Seiji Takagi1, Michiko Mandai2, Kiyoko Gocho3, Yasuhiko Hirami4, Midori Yamamoto5, Masashi Fujihara6, Sunao Sugita7, Yasuo Kurimoto4, Masayo Takahashi7. 1. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Teikyo University, University Hospital Mizonokuchi, Kanagawa, Japan. 2. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan. Electronic address: michiko.mandai@riken.jp. 3. Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Chiba, Japan. 4. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan. 5. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan. 6. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Ophthalmology, Kobe City Eye Hospital, Kobe, Japan; Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, Kobe, Japan.
Abstract
PURPOSE: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging. DESIGN: Follow-up of a single case. PARTICIPANT: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: Transplantation of an autologous iPSC-derived 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 (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera. RESULTS: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had 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 showed acceptable thickness and an organized structure. Fluorescein angiography 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 agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived 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 intercell distance was found to be stable over time. CONCLUSIONS: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.
PURPOSE: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging. DESIGN: Follow-up of a single case. PARTICIPANT: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: Transplantation of an autologous iPSC-derived 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 (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera. RESULTS: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had 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 showed acceptable thickness and an organized structure. Fluorescein angiography 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 agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived 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 intercell distance was found to be stable over time. CONCLUSIONS: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.
Authors: Sara J Coulon; Joel S Schuman; Yiqin Du; Mohammad Reza Bahrani Fard; C Ross Ethier; W Daniel Stamer Journal: Prog Retin Eye Res Date: 2022-04-06 Impact factor: 19.704