Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: a phase I clinical safety study

This prospective clinical case series aimed to investigate the safety of subretinal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in advanced stage retinitis pigmentosa (RP).

Stem cell treatment with subretinal implantation of ADMSCs seems to have some ocular complications and should be applied with caution. The results of this study provide the first evidence of the short-term safety of ADMSCs in humans, and clarifies the complications of the therapy which would be beneficial for future studies. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with a larger number of cases will be necessary.

This study included 11 patients with end-stage RP who received subretinal implantation of ADMSCs. All patients had a total visual field defect and five of them only had light perception. The best corrected visual acuity (BCVA) in the study was 20/2000. All patients had undetectable electroretinography (ERG). The worst eye of the patient was operated on and, after total vitrectomy with a 23 gauge, ADMSCs were injected subretinally. Patients were evaluated at day 1, at weeks 1-4, and then once a month for 6 months, postoperatively. BCVA, anterior segment and fundus examination, color photography, and optical coherence tomography (OCT) were carried out at each visit. Fundus fluorescein angiography (FFA), perimetry, and ERG recordings were performed before treatment and at the end of month 6, and anytime if necessary during the follow-up.

All 11 patients completed the 6-month follow-up. None of them had systemic complications. Five patients had no ocular complications. One of the patients experienced choroidal neovascular membrane (CNM) at the implantation site and received an intravitreal anti-vascular endothelial growth factor drug once. Five patients had epiretinal membrane around the transplantation area and at the periphery, and received a second vitrectomy and silicon oil injection. There was no statistically significant difference in BCVA and ERG recordings from baseline. Only one patient experienced an improvement in visual acuity (from 20/2000 to 20/200), visual field, and ERG. Three patients mentioned that the light and some colors were brighter than before and there was a slight improvement in BCVA. The remaining seven patients had no BCVA improvement (five of them only had light perception before surgery). Conclusions: Stem cell treatment with subretinal implantation of ADMSCs seems to have some ocular complications and should be applied with caution. The results of this study provide the first evidence of the short-term safety of ADMSCs in humans, and clarifies the complications of the therapy which would be beneficial for future studies. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with a larger number of cases will be necessary.