EP2032205A2 - Procédé permettant de stimuler électriquement la rétine humaine à l'aide de trains d'impulsions - Google Patents

Procédé permettant de stimuler électriquement la rétine humaine à l'aide de trains d'impulsions

Info

Publication number
EP2032205A2
EP2032205A2 EP07809536A EP07809536A EP2032205A2 EP 2032205 A2 EP2032205 A2 EP 2032205A2 EP 07809536 A EP07809536 A EP 07809536A EP 07809536 A EP07809536 A EP 07809536A EP 2032205 A2 EP2032205 A2 EP 2032205A2
Authority
EP
European Patent Office
Prior art keywords
pulse
pulses
amplitude
threshold
visual
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07809536A
Other languages
German (de)
English (en)
Inventor
Alan Matthew Horsager
Scott H. Greenwald
Mark S. Humayun
Matthew J. Mcmahon
Ione Fine
Robert J. Greenberg
Geoffrey M. Boynton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Doheny Eye Institute of USC
Vivani Medical Inc
Original Assignee
Doheny Eye Institute of USC
Second Sight Medical Products Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Doheny Eye Institute of USC, Second Sight Medical Products Inc filed Critical Doheny Eye Institute of USC
Publication of EP2032205A2 publication Critical patent/EP2032205A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36046—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the eye

Definitions

  • the present disclosure is generally directed to neural stimulation and more specifically to an apparatus and method for providing intensity control.
  • Neural tissue can be artificially stimulated and activated by prosthetic devices that pass pulses of electrical current through electrodes on such a device. The passage of current causes changes in electrical potentials across visual neuronal membranes, which can initiate visual neuron action potentials, which are the means of information transfer in the nervous system.
  • One typical application of neural tissue stimulation is in the rehabilitation of the blind.
  • Some forms of blindness involve selective loss of the light sensitive transducers of the retina.
  • Other retinal neurons remain viable, however, and may be activated in the manner described above by placement of a prosthetic electrode device on the inner (toward the vitreous) retinal surface (epiretinal). This placement must be mechanically stable, minimize the distance between the device electrodes and the visual neurons, and avoid undue compression of the visual neurons.
  • Bullara U.S. Pat. No. 4,573,481 patented an electrode assembly for surgical implantation on a nerve.
  • the matrix was silicone with embedded iridium electrodes.
  • the assembly fit around a nerve to stimulate it.
  • the Michelson '933 apparatus includes an array of photosensitive devices on its surface that are connected to a plurality of electrodes positioned on the opposite surface of the device to stimulate the retina.
  • Electrodes are disposed to form an array similar to a "bed of nails" having conductors which impinge directly on the retina to stimulate the retinal cells.
  • U.S. Patents 4,837,049 to Byers describes spike electrodes for neural stimulation. Each spike electrode pierces neural tissue for better electrical contact.
  • U.S. Patent 5,215,088 to Norman describes an array of spike electrodes for cortical stimulation. Each spike pierces cortical tissue for better electrical contact.
  • Retinal tacks are one way to attach a retinal array to the retina.
  • U.S. Patent 5,109,844 to de Juan describes a flat electrode array placed against the retina for visual stimulation.
  • U.S. Patent 5,935,155 to Humayun describes a retinal prosthesis for use with the flat retinal array described in de Juan.
  • a visual prosthetic apparatus for retinal stimulation comprising an implantable portion and an external portion, wherein the implantable portion comprises a cable, an RF receiver, an inductive coil and an array of electrodes, for stimulating visual neurons, and the external portion comprises a frame, a camera, an external coil and a mounting system for the external coil.
  • a retinal stimulation method comprising: generating a stimulation pattern by stimulating a retina of a patient with an impulsive electrical signal; and determining how visual perception depends on the generated stimulation pattern by observing perceptual threshold as a function of features of the impulsive electrical signal.
  • a method for determining visual perceptual threshold comprising: exposing subjects to a series of variable current stimuli; decreasing amplitude of the variable current stimuli if subject answers correctly to a current stimulus; increasing amplitude of the current stimuli if subject answers incorrectly to the current stimulus; and generating a psychometric function based on answers of the subject.
  • a retinal stimulation device comprising: a stimulation pattern generator to provide a signal to a retina, wherein the stimulation pattern generator generates an impulsive electrical signal comprising a pulse train of biphasic pulses, the pulse train having a delay between pulses and a pulse train frequency.
  • a retinal stimulation apparatus comprising: means for generating a stimulation pattern by stimulating a retina of a patient with an impulsive electrical signal; and means for determining how visual perception depends on the generated stimulation pattern by observing perceptual threshold as a function of features of the impulsive electrical signal.
  • FIG. 1 is a brief schematic view of an implanted visual prosthesis.
  • FIG.2 is a prospective view of a visual prosthesis.
  • FIG.3 is a top view of the visual prosthesis shown in Figure 2.
  • FIG. 4 is a perspective view of the implantable portion of a visual prosthesis.
  • FIG. 5 is a side view of the implantable portion of a visual prosthesis showing the fan tail in more detail.
  • FIG. 6 is a graph showing linear-nonlinear models can predict retinal firing to light stimuli.
  • FIG. 7 is a graph showing the effect of pulse duration.
  • FIG.8 is a graph showing a method for determining visual perceptual threshold.
  • FIG. 9 is a graph showing threshold as a function of pulse width.
  • FIGS. 1 OA-IOC are graphs showing the varying integration rates of different cell types.
  • FIG. 11 is a graph showing summation across pulse pairs.
  • FIG. 12 is a graph showing threshold for pulse pairs.
  • FIG. 13 is a graph showing fixed duration pulse trains.
  • FIG. 14 is a graph showing threshold for fixed duration pulse trains of .075 ms pulse width.
  • FIG. 15 is a graph showing threshold for fixed duration pulse trains of .0975 ms pulse width.
  • FIGS. 16A, 16B are graphs showing threshold for variable duration pulse trains.
  • FIG. 17 is a graph showing the relationship between threshold, frequency and the number of pulses.
  • FIG. 18 is a graph showing that the thresholds of pulse trains with frequency below
  • FIG. 19 is a graph showing that thresholds for pulse trains with frequencies above
  • FIG. 20 is a schematic of a retinal stimulation device comprising a stimulation pattern generator.
  • Figure 1 is a schematic view of a prosthesis for stimulating retinal cells. Patients suffering from retinitis pigmentosa (RP) sustain severe vision loss as a result of photoreceptor death.
  • the electrode array is aligned in a 4x4 matrix implanted epiretinally, which covers about 10 degrees of visual angle.
  • the upper sub figure shows a schematic of an electrode array in a 4x4 configuration.
  • the subfigure from this schematic details a graphic representation of the system of neural cells under each electrode, wherein the neural cells shown are no longer organized, but unorganized with significant cell death.
  • FIGS 2 and 3 show two different perspective views of a visual prosthesis apparatus according to the present disclosure.
  • the visual apparatus provides an implantable portion 100 and an external portion 5.
  • Portion 5 is shown in Figures 2 and 3.
  • Portion 100 is shown in Figures 4 and 5.
  • the external portion 5 comprises a frame 10 holding a camera 12, an external coil 14 and a mounting system 16 for the external coil 14.
  • the mounting system 16 also encloses the RF circuitry.
  • Three structural features are provided in the visual prosthesis to control the distance, and thereby reduce the distance, between the external coil 14 and the inductive (internal) coil (116, Figure 4).
  • the three structural features correspond to movement of the external coil along the three possible spatial axes occupied by the two coils. That is, the external and inductive coils can be viewed as being separated in anatomical axes: the medial-lateral, superior-inferior, and the anterior-posterior axis.
  • the first structural feature reduces the distance between the coils along the medial-lateral axis by bending the external coil 14.
  • the distance in this medial-lateral axis should be equivalent to the separation distance of the coils if the centers of the coils are aligned.
  • the enclosure of the external coil 14 is attached to the mounting system 16, which is attached to the leg frame 10 of the visual apparatus. While the RF circuitry within the mounting system 16 is in line with the leg frame, the external coil has been given a preferential bend 18 towards the face using a flexible connector. With the external coil 14 angled toward the face (e.g.
  • the external coil 14 makes contact with the subject's face and the flexible connector allows conformation to the subject's facial contours.
  • the external coil 14 is brought in as close as possible in the medial-lateral axis for the subject.
  • the second structural feature is a sliding bar mechanism controlling movement along the anterior-posterior axis.
  • the point at which the mounting system 16 connects to the visor allows for 7 mm of adjustment along this anterior-posterior axis.
  • the sliding bar mechanism can be fixed in place when the optimal position is found by tightening two screws on the sides of the sliding bar.
  • the third structural feature is adjustment of the visual apparatus along the superior- inferior axis by varying the placement of the visual apparatus along the subject's nose.
  • the external coil 14 is higher, and when worn further from the face, the external coil 14 is lower.
  • the coil separation distance can be adjusted to obtain an optimal RF link for individual subjects.
  • FIG 4 shows a perspective view of an implantable portion 100 of a retinal prosthesi as disclosed.
  • An electrode array 110 is mounted by a retinal tack or similar means to the epiretinal surface.
  • the electrode array 110 is electrically coupled by a cable 112, which can pierce the sclera and be electrically coupled to an electronics package 114 external to the sclera.
  • Electronic package 114 includes the RF receiver and electrode drivers.
  • the electronics package 114 can be electrically coupled to a secondary inductive coil 116.
  • the secondary inductive coil 116 is made from wound wire.
  • the secondary inductive coil may be made from a thin film polymer sandwich with wire traces deposited between layers of thin film polymer.
  • the electronics package 114 and secondary inductive coil 116 are held together by a molded body 118.
  • the molded body 118 may also include suture tabs 120.
  • the molded body narrows to form a strap 122 which surrounds the sclera and holds the molded body 118, secondary inductive coil 116, and electronics package 114 in place.
  • the molded body 118, suture tabs 120 and strap 122 are preferably an integrated unit made of silicone elastomer.
  • Silicone elastomer can be formed in a pre-curved shape to match the curvature of a typical sclera. Furthermore, silicone remains flexible enough to accommodate implantation and to adapt to variations in the curvature of an individual sclera.
  • the secondary inductive coil 116 and molded body 118 are oval shaped, and in this way, a strap 122 can better support the oval shaped coil.
  • the entire implantable portion 100 is attached to and supported by the sclera of a subject.
  • the eye moves constantly.
  • the eye moves to scan a scene and also has a jitter motion to prevent image stabilization. Even though such motion is useless in the blind, it often continues long after a person has lost their sight.
  • the entire implantable portion 100 of the prosthesis is attached to and supported by the sclera of a subject.
  • Figure 5 shows a side view of the implantable portion of the retinal prosthesis, in particular, emphasizing the fan tail 124.
  • the secondary inductive coil 116 and molded body 118 must also follow the strap under the lateral rectus muscle on the side of the sclera.
  • the implantable portion 100 of the retinal prosthesis is very delicate. It is easy to tear the molded body 118 or break wires in the secondary inductive coil 116.
  • the molded body 118 In order to allow the molded body 118 to slide smoothly under the lateral rectus muscle, the molded body is shaped in the form of a fan tail 124 on the end opposite the electronics package 114.
  • Element 123 shows a retention sleeve, while elements 126 and 128 show holes for surgical positioning and a ramp for surgical positioning, respectively.
  • the degenerated retinal system is likely to have different temporal properties than a normal retina.
  • a temporal integration was studied during electrical stimulation. The objectives of this include: (1) determination of the potential neurophysiological elements underlying visual perception; and (2) development of a linear-nonlinear model of the temporal integration dynamics of electrical stimulation. It is of interest to understand temporal integration properties because it is thought that this information will help to generate the most effective stimulation patterns. The first step is to look at how visual perception depends on the timing of electrical stimulation patterns.
  • Figure 6 shows a graph of how linear-nonlinear models can predict retinal firing to light stimuli.
  • models in the art that evaluate the early visual system's response to light stimuli.
  • One example is a model of temporal contrast adaptation in retinal ganglion cells, where the resulting spike train can be predicted based solely upon the light stimulation input (Chander, D. and E. J. Chichilnisky (2001), Journal of Neuroscience 21(24): 9904-16; Kim, K. J. and F. Rieke (2001), J Neuroscience 21(1): 287-99; Baccus, S. A. and M. Meister (2002), Neuron 36(5): 909- 19.)
  • the linear/nonlinear model aides in the prediction of ganglion cell responses to light stimuli, wherein a light flicker stimulus is convolved with a linear filter with a particular time constant. The output of this convolution is then passed through an expanding nonlinearity to ultimately predict the neural response.
  • perceptual threshold is observed as a function of pulse width.
  • FIG. 7 shows a graph of a biphasic pulse.
  • the stimuli are single, biphasic, cathodic-first, charge-balanced pulses, wherein the pulse width varied between 0.075 milliseconds (ms) and 4 ms, per phase.
  • Anodic pulses are approximately fifty percent as effective as cathodic pulses, thus the anodic pulses are not necessary to consider (Jensen, R. J., O. R. Ziv, et al. (2005), Invest Ophthalmol Vis Sci 46(4): 1486-96).
  • the anodic pulses are considered to be far less effective at driving a response in the in vitro retina. This is the result of the orientation of the stimulating electrode relative to the ganglion cell, hi this configuration, the negatively-charged cathodic pulse 'pulls' the positive cations within the cell towards the axon hillock, where there is the highest concentration of voltage-gated channels. Therefore, for the method according to the present disclosure, the anodic phase should not be considered when it comes to evaluating the biphasic pulse and its influence on perception.
  • FIG. 8 shows a graph of a method for determining visual perceptual threshold, wherein the threshold was determined as follows. Subjects were exposed to a series of stimuli using a yes-no paradigm wherein half the trials contained no stimulus. The subjects reported whether the trial contained a stimulus or not. The current amplitude was varied using a 3 up, 1 down staircase. In other words, if the subjects got 3 correct answers in a row the subsequent current signal was made more difficult by decreasing the current a step. Likewise, if the subject answered incorrectly, the subsequent current signal was made easier by increasing the current by one step.
  • the curve shown in Figure 8 is an example of a generated psychometric function, which was used to analyze the behavioral data.
  • the x-axis is the current amplitude and the y-axis is the probability that the subject saw the stimulus, 1 being that the subject saw it every time at that particular current.
  • the black dots are the subject/patient responses for a specific stimulus condition (a specific current amplitude), with the larger dots representing a greater number of trials at that condition.
  • the curve was fit with a Weibull function and the 50% point was the determined threshold.
  • the Weibull function allows for many different distributions. This function is a common cumulative distribution that is frequently used for life data because its slope parameter can be adjusted to allow the curve to represent different distributions.
  • Figure 9 is graph showing threshold as a function of pulse duration or width.
  • Figure 9 is an example curve (typical of data from 10 electrodes, 2 subjects).
  • Data can be modeled using a simple leaky integrator model.
  • a leaky integrator model represents the accumulation and dissipation of some input (e.g. electric current or charge) that accumulates and dissipates with a specific rate that depends on the value of the time constant.
  • time constants of ⁇ lms are found, which is consistent with chronaxie values for ganglion cell integration periods (Jensen et al, 2005).
  • the pulse width is on the x-axis varying between 0.075 ms and 4 ms, and the y- axis is the amplitude to reach threshold.
  • the eight boxes shown in the figure represent measured thresholds at their corresponding pulse widths. So, for example, at 0.075 ms, it requires approximately 425 microAmperes ( ⁇ A) of current for the patient to be able to see that stimulus 79% of the time.
  • the data show that as the pulse width is increased, there is a decrease in current amplitude needed to reach the threshold.
  • the black line represents the current model and the fit estimation of this particular data set. Additionally, this data can be fit using a simple leaky integrator model (Kandel, E. R., J. H. Schwartz, et al. (1991). Principles of Neural Science. Norwalk, Connecticut, Appleton & Lange) having a single free parameter (tau or time constant) that represents the integrative behavior of the system.
  • Figures lOA-lOC show that different cell types integrate charge at different rates with cathodic phases in grey and anodic phases in black.
  • Figure 10 also shows how a leaky integrator model would integrate a biphasic pulse (Fig. 10A) using a short (Fig. 10B) and long (Fig. 10C) time constant.
  • Figure 1OA represents an input stimulation pattern (biphasic pulse).
  • Figure 1OB represents a fast integrator response to the input, typical of ganglion cells.
  • Figure 1OC represents a slow integrator response, typical of bipolar cells.
  • two different biphasic pulses that differ in their pulse width, where one is relatively long and the other is short.
  • FIG 11 is a graph showing summation across pulse pairs. Stimuli were 0.075 ms pseudo-monophasic cathodic pulses. The first pulse had fixed current amplitude (sub-threshold). The second pulse followed with a variable delay (0.15-12 ms). The experiment, illustrated by Figure 11, evaluates the summation across pulse pairs. In other words, the experiment determines how the first pulse, ⁇ i.e. the conditioning pulse) contributes to the threshold response of the second pulse, (i.e. the test pulse).
  • the stimuli were pseudo-monophasic because, for obvious safety reasons, a charge-balanced anodic phase is included, as shown by the positive pulse to the right of Figure 11. The difference here is that the anodic pulses were presented later in time by about 30 ms.
  • Figure 12 is a graph showing threshold for pulse pairs. The graph derives from a data set of 8 different electrodes across two subjects. The time constants were the same ( ⁇ lms) as the single pulse data are consistent with ganglion cell stimulation. With pulse pair summation it was determined that there is a critical window of integration. [063] In particular, the x-axis of Figure 12 shows the delay between pulse pairs, and the y-axis is the amplitude to reach threshold. The critical window of integration was observed to be somewhere short of one millisecond. More specifically, looking at the portion of the curve before the 1 ms delay value, a short increase in delay provides a large increase in amplitude to reach threshold.
  • Figure 13 is a graph showing a fixed duration pulse train, i.e. a series of multiple pulses where every pulse has the same width.
  • stimuli were fixed duration pulse trains of 200 milliseconds. Pulses were either 0.975 or 0.075 milliseconds in duration, and frequency varied between 5 Hz and 225 Hz. Amplitude of all pulses in the train varied simultaneously to find threshold. In other words, the amplitude of each pulses within the pulse train increased and/or decreased at the same time.
  • Figures 14 and 15 show graphs indicative of threshold for fixed duration pulse trains like the one shown in Figure 9. [067] It has already been discussed above that the reduction in the amount of current needed to reach the threshold is due to interactions between pulses. Figure 14 and Figure 15 show that the decrease in threshold is driven by the frequency of the pulses.
  • the graph of Figure 14 refers to data coming from pulse trains having widths (duration of each pulse) of 0.075 ms.
  • the graph of Figure 11 refers to data coming from pulse trains having widths of 0.975 ms.
  • the x-axis frequency range is the same, i.e. 5 Hz to 225 Hz.
  • the values of Fig. 14 (between about 300 and about 100 microAmperes) are an order of magnitude greater than the values of Fig. 15 (between about 40 and about 20 microAmperes).
  • solid lines have been added to show the behavior of the model.
  • FIGS 16A and 16B are graphs showing threshold values for variable duration pulse trains.
  • the stimuli consisted of pulse trains of 2, 3, and 15 pulses (where the 2 and 3 pulses examples are shown in Figure 12).
  • the frequency of these pulse trains was varied by changing the delay between the biphasic pulses.
  • the delay varied from 0.075 ms to 300 ms, corresponding to a range of frequencies between approximately 3000 and approximately 3 Hz.
  • perceptual threshold was measured by varying the amplitude of all the pulses within the pulse train simultaneously. In other words, the amplitude of each pulse within the pulse train increased and/or decreased at the same time.
  • Figure 17 is a frequency vs. amplitude-to-reach-threshold graph similar to the ones shown in Figures 10 and 11, where relationship between frequency and number of pulses is also shown.
  • the x-axis is represented in a logarithmic scale. Three curves are shown. The curve on top corresponds to a 2 pulse train. The curve in the middle corresponds to a 3 pulse train. The curve on the bottom corresponds to a 15 pulse train.
  • Figure 18 is a graph showing that thresholds for pulse trains with frequencies below about 50 Hz are independent of the number of pulses.
  • the graph refers to data for thresholds for the two (grey bar), three (diagonal-lined bar) and fifteen (horizontal-lined bar) pulse train data of Figure 17, averaged over six electrodes and over two subjects, plotted for frequencies of 3, 7, 10 and 20 Hz, wherein the error bars represent the standard error.
  • the error bars represent the standard error.
  • Figure 20 shows a stimulation pattern generator 310 which can provide the impulsive electrical signals to implement a determined stimulation pattern from observing a perceived threshold.
  • This stimulation pattern generator can be programmed to provide a pattern of pulse trains having a pulse train frequency and a pulse width.
  • the stimulation pattern generator can be programmed to provide a pulse train having a frequency less than 50 Hz, wherein the pulse width is fixed at 0.075 ms or 0.975 ms.
  • the stimulation pattern generator can provide a pulse train having a frequency higher than 50 Hz, wherein the pulse width is variable.
  • the stimulation pattern generator is connected to a retinal stimulating device 300.
  • An example of a retinal stimulating device is shown in Figures 1 and 2.
  • a process for designing an apparatus and a method for stimulating neural tissue is provided.
  • the apparatus provides a means for adjusting the RF link to the internal coils, and the method provides the maximum intensity with minimum current by modeling responses to varying stimulation parameters including frequency, pulse width, and pattern of pulse series (trains).

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  • Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)
  • Electrotherapy Devices (AREA)

Abstract

Cette invention a pour objet un appareil et un procédé pour une stimulation rétinienne. L'appareil comprend une partie implantable et externe, et le procédé comprend des paramètres amenés à varier, comprenant la fréquence, la largeur d'impulsion et le motif des trains d'impulsion pour déterminer un motif de stimulation et un seuil de perception visuelle.
EP07809536A 2006-06-16 2007-06-14 Procédé permettant de stimuler électriquement la rétine humaine à l'aide de trains d'impulsions Withdrawn EP2032205A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US81430806P 2006-06-16 2006-06-16
US87664506P 2006-12-22 2006-12-22
PCT/US2007/013918 WO2007149291A2 (fr) 2006-06-16 2007-06-14 Procédé permettant de stimuler électriquement la rétine humaine à l'aide de trains d'impulsions

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EP2032205A2 true EP2032205A2 (fr) 2009-03-11

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WO2010033728A2 (fr) * 2008-09-18 2010-03-25 Second Sight Medical Products Techniques et stimulation électrique fonctionnelle pour éliminer un inconfort durant une stimulation électrique de la rétine

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US6507758B1 (en) * 1999-03-24 2003-01-14 Second Sight, Llc Logarithmic light intensifier for use with photoreceptor-based implanted retinal prosthetics and those prosthetics
EP1171188B1 (fr) * 1999-03-24 2009-05-06 Second Sight Medical Products, Inc. Prothese retinienne de couleur pour restituer la vision des couleurs
US7103416B2 (en) * 2001-01-16 2006-09-05 Second Sight Medical Products, Inc. Visual prosthesis including enhanced receiving and stimulating portion
EP1383577A2 (fr) * 2001-05-03 2004-01-28 Universite Catholique De Louvain Methode et dispositif de reeducation de la vision
US7321796B2 (en) * 2003-05-01 2008-01-22 California Institute Of Technology Method and system for training a visual prosthesis
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WO2007149291A2 (fr) 2007-12-27

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