Cell-injection therapy using highly purified mature cultured human corneal endothelial cells (hCECs) is more effective — producing better corneal restoration — than therapy using heterogeneous cultured hCECs in patients with corneal endothelial failure at both early and mid-term postoperative periods, according to a study published in the American Journal of Ophthalmology.
The researchers had previously demonstrated the efficacy and safety of cell-injection therapy with hCECs in other keratopathies; however, they noted in the new publication that quality and purity of the cultured hCECs previously used for injection therapy were not strictly regulated. Thus, they conducted a comparative, interventional case series to evaluate the safety and efficacy of cultured cell-injection therapy with heterogeneous or highly purified hCEC subpopulations for treatment of corneal endothelial failure.
The study included 18 eyes of 18 patients with pseudophakic corneal endothelial failure conditions. All patients underwent cultured hCEC injection therapy, receiving either a relatively low proportion (0.1-76.3%) of mature cells (n=11 eyes) or a relatively high proportion (>90%) of mature cells (n=7 eyes).
The investigators evaluated postoperative CEC density, central corneal thickness, and best-corrected visual acuity and calculated the ‘spring constant’ of the CECs (a higher value indicates better cell quality) at follow up times between 1 week and 3 years.
At 3 years, most patients (10/11) who received fewer mature cells and all patients (7/7) who received more mature cells showed corneal restoration with improved best-corrected visual acuity. The median CEC density of patients who received more mature cells was higher than that of patients who received fewer mature cells (3083 vs 1349 cells/mm2; P <.001). The spring constant indicated that the CECs in eyes of patients who received more mature cells had a more ordered corneal structure than those in the eyes of patients who received fewer mature cells (15×10-3/μm2 vs 53×10-3/μm2; P =.003).
Between 24 weeks and 3 years, the decrease in median percentage of CEC density was significantly less in the eyes of patients who had received more mature cells than those of patients who received fewer mature cells (3.2% vs 23.6%; P <.005). The investigators noted that central corneal thickness recovery was prompt and well-maintained at the 3-year follow up in the eyes of patients who had received more mature cells, while it varied across the eyes of patients who received fewer mature cells.
The investigator did not observe any adverse events, local or systemic, during the 3-year follow-up period.
The primary limitations of the study included the small sample size, lack of study blinding and randomization, and exclusion of the patients who underwent cultured hCEC-injection therapy for complete graft failure-related corneal endothelial failure.
“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 [corneal endothelial failure] post-surgery,” the study says.
Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Ueno M, Toda M, Numa K, et al. Superiority of mature differentiated cultured human corneal endothelial cell injection therapy for corneal endothelial failure. Am J Ophthalmol. Published online November 14, 2021. doi:10.1016/j.ajo.2021.11.012