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

Abstract

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). Comparative, interventional case series. 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. 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. 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.

Highlights

The treatments for moderate corneal endothelial dysfunction and corneal endothelial failure (CEF), classically termed "bullous keratopathy", include Descemet stripping automated endothelial keratoplasty (DSAEK),[1,2,3] Descemet membrane endothelial keratoplasty (DMEK),[4,5] and penetrating keratoplasty,[6,7] all of which require the use of a fresh donor cornea
CHARACTERISTICS OF THE CULTURED HUMAN CORNEAL ENDOTHELIAL CELLS: For the cultured hCEC-injection therapy, 7 lots of Gr1 cultured hCECs were used for the 11 treated eyes in Gr1, and 4 lots of Gr2 cultured hCECs were used for the 7 treated eyes in Gr2
These findings suggested that the CECDs in culture were similar, there were more mature cultured hCECs in the Gr2 lots than in the Gr1 lots (Table 2)

Summary

Introduction

The treatments for moderate corneal endothelial dysfunction and corneal endothelial failure (CEF), classically termed "bullous keratopathy", include Descemet stripping automated endothelial keratoplasty (DSAEK),[1,2,3] Descemet membrane endothelial keratoplasty (DMEK),[4,5] and penetrating keratoplasty,[6,7] all of which require the use of a fresh donor cornea. For mild corneal endothelial dysfunction, such as Stage 1 or Stage 2 Fuchs endothelial corneal dystrophy (FECD),[8] Descemet membrane stripping only (DSO), a surgical procedure that involves the removal of a small central corneal area of the Descemet membrane with guttae and degenerated endothelium, has been proposed.[9] The benefit of DSO is that it does not involve the use of donor corneal tissue, while the disadvantage is a relatively low corneal endothelial cell (CEC) density (CECD) postoperative. Previous studies have reported the preliminary findings between the administration, or no administration, of Rho-associated protein kinase (ROCK) inhibitor eye drops following DSO.[10,11]

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