Promising treatments for those blinded by an often-hereditary, retina-damaging disease are expanding throughout Europe and making their way across the pond, offering a ray of hope for the hundreds of thousands of people in the U.S. left in the dark by retinitis pigmentosa. The disease—which affects about one in 4,000 people in the U.S. and about 1.5 million people worldwide—kills the retina's photoreceptors, the rod and cone cells that convert light into electrical signals, which are transmitted via the optic nerve to the brain's visual cortex for processing.

There is no effective treatment for the condition, but researchers are making great strides to remedy this through implants that stimulate still-active nerves in the retina, the layer of tissue at the back of the inner eye. In mid-November Retina Implant, AG, got approval to extend the yearlong phase II human clinical trial of its retinal implant outside its native Tübingen, Germany, to five new sites—Oxford, London and Budapest, along with two additional locations in Germany.

The company's implant is a three- by three-millimeter microelectronic chip (0.1-millimeter thick), containing about 1,500 light-sensitive photodiodes, amplifiers and electrodes surgically inserted beneath the fovea (which contains the cone cells) in the retina's macula region. The fovea enables the clarity of vision that people rely on to read, watch TV and drive. The chip helps generate at least partial vision by stimulating intact nerve cells in the retina. The nervous impulses from these cells are then led via the optic nerve to the visual cortex where they finally lead to impressions of sight.

Thus far, some patients report having a narrow field of vision partially restored, providing them with enough acuity to locate light sources such as windows and lamps as well as detect lighted objects against dark backgrounds. The chip's power source is positioned under the skin behind the ear and connected via a thin cable.

Window on the world
For those suffering with retinitis pigmentosa, Retina Implant's technology creates a small black-and-white window on the world, says Eberhart Zrenner, the company's co-founder and director and chairman of the University of Tübingen's Institute for Ophthalmic Research in Germany. Retina Implant has successfully placed chips beneath the retina of nine patients since May 2010. A 10th patient experienced a problem when their optic nerve did not forward the information on the chip to the brain.

Looking ahead, Zrenner hopes to widen patients' field of vision further. "Because our chip has independent miniature photodiodes, we could arrange three of them in a row beneath the retina," he says. The ability to produce accurate colors via retinal implants, however, is very complicated and may not be possible for years, he adds. Retina Implant has also developed an outpatient treatment for early-stage retinitis pigmentosa called Okuvision, which uses electric stimulation to help preserve retinal cells.

Sights set on the U.S.
The phase II extension expands Retina Implant's trial to an additional 25 patients beginning early next year and follows a partnership the company struck in March with the Wills Eye Institute in Philadelphia. Wills is looking to become the lead U.S. clinical trial investigator site for Retina Implant's technology and to help the company through the U.S. Food and Drug Administration's (FDA) review process.

Cutting-edge technologies such as sub-retinal implants are typically at a disadvantage when seeking FDA approval due to the lack of a track record, but Retina Implant's work in Europe provides a precedent for the FDA to consider, says Julia Haller, Wills's ophthalmologist in chief. "There's information available to U.S. regulators about how patients have responded so far," she adds.

Commercial implant
Whereas Retina Implant's technology is just getting started in the U.S., another retinal implant–maker is already in FDA human clinical trials, which are expected to conclude in July 2014. Second Sight Medical Products sells its Argus II Retinal Prosthesis System in Europe—the first commercial implantation of their device took place October 29 in Pisa, Italy (pdf).

Second Sight's technology is fundamentally different, converting video images captured by a miniature camera—housed in a special pair of glasses worn by the patient—into a series of small electrical pulses transmitted wirelessly to an array of electrodes implanted on the retina's surface, rather than under it. These pulses are intended to stimulate the retina's remaining cells and create the perception of patterns of light in the brain. Epiretinal devices (overlying the retina) such as the Argus II preprocess an image before sending it to the retina. Because the camera does not create an exact simulation of normal retinal outputs, patients need time to learn how to process the information that their brain receives.

Although both Retina Implant and Second Sight's technologies are still relatively unproved, their potential is great. "As somebody who has to tell families that their child is going to lose all vision and not be able to do any of the things they had dreamed he or she would be able to do, I know that every little step you make, from absolute blindness to being able to see shapes to being able to count fingers and read words makes an incredible impact on a person's life," says Haller, who, in addition to being familiar with Retina Implant, has experience implanting Second Sight's retinal prosthetic devices.

Alternative implants
Retina Implant and Second Sight's technologies may be the furthest along in terms of testing but they are not the only ones working on ways to treat, and even prevent, retinitis pigmentosa.

A sub-retinal implant under development by Optobionics in Glen Ellyn, Ill., most closely resembles the work of Retina Associates. Optobionics's Artificial Silicon Retina (ASR) microchip is designed as a stand-alone implant placed behind the retina to directly stimulate the remaining viable cells of the retina. Instead of an external power supply, the Optobionics chip has an array of micro-photodiodes that convert light energy to electrical signals, which stimulate retinal cells. Haller implanted several Optobionics sub-retinal chips as part of a study conducted at the Wilmer Eye Institute at Johns Hopkins in Baltimore throughout 2004 and 2005 while she was a surgeon there (pdf). The company's funding subsequently ran out, however. Only recently were Optobionics' co-founders able to acquire the rights to the ASR implant technology. They plan to reorganize a new company under the Optobionics name.

Neurotech Pharmaceuticals, Inc. in Lincoln, R.I., is developing a different type of implant. Their intraocular implant consists of human cells genetically modified to secrete a nerve growth factor they say is capable of rescuing and protecting dying photoreceptors. The implant does not replace retinal tissue but rather is a way to resuscitate damaged retinal cells.

At Weill Cornell Medical College of Cornell University in New York City, neuroscientist Sheila Nirenberg is leading a project to develop an artificial retina with the capacity to reproduce normal vision. Rather than increasing the number of electrodes placed in an eye to capture more information and send signals to the brain, Nirenberg's work focuses on the quality of the artificial signals themselves so as to improve their ability to carry impulses to the brain.

It will take some time to see which approach works best, Haller says, adding, "All of the treatments for retinitis pigmentosa are experimental right now, so there's no real comparison yet between what works and what doesn't."