Microchips in the Eye

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Published: February 3, 2011

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Microchips in the Eye

Electronic retinal implants are gaining popularity as research into the technology continues to show improvements for patients.

About 30 research groups worldwide are currently working on an electronic retinal implant. Retina Implant AG, a company in Reutlingen, Germany, has conducted a successful clinical pilot study demonstrating that the technique of subretinal stimulation permits visual recognition of patterns and letters of the alphabet. This study confirms electronic retinal implants can give very useful visual perceptions to the blind (See three videos regarding Retina AG study results and demonstrations).

Hereditary retinal degeneration (retinitis pigmentosa) results in a progressive loss of photoreceptors and in most cases leads gradually to a complete loss of vision. More than 100,000 people in the United States and an estimated three million people worldwide suffer from various forms of this disease. Although drugs are currently under development, there is as yet no therapy for this ailment. However, many of those affected may soon be able to recover a certain degree of vision by means of an implanted camera chip.

In the normal eye, incident light passes through the transparent tissue of the retina and falls on some 120 million rods and six million cones at the fundus of the eye. The light is converted in a multiple-stage process into electrical signals. These signals undergo preliminary processing in the underlying layers of bipolar, horizontal, and amacrine cells and are then passed on to the ganglion cells. For their part, the axons of the ganglion cells communicate with the optic nerve, which forwards the information gained thus far to the visual cortex (i.e., visual center) of the brain.

Subretinal Implants

Diseases like retinitis pigmentosa (RP) are distinguished by the fact that a large part of the retina remains functional even after loss of sight. Although the rods and cones that normally convert light into nerve signals are destroyed by this disease, most of the retinal nerve tissue, which has the task of pre-processing information on its way to the brain, remains intact. In other words, the visual apparatus is functional; it just lacks input. Based on this concept, Eberhart Zrenner at the University Eye Clinic of Tübingen has developed a subretinal implant in cooperation with that university’s Institute of Natural Science and Medicine (NMI).

For the university’s implant, natural optical stimulus is simply replaced by pulsed, light-dependent electrical stimuli, resulting in the perception of phosphenes (artificially triggered light phenomena). Because the electrical excitation invariably involves a number of cells, the patients cannot visualize objects sharply, but are nevertheless able to locate light sources and localize physical objects.

The subretinal chip replaces the degenerated photoreceptors.

The implant is located subretinally, i.e. behind the retina. From an anatomical point of view, it exactly replaces the photoreceptors that have been lost (see Figure 1). From the viewpoint of signal processing, this is an all-important advantage; the implant’s subretinal excitation exploits the full range of neuronal circuitry in the retina along the way to the optic nerve. The electrical signal is triggered at the point of brightness, and the stimulation strength corresponds to the intensity of the incident light. The optical image is thus exactly replaced by an electrical pattern of excitation.

The retinal implant consists of a silicon chip about 3 × 3 mm in size and 70-µm thick, with 1500 individual pixels. Each of these pixel cells contains a light-sensitive photodiode, a logarithmic differential amplifier, and a 50 × 50-µm iridium electrode into which the electrical stimuli at the retina are guided. The circuitry was developed in collaboration with the IMS in Stuttgart and is made by applying 0.8-µm CMOS technology.² The result is a pure analog chip, with the advantage that its power consumption is very low (maximum 10 mW), and the heat passed on to the retina by electrical power from the chip remains below 0.5 K. The microchip is positioned on a thin, highly flexible circuit board of polyimide with gold circuits that transmit power and control signals (See Figure 2). The very fine polyimide strip is connected in turn to a thin, coiled cable through which the electricity of the chip is supplied. This elastic cable passes through the orbital cavity to the bone of the temple and from there to a point behind the ear, where it is connected to an inductive power supply unit in a ceramic housing. The electrical energy is received inductively from the outside through a second coil that is located on the skin. Permanent magnets in the two coils ensure close contact.

The CMOS camera chip on polyimide carrier is connected via a silicone cable to the wireless power receiver.5

All of the components must of course be biocompatible—that is, well tolerated by the body—and must possess long-term stability. This is an enormous technological challenge that requires, among other things, the use and combination of new materials. The components must be provided with a hermetically sealed protective layer at the point of contact with the surrounding tissue. They must undergo numerous tests to demonstrate the device’s ability to withstand the corrosive environment within the body. An especially critical point is that the presence of electrical voltage can greatly accelerate the corrosion process. The selection of materials and the manner in which they are processed is critical.

Above all, the electrodes and their contact points on the chip are of decisive importance. The useable electrode surface must be as small as possible but also offer as large a surface as possible to ensure good contact with the retina. For this reason, the electrodes are manufactured of fractal iridium, whereby the materials permit a higher transmission of charges.
Optimal visual perception is present when pulse durations are around 1 microsecond and the charge amounts to 2–5 nC per pixel. This corresponds to a voltage of up to 2 V. The repetition rate of excitation is normally 5–7 Hz, because higher rates would result in overstimulation of the retina. The patient’s visual perception therefore flickers somewhat.

Clinical Studies and Results

During a clinical pilot study at the University Eye Clinic in Tübingen, the retinal implant was first tested over a period of up to four months in 11 patients. The development of a new type of surgical procedure was given high priority in collaboration with the University Eye Clinic in Regensburg, Germany. It involves creating a small access opening through the external sclera of the eye. After removal of the vitreous, the retina is lifted up from its underlying support layer so that the flexible film with the chip can be advanced under the retina to the vicinity of the macula. This is the point at which density of the nerve cells is greatest and can be expected to result in the most effective stimulation. Following exact positioning, the small window through the sclera is again closed, thus attaching the film securely in the globe of the eye so that the chip can assume a stable position and is not subjected to tension due to movements of the eye.

Subdermal positioning of power supply and cabling for the subretinal implant.

It was already possible to conduct initial tests with the patients only one week after implantation. The majority of patients recognized not only horizontal and vertical lines but also the direction in which electrodes were activated one after another and simple geometric patterns. However, the threshold value for triggering a stimulus varied widely in the different patients. In some cases, it was possible to trigger a phosphene with individual electrodes and a charge transfer of only a few nanocoulombs. However, many of the patients experienced visual perception only when several adjacent electrodes were stimulated simultaneously.³ The causes of these patient-specific threshold values may be both the position of the electrodes relative to the macula and the distance between the electrodes and the bipolar cells in the retina.

Most of the patients reported blurred visual perception. Many were able to distinguish light sources or bright objects against a dark background. As the ability to recognize objects grew in each patient, it became possible to continuously optimize the stimulation parameters and the position of the chip in the eye so that three of the 11 patients were reliably able to recognize simple patterns when the chip was turned on and even bright objects against a dark background. In fact, the last test subject correctly recognized letters of the alphabet that measured ca. 8 cm high, was able to localize people in a room, and identified their size. A standard visual examination of this patient with Landolt C Rings resulted in a visual acuity of 1/50, which is slightly above the threshold of legally defined blindness (according to WHO). This was conclusive proof that the basic concept of the subretinal implants functions successfully and can lead to usable visual perception.⁴

The learning effects that the authors observed were noteworthy: the patients needed only a few hours to learn how to process visual perceptions that were new to them. One patient who had been completely blind for the last 15 years was able to see the letters of the alphabet, and told the investigator that the letters looked “exactly as I learned them at school.” When his name was presented to him, he immediately recognized a spelling error in it. In addition, hand-eye coordination was also relearned within a few hours. The patients were able to localize physical objects precisely and point to them immediately.

Geometric patterns and physical objects from daily life were recognized, especially when they had very characteristic forms (such as a banana). They were also able to distinguish items of tableware (spoons, knives, forks) from one another.
Now that the pilot study is complete, the implant has become the subject of a multicentered main study with a larger patient set. The aim of the investigation is to gain regulatory approval for use as a medical product in 1-2 years. After it has been successfully used in retinitis pigmentosa patients, the plan is to test and apply the visual chip in patients with age-related macula degeneration (AMD) as well.

Acknowledgements

This research was supported by the German Federal Ministry of Education and Research, the Kerstan Foundation, and ProRetina Germany.

References

1. E Zrenner, “Will Retinal Implants Restore Vision?” Science 295, no. 5597 (February 2002): 1022–1025.
2. HG Graf et al., “High Dynamic Range CMOS Imager Technologies for Biomedical Applications,” IEEE Journal of Solid-State Circuits 44, no. 1 (January 2009):  281–289.
3. E Zrenner, “Restoring Neuroretinal Function: New Potentials, Documenta Ophthalmologica (2007): 56–59.
4. E Zrenner et al., “Subretinal Electronic Chips Allow Blind Patients to Read Letters and Combine Them to Words,” Proceddings of the Royal Society, Biological Sciences, online (November 3, 2010): doi:10.1098/rspb.2010.1747.
5. L Rothermel et al., “A CMOS Chip With Active Pixel Array and Specific Test Features for Subretinal Implantation” IEEE Journal of Solid-State Circuits 44, no. 1 (January 2009): 290–300.

Walter-G. Wrobel, PhD, is president and CEO of Retina Implant AG. Alex Harscher, PhD, is vice president of operations at the company.

Published in MD+DI, March 2011, Volume 33, No. 3

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