bioengineered implant of human embryonic stem-cell-derived retinal pigment epithelium (RPE) may be of benefit in advanced dry age-related macular degeneration (AMD), according to preliminary research.

"This is the first human trial of the novel stem-cell-based implant designed to replace a single cell layer that degenerates in patients with dry age-related macular degeneration," Dr. Amir H. Kashani of the University of Southern California, Los Angeles, told Reuters Health by email. "In this study, one subject's vision improved by 17 letters and two subjects demonstrated improved ability to use the treated retina to fixate on a target."

In a paper online April 4 in Science Translational Medicine, Dr. Kashani and colleagues note that RPE dysfunction in AMD as well as alteration of Bruch's membrane structure and function are likely important factors in the development of geographic atrophy.

To help address these problems, the team developed a composite implant consisting of a polarized monolayer of RPE on an ultrathin, synthetic parylene substrate designed to mimic Bruch's membrane.

Four of five subjects enrolled in the study successfully received the implant. Delivery was prevented in one patient by intraoperative fibrinoid debris in the subretinal space, but in all five there were no unanticipated severe adverse events related to the implant, surgical procedure, or immunosuppression.

All patients experienced some bleeding, and there was one serious adverse event involving a subretinal hemorrhage possibly related to the surgery. At last follow-up, the hemorrhage had substantially resolved, and the implant was unaffected.

Follow-up for a mean of 260 days showed no change in the overall appearance and location of the implant indicating that it was stable and not prone to migration.

One patient had improvement in visual acuity and two had gains in visual function. None showed evidence of progression in vision loss.

These findings, continued Dr. Kashani, "suggest that the implant has the potential to stop the progression of the disease or even improve patients' vision. Larger studies are needed to assess the implant's efficacy."

"Proving its safety in humans," he concluded in a statement, "is the first step in accomplishing that goal."

Rajesh C. Rao, an ophthalmologist at the University of Michigan, Ann Arbor, told Reuters Health by email, "There was no evidence that visual acuity changed, but fixation of the eye improved in two of four implanted patients; fixation is a relatively crude measure of visual function."

He noted that one patient "who had improved fixation also had a significant retinal hemorrhage/bleed. Thus, it is hard to know if the change in fixation could be related to the bleeding—which can happen in macular degeneration or as a result of the procedure."

"Importantly, while all four successfully implanted patients had some degree of bleeding during the procedure, one of the four had significant bleeding, likely as a result of the procedure," said Dr. Rao, who was not involved in the study.

Overall, he concluded, these are "very preliminary, but possibly promising, results. Bleeding associated with the procedure is a major concern and further study is needed to determine whether this is a safe and effective treatment."

The study did not have commercial funding, but several of Dr. Kashani's co-authors report a financial interest in the implant.

—David Douglas

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