Preliminary Report Of Transplantation Of Human Fetal Retinal Pigment Epithelial Cells On Age-related Macular Degeneration Patients

Aim:To investigate the safety and efficacy of the subretinal transplantation of fetal retinal pigment epithelial cells(RPE)in the treatment of dry and/or non-exudative age-related macular degeneration.Methods:Modified GMP fetal RPE(fRPE)primary culture system was established.After the safety and efficacy of these RPE cells were confirmed by a sodium iodate induced retinopathy primate model,the cells were further evaluated in 5 patients with non-exudative age-related macular degeneration(AMD)and AMD with scarring of neovascularization for the safety and feasibility.The study enrolled one dry AMD patient and four non-exudative AMD patients.Subretinal transplantation of fRPE with three dosage cohorts were performed on P1(1×10~5),P2,P3(2×10~5),P4,P5(5×10~5)respectively.All subjects were required to sign informed consent,and a comprehensive and systematic screening were performed before enrollment,including ETDRS,optic coherent tomographic imaging(OCT),color fundus(CF),fundus fluorescent angiography(FFA),autofluorescence,microperimetry examination and systemic tests,such as routine examination of blood urine and feces,detection of biochemical function and human leukocyte antigen typing(HLA).After the transplantation surgery,the patients were followed up at 3 days,1 week,2weeks,1 month,and then once every month,and once every 3 months after 6months for clinical observation for a total of 9 months.The study were registered at ClinicalTrials.gov(numbers NCT02868424)and Chinese Clinical Trial Registry(numbers ChiCTR-OPC-15006757).Results:During the nine-month follow-up period,no endophthalmitis,no vitreous hemorrhage,and no proliferative vitreoretinopathy was observed in neither of the five clinical cases,although epiretinal membrane(1 case)and retinal hole(1 case)appeared due to intraoperative injury.Four out of five patients achieved an increase in ETDRS visual acuity(VA),among which the greatest was 19 letters and the least was 9 letters improvement at the end of 9 months follow-up,while the visual acuity of the other case remained stable at the preoperative level.Color fundus photos and OCT images demonstrated the existence of the fRPE cells,microperimetry showed improved retinal sensitivity and concentrated fixation point,and the autofluorescence revealed that the abnormal fluorescence at the lesion site reduced.Conclusions:Preliminary data indicate that transplanted fRPE are safe in the surgical eyes and can be tolerated for at least 9 months.fRPE can help restore the anatomy and improve visual function of AMD patients to some extent.fRPE transplantation is safe and feasible and is expected to be a new measure for the treatment of dry AMD or neovascular AMD with fibrous scarring.