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The safety and feasibility of intravitreal autologous CD34+ bone marrow cells as a potential therapy for retinal disease were evaluated in a pilot study. Preliminary findings demonstrated the treatment was feasible and researchers intend to pursue a larger, prospective study with longer follow-up.
Take-home message: The safety and feasibility of intravitreal autologous CD34+ bone marrow cells as a potential therapy for retinal disease were evaluated in a pilot study. Preliminary findings demonstrated the treatment was feasible and researchers intend to pursue a larger, prospective study with longer follow-up.
By Michelle Dalton, ELS
Sacramento, CA-Intravitreal injection of autologous CD34+ stem cells from bone marrow may be both feasible and well tolerated in eyes with degenerative or ischemic retina diseases, said Susanna S. Park, MD, PhD.
Such conditions included age-related macular degeneration (AMD) and Stargardt’s disease, said Dr. Park, professor, Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, Sacramento.
In an initial exploratory study, Dr. Park and colleagues prospectively enrolled six subjects (6 eyes) who had irreversible vision loss from either retinal vascular occlusion, hereditary or nonexudative AMD, or retinitis pigmentosa in a pilot study to evaluate both the safety and feasibility of intravitreal autologous CD34+ bone marrow cells as a potential therapy.1
As the authors noted in their paper, the potential for tissue regeneration using cellular therapy exists. Other groups had already developed partially differentiated retinal pigment epithelial cells derived from embryonic stem cells and inducible pluripotent stem cells, and early studies “suggest that these cells may slow progression of retinal degeneration when injected into the subretinal space.”1
Human bone marrow may be a useful source of stem cells that can be transplanted to “kick start” tissue regeneration. Animal models indicated they could serve as a potential therapy for certain retinal conditions because of their propensity to induce local trophic effects, Dr. Park’s group said.
A subclass of these cells, CD34+ cells, are unique to humans and have been used safely to treat patients with blood disorders or coronary artery disease. In animal models of retinal ischemia or other types of damage, intravitreally injected CD34+ cells rapidly incorporated into the damaged tissue. These human cells could be detected in mouse retina as long as 6 months after injection and no associated safety issues were noted.
These results led Dr. Park and colleagues to pursue the therapy as potential treatment for degenerative or ischemic retinal disorders.
The study enrolled patients from November 2012 through August 2014. All enrolled subjects had irreversible vision loss for at least 6 months.
Best-corrected visual acuity (BCVA) could range from 20/100 to counting fingers, with equal or better vision in the non-study eye. Comprehensive eye examinations were performed at baseline, day 1, weeks 1 and 2, and months 1, 3, and 6 after injection.
Primary outcome measures included the incidence and severity of ocular and systemic adverse events and the number of CD34+ cells isolated and injected intravitreally from a single bone marrow aspirate.
The two AMD patients were 76 and 85 years old at enrollment; the remaining study subjects were males under age 40. On average, baseline vision ranged from 20/200 to 20/800. One patient had a unilateral vision loss of 9+-months’ duration from a combined central retinal artery and vein occlusion with persistent hemorrhages but no macular edema or retinal neovascularization. All other patients had vision loss of at least 5 years’ duration.
According to the study details, a mean of 3.4 million (range, 1 to 7 million) CD34+ cells were isolated and the entire 0.1-mL volume of the isolated cells were injected at 4 mm posterior to the infratemporal limbus with a 30-gauge short needle. Researchers used adaptive optics optical coherence tomography (AO-OCT) to image the macula for changes.
The therapy was well tolerated with no intraocular inflammation or hyperproliferation. The only adverse event reported was grade 1 local pain immediately after the bone marrow aspiration.
Improvement in BCVA ranged from 0 to 11 lines in the ETDRS visual acuity chart, study authors said.
“In four of the six subjects, improvements of two or more lines were noted,” they said.
However, the time course for the improvement varied among the subjects. One of the two AMD patients improved from 20/200 to 20/80 (18 letter gain). The other AMD patient lost one letter at 6-month follow-up. The one patient with unilateral vision loss gained 55 letters, improving from 20/800 to 20/63.
Multifocal electroretinogram (ERG) showed a trend toward stabilization in the study eye compared to the contralateral eye. Full-field ERG showed stable or enhanced amplitude in the study eye. AO-OCT imaging showed new punctuate hyperreflectivity within the retinal layers suggestive of intraretinal incorporation of the stem cells in the eye with Stargardt’s disease.
“This study is based on the first Investigational New Drug approved by the FDA for this route of CD34+ cell administration,” Dr. Park’s group said. While the findings are preliminary, “they demonstrate that the treatment was feasible, without any major safety concerns for the duration of the study follow-up.”1
Dr. Park said these results support those found in preclinical observations. Her group intends on pursuing a larger, prospective study with longer follow-up to “further explore the safety and potential efficacy of this cellular therapy.”
1. Park SS, Bauer G, Abedi M, et al. Intravitreal autologous bone marrow CD34ï¬ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest Ophthalmol Vis Sci. 2015;56:81–89.
Susanna S. Park, MD, PhD
Dr. Park did not indicate any proprietary interest in the subject matter.