Phase I/II study finds intravitreal CD34+ stem cells safe and feasible in CRVO

A newly published study found that intravitreal injection of autologous CD34+ stem cells is well tolerated and feasible for treating loss of vision resulting from central retinal vein occlusion (CRVO), according to a press release issued by the Emmes Company working in collaboration with the UC Davis Eye Center, Sacramento, CA.

The results show that the injection of the stem cells was deemed well tolerated and feasible, establishing an important safety foundation for future studies, according to Susanna S. Park, MD, PhD, and colleagues. She is from the Department of Ophthalmology & Vision Science, University of California Davis Health, Sacramento.

The researchers published their results in Ophthalmology Science.¹

The rationale for their study was that visual loss associated with RVO results from retinal ischemia and secondary macular edema, a complication of the retinal ischemia.^2,3 While macular edema is treatable with intravitreal drugs or laser, the visual loss associated with retinal ischemia is not and may lead to retinal degeneration and dysfunction.^4,5 Park and colleagues emphasized the RVO is one of the leading causes of unilateral blindness in the elderly population.

Stem cell study methodology

The investigators wanted to assess the safety and feasibility of intravitreal injection of autologous CD34+ bone marrow stem cells (BMSCs) in eyes with vision loss from CRVO. They undertook a phase I/II single-center, prospective, randomized, sham-controlled, double-masked study that included patients who had had CRVO for 6 to 42 months, a 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, they recounted.

Sixteen patients (16 eyes) were randomized to either immediate cell injection followed by sham injection at month 6 or immediate sham injection followed by cell injection at month 6. All patients underwent an intravitreal injection of a mean of 4.3 million autologous CD34+ BMSCs.

The cell injection included bone marrow aspiration and intravitreal injection of autologous CD34+ bone marrow stem cells (BMSCs) that had been isolated from the mononuclear cell fraction of bone marrow. All patients underwent an ocular examination, microperimetry, fundus photography, fluorescein angiography, electroretinography, optical coherence tomography (OCT), and OCT angiography at baseline and during the 12-month follow-up.

The main outcome measures were the development of adverse events (AEs) associated with the treatment and the number of CD34+ BMSCs injected intravitreally.

What did the evaluation of the stem cell injections determine?

All patients completed the study follow-up.

Only one serious ocular AE occurred, ie, rubeosis with vitreous hemorrhage occurred in one study eye, less than 1 month after sham injection and in one eye 7 months after cell injection. The investigators considered this to be associated with the normal progression of CRVO. No other serious ocular AEs developed, Park and colleagues reported.

The most common AE was related to the study cell injection, ie, new floaters in 15 of the 16 eyes (93%). Other ocular AEs were similarly noted after sham injection. There was no persistent VA loss of 15 letters or more in any eye after injection of the stem cells.

The investigators concluded that the intravitreal injection of autologous CD34+ BMSCs is feasible and well tolerated in patients with vision loss associated with CRVO.

Park and colleagues also pointed out that the findings of the study “further substantiate the observations made in their two prior smaller phase I studies also showing safety and feasibility of this cell therapy.^6,7”

They also learned that “high-quality CD34+ BMSCs could be isolated from bone marrow aspirate under current good manufacturing practices conditions in all study participants for intravitreal injection.”

“The current study also provides invaluable insight to the study design that can be used in planning future larger clinical trials exploring this cell therapy for retinal disorders,” they stated.

Park was joined in this study by colleagues from The Emmes Company, LLC; the Stem Cell Program, Institute for Regenerative Cures, University of California Davis Health, Sacramento; and the Division of Hematology Oncology and Malignant Hematology/Cellular Therapy and Transplantation, Department of Internal Medicine, University of California Davis Health, Sacramento.

References

1. Park SS, McCormack J, Salazar D, et al. CD34+ stem cells in central retinal vein occlusion (treatment of retinal vein occlusion using stem cells [TRUST] Report 1): safety and feasibility. Ophthalmol Sci. 2026;6. https://doi.org/10.1016/j.xops.2025.100905

2. Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. The central retinal vein occlusion group. Arch Ophthalmol. 1997;115:486-91.

3. McIntosh RL, Rogers SL, Lim L, et al. Natural history of central retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010;117:1113-23.

4. The SCORE Study Research Group. SCORE study report 5. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion. Arch Ophthalmol. 2009;127:1101-14.

5. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion. Six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1124-33.

6. Park SS, Bauer G, Abedi M, et al. Intravitreal autologous bone marrow-derived CD34+ cells for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trials findings. Invest Ophthalmol Vis Sci. 2014;56:81-9.

7. Park SS, Bauer G, Fury B, et al. Phase I study of intravitreal injection of autologous CD34+ stem cells from bone marrow in eyes with vision loss from retinitis pigmentosa. Ophthalmol Sci. 2024;5:100589.