In a clinical trial designed as a Phase I, open-label, safety and feasibility study, researchers from London studied the implantation of a human embryonic stem cell (hESC) retinal pigment epithelium patch in two patients with acute wet age-related macular degeneration and recent rapid vision decline. They reported their primary and secondary outcomes from the first two patients of the series in an article published in the journal Nature Biotechnology in March. Based on the results, the researchers say that this stem-cell-based tissue transplantation is a potentially effective strategy for treating neurodegenerative diseases with otherwise irreversible cell loss.
The researchers used a surgical delivery tool to place one RPE patch in the subretinal space, under the fovea, in the affected eye of each patient. They verified its placement with stereo-biomicroscopy, fundus photography and spectral domain optical coherence tomography.
For both patients, hESC-RPE was present over the full area of the patch at 12 months. The patches showed uneven autofluorescence, which the researchers say suggests functioning RPE phagocytosis. The investigators add that the patients also presented with darker-pigmented areas contiguous with the patch, which may represent RPE cell migration from the patch onto adjacent RPE-deficient areas. These areas spread from the patch edge outward over the first six months after surgery.
The researchers observed visual recovery in both cases. The Early Treatment Diabetic Retinopathy Study letter chart was used to define best-corrected vision, which improved over 12 months from 10 to 39 and from 8 to 29 letters in patients one and two, respectively. There was no increase in intraocular pressure in either patient.
Lyndon da Cruz, PhD, FRCOphth, FRACO, one of the study’s authors, says the treatment may home in on the ocular anatomy that’s crucial for a good outcome. “In AMD, the primary part of the eye that’s affected is the retinal pigment epithelium,” he notes. “If that’s damaged but the rest of the structures remain the same, what we’ve been able to do is replace it with a perfect copy we’ve grown in the laboratory. That’s the breakthrough. Theoretically, this could conceivably work for any disease where it is isolated in that layer and all other [layers] remain the same.
“Now because this is our first test of this in humans, we’re taking a select group that has very sudden or severe vision loss, so that if it doesn’t work, there’s no vision loss involved,” Dr. da Cruz continues. “But if it does work, then we have these great visual recoveries. This is what we’ve been able to achieve while showing the proof-of-principle. It’s a lower risk to patients and a clear-cut signal that the transplant of the layer works because they have a visual recovery. We were able to replace the damaged layer of the retina.”
Dr. da Cruz says patients with sudden vision loss were a key part of the study’s design. “We’re looking at severe or sudden vision loss because due to its sudden nature—they were able to see the day before—we know all the ocular structures must be intact,” he says. “We know that the disease is centered in this area. These conditions are optimal for the particular type of transplant that we’re doing. Specifically, we want to look at patients with sudden vision loss with a large hemorrhage or a pigment epithelial tear. When they present, we can resolve whatever has happened to cause their sudden vision loss, while sliding the patch into the layer so we can also recover their vision. However, we also know if you leave the bleeding—or whatever the problem is—for six to eight weeks, the rest of the layers will be damaged, so there’s a small window right after they’ve suddenly lost their vision during which we can perform this procedure.”
Dr. da Cruz is excited about the future of the study. “The first cases are the hardest,” he says. “We’d like to do more in order to show that this is as reproducible as the first two patients. We want to show this works, then go on to a more definitive study involving a control group and maybe look at a licensing study. We’d also want to look at a broader array of patient groups, maybe including people with early dry macular degeneration or, in some cases, we may look at patients with early inherited retinal dystrophies and then run a pilot study to see if there’s any chance this implant will work for them, as well.”
1. da Cruz L, Fynes K, Georgiadis O, et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nature Biotechnology 36;328-337.