Safety and Efficacy of Mature Cultured Corneal Endothelial Cell Therapy (Vyznova) in Eyes With Declining Long-term Efficacy After Prototype Cell Transplantation.

PURPOSE: To report the efficacy and safety of mature cultured corneal endothelial cell (CEC) transplantation using neltependocel combined with the Rho kinase inhibitor Y-27632 (Vyznova) in eyes with declining long-term efficacy after transplantation of immature cultured CECs (prototype cells). METHODS: In the first-in-human CEC therapy study conducted in 2014, 2 patients (#4 and #11) who received prototype cultured CEC initially demonstrated restoration of corneal transparency, but the patients' endothelial function deteriorated after several years. These 2 patients were later treated with Vyznova in 2024. Clinical outcomes assessed included corneal thickness, CEC density, best-corrected visual acuity (BCVA), and intraocular pressure. RESULTS: In patient 4 (pseudoexfoliation syndrome), corneal thickness improved from 786 to 572 μm, and CEC density was 2292 cells/mm2 at 1 year postoperatively. BCVA improved from 0.03 to 0.4 (decimal visual acuity). In patient 11 (Fuchs endothelial corneal dystrophy), corneal thickness improved from 688 to 523 μm, and CEC density was 2552 cells/mm2 at 1 year postoperatively. BCVA improved from 0.07 to 1.0 (decimal visual acuity). Neither case exhibited graft rejection, elevated intraocular pressure, or anterior uveitis. CONCLUSIONS: Administration of Vyznova was safe and demonstrated favorable clinical outcomes in eyes with declining long-term efficacy after initial treatment with prototype CECs. These findings support the feasibility of Vyznova as a treatment strategy for corneal endothelial failure in patients previously treated with cultured CECs.