Vision loss treated with stem cells-monolayer polymer composites
Age-related macular degeneration (AMD) affects nearly two million people in the United States. Now a team of ophthalmologists and biomedical engineers at various institutions in California are working toward a cure for AMD and have developed an innovative combination of materials that can act as a reparative patch on the damaged tissue in the eye.
The macula, which is located in the central portion of the retina at the back of the eye, provides the high-resolution central vision required for most daily activities. Researchers believe that vision loss in a common type of AMD known as non-neovascular AMD, or NNAMD, is related to a loss of retinal pigment epithelium (RPE) in the macula. The RPE is a monolayer of pigmented cells that lies between the retina and a layer of blood vessels. In theory, replacing the RPE in the damaged regions of the macula could restore vision in people with NNAMD. Mark S. Humayun and Amir H. Kashani—both at the University of Southern California (USC)—and their colleagues have developed a composite material as well as an associated surgical procedure to achieve this goal.
The study, which was recently published in Science Translational Medicine, combined human embryonic stem cells-derived RPE with a biocompatible polymer [poly(###i
/i###-xylylene)] 4-6 µm thick to create an RPE patch that mimics the structure and function of biological RPE in the retina. The researchers developed a surgical procedure that allows Humayun’s team to unroll the thin RPE-polymer implant (3.5 mm × 6.25 mm x ~4-6 µm) onto an area of high RPE loss.
“This implant and procedure represent the most cutting-edge developments in science, medicine, and engineering, all of which are seamlessly merged into a novel therapeutic implant that is in clinical trials,” says Humayun.
Five subjects with advanced NNAMD were enrolled in a prospective Phase I/IIa trial approved by the US Food and Drug Administration. The joint Phase I and Phase II classification allows for the simultaneous assessment of the safety and efficacy of the implanted patch. For four out of the five subjects, the thin RPE-polymer composite was successfully implanted in one eye, and the other eye was used as a control.
The trial results were promising: after 120 days, the implants remained in place, vision was stable or improved in the treated eye, and there was evidence that the host retina was integrating with the implant. Together, these findings demonstrate implant tolerability and potential effectiveness. One subject had a notable increase of 17 letters using the Early Treatment of Diabetic Retinopathy Severity Score, roughly equivalent to a change from 20/600 visual acuity to 20/300, which suggests striking improvements in vision are possible in just 120 days.
Kapil Bharti, a researcher at the National Eye Institute in Bethesda, Maryland who is developing a similar type of implant, affirms that a sub-retinal patch offers a viable “one-time fix” treatment for AMD. Bharti is enrolling subjects for his own clinical trial for a similar patch that would degrade in five weeks, and he believes that the nondegradable and degradable polymer substrates used may perform differently in helping RPE-monolayer integrate in the back of the eye.
Kashani, lead author and surgeon for the USC study, agrees that AMD treatment with an RPE replacement patch is in the early stages, but he is optimistic. “While this is an interim analysis of the Phase I/IIa study, the changes in retinal structure and improvements in visual function suggest that we may be able to restore vision in people suffering from NNAMD. We look forward to an analysis of the complete data set and a larger clinical study that will definitively demonstrate efficacy,” Kashani says.
Read the abstract in Science Translational Medicine.