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Odysseas Georgiadis, Kate Fynes, Yvonne Luo, Britta Nommiste, Jiangjian Zhong, Conor Ramsden, Peter J Coffey, Lyndon daCruz; Human Embryonic Stem Cell-derived Retinal Pigment Epithelium sheet transplantation in severe neovascular Age-Related Macular Degeneration: 18-month survival and structural outcomes. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2984.
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We present the first 2 cases of a prospective interventional clinical study to assess the medium-term survival and characteristics of retinal pigment epithelium (RPE), choroid and neuroretina, after submacular implantation of a human embryonic stem cell (hESC)-derived RPE sheet in patients with recent rapid vision loss due to neovascular age-related macular degeneration (nAMD).
Transplantation of a monolayer of hESC-RPE cells immobilized on a vitronectin coated polyester artificial basement membrane (BM) was performed in 2 eyes of 2 patients (61 y.o. female, 84 y.o male) within 1 month (m) of acute vision loss due to nAMD. Fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), autofluorescence (AF) and adaptive optics (AO) retinal imaging were performed on 6, 12 and 18 m post-operatively, to assess the structural integrity and characteristics of RPE, choroid and neuroretina associated with the transplant.
At 18 m follow-up, the retina was fully attached in both subjects and the hESC-RPE sheet was flat and stable under the macula. It was pigmented throughout the bulk of its surface. From 6 to 18 m, case 1 showed a local depigmentation, while case 2 showed increased hue homogeneity. Boths sheets had hyperpigmented areas and showed expansion of pigment outside their borders under the host retina, which remained stable after m 6. In both cases SD-OCT showed a continuous hyperreflective outer retina band, corresponding to the hESC-RPE-BM complex. This band extended uninterrupted into the area of pigment expansion outside the sheet. Case 1 showed general retinal thinning with preservation of segmentation. Case 2 showed regional retinal thickening with ill-defined layers. Both sheets showed perfusion in FFA, regional AF and the presence of cone photoreceptor-like structures in AO imaging. There were no signs of uncontrolled proliferation.
Our results support the feasibility of structural regeneration of the RPE-BM complex by hESC-derived tissue transplantation in nAMD. Whilst histological correlation is not possible in this study, the evidence of the implant's structural integrity, photoreceptor rescue and the absence of serious adverse events combine to provide a promising development in regenerative strategies for retinal disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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