Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image processing” inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density.

Objective To develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. Approach A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 μm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 μm-wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280μm, 140 μm, and 70 μm) with active electrodes of 80 μm, 40 μm and 20 μm in diameter were fabricated. Main results The turn-on voltages of one-, two- and three-series-connected photodiode structures are approximately 0.6V, 1.2V and 1.8V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ~0.36 A/W, at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. Significance The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution.

The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10• visual field, with a full 30• field accessible via eye movements. Pixel sizes are scalable from 100 to 25 µm, corresponding to 640-10 000 pixels on an implant 3 mm in diameter.

Boinagrov D, Loudin J, Palanker D. Strength-duration relationship for extracellular neural stimulation: numerical and analytical models. J Neurophysiol 104: 2236 -2248, 2010. First published August 11, 2010 doi:10.1152/jn.00343.2010. The strength-duration relationship for extracellular stimulation is often assumed to be similar to the classical intracellular stimulation model, with a slope asymptotically approaching 1/ at pulse durations shorter than chronaxy. We modeled extracellular neural stimulation numerically and analytically for several cell shapes and types of active membrane properties. The strength-duration relationship was found to differ significantly from classical intracellular models. At pulse durations between 4 s and 5 ms stimulation is dominated by sodium channels, with a slope of Ϫ0.72 in log-log coordinates for the Hodgkin-Huxley ion channel model. At shorter durations potassium channels dominate and slope decreases to Ϫ0.13. Therefore the charge per phase is decreasing with decreasing stimulus duration. With pulses shorter than cell polarization time (ϳ0.1-1 s), stimulation is dominated by polarization dynamics with a classical Ϫ1 slope and the charge per phase becomes constant. It is demonstrated that extracellular stimulation can have not only lower but also upper thresholds and may be impossible below certain pulse durations. In some regimes the extracellular current can hyperpolarize cells, suppressing rather than stimulating spiking behavior. Thresholds for burst stimuli can be either higher or lower than that of a single pulse, depending on pulse duration. The modeled thresholds were found to be comparable to published experimental data. Electroporation thresholds, which limit the range of safe stimulation, were found to exceed stimulation thresholds by about two orders of magnitude. These results provide a biophysical basis for understanding stimulation dynamics and guidance for optimizing the neural stimulation efficacy and safety.