Subretinal electronic chip shows encouraging results, further improvements

A study has begun with a novel wireless version of the chip, with greater power and higher resolution, for subretinal implantation.

Results of an active subretinal implant developed by scientists and physicians at the University of Tübingen, Germany, along with Retina Implant AG and NMI Reutlingen show that the device can provide useful vision in patients who are blind from retinitis pigmentosa and similar hereditary degenerative disorders.

“We have now developed a new wireless version of the implant, with stronger power delivery and higher resolution,” Eberhart Zrenner, MD, PhD, professor of ophthalmology and director of the Institute for Ophthalmic Research at the University of Tübingen, said at the Euretina meeting in Paris. “All parts of the device are implanted invisibly in the body. Patients only have to carry a small box for power supply in the pocket and use the device outside and at home.”

The project has been supported since 1995 by the Federal Ministry of Research in Germany and since 2005 by Retina Implant AG, Germany.

The core of the implant is a 3-mm wide, 0.1-mm thick microchip that is placed in the subretinal space as a substitute for degenerated photoreceptors. The chip contains 1,500 photodiodes, each individually connected to a differential light amplifier coupled to a titanium nitrate electrode. A subcutaneous silicone cable connected to the chip leads under the temporal muscle to a wireless power control unit under the skin behind the ear.

A previously blind patient identifies a banana and its location on the table.

A previously blind patient reads a word and identifies a spelling error. Images: Univ. of Tuebingen/Retina Implant AG

“As the light comes the natural way, through the crystalline lens, the image is projected onto the chip under the retina and point by point is translated into an electric impulse and forwarded to the retinal neurons, the optic nerve and eventually the brain,” Dr. Zrenner explained.

Surgical procedure

The first part of the surgical procedure is performed by a strabologist and an ENT specialist. The implant, protected by a steel tube, is guided subcutaneously through a retroauricular incision inside the orbit orbital rim near the lid corner. Then the steel rod is removed and a posterior segment surgeon takes over. Pars plana vitrectomy is performed and a localized retinal detachment is induced by saline injection. The implant is advanced through the choroid via a scleral flap and into the subretinal space until it reaches the defined position.

On the fingertip: Light sensitive subretinal chip positioned on a foil that carries wires for power supply and function control. The middle part has a prolongation cord that leads from the eye socket to a spot behind the ear. Image: Retina Implant AG

The preset model has wireless power and signal transmitting coil under the skin behind the ear. Image: Univ. of Tuebingen/Retina Implant AG

“Surgery requires high expertise, but all our patients were successfully implanted. No intraoperative or postoperative major complications such as inflammation, retinal detachment or vitreous traction were observed,” Dr. Zrenner said.

Top: The complete implant. Left end: The light sensitive subretinal chip positioned on a foil that carries wires for power supply and function control. Middle: The prolongation cord that leads from the eye socket to a place behind the ear. Right: plug to connect to wireless control box. Bottom: The magnification of chip with 1,500 pixels in the middle and test field with 16 electrodes on the left. Image: Retina Implant AG

Pilot study

The first pilot study with a cable-bound implant started in 2005 and included 12 patients. Six patients have more recently been implanted with the new wireless system. Only one patient has dropped out.

All patients were periodically tested beginning at 7 days to 9 days after surgery. Direct electric stimulation of photodiodes was applied, resulting in perception of dot-like or elongated luminous patterns on the first day. Within days, patients could distinguish vertical lines from horizontal and diagonal lines as well as more complex geometrical patterns and letters of the alphabet produced by pulsing the electrodes sequentially.

“Patients were also tested on their ability to distinguish white, luminous patterns on a black background. Single letters and Landolt C rings were presented on the screen. Not all but some of the patients were able to see them correctly,” Dr. Zrenner said.

In some cases, patients were able to perceive objects in more naturalistic settings, such as on a dining room table.

“They could perceive the knife and fork as two straight lines and the plate as a round shape. They could see the glass of beer and immediately grasp it without having to use their hands to obtain tactile information. One patient could localize and describe an apple and a banana, as well as a cup and saucer on the table, things he could not see when the power to the chip was switched off,” Dr. Zrenner said.

The stimulation chip is positioned at the posterior eye pole under the retina, takes the image, translates it point by point with 1,500 pixels into an electrical image that stimulates retinal bipolar cells. From there, the image is processed in the natural circuits of inner retina and forwarded via the optic nerve to the brain. Image: Retina Implant AG

Patients who had successfully performed previous tasks were asked to read full words spelled out in white against a black background. One patient was able to read all words correctly. He surprised the testing team by pointing out a spelling mistake in his name.

Intra-individual differences in visual outcomes were probably due to the respective stages of retinal degeneration, Dr. Zrenner said.

He said that subretinal as opposed to epiretinal stimulation leads to better visual-spatial perception, probably due to the preferential stimulation of bipolar cells.

“Thanks to this retinotopically correct spatial transmission, our patients can perceive very quickly the complete entity of an object with no need for a learning procedure. However, time and practice lead to even better visual performance and visuomotor abilities,” he said.

Another important point in this active subretinal approach is that the chip is permanently moving with the eye microsaccades, so the image on the retina is permanently refreshed.

“Our eyes permanently move, even during fixation, in order to refresh the image by constantly changing photoreceptors. Similarly, since the sensors of the chip are moving with the eye, different electrodes are used all the time, and the image remains fresh,” Dr. Zrenner said. – by Michela Cimberle

References:

• A recent publication on this project in the Proceedings of the Royal Society can be found at http://rspb.royalsocietypublishing.org/content/early/2010/11/01/rspb.2010.1747.full.html.
• Video clips can be found in the data supplement at http://rspb.royalsocietypublishing.org/content/early/2010/11/01/rspb.2010.1747/suppl/DC1.

• Eberhart Zrenner, MD, PhD, can be reached at Institute for Ophthalmic Research, Schleichstrasse 12-16, D-72076, Tübingen, Germany; +49-70712984786; fax: +49-7071295083; email: ezrenner@uni-tuebingen.de.
• Disclosure: Dr. Zrenner is one of the founders of Retina Implant but receives no compensation for advisory tasks for this project.