Restoring sight to the blind
Retinal degenerative diseases lead to loss of image-capturing photoreceptors, while image-processing inner retinal neurons survive to a large extent.1 Electrical stimulation of these neurons can produce visual percepts, providing an alternative route for visual information and raising hope for the restoration of sight to the blind. Indeed, recent clinical trials with electrode arrays implanted either facing ganglion cells on top of the retina or photoreceptors on the bottom have restored visual acuity on the order of 20/1200 (60 times worse then normal visual acuity) to subjects blinded by retinal degeneration.2, 3 While this serves as an important proof of concept with clinically useful implications, existing retinal prostheses rely on cables entering the eye to deliver power to the retinal electrode array.
Our design overcomes these problems by using micro-fabricated arrays of photodiodes driven photovoltaically.4 The retinal prosthetic system includes a miniature video camera capturing the images of the visual scene: see Figure 1. The video stream processed by the pocket computer is displayed on the near-to-eye projection system (similar to conventional video goggles). These images are projected onto the subretinal implant using pulsed near-IR (NIR, 880–915nm) light.4 Photodiodes in each pixel of the array convert this light into pulsed electric current flowing through the retina and stimulating the inner retinal neurons.
Direct optical activation of each pixel in the subretinal implant eliminates the need for complex electronics and wiring schemes, and preserves the natural link between image perception and eye movements. This wireless system is scalable to thousands of electrodes, surgery is greatly simplified, and modular design of the implant allows expanding the visual field by tiling.
To maximize the charge injection but stay within the electrochemical safety limits, each pixel has three photodiodes connected in series between the central active electrode and a circumferential return electrode, both coated with sputtered iridium oxide film. The smallest pixel size in the current implants is 70μm, having a 20μm disk electrode in its center: see Figure 2. A local return electrode in each pixel helps confine the electric field and reduces cross-talk between multiple simultaneously activated pixels in the array, a feature essential for high-resolution stimulation. However, tighter lateral confinement of the electric field reduces its penetration into the retina, making this design more susceptible to variations in proximity to the target neurons.
We successfully tested our design by stimulating healthy and degenerate rat retinas. With the 140μm pixels, the in vitro stimulation threshold for 4ms pulses was 0.3mW/mm2 for the normal retina, and 0.8mW/mm2 for the degenerate retina. These peak irradiances are about a thousand times higher than the brightest ambient light on the retina. Since most legally blind people retain light sensitivity, we cannot safely use visible light of such extreme brightness to activate the photovoltaic implants. Instead, we use NIR light, which is invisible to photoreceptors but sufficiently short to activate silicon photodiodes. With a pulse repetition rate of 15Hz, the average irradiance is 0.05mW/mm2, two orders of magnitude below the safety limit for this wavelength range.5
Photovoltaic arrays 0.8×1.2mm in size and 30μm in thickness were well tolerated in the subretinal space in rats during six months' follow-up. We recorded the visual evoked potentials in vivo, showing elicited activity in the brain, with stimulation thresholds similar to the corresponding in vitro values for normal and degenerate rat retinas.
We could modulate the elicited responses with both light intensity and pulse width. The described optical system uses a liquid crystal display illuminated by a laser beam to form patterns of NIR light, enabling intensity modulation within each video frame. DLP® technology, based on an array of high-speed actuated micromirrors, can be used to modulate retinal response by varying the pulse width in each pixel. Such a device would allow precise control of both the duration and timing of exposures, allowing sequential activation of nearby pixels to further reduce the pixel crosstalk. In addition, holographic pattern projection using spatial light modulators may allow higher throughput and precise timing control in each pixel.
In summary, optical activation of a photovoltaic retinal prosthesis makes it scalable to thousands of electrodes. It maintains the natural link between eye movements and image perception, and allows easy implantation of multiple modules to provide a larger field of view. Such a versatile system could be used to address the divergent needs of patients with various forms of retinal degeneration. Future research will define the limits of resolution in retinal stimulation with photovoltaic arrays in vitro, and corresponding visual acuity in vivo.
The authors thank Stuart Cogan at EIC Labs for iridium oxide electrode deposition. Funding was provided by the National Institutes of Health grant R01-EY-018608, the Air Force Office of Scientific Research grant FA9550-04, a Stanford Bio-X IIP grant, an SU2P Science Bridges award, and a Burroughs Wellcome Fund Career award.
Daniel Palanker is an associate professor in the Department of Ophthalmology and in the Hansen Experimental Physics Laboratory. He studies interactions of electric field and light with biological cells and tissues, and develops their diagnostic, therapeutic, and prosthetic applications, primarily in ophthalmology.