Cultured Human Corneal Endothelial Cell Injection therapy provide rapid recovery of corneal endothelial failure

The postoperative outcomes of DSAEK and DMEK are quite well known. However, for mild corneal endothelial dysfunction, such as Stage 1 or Stage 2 Fuchs endothelial corneal dystrophy (FECD), 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. 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. Moreover, the long-term efficacy of DSO has yet to be fully elucidated.

Ideally, for cases of corneal endothelial dysfunction or CEF, the optimal therapy would be a minimally invasive procedure that reconstructs the cornea with a high CECD of homeostatic ordered CECs, thus maintaining a normal healthy corneal structure for a long-term period post treatment. Morio Ueno et al previously reported their novel surgical procedure involving the injection of allogeneic cultured human CECs (hCECs) with a ROCK inhibitor into the anterior chamber, and 5-year postoperative results revealed that new cultured hCEC-injection therapy is safe and effective with reasonably good long-term outcomes.

In this present study, in order to investigate and verify the superiority of the clinical outcomes in CEF patients treated with cultured hCEC-injection therapy using highly purified mature cultured hCECs (Group 2; Gr2), authors organized and initiated a small case series clinical trial. Moreover, they analyzed the collective order of the cultured hCECs prior to injection, and at 24-weeks and 3-years postoperative via our previously reported newly-developed method. Thus, the purpose of this current interventional study was to present clinical findings on the safety and efficacy of the cultured hCEC-injection therapy using the highly purified mature cultured hCECs (Gr2 treated eyes) compared with the findings obtained using the previously-reported Gr1 cultured hCECs (Gr1 treated eyes).

This study involved 18 eyes with CEF that underwent cultured hCEC injection therapy, categorized into two 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 postoperative, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameters, 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 postoperative, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3,083 cells/mm2; range, 2,182-4,417 cells/mm2 ) was higher than that in Gr1 (1,349 cells/mm2 ; range, 746-2,104 cells/mm2 ) (P < 0.001), and the spring constant verified the superiority of the mature cultured hCECs. From 24-weeks through 3-years postoperative, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < 0.005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed.

The findings in this interventional study confirmed that although the number of cells injected into the anterior chamber and the surgical procedure and postoperative care was identical between the two groups, cell-injection therapy using Gr2 cultured hCECs resulted in a better corneal restoration in terms of CECD than that using Gr1 cultured hCECs at both 24-weeks and 3-years postoperative, thus indicating the superiority of the Gr2 cultured hCECs, both at the early and mid-term postoperative periods.

Comparison of the early postoperative period between the two groups revealed that Gr2 cultured hCECs produced a faster recovery of corneal thinning than Gr1 cultured hCECs, probably due to the rapid functional recovery for corneal dehydration (i.e., the pump and barrier function).

In conclusion, the findings in this study suggest that a higher biological quality of cultured hCECs acquired via maximum quality control of the cell-culture procedure for the production of cells for hCEC-injection therapy can improve the long-term clinical outcomes and help prevent late-stage CEF post surgery.

Source: Morio Ueno , Munetoyo Toda , Kohsaku Numa et al, Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure, American Journal of Ophthalmology (2021)

doi: https://doi.org/10.1016/j.ajo.2021.11.012