The Phase I/II Randomized, Prospective, Double-blinded, Sham-controlled Cross-over Study of Intravitreal Autologous Bone Marrow CD34+ Stem Cell Therapy for Retinal Vein Occlusion

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Project Summary: The goal of this phase I/II prospective, randomized, sham-controlled, double-blinded clinical trial is to determine whether intravitreal autologous CD34+ cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from retinal vein occlusion (RVO). RVO is a leading retinal vascular cause of vision loss in the elderly. CD34+ cells in human bone marrow are mobilized into the circulation in response to tissue ischemia for tissue revascularization and repair. Since local delivery of CD34+ cells benefits ischemic tissue, intravitreal delivery of CD34+ cells may benefit vision and retinal ischemia in eyes with RVO. A pilot clinical trial has shown no major safety or feasibility concerns using intravitreal autologous CD34+ bone marrow cells. In this expanded phase I/II study, 15 subjects (15 eyes) with persistent vision loss from RVO will be enrolled and follow for 2 years. Total study duration will be 60 months. This single- center study will be at the University of California Davis. The Coordinating Center will be Emmes Corporation. The Study Chair/Principal Investigator will be Dr. Susanna Park. The study will be conducted under an IND cleared from FDA. A Data and Safety Monitoring Committee will oversee the study. Subjects will be randomized at enrollment 2:1 to cell therapy or sham/deferred cell therapy. The cell therapy involves bone marrow aspiration, isolation of CD34+ cells from the aspirate under Good Manufacturing Practice conditions, and intravitreal injection of isolated CD34+ cells. Sham therapy involves sham bone marrow aspiration and intravitreal injection without penetrating the bone or eye. The subject, examining ophthalmologist and visual acuity examiner will remain masked to study treatment randomization till month six. Thereafter, the study will be unmasked and the sham-treated subjects will undergo bone marrow aspiration and cell therapy. A comprehensive eye examination with ETDRS best-corrected visual acuity, optical coherence tomography, auto- fluorescence, fundus photography, fluorescein angiography, microperimetry and electroretinography will be performed at baseline and serially. The primary outcome measures will be the incidence and severity of ocular and systemic adverse events associated with cell therapy and the number of CD34+ cells isolated for injection. The secondary outcome measures will be the changes in visual function, retinal perfusion and morphology following cell therapy. The long-term objective is to determine whether intravitreal autologous CD34+ cell therapy can minimize or reverse vision loss associated with retinal ischemia without compromising safety.