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

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 optical coherence tomography (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 (SD)-OCT and PS-OCT, and near-infrared autofluorescence (NIRAF), throughout the post-transplantation period.

RESULTS

The patient was aged 88 years at the 10-year post-transplantation follow-up. There was stable anatomic appearance of the persistent subretinal pigmentation on color fundus photography. SD-OCT revealed the preservation of the outer nuclear layer over the graft. Choroidal thickness analysis indicated sustained structural preservation beneath the graft. PS-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-iso-autofluorescence 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.