4. Kengo Yoshii5,
  5. Morio Ueno1,
  6. Haruna Yoshikawa6,
  7. Chie Sotozono1,
  8. Shigeru Kinoshita7
  1. 1 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  2. 2 Department of Ophthalmology, Kyoto First Red Cross Hospital, Kyoto, Japan
  3. 3 Department of Ophthalmology, Saiseikai Shiga Hospital, Ritto, Shiga, Japan
  4. 4 Department of Ophthalmology, Oike-Ikeda Eye Clinic, Kyoto, Japan
  5. 5 Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
  6. 6 Department of Ophthalmology, Kyoto Second Red Cross Hospital, Kyoto, Japan
  7. 7 Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  1. Correspondence to Dr Yoko Ikeda, Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan; yikeda{at}


Background/Aims To investigate the time-dependent change of corneal endothelial cell (CEC) morphology and density (CECD) in patients with glaucoma post instillation of rho-associated protein kinase inhibitor ripasudil (Rip) 0.4% eye drops.

Methods This observational study involved 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via non-contact specular microscopy (NCSM) before and at 1 or 3 months post-Rip instillation. The change of CECD was plotted along with elapsed time from last instillation of Rip. The patients were divided into the following three groups based on the elapsed time post-Rip instillation: Early Group (<2 hours), Middle Group (≥2 hours, yet <6 hours) and Late Group (≥6 hours). The rate of CECD change was then analysed and compared among the three groups. An additional eight eyes of four patients with glaucoma were enrolled for a time-dependent study, with NCSM images evaluated before and at 1, 2, 3, 4 and 6 hours post-Rip instillation.

Results Morphological changes in the CECs appeared within 1 hour and recovered to normal within 6 hours post instillation. In the Early, Middle and Late Group, the median rate of CECD change as calculated by the NCSM automated software was −5.68%, −4.95% and −0.07%, respectively. The CEC images showed the same morphological changes with observational study in all four cases.

Conclusion Due to transient morphological changes, the NCSM software produced misleading data for determining CECD within 1 hour post-Rip instillation, yet revealed that CEC morphology gradually recovered to normal within 6 hours.

  • glaucoma
  • cornea
  • drugs

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  • YM and YI contributed equally.

  • Presented at This work was presented as a poster at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting 2018 in Honolulu, USA and the European Glaucoma Society (EGS) 2018 in Florence, Italy.

  • Contributors YI, KM and MU were responsible for collecting data. YM, YI, KY and HY were responsible for statistical analysis, data review and interpretation. CS and SK were responsible for the study management and for the supervision of the setup and conduct of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SK reports financial support from Kowa Co., Ltd.

  • Patient consent for publication Not required.

  • Ethics approval Institutional Review Board of Kyoto Prefectural University of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available. If you would like to contact us, please send email to Yoko Ikeda. (

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