Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007

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Figure 14.8. (a) Concept of protruding electrodes on the sub-retinal array penetrating deep into the retina after migration of the retinal cells into the empty spaces between the pillars. Penetration depth is set by the length of the pillars, which are insulated at the sides and exposed at the top. (b) Lithographically fabricated array of pillars of 10 m in diameter and 70 m in height having pillar spacing varying between 20 and 60 m (center-to-center) on various parts of the implant. (c) Lithographically fabricated 10- m- wide pillars penetrating into the inner nuclear layer of the RCS rat retina 15 days after the implantation. Horizontal dark lines between the pillars are histological artifacts due to folding.

the stimulating signal in each pixel by projecting light from the goggles-mounted LCD display onto a retinal implant having an array of powered photodiodes, as diagrammatically shown in Figure 14.9. An image from the small video camera located on the patient’s goggles is processed using a portable microcomputer. The processed image is displayed on the LCD micro-display similar to those used for “virtual reality” imaging systems (medical, military, etc.). The LCD display will emit pulsed near-infrared (IR) light (800–900 nm). The IR image

Figure 14.9. Diagram of the prosthetic system including video camera, image processing unit, and IR image projection from the goggles display onto the retina. Part of the image which is projected onto retinal chip activates its photo-sensitive stimulating pixels using inductively–coupled radiofrequency–driven pulsed power supply.

from the display is reflected from the transparent goggles and projected onto the retina using natural optical properties of the eye, as shown in Figure 14.9. The projected IR image is thus superimposed onto a normal image of the world observed through the transparent goggles. The retinal chip has an array of photosensitive elements converting the pulsed IR light into stimulating current in each pixel using an intraocular pulsed bi-phasic power supply, as described below. Advantages of this system as compared to current approaches to visual prosthesis include the following:

–The video display projects an image corresponding to the visual field of about 30 , which is much larger than the retinal chip (about 10 ). With this system,

the patient can use his natural eye movements in order to observe the larger field of view, rather than scanning it by moving his head-mounted video camera.

–Optical transmission of information from the LCD screen to all the pixels in the chip is conducted simultaneously, i.e. pixels are activated in a parallel fashion, and there is no need for serial decoding in the implant multiplexer, as it is done for the single emitter–receiver links (either optical [38] or radio frequency [5, 6]).

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–The IR video display on the goggles can emit as much power as the eye can thermally tolerate thus providing a robust signal to each pixel at any level of ambient illumination.

–The implant-stimulated vision is provided simultaneously with the residual natural vision in the areas outside the retinal implant. The infrared projected image is not detected by photoreceptors. Conversely, the implant’s response to natural visible light in the eye is negligible compared to the bright and pulsed infrared image.

–Intensity, duration, and repetition rate of the stimulating signal produced by the retinal chip can be controlled by the intensity, duration, and repetition rate of the light-emitting pixels in the LCD screen. These parameters can be adjusted without need for any changes in the retinal chip itself. This feature provides flexibility in optimization of the stimulation parameters and image-processing algorithm, which might have to be adjusted for each patient.

–This projection system can be used for both epiretinal and subretinal implants.

As described above, the stimulation current for an electrode of 10 m in diameter is on the order of 2 A. The photodiode converts photons into electric current with efficiency of up to 0.6 A/W, thus 3 4 W of light power will be required for activation of one pixel. If light pulses are applied for 0.5 ms at 25 Hz, the average power will be 42 nW/pixel. With 18,000 pixels on the chip, the total light power irradiating an implant will be 0.75 mW.

The LCD screens used in video goggles emit light into a wide angle, and only a small fraction of it (typically <1%) reaches the retina, while most of it is absorbed by the sclera and iris. In addition, only a small part of the retina (about 5%) is covered by an implant. To provide 1 mW of light on a 3 mm retinal implant, the LCD goggles should in total emit about 2 W of light power! This is certainly not practical.

This problem can be resolved by addressing both aspects of the loss of light:

(1) providing a collimated illumination, and (2) activating only a small part of the screen – that which is projected onto the implant, position of which will be constantly monitored with a tracking system. The pulsed illumination for the implant will be provided by the near-IR LED array or laser diode illuminating the LCD with collimated beam. A condenser lens directs the main axis of the diodes into the center of the eyeball. Assuming no magnification between the screen

and the retina, the diameter of the light spot on the pupil will be D = dchip + L, where dchip is the implant size, = 8 is the divergence of the LED beam, and L = 17 mm is the distance between the implant and the pupil. With these

assumptions the spot of light on iris can be as small as 5.3 mm in diameter. To provide for a eye scanning range of 30 , a spot size on the iris should be actually a little larger – about 9 mm in diameter, thus with the pupil of 3 mm in diameter, 10% of light will be transmitted into the eye, thus only 10 mW of power would be required from the LCD screen.

Tracking System

Since the eye is frequently moving, the proper activation of the display requires information about position of the retinal chip at each moment. With the angular size of the retinal implant being 10 1 of precision in tracking will suffice for the purpose of limiting the amount of IR light on the retina by emitting only from a part of the display which is projected on the implant. Such precision can be provided with one of the standard pupil tracking systems, which are capable of detecting the direction of gaze with accuracy of up to 0 25 .

For a more advanced image processing the pixel-specific adjustments might be required, which requires a significantly more precise link between the display and the implant. To be able to address a specific pixel on the moving implant, precision of tracking should not exceed the pixel size (20 m, or 0 06 ). During fixation, the human eye drifts at an average angular velocity of 0.5 deg/s, up to 2 deg/s [39]. Such precision and tracking rate can be achieved with retinal tracking [40]. However, during saccades, large ballistic movements, the eye can move with a velocity of hundreds of degrees per second, and tracking most probably will be lost at these moments. On the other hand, normal visual perceptions greatly decrease during saccades, especially sensitivity to motion, so real-time image processing will not be required at these rates.

The retinal tracking system can monitor positions of a few reference points on the retinal implant. The reference points reflect (or emit) light back through the pupil and are imaged onto the tracking array that is positioned in the plane conjugated to the LCD display. For tracking of the location and the torsional orientation of the retinal chip only 2 reference points on its surface should be sufficient. More reference points may provide higher reliability and precision in localization of the chip. Reference points on the implant can be made as back-reflectors, for example, in the shape of 3-sided pyramidal indentations with highly reflective walls. They also may be made as small LEDs emitting a wavelength or temporal pattern different from that emitted by the image display. This will allow for discrimination between the emission by the reference points and the scattering from elsewhere in the eye.

Optoelectronic Implant Design

As described above, proximity of retinal cells in the inner nuclear layer to the stimulating electrodes can be achieved by promoting cellular migration into the sub-retinal implant. One possible design of a sub-retinal photosensitive stimulating array that takes advantage of this effect is shown in Figures. 14.7 and 14.8. A wafer of about 15–25 m in thickness is divided into separate photosensitive pixels similarly to a CCD array. Each pixel is a biased photodiode which converts local light intensity into bi-phasic charge-balanced pulses using a commonbiphasic power line. Current in the negative phase of the waveform is proportional to the light intensity. Current in the positive phase passes through the diodes freely and provides the charge balance compensation for the electrodes. In experiments with such circuits, we verified preservation of the charge balance on Pt

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electrodes with precision better than 0.01% independently of the light intensity in individual pixels. The stimulating bi-phasic pulse conducted through the photodiodes is applied to either the inner electrode in the cavity (1) or to the pillar electrode exposed at its tip (1), while the return electrode (2) is common to all pixels. The current from the inner electrode in each chamber is concentrated inside the aperture and thus the cells located near this bottleneck will be affected by electric field the most. The stimulation zone can be extended up and around the aperture by positioning the return electrode (2) away from the edge of the aperture.

As shown in Figure 14.3, the optoelectronic prosthesis having 18,000 pixels with electrodes of 10 m in diameter can consume about 0.2 mW of power if the target cells are located within 20 m from the array. This power can be provided by a pulse bi-phasic voltage generator driven by the inductive RF transmission of energy from the coil located on the goggles into a coil located under the conjuctiva or inside the eye [41]. Power supply will provide positive voltage between the pulses and the negative voltage during the light pulse, as diagrammatically shown in Figure 14.9.

Location-Dependent Image Processing

The central part of the macula (fovea) does not contain bipolar and ganglion cells. Photoreceptors in this area radiate their synaptic connections outside the fovea (Henle’s fibers), to a distance of about 0.5 mm in diameter. Thus if the retinal chip covers the macula, the image should be processed so that stimuli are delivered to the bipolar or ganglion cells outside the foveola. This means that an image projected onto the retinal stimulating array should have a black spot in the foveola (since there are no cells to stimulate in that area), and the rest of the macular area should be stretched in a radial pattern matching the retinal organization in the macula. The fact that retinal architecture is non-uniform around the center of the macula necessitates image processing that depends on position of the foveola relative to the projected image, i.e. it depends on direction of gaze.

There are several additional reasons necessitating the position-sensitive image processing for the visual chip controlled by the optical projection system:

–Various pixels in the array may have different impedances (due to the tissue growth or electrode contamination) or different distances from the cells and thus may require different pulse intensity.

–The retina has a complex system of image processing involving intertwined patterns of “ON” and “OFF” cells with large receptive fields having centersurround organization. For correct transmission of the image there might be a need for the stimulation pattern matching this cellular organization. In addition, there might be a need for temporal variation of the stimulation of the neighboring pixels [42]. (We must state, however, that many visual neurons have rectified responses, reacting similarly to either sign, and thus a number of aspects of visual processing might not be substantially affected.

For example, many ganglion cells are of the “ON-OFF” type, responding to either increases or decreases in light intensity. Additionally, in the retinal pathway that distinguishes moving objects from background motion, signals are rectified, and exchanging black for white does not change the firing patterns of object motion–sensitive retinal ganglion cells [43]. Adjustment of the image-processing algorithm for humans would be performed based on communication with the patient [44].

Summary. (a) High resolution in retinal stimulation cannot be achieved unless very close proximity (on the order of cellular size) between the electrodes and the target cells will be established along the whole interface of the implant with the retina, (b) For normal visual perception, the image should not be dissociated from the eye movements, and (c) The image processing between the camera and the implant should depend on the implant location, i.e. direction of gaze. The system described in this article includes: (1) an optically controlled implant enabling delivery of visual information related to the natural eye movements,

(2) position-sensitive image processing, and (3) techniques for bringing retinal neurons into required proximity with stimulus elements.

Acknowledgments. Authors would like to thank Professor Michael Mirkin from Queens College at CUNY for consultation on issues of electrochemistry and Professor Stephen Baccus from the Department of Neurobiology at Stanford for discussions on issues of image processing. Authors also would like to thank Yev Freyvert (UC Berkeley) for his help with fabrication and assembly of the implants.

Funding was provided in part by the Medical FEL program (Air Force Office of Scientific Research) and by VISX Corp.

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