Spatially patterned bi-electrode epiretinal stimulation for axon avoidance at cellular resolution.

Objective.Epiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells.Approach.In this work, a custom multi-electrode array (512 electrodes, 10µm diameter, 60µm pitch) was used to stimulate and record RGCs in macaque retinaex vivoat single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation.Main results.On average, across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds (∼21%) while increasing axonal activation thresholds (∼14%), thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode.Significance.This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision.

A Three-Dimensional Microelectrode Array to Generate Virtual Electrodes for Epiretinal Prosthesis Based on a Modeling Study.

Despite many advances in the development of retinal prostheses, clinical reports show that current retinal prosthesis subjects can only perceive prosthetic vision with poor visual acuity. A possible approach for improving visual acuity is to produce virtual electrodes (VEs) through electric field modulation. Generating controllable and localized VEs is a crucial factor in effectively improving the perceptive resolution of the retinal prostheses. In this paper, we aimed to design a microelectrode array (MEA) that can produce converged and controllable VEs by current steering stimulation strategies. Through computational modeling, we designed a three-dimensional concentric ring-disc MEA and evaluated its performance with different stimulation strategies. Our simulation results showed that electrode-retina distance (ERD) and inter-electrode distance (IED) can dramatically affect the distribution of electric field. Also the converged VEs could be produced when the parameters of the three-dimensional MEA were appropriately set. VE sites can be controlled by manipulating the proportion of current on each adjacent electrode in a current steering group (CSG). In addition, spatial localization of electrical stimulation can be greatly improved under quasi-monopolar (QMP) stimulation. This study may provide support for future application of VEs in epiretinal prosthesis for potentially increasing the visual acuity of prosthetic vision.

Modeling electrical stimulation of retinal ganglion cell with optimizing additive noises for reducing threshold and energy consumption.

BACKGROUND: Epiretinal prosthesis is one device for the treatment of blindness, which target retinal ganglion cells (RGCs) by electrodes on retinal surface. The stimulating current of epiretinal prosthesis is an important factor that influences the safety threshold and visual perception. Stochastic resonance (SR) can be used to enhance the detection and transmission of subthreshold stimuli in neurons. Here, it was assumed that SR was a potential way to improve the performance of epiretinal prosthesis. The effect of noises on the response of RGCs to electrical stimulation and the energy of stimulating current was studied based on a RGC model. METHODS: The RGC was modeled as a multi-compartment model consisting of dendrites and its branches, soma and axon. To evoke SR, a subthreshold signal, a series of bipolar rectangular pulse sequences, plus stochastic biphasic pulse sequences as noises, were used as a stimulus to the model. The SR-type behavior in the model was characterized by a "power norm" measure. To decrease energy consumption of the stimulation waveform, the stochastic biphasic pulse sequences were only added to the cathode and anode phase of the subthreshold pulse and the noise parameters were optimized by using a genetic algorithm (GA). RESULTS: When certain intensity of noise is added to the subthreshold signal, RGC model can fire. With the noise's RMS amplitudes increased, more spikes were elicited and the curve of power norm presents the inverted U-like graph. The larger pulse width of stochastic biphasic pulse sequences resulted in higher power norm. The energy consumption and charges of the single bipolar rectangular pulse without noise in threshold level are 468.18 pJ, 15.30 nC, and after adding optimized parameters's noise to the subthreshold signal, they became 314.8174 pJ, 11.9281 nC and were reduced by 32.8 and 22.0%, respectively. CONCLUSIONS: The SR exists in the RGC model and can enhance the representation of RGC model to the subthreshold signal. Adding the stochastic biphasic pulse sequences to the cathode and anode phase of the subthreshold signal helps to reduce stimulation threshold, energy consumption and charge of RGC stimulation. These may be helpful for improving the performance of epiretinal prosthesis.

Reading visual braille with a retinal prosthesis.

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2-4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients.

Epiretinal prosthesis for outer retinal degenerative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

·Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are common outer retinal degenerative problems, which are also the predominant causes of most blinding retinal diseases. Retinal prosthesis is a promising solution for such photoreceptor degeneration diseases.Most of current concepts for a retinal prosthesis are based on neuronal electrical stimulation. In the past twenty years, retinal prosthesis has been developed in two different directions: epiretinal prosthesis and subretinal prosthesis. Each prosthesis technique has its advantages and disadvantages. For epiretinal prosthesis, it is easier to be implanted and has the advantage of keeping most of the electronics in the vitreous cavity, off the retinal surface, which greatly helps in dissipating the heat generated by the implant device. In this paper, a brief overview of retinal prostheses concepts is introduced. After that, several important aspects of epiretinal electrical stimulation will be discussed. Moreover, some practical epiretinal prosthesis devices developed by researchers in United States, Germany and Japan in the past have been reviewed. We hope that the devices will be used widely in the near future.