Long-Term Corneal Rejuvenation after Transplantation of Cultured Human Corneal Endothelial Cells

Shigeru Kinoshita; Morio Ueno; Munetoyo Toda; Kojiro Imai; Yasufumi Tomioka; Kohsaku Numa; Hiroshi Tanaka; Tsutomu Inatomi; Takanori Kameda; Akitaka Tsujikawa; Michio Hagiya; John Bush; Satomi Sakabayashi; Satoshi Teramukai; Junji Hamuro; Chie Sotozono

doi:10.1016/j.ophtha.2025.05.020

Long-Term Corneal Rejuvenation after Transplantation of Cultured Human Corneal Endothelial Cells

Ophthalmology. 2025 May 28:S0161-6420(25)00336-7. doi: 10.1016/j.ophtha.2025.05.020. Online ahead of print.

Authors

Affiliations

¹ Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: fmstoph@koto.kpu-m.ac.jp.
² Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
³ Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁵ National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
⁶ Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁷ Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan.

PMID: 40447112
DOI: 10.1016/j.ophtha.2025.05.020

Abstract

Purpose: To investigate the long-term efficacy of cultured human corneal endothelial cell (CEC) transplantation with rho-associated protein kinase (ROCK) inhibitor for the treatment of corneal endothelial failure (CEF).

Design: Prospective observational study.

Participants: This study involved 65 patients with corneal endothelial failure treated via cell therapy using cultured allogeneic human CECs (0.2-1.0 x10⁶ cells) supplemented with a ROCK inhibitor injected into the anterior chamber of the eye who were followed up to 10-years postoperative.

Methods: At 24-weeks and 1 to 10-years postoperative, corneal transparency, corneal endothelial cell density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) on a Landolt C eye chart were recorded. The Kaplan-Meier method was used to estimate the postoperative probability for restoration and persistence of corneal transparency.

Main outcome measures: The primary outcome was the corneal restoration and transparency post-surgery. Secondary outcomes were a CEC density exceeding 500 cells/mm² and 1000 cells/mm², corneal thickness of below 630 μm, and an improvement in BCVA equivalent to a decrease of at least 0.2 in logMAR BCVA at 24-weeks and 5-years postoperative.

Results: For the primary outcome, the overall success in maintaining corneal transparency at 24-weeks, 5-years, and 10-years postoperative was 98.5% (95% confidence interval [CI], 89.6-99.8%), 93.0% (95% CI, 82.4-97.3%), and 83.7% (95% CI, 54.4-95.0%), respectively. A CEC density of greater than 1000 cells/mm² was achieved in 79.6% (95% CI, 65.7-89.8%), a corneal thickness of below 630 μm was achieved in 85.4% (95% CI, 72.2-93.9%), and a BCVA improvement was achieved in 85.7% (95% CI, 72.8-94.1%) at 5-years postoperative. There were no severe adverse reactions.

Conclusions: Cultured human CEC-transplantation therapy was found to be safe and effective over a long-term period for the treatment of CEF.

Keywords: cell injection; cell transplantation; corneal endothelial cell; corneal endothelial failure; long-term follow-up; regenerative medicine; rho-associated protein kinase (ROCK) inhibitor.