EP3325089A1 - Implant rétinien actif - Google Patents

Implant rétinien actif

Info

Publication number
EP3325089A1
EP3325089A1 EP17710266.2A EP17710266A EP3325089A1 EP 3325089 A1 EP3325089 A1 EP 3325089A1 EP 17710266 A EP17710266 A EP 17710266A EP 3325089 A1 EP3325089 A1 EP 3325089A1
Authority
EP
European Patent Office
Prior art keywords
stimulation
signal
retina
implant according
image
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Withdrawn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
EP17710266.2A
Other languages
German (de)
English (en)
Inventor
Günther Zeck
Thoralf Herrmann
Florian Jetter
Alfred Stett
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.)
NMI Naturwissenschaftliches und Medizinisches Institut
Original Assignee
NMI Naturwissenschaftliches und Medizinisches Institut
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 NMI Naturwissenschaftliches und Medizinisches Institut filed Critical NMI Naturwissenschaftliches und Medizinisches Institut
Publication of EP3325089A1 publication Critical patent/EP3325089A1/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Withdrawn legal-status Critical Current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
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0543—Retinal electrodes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0622—Optical stimulation for exciting neural tissue

Definitions

  • the present invention relates to an active retina implant for implantation in an eye, comprising an array of stimulation electrodes that deliver stimulation signals to cells of the retina.
  • Such a retina implant is known for example from WO 2005/000395 A1.
  • the known retina implant serves to counteract loss of vision due to retinal degeneration.
  • the basic idea is to implant a microelectronic stimulation chip into a patient's eye, which replaces the lost vision with electrical stimulation of nerve cells.
  • the subretinal approach described in the aforementioned WO 2005/000395 A1 and also, for example, in EP 0 460 320 A2 uses a stimulation chip implanted in the subretinal space between the outer retina and the pigment epithelium of the retina, which responds to an integrated array in the stimulation chip Photodiodes conspicuous environmental converts light into electrical stimulation signals for nerve cells. These stimulation signals drive an array of stimulation electrodes that stimulate the neurons of the retina with spatially resolved electrical stimulation signals that correspond to the image information "seen" by the array of photodiodes.
  • This retina implant thus stimulates the remaining, intact neurons of the degenerated retina, ie horizontal cells, bipolar cells, amacrine cells and possibly also ganglion cells.
  • the visual image impinging on the array of photodiodes or more complex elements is converted to an electrical stimulation pattern on the stimulation chip.
  • This stimulation pattern then leads to the electrical stimulation of neurons, from which the stimulation is then directed to the ganglion cells of the inner retina and from there via the optic nerve into the visual cortex.
  • the subretinal approach exploits the natural interconnection of the formerly present and now at least partially degenerated or lost photoreceptors with the ganglion cells, in order to supply the visual cortex in the usual way with nerve impulses corresponding to the image seen.
  • the known implant is therefore a substitute for the lost photoreceptors; it converts image information into electrical stimulation patterns.
  • the epiretinal approach uses a device consisting of an extra-ocular and an intra-ocular part, which communicate with each other in an appropriate manner.
  • the extra-ocular part comprises a type of camera and a microelectronic circuit to encode captured light, ie the image information, and to transmit it as a stimulation pattern to the intra-ocular part.
  • the intra-ocular part contains an array of stimulation electrodes, which contacts neurons of the inner retina and thus directly electrically stimulates the ganglion cells located there.
  • the stimulation signals are transmitted as rectangular monophasic or biphasic signal pulses which have a specific repetition frequency, amplitude and pulse duration.
  • the incident light is converted, for example, into voltage pulses with a pulse length of about 500 microseconds and a pulse interval of preferably 50 milliseconds, so that a repetition frequency of 20 Hz results which is sufficient for flicker-free vision.
  • the pulse spacing is also sufficient to completely return the electrode polarization. It is mentioned that 20 Hz corresponds to the physiological flicker frequency at low ambient brightness.
  • the inventors report experiments in which the retina of a blind patient was subretinally stimulated with an electrode having biphasic, anodic starting pulses of up to 4 milliseconds duration.
  • an electrode having biphasic, anodic starting pulses of up to 4 milliseconds duration When using different repetition frequencies, that is to say with an excitation with a continuous sequence of "flashes" of a certain frequency, the following observation emerged:
  • Implants WO 2007/128404 A1 proposes to subdivide the plurality of stimulation electrodes into at least two groups of stimulation electrodes, which are actuated successively in time for the delivery of stimulation signals.
  • the image seen is therefore not imaged as a whole with a high repetition frequency on the stimulation electrodes, but rather the image is decomposed, so to speak, into at least two partial images, which are alternately "switched through” to the stimulation electrodes with a lower repetition frequency.
  • the local resolution may be somewhat reduced, but the refresh rate of 20 Hz required for physiologically flicker-free vision is achieved.
  • the repetition frequency of the individual partial image can then be reduced even further, whereby a new partial image in the form of a pattern of stimulation pulses is output every 50 milliseconds, that is to say with a refresh rate of 20 Hz.
  • epiretinal pacing has a pulse duration of 25 milliseconds compared to shorter pulse durations allows the patient higher-resolution image recognition. They mention that sinusoidal stimulation pulses of 20 Hz stimulate bipolar cells in blind ex vivo retina more effectively than rectangular pulses of the same frequency.
  • LFSS sinusoidal stimulation signals
  • the stimulation electrodes of the retinal electrical implant are placed in epi- or subretinal contact with the tissue to be stimulated in order to deliver the stimulation signals.
  • the stimulation signals should be selected so that the patient as possible a flicker-free vision with a correspondingly high time resolution is possible so that he not only quasi-static environment (orientation viewing) but also can detect rapidly changing environmental impressions.
  • the aim is also to enable the patient to record high-resolution images which may be changing rapidly, for example during running or television viewing, which is not yet satisfactorily possible with the currently used retina implants.
  • Another problem with the known retina implants is the energy supply of the stimulation chip.
  • the energy for generating the electrical stimulation signals can not be obtained from the incident useful light even in subretinal implants, so that additional external energy is needed.
  • this external energy is either obtained from additional non-visible light which is injected into the eye, externally coupled in inductively via a coil, for example, or passed through a cable guided into the eye.
  • the implant known from WO 2005/000395 A1 is supplied with electrical energy wirelessly via irradiated IR light or inductively coupled RF energy, wherein information about the control of the implant can be contained in this externally supplied external energy.
  • wireless retinal implants are not yet available to patients with satisfactory quality for human applications, not only epiretinal but also subretinal implants are currently being used, which receive the required external energy via cables.
  • WO 2007/121901 A1 describes, for example, a subretinal retina implant, in which the external energy and control signals are conducted by cable to the stimulation chip implanted in the eye.
  • the cable is applied to the sclera of the eye and fixed in order to avoid forces on the implant.
  • WO 2008/037362 A2 therefore proposes to implant the implant with at least one im
  • Substantially rectangular electrical AC voltage to provision which is at least almost DC-free with respect to the tissue mass on average over time.
  • the potential position can be selected such that the supply voltage is at least almost DC-free over the time average. In this way, the disturbing electrolytic decomposition processes are at least largely avoided.
  • Suitable for patients suffering from visual impairment due to loss of natural photoreceptors such as retinitis pigmentosa or age-related macular degeneration.
  • a further requirement for retinal implants is that a robust neural activity is triggered with the lowest possible stimulation intensity (voltage or current amplitude). Robust, reliable stimulation is the ability of the stimulated neuronal tissue to generate an electrical response every time the stimulus is presented.
  • the stated goal of all electrical implants is further to reduce the voltage required for the robust activation of the cells. This can e.g. can be achieved by using low impedance materials while still having to verify the long term stability of these materials.
  • the object of the present invention is to provide a retina implant which takes these observations into account and avoids or reduces disadvantages of the prior art.
  • the above-mentioned active retina implant has at least one signal generator that generates at least one continuous sinusoidal stimulation signal that comprises at least one adjustable signal parameter, and that the at least one signal generator is electrically connected to at least one stimulation electrode, he leads the stimulation signal, wherein preferably the signal parameter is selected from frequency, amplitude, phase, offset and / or waveform.
  • the stimulation is thus carried out with an array of stimulation electrodes, which are supplied with sinusoidal signals. These originate, for example, from at least one continuously operated sinusoidal signal generator.
  • the amplitude, frequency, offset or phase relationship of the sinusoidal signals applied to the individual stimulation electrodes can be adjusted individually and in a time-variable manner for each stimulation electrode or for groups of stimulation electrodes.
  • These signal parameters are adjusted according to the intensity of the light incident on the retina and measured by photodiodes.
  • An increased incidence of light is converted into an increased stimulation amplitude or increased stimulation frequency.
  • Suppression of the activity as it occurs when the field of view is obscured is achieved by a decreased stimulation amplitude or a phase-shifted stimulation.
  • a shift in the voltage zero line that is to say an offset, can likewise be used to take account of increased or reduced incidence of light.
  • the stimulation parameter of the delivered stimulation signal can be the
  • Result of a mathematical calculation is, whereby the calculation takes place either analog or digitally.
  • Invention understood both a "pure" sinusoidal signal following the trigonometric formulas and a continuous, for example mathematically derived signal from a pure sinusoidal signal, with respect to the aspect ratio and / or time component of the positive and negative half wave and / or ratio between the slopes of the positive and negative edges is asymmetric.
  • the stimulation signal delivered to adjacent stimulation electrodes may have an adjustable phase relationship, wherein the capacitance of the stimulation electrodes may contribute to adjusting the phase of the stimulation signal.
  • the stimulation electrodes used can be either metal-based or based on a capacitive material. When capacitive electrodes are used, sinusoidal stimulation results in a phase shift.
  • a reduction of the voltage required for a robust activation of the cells is thus not achieved by the use of previously untried materials with low impedance, but by a new stimulation protocol that allows the use of already established materials.
  • the new implant has at least one signal generator, which in the simplest case comprises a sinusoidal signal generator with specific signal parameters, which can be changed via external control parameters.
  • the implant may, however, also have a plurality of sinusoidal signal generators or a complex signal generator in which current sources, digital / analog converters, microcontrollers etc. are provided in order to generate stimulation signals of any desired waveform, frequency, amplitude and phase relationship.
  • US Pat. No. 6,591,138 B1 describes a control device which can be implanted in the brain of a patient and metrologically detects the electrical activity of the brain and transmits sinusoidal stimulation signals, which have a fundamental frequency below 10 Hz, via implanted electrodes in the case of certain measurement signals.
  • the stimulation signals may vary in terms of frequency, phase, waveform, duration and amplitude from electrode to electrode. In this way, unwanted neurological conditions should be prevented or terminated.
  • a wireless implantable multichannel microstimulating system-on-a-chip with modular architecture IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 15, No. 3, September 2007, describe a microsystem conceived, inter alia, as an epiretinal implant, which can last up to 64, in a further development up to 2048 Stimulation points mono- or biphasic stimulation pulses can deliver.
  • the implant is constructed monolithically as an ASIC and allows the generation of arbitrary waveforms for the stimulation pulses as well as an extensive adjustment of the parameters of the individual stimulation signals.
  • Stimulation with an array of pacing electrodes individually applied with a sinusoidal pacing signal allows the stimulation voltage needed for stable pacing to be reduced. This protects both the stimulation electrodes and the stimulated tissue.
  • Phase relationship to each other may allow site specific stimulation.
  • the stimulation is carried out with small current or voltage amplitudes, the maximum voltage amplitude of each half-wave can now be less than 1 volt, it is preferably in a range of 50 mV to 300 mV.
  • the stimulation signal With a voltage amplitude of, for example, 100 mV per half-wave, the stimulation signal thus has a total voltage swing of 200 mV, which may be symmetrical to a zero line, or may also have an offset if the zero line has been shifted.
  • a continuous stimulation with a frequency greater than 10 Hz, preferably in the range of 10 - 100 Hz is possible.
  • the desired pacing effect occurs permanently with each repetition of a pacing sequence. With subretinal stimulation there is thus no fading.
  • the invention also provides the ability to apply complex spatiotemporal stimulation patterns to individually maximize the physiological effect.
  • the signal parameter is individually adjustable for each stimulation electrode, wherein more preferably the signal generator has a separate sinusoidal signal generator for each stimulation electrode.
  • an image receiver which converts incident ambient light into electrical signals which are fed to the at least one signal generator in order to influence the at least one signal parameter.
  • These electrical signals thus contain spatially resolved the required image information, with which the signal generator is then driven so that it emits a pattern of electrical stimulation signals with adjusted signal parameters for the individual stimulation electrodes, so that the stimulation signals stimulate the neurons so that the patient from the Image receiver can see "received” image.
  • the image receiver has an array of image cells, each image cell is assigned to a stimulation electrode, and the electrical signal generated by a image cell is used to set the signal parameters of the stimulation signal which is fed to the associated stimulation electrode.
  • the image receiver can be designed as an external image receiver, which is arranged outside the eye.
  • the externally recorded and processed image information is transmitted as in the known epiretinal implants in the form of electrical signals via cable or wirelessly to the implant. There, these signals are possibly further processed and then used as an "internal image" to control the signal generator (s) so that the signal parameters of the stimulation signals are changed such that the neurons are then stimulated via the stimulation electrodes so that the viewed image is recognized ,
  • the image receptor may also be formed as an implantable image receptor, which is also implanted in the eye.
  • Eye movement can not be used, which fulfills an important function in object finding.
  • the patient would therefore always see the same picture despite different eye positions, as long as he keeps his head still. This is confusing for him and, according to the inventors, would reduce the benefit of the implant.
  • eye-tracking control for externally mounted image receivers, with which the eye movement is to be detected and used.
  • this approach proves to be very time-consuming, although there is still no experience as to whether this will be possible with sufficient accuracy.
  • the image receptor is also implanted in the eye, the patient may use natural eye movement and head movement in the usual manner to view images and scan for objects.
  • the new implant can thus be used sub- or epiretinally.
  • the new chip can be implanted easier than an implant of two chips or components.
  • the implant comprises a shutdown device, which in
  • At least the one or more signal generators on and off.
  • Closing the eyelids can be achieved.
  • Fig. 1 is a schematic representation of a first embodiment of the new
  • FIG. 2 shows a schematic illustration of a second exemplary embodiment of the new retina implant in a representation which is not true to scale;
  • FIG. 3 shows a schematic representation of a human eye into which the retina implant according to FIG. 2 is inserted, likewise not to scale;
  • Fig. 4 is a schematic representation of a third embodiment of the new
  • FIG. 5 shows a schematic representation of a signal generator as used in the implants of FIGS. 1 to 4 in order to generate the sinusoidal stimulation signals with corresponding signal parameters from the received image signals;
  • FIG. 6 shows a sinusoidal waveform with asymmetrical aspect ratio that can be used for the stimulation signals
  • FIG. 7 shows a further sinusoidal waveform with asymmetrical slopes that can be used for the stimulation signals
  • Fig. 8 is a summary of the results of a 5-minute
  • Figure 9 is a summary of the results of a 5 minute continuous subretinal stimulation of a blind ex vivo retina with a 40 Hz sinusoidal excitation signal;
  • Fig. 10 is a summary of the results of a 5-minute
  • Fig. 1 1 is a summary of the results of a 5-minute
  • epiretinal continuous wave stimulation of a blind ex vivo retina alternating with a sinusoidal excitation signal of 10 Hz and with a sinusoidal excitation signal of 25 Hz.
  • FIG. 1 shows a schematic representation of a first exemplary embodiment of an active retina implant 10, wherein the dimensions are not shown to scale.
  • the retina implant 10 is connected via a cable 11 to a supply unit 12 and to an implantable image receiver 13, on which an array 14 of image cells 15 is arranged, which are formed, for example, as photodiodes.
  • an array 16 of stimulation electrodes 17 for the delivery of electrical stimulation signals is arranged on the retina implant 10.
  • the supply unit 12 supplies the retina implant 10 via the cable 1 1 with electrical energy and possibly with control signals via which various functions of the retina implant can be influenced or adjusted.
  • the image receiver 13 converts via its image cells 14 incident ambient light into spatially resolved electrical signals, which are passed to the retina implant 10 and there - optionally after further processing - delivered via the stimulation electrodes 17 as electrical stimulation signals to cells of the retina to these stimulate.
  • the retina implant 10 can be used epi- or subretinally.
  • On the cable 1 1 mounting tabs 18 are provided with which the cable 1 1 can be attached to the sclera of the eye of the person, who is implanted the retina implant 10. In this way it is avoided that forces are exerted on the retina implant 10, which could lead to a mechanical load and / or displacement of the retina implant 10.
  • the image receiver 13 is arranged outside the eye, for example in a pair of glasses which the patient wears.
  • the retina implant 10 is then epiretinal implanted, for example, wherein the transmission of energy, control signals and image information can also be wireless, as is known as such from various publications.
  • the image receptor 13 is implantable such that it is implanted into the eye, such as the retina implant 10 itself. This arrangement is shown in Fig. 2, where the image receptor 13 is disposed adjacent to the retina implant 10, to which it is connected in the embodiment shown via a cable 19.
  • this subretinal implant also implants the image receptor in the eye, the patient can use natural eye movement and head movement in the usual way to view images and scan for objects.
  • the retinal implant 10 and the image receptor 13 of FIG. 2 are intended to be implanted in a human eye 20, which is shown very schematically in FIG. For the sake of simplicity, only the lens 21 and the retina 22 into which the implant 10 and the image receptor 13 have been implanted are shown. Retina implant 10 and image receptor 13 are preferably in the so
  • the retina implant 10 is placed in such a way that the stimulation electrodes 17 shown in FIG. 2 can deliver the electrical stimulation signals to cells in the retina 22.
  • Retinal implant 10 and implantable image receptor 13 can be arranged side by side, as shown in FIG. 2, whereby they can be embodied as separate units in, for example, different technologies. Both implants 10, 13 can also be arranged side by side or one above the other on a common foil or integrated into a microchip.
  • the array 14 of image cells 15 is shown in FIG. 3 as a black area.
  • the stimulation electrodes 17 are provided in a defined geometric arrangement and have a distance of 50 ⁇ each other, which is designated in Fig. 2 with a.
  • This arrangement can be matrix-shaped with rows and columns - as in FIGS. 1 and 2
  • Fig. 3 can still be seen that the cable 1 1 led out laterally out of the eye and out there on the sclera with the mounting tabs 18 is attached before the cable continues to the external supply unit 12.
  • the supply unit 12 is then fastened in a manner not shown in detail outside the eye, for example on the skull of the patient. Via the supply unit 12, electrical energy is sent to the implant 10 and the image receiver 13, wherein at the same time control signals can be transmitted which influence the functioning of the implant as described, for example, in the aforementioned WO 2005/000395 A1, the content thereof is hereby made the subject of the present application.
  • the energy supply can take place via substantially rectangular electrical alternating voltage voltages, which are virtually DC-free with respect to the tissue mass over a period of time, as described in the aforementioned WO
  • Image receiver 13 and retina implant 10 can alternatively also be integrated in a chip 26, as shown schematically in FIG.
  • the chip 26 is easier to implant than an implant of two chips or components. Furthermore, then the location of the image information (by the image receiver 13) and the location of the delivery of the electrical stimulation signals are very close together, so that the patient perceives no or almost no prism errors.
  • the chip 26 has a carrier 27, on which an input stage 28 can be seen, which is supplied via the cable 1 1 external external energy and possibly control signals.
  • the input stage 28 is connected to a unit 29, which in this case has a multiplicity of image cells 15 which convert incident visible light into electrical signals which are then emitted via the stimulation electrodes 17 indicated next to the respective image cells 15 as electrical excitation patterns to nerve cells of the retina become.
  • the processing of the electrical signals generated by the image cells 15 takes place in a signal generator 31, which generates sinusoidal stimulation signals with individual signal parameters for the various stimulation electrodes 17, which are then fed back to the stimulation electrodes 17.
  • FIG. 4 is merely a schematic, logical representation of the chip 26, the actual geometric arrangement of the individual components may result, for example, in the immediate vicinity of each image cell 15 having a signal generator 31.
  • the chip 26 is connected via an indicated at 32 external mass with the tissue into which the implant is introduced. Furthermore, an internal electrical ground 33 is indicated, which is not connected to the external ground 32 in the embodiment shown.
  • the chip 26 can also be inductively supplied with HF energy via an external transmitting coil which is received by a receiving coil in / on the eye and then rectified in order to supply the chip 26 with the required DC voltage. like this eg in WO 2009 / 090047A1.
  • FIG. 5 shows, by way of example, a signal generator 31 to which a retina 22 and, subsequently, neuronal tissue 33, which is connected via nerve tracts 34 to the visual cortex (not shown), are indicated very schematically.
  • incident light see arrow 23
  • the object of the patient in question here is not or no longer fully functional retina 22 takes over the inventive retina implant 10th
  • the signal generator 31 has for each stimulation electrode 17 a sinusoidal signal generator 35 which generates a sinusoidal stimulation signal with adjustable signal parameters.
  • Each sinusoidal signal generator 35 is associated with an adjusting device 36, which via
  • Lines 37 are supplied from the image cells 15 output electrical signals representing the viewed image.
  • the electrical signals of the image cells 15 affect frequency, amplitude, relative
  • the signal generator 31 can be a function of the individual, by the electrical
  • Signals on the lines 37 certain signal parameters that generate stimulation signals with the help of current sources, analog-to-digital converters, microprocessors, etc.
  • the lines 37, 38 are also shown in Fig. 4, where indicated by double-dashed lines, that in each case a plurality of lines 37 and 38 are provided.
  • the patient may, for example, the retinal implant 10 via control signals on the
  • the shut-off device 39 provided for this purpose is indicated in FIG. 4 by a rectangle in the input stage 28.
  • the shutdown function can be implemented as a hardware component or as a software component.
  • Stimulation electrodes 17 or groups of stimulation electrodes 17 are fed individually adjusted so that the patient perceives an even over the entire stimulated image visual impression.
  • this individual frequency setting allows the physiologically different conditions of the individual patients to be taken into account so that all the stimulation electrodes 17 deliver their stimulation signals to the respectively assigned cells of the neuronal tissue 33.
  • stimulation signals deviating from the pure sinusoidal form may also be used, as shown by way of example in FIGS. 6 and 7.
  • FIG. 6 shows a sinusoidal signal 41 having an amplitude deviation 40 with asymmetrical aspect ratio, in which the anodic component 42 has a different amplitude, here greater, than the cathodic component 43.
  • Signals can be generated by simple mathematical operations from pure trigonometric sinusoidal signals.
  • Retinas with sinusoidal electrical voltages can be stimulated via subretinal and via epiretinally positioned electrodes.
  • the experiments involved recording ganglion cell activity and recording the total current flowing during stimulation to later determine the charge transferred per stimulation phase.
  • retinas were stimulated with biphasic stimulation pulses of the same duration as well as with short, pulse-shaped anodic stimulation pulses of the same frequency.
  • STG 2004 Multi Channel Systems MCS GmbH
  • the electrostimulated cell responses were measured for subretinal stimulation using a flexible microelectrode array (Flex MEA).
  • the stimulation current was determined by a resistor (10 ohms) between Ag / AgCl electrode and system ground.
  • Sinusoidal stimulation signals with frequencies of 10 and 25 Hz were included
  • Steady pacing generates stable responses in which 70% (and often 100%) of pacing cycles generate at least one retinal action potential over 5 minutes.
  • Rectangular stimuli or after anodic, short pulses Rectangular stimuli or after anodic, short pulses. With sinusoidal voltages, more action potentials can be triggered per stimulation than via the control stimuli.
  • Cyst stimulation of a blind ex vivo retina is shown. Each stroke in the upper figure corresponds to a measured action potential. Shown are the measurement results for the first and last twenty sinusoids.
  • the lower figure shows the timing of the excitation signal, which was a pure sine wave with a frequency of 25 Hz and a total stroke of 400 mV.
  • FIG. 8 shows that the stimulation is robust, and even after 5 minutes of continuous stimulation the action potentials are still stimulated in a reproducible manner, fading is not recognizable.
  • Fig. 9 shows in a representation as in Fig. 8, the results of a 5-minute
  • subretinal continuous wave stimulation of a blind ex vivo retina but for an excitation signal that was a pure sine with a frequency of 40 Hz and a total stroke of 400 mV.
  • Fig. 10 shows an asymmetric excitation signal of 120 ms period and with steeply rising sinusoidal edge and flat falling edge; see also Fig. 7. Above in Fig. 10, the cell response is shown, which is stimulated by the beginning of the falling edge of the excitation signal.
  • FIG. 11 shows in a representation as in FIG. 8 that the retinal network follows a change of the frequency from 10 Hz to 25 Hz and back to 10 Hz.
  • the cell responses shift reproducibly in the time axis.
  • the number of triggered cell responses per second also changes, which represents a possibility for the conversion of the incident light signal into cell responses.
  • the results shown in FIG. 11 prove that the cell response can be modulated within a few milliseconds via a change in the stimulation frequency.
  • the experimental set-up as well as the measurement evaluation for the results shown in Figs. 8 and 9 corresponded to the setting discussed above in the forefront of the discussion of Fig. 8.
  • the experiments for Figs. 8 and 9 were performed with subretinal, those for Figs. 10 and 11 with epiretinal stimulation.
  • the experimental set-up and the measurement evaluation for the results shown in Fig. 10 1 1 were obtained with a commercial CMOS-based microelectrode array "CMOS MEA 5000" (Multi Channel System MCS GmbH)
  • the stimulation current was 500 nA Titanium nitride isolated with a 25 nm thin titanium oxide layer.
  • CMOS MEA CMOS MEA 5000 system.
  • the stimulation current was determined by a resistor (10 ohms) between Ag / AgCl electrode and system ground.

Landscapes

  • 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)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Prostheses (AREA)

Abstract

La présente invention concerne un implant rétinien actif destiné à être implanté dans un oeil, comportant un ensemble d'électrodes de stimulation (17) qui livrent des signaux de stimulation aux cellules de la rétine. Selon l'invention, au moins un générateur de signaux (31) produit au moins un signal de stimulation continu sinusoïdal qui comporte au moins un paramètre de signal réglable, et ledit générateur de signaux (31) est électriquement connecté à au moins une électrode de stimulation (17).
EP17710266.2A 2016-03-21 2017-03-13 Implant rétinien actif Withdrawn EP3325089A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102016105174.8A DE102016105174A1 (de) 2016-03-21 2016-03-21 Aktives Retina-Implantat
PCT/EP2017/055802 WO2017162458A1 (fr) 2016-03-21 2017-03-13 Implant rétinien actif

Publications (1)

Publication Number Publication Date
EP3325089A1 true EP3325089A1 (fr) 2018-05-30

Family

ID=58266661

Family Applications (1)

Application Number Title Priority Date Filing Date
EP17710266.2A Withdrawn EP3325089A1 (fr) 2016-03-21 2017-03-13 Implant rétinien actif

Country Status (6)

Country Link
US (1) US20190022376A1 (fr)
EP (1) EP3325089A1 (fr)
CN (1) CN109152919A (fr)
DE (1) DE102016105174A1 (fr)
IL (1) IL261891A (fr)
WO (1) WO2017162458A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020086612A1 (fr) * 2018-10-22 2020-04-30 The Regents Of The University Of California Stimulateur rétinien
KR102332169B1 (ko) * 2021-02-24 2021-12-01 주식회사 셀리코 증강현실 기반의 인공망막 시스템
CN116440409B (zh) * 2023-03-21 2024-05-14 北京工业大学 基于红外光激励的人类视网膜细胞刺激设备及方法

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5024223A (en) 1989-08-08 1991-06-18 Chow Alan Y Artificial retina device
CN1277062A (zh) * 1999-06-09 2000-12-20 真道恒平 眼睛的治疗方法和装置
US6591138B1 (en) 2000-08-31 2003-07-08 Neuropace, Inc. Low frequency neurostimulator for the treatment of neurological disorders
DE10304831A1 (de) 2003-01-31 2004-08-26 Eberhard-Karls-Universität Tübingen Universitätsklinikum Retina-Implantat zum Stimulieren einer Retina in Abhängigkeit von einfallendem Licht
DE10329615A1 (de) 2003-06-23 2005-03-03 Eberhard-Karls-Universität Tübingen Universitätsklinikum Aktives Retina-Implantat mit einer Vielzahl von Bildelementen
US7117034B2 (en) * 2003-06-24 2006-10-03 Healthonics, Inc. Apparatus and method for bioelectric stimulation, healing acceleration, pain relief, or pathogen devitalization
US20070250135A1 (en) 2006-04-21 2007-10-25 Bartz-Schmidt Karl U Compound subretinal prostheses with extra-ocular parts and surgical technique therefore
DE102006021258B4 (de) 2006-04-28 2013-08-22 Retina Implant Ag Aktives subretinales Retina-Implantat
DE102006047117A1 (de) 2006-09-26 2008-04-17 Retina Implant Gmbh Implantierbare Vorrichtung
CN101468238A (zh) * 2007-12-24 2009-07-01 谢刚 弱视治疗仪
DK2229212T3 (da) 2008-01-14 2015-06-08 Pixium Vision Sa Retinaimplantat med ensrettet vekselstrømsdrevet fotodiode
EP2313148B1 (fr) * 2008-07-30 2013-08-21 Ecole Polytechnique Fédérale de Lausanne Appareil de stimulation optimisee d'une cible neurologique
US8442641B2 (en) * 2010-08-06 2013-05-14 Nano-Retina, Inc. Retinal prosthesis techniques
DE102009061008B4 (de) * 2009-03-20 2014-09-25 Retina Implant Ag Verwendung einer Testvorrichtung und Verfahren zum Test von Zellen, Zellkulturen und/oder organotypischen Zellverbänden
US20120083861A1 (en) 2010-10-04 2012-04-05 The General Hospital Corporation Selective activation of neurons by sinusoidal electric stimulation
KR101209357B1 (ko) * 2011-03-23 2012-12-06 서울대학교산학협력단 나노와이어 광 검출기를 이용한 인공 망막 시스템 및 그 제조 방법
WO2014190245A1 (fr) * 2013-05-24 2014-11-27 The General Hospital Corporation Système et procédé d'activation neuronale sélective à l'aide d'une stimulation électrique à haute fréquence

Also Published As

Publication number Publication date
IL261891A (en) 2018-10-31
CN109152919A (zh) 2019-01-04
WO2017162458A1 (fr) 2017-09-28
US20190022376A1 (en) 2019-01-24
DE102016105174A1 (de) 2017-09-21

Similar Documents

Publication Publication Date Title
DE102006021258B4 (de) Aktives subretinales Retina-Implantat
EP1960040B1 (fr) Insertion d'une prothese neurale au moyen de l'impedance et de la hauteur des electrodes
DE60030170T2 (de) Elektronisches körperimplantat und system zum künstlichen sehen
DE102007051848B4 (de) Vorrichtung zur Stimulation von Neuronenverbänden
DE102005017740A1 (de) Vorrichtung zur elektrischen Stimulation von biologischem Material
DE102016104913B4 (de) Vorrichtung zur effektiven, invasiven und amplitudenmodulierten Neurostimulation
DE102014014942A1 (de) Implantierbare Anordnung
DE102006047118B4 (de) Implantierbare Vorrichtung
EP3325089A1 (fr) Implant rétinien actif
EP2066401B1 (fr) Dispositif implantable
DE102007038160B4 (de) Vorrichtung zur Stimulation des Riechepithels
EP2943250B1 (fr) Dispositif destiné à la mise en contact électrique et/ou à l'électrostimulation d'un tissu biologique
DE19632705A1 (de) Vorrichtung zur Stimulation der Corpora Cavernosi Penis
Wong et al. Optical imaging of electrically evoked visual signals in cats: I. Responses to corneal and intravitreal electrical stimulation
Ren et al. Bionic vision: Current progress and future chanllege
EP3579917A1 (fr) Système d'implant doté d'une interface optique
Ferrandez et al. Development of a Cortical Visual Neuroprostheses for the Blind

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20180219

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20210223