Randomized Study of Intravitreal Autologous CD34+ Stem Cells in Central Retinal Vein Occlusion (Treatment of Retinal vein occlusion Using STem cells [TRUST] Report 1): Safety and Feasibility.

Purpose: To assess the safety and feasibility of intravitreal injection of autologous CD34+ bone marrow stem cells (BMSCs) in eyes with vision loss from central retinal vein occlusion (CRVO). Design: Phase I/II single-center, prospective, randomized, sham-controlled, double-masked study. Participants: Participants with CRVO of 6 to 42 months duration, best-corrected visual acuity (VA) of 20/40 to 20/400, and no concurrent retinopathy or optic neuropathy contributing to vision loss in the study eye. The exclusion criteria include any concurrent systemic condition that would alter bone marrow components. Methods: Participants were randomized to immediate cell injection followed by sham injection at month 6 or immediate sham injection followed by cell injection at month 6. Cell injection consisted of a bone marrow aspiration and intravitreal injection of autologous CD34+ BMSCs. CD34+ BMSCs were isolated from the mononuclear cell fraction of bone marrow using Miltenyi CliniMACS system under current good manufacturing practices. Isolated cells were released for intravitreal injection if they passed the release criteria for quantity, sterility, and viability accepted by the US Food and Drug Administration. Sham injection consisted of a sham bone marrow aspiration and intravitreal injection without entering bone or eye. Eye examination, microperimetry, fundus photography, fluorescein angiography, electroretinography, OCT, and OCT angiography were performed at baseline and during study follow-up of 12 months. Main Outcome Measures: Adverse events (AEs) associated with study treatment, number of CD34+ BMSCs injected intravitreally. Results: Sixteen participants (16 eyes) were randomized to 1 of 2 study groups. All received intravitreal injection of autologous CD34+ BMSCs (mean 4.3 million cells) and completed the study follow-up. Rubeosis with vitreous hemorrhage occurred in 1 study eye, <1 month after sham injection and 7 months after cell injection, attributed to normal progression of CRVO. There were no other serious ocular AEs. The most common AE related to the study cell injection was new floaters (15/16, 93%). Other ocular AEs were similarly noted after sham injection. No eye had persistent VA loss of ≥15 letters after cell injection. Conclusions: Intravitreal injection of autologous CD34+ BMSCs appears well-tolerated and feasible in eyes with vision loss from CRVO. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.