Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration

Abstract Purpose To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) sheet autologous transplantation using multimodal imaging. Design Follow-up of a single case. Subject A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Intervention Transplantation of an autologous iPS-RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014. Main Outcome Measures The function of the graft was assessed 4 years after surgery by color fundus photography, spectral domain-optical coherence tomography (SD-OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), and an adaptive optics (AO) retinal camera. Results At the 4-year follow-up, the transplanted autologous iPS-RPE sheet has survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft has acceptable thickness and an organized structure. FA and SD-OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor drug. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the choroidal neovascularization. ICGA revealed a preserved choriocapillaris around the iPS-RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average inter-cell distance was found to be stable over time. Conclusions Thus far, the grafted iPS-RPE sheet has survived for 4 years and appears to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.