Ten-Year Survival of First-in-Human Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Sheet Transplantation.

Abstract

Purpose: This study aimed to report the 10-year follow-up results of the first-in-human study of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet transplantation, with a focus on long-term graft persistence assessed using multimodal imaging, including polarization-sensitive OCT (PS-OCT)-based melanin evaluation.

Design: Follow-up of a single patient.

Participant: A patient with neovascular age-related macular degeneration.

Methods: Autologous iPSC-derived RPE sheets were transplanted into the subretinal space in 2014.

Main outcome measures: Engraftment of the transplanted RPE sheet and preservation of the host retinal structure were evaluated using multimodal imaging, including color fundus photography, spectral-domain OCT, PS-OCT, and near-infrared autofluorescence (NIRAF), throughout the posttransplantation period.

Results: The patient was aged 88 years at the 10-year posttransplantation follow-up. There was a stable anatomic appearance of the persistent subretinal pigmentation on color fundus photography. Spectral-domain OCT revealed the preservation of the outer nuclear layer over the graft. Choroidal thickness analysis indicated sustained structural preservation beneath the graft. Polarization-sensitive OCT demonstrated persistent depolarization signals of the RPE layer, which were separated from the overlying retina and corresponded to the pigmented area observed on color fundus photography. The combination of high polarimetric entropy on PS-OCT and low-to-isoautofluorescence on NIRAF further delineated the grafted area, distinguishing it from healthy and atrophic regions.

Conclusions: Sustained preservation of the overlying neurosensory retina and underlying choroid, in conjunction with long-term pigment persistence, provides important evidence of the safety and structural stability of iPSC-based cell therapy. These findings support the potential of this approach for broader clinical application in regenerative medicine.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.