Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure

Morio Ueno; Munetoyo Toda; Kohsaku Numa; Hiroshi Tanaka; Kojiro Imai; John Bush; Satoshi Teramukai; Naoki Okumura; Noriko Koizumi; Akihisa Yamamoto; Motomu Tanaka; Chie Sotozono; Junji Hamuro; Shigeru Kinoshita

doi:10.1016/j.ajo.2021.11.012

Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure

Am J Ophthalmol. 2022 May:237:267-277. doi: 10.1016/j.ajo.2021.11.012. Epub 2021 Nov 14.

Authors

Affiliations

¹ From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan (M.U., K.N., H.T., K.I., J.B., C.S., J.H.).
² Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan (M.To., S.K.).
³ Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan (S.T.).
⁴ Department of Biomedical Engineering, Doshisha University, Kyotanabe, Japan (N.O., N.K.).
⁵ Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, Japan (A.Y., M.Ta.).
⁶ Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, Japan (A.Y., M.Ta.); Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany (M.Ta.).
⁷ Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan (M.To., S.K.). Electronic address: [email protected].

PMID: 34788595
DOI: 10.1016/j.ajo.2021.11.012

Abstract

Purpose: To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC) injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial failure (CEF).

Design: Comparative, interventional case series.

Methods: This study involved 18 eyes with CEF that underwent cultured hCEC injection therapy, categorized into 2 groups: (1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs (group 1 [Gr1]), and (2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs (group 2 [Gr2]). From 1 week to 3 years postoperation, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's "spring constant" was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers.

Results: At 3 years postoperation, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3083 cells/mm²; range, 2182-4417 cells/mm²) was higher than that in Gr1 (1349 cells/mm²; range, 746-2104 cells/mm²) (P < .001), and the spring constant verified the superiority of the mature cultured hCECs. From 24 weeks through 3 years postoperation, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < .005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed.

Conclusion: Our findings showed that mature cell SPs for hCEC injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years postsurgery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Count
Cell Differentiation
Cells, Cultured
Cornea*
Endothelial Cells
Endothelium, Corneal*
Humans