Argus Ⅱ retinal prosthesis system:an update / 中华实验眼科杂志

Argus Ⅱ retinal prosthesis system (Argus Ⅱ;Second Sight Medical products,Sylmar,CA) is the first prosthetic retinal device approved for humanitarian use by both FDA in America and CE in Europe.It is a potential treatment for patients with end-stage outer retinal diseases.The system contains several parts,the camera first captures image and transfers it into electrical stimulating parameters conveying spatial-temporal information.The microelectrode epiretinal array then stimulate underlying bipolar cells and retinal ganglion cells.Patients present significant increases on levels of discrimination,target localization,motion detection and navigation.Possible adverse events include conjunctival erosion,hypotony and culture-negative presumed endophthalmitis.Future developments of the Argus Ⅱ system will not only comprise upgrading of image processing software and hardware,but also further disclosing retinal and visual signal processing mechanism.

Ayudas externas para mejorar la independencia en personas con discapacidad visual / External aids for improving the Independence of persons with visual impairment

En los últimos años se ha incrementado la investigación con respecto al desarrollo de ayudas que mejoren la independencia de los discapacitados visuales. El propósito de esta revisión es determinar la evidencia científica relacionada con ayudas externas para mejorar la independencia en personas con discapacidad visual severa o ceguera. Para efectuar el trabajo fueron consultadas las bases de datos de PubMed, Cochrane Database-Wiley Online Library, LILACS y Scielo, además de las publicaciones de la Organización Mundial de la Salud, el Instituto Nacional de Ciegos en Colombia, el Consejo Internacional de Oftalmología y los patrones preferidos de práctica en rehabilitación visual, de la Academia Americana de Oftalmología. Se incluyó un total de 43 artículos y documentos en los idiomas inglés, portugués y español para ser analizados. La mayoría de estos estudios fueron descriptivos, y no se encontraron ensayos controlados ni metanálisis. La tendencia observada es hacia ayudas tecnológicas con un diseño dirigido al usuario y cada vez más pequeñas, discretas, con múltiples funciones que comprenden sus actividades de la vida diaria(AU)

In the last few years, research on the development of aids to improve the independence of visually impaired people has increased. The objective of this review was to determine the scientific evidence related to external aids to improve the independence of persons with severe visual impairment or blindness. To carry out the study, PubMed, Cochrane Database-Wiley Online Library, LILACS and Scielo databases were consulted in addition to publications by the World Health Organization, National Institute of Blind People in Colombia, the International Council of Ophthalmology and the preferred patterns in visual rehabilitation practice of the American Academy of Ophthalmology. A total number of 43 articles and documents in English, Portuguese and Spanish were included to be analyzed. Most of the studies were descriptive ones and neither controlled assays nor meta-analysis were found. The observed tendency is the use of technological aids with a user-tailored design and increasingly small, discreet, having many functions that cover the daily life activity of those persons(AU)

The advantage of topographic prominence-adopted filter for the detection of short-latency spikes of retinal ganglion cells

Electrical stimulation through retinal prosthesis elicits both short and long-latency retinal ganglion cell (RGC) spikes. Because the short-latency RGC spike is usually obscured by electrical stimulus artifact, it is very important to isolate spike from stimulus artifact. Previously, we showed that topographic prominence (TP) discriminator based algorithm is valid and useful for artifact subtraction. In this study, we compared the performance of forward backward (FB) filter only vs. TP-adopted FB filter for artifact subtraction. From the extracted retinae of rd1 mice, we recorded RGC spikes with 8×8 multielectrode array (MEA). The recorded signals were classified into four groups by distances between the stimulation and recording electrodes on MEA (200-400, 400-600, 600-800, 800-1000 µm). Fifty cathodic phase-1(st) biphasic current pulses (duration 500 µs, intensity 5, 10, 20, 30, 40, 50, 60 µA) were applied at every 1 sec. We compared false positive error and false negative error in FB filter and TP-adopted FB filter. By implementing TP-adopted FB filter, short-latency spike can be detected better regarding sensitivity and specificity for detecting spikes regardless of the strength of stimulus and the distance between stimulus and recording electrodes.

Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration (rd1) mice

A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an 8x8 multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than 10 microA and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to 500 micros (30 microA), changing the intensities (or duration) from 2 to 60 microA (60 to 1000 micros). RGCs were classified as response-positive when PSTH showed multiple (3~4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.

Comparison of Retinal Ganglion Cell Responses to Different Voltage Stimulation Parameters in Normal and rd1 Mouse Retina / 의학물리

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Since retinal prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. Therefore, in this paper, we focused on retinal ganglion cell (RGC) responses to different voltage stimulation parameters and compared threshold charge densities in normal and rd1 mice. For this purpose, we used in vitro preparation for the retina of normal and rd1 mice on micro-electrode arrays. When the neural network of rd1 mouse retinas is stimulated with voltage-controlled pulses, RGCs in degenerated retina also respond to voltage amplitude or voltage duration modulation as well in wild-type RGCs. But the temporal pattern of RGCs response is very different; in wild-type RGCs, single peak within 100 ms appears while in RGCs in degenerated retina multiple peaks (~4 peaks) with ~10 Hz rhythm within 400 ms appear. The thresholds for electrical activation of RGCs are overall more elevated in rd1 mouse retinas compared to wild-type mouse retinas: The thresholds for activation of RGCs in rd1 mouse retinas were on average two times higher (70.50~99.87micronC/cm2 vs. 37.23~61.65micronC/cm2) in the experiment of voltage amplitude modulation and five times higher (120.5~170.6micronC/cm2 vs. 22.69~37.57micronC/cm2) in the experiment of voltage duration modulation than those in wild-type mouse retinas. This is compatible with the findings from human studies that the currents required for evoking visual percepts in RP patients is much higher than those needed in healthy individuals. These results will be used as a guideline for optimal stimulation parameters for upcoming Korean-type retinal prosthesis.

Accurate Representation of Light-intensity Information by the Neural Activities of Independently Firing Retinal Ganglion Cells

For successful restoration of visual function by a visual neural prosthesis such as retinal implant, electrical stimulation should evoke neural responses so that the information on visual input is properly represented. A stimulation strategy, which means a method for generating stimulation waveforms based on visual input, should be developed for this purpose. We proposed to use the decoding of visual input from retinal ganglion cell (RGC) responses for the evaluation of stimulus encoding strategy. This is based on the assumption that reliable encoding of visual information in RGC responses is required to enable successful visual perception. The main purpose of this study was to determine the influence of inter-dependence among stimulated RGCs activities on decoding accuracy. Light intensity variations were decoded from multiunit RGC spike trains using an optimal linear filter. More accurate decoding was possible when different types of RGCs were used together as input. Decoding accuracy was enhanced with independently firing RGCs compared to synchronously firing RGCs. This implies that stimulation of independently-firing RGCs and RGCs of different types may be beneficial for visual function restoration by retinal prosthesis.

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing - narrow correlation - was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. We suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.

Electrical Stimulation Parameters in Normal andDegenerate Rabbit Retina / 의학물리

Retinal prosthesis is regarded as the most feasible method for the blind caused by retinal diseases such as retinitis pigmentosa (RP) or age related macular degeneration (AMD). Recently Korean consortium launched for developing retinal prosthesis. One of the prerequisites for the success of retinal prosthesis is the optimization of the electrical stimuli applied through the prosthesis. Since electrical characteristics of degenerate retina are expected to differ from those of normal retina, we performed voltage stimulation experiment both in normal and degenerate retina to provide a guideline for the optimization of electrical stimulation for the upcoming prosthesis. After isolation of retina, retinal patch was attached with the ganglion cell side facing the surface of microelectrode arrays (MEA). 8x8 grid layout MEA (electrode diameter: 30micrometer, electrode spacing: 200micrometer, and impedance: 50 k omega at 1 kHz) was used to record in-vitro retinal ganglion cell activity. Mono-polar electrical stimulation was applied through one of the 60 MEA channel, and the remaining channels were used for recording. The electrical stimulus was a constant voltage, charge-balanced biphasic, anodic-first square wave pulse without interphase delay, and 50 trains of pulse was applied with a period of 2 sec. Different electrical stimuli were applied. First, pulse amplitude was varied (voltage: 0.5~3.0 V). Second, pulse duration was varied (100~1,200microns). Evoked responses were analyzed by PSTH from averaged data with 50 trials. Charge density was calculated with Ohm's and Coulomb's law. In normal retina, by varying the pulse amplitude from 0.5 to 3 V with fixed duration of 500 microns, the threshold level for reliable ganglion cell response was found at 1.5 V. The calculated threshold of charge density was 2.123 mC/cm2. By varying the pulse duration from 100 to 1,200microns with fixed amplitude of 2 V, the threshold level was found at 300microns. The calculated threhold of charge density was 1.698 mC/cm2. Even after the block of ON-pathway with L-(1)-2-amino-4-phosphonobutyric acid (APB), electrical stimulus evoked ganglion cell activities. In this APB-induced degenerate retina, by varying the pulse duration from 100 to 1200 microns with fixed voltage of 2 V, the threshold level was found at 300microns, which is the same with normal retina. More experiment with APB-induced degenerate retina is needed to make a clear comparison of threshold of charge density between normal and degenerate retina.

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.

Cortical Responses Evoked by the Light and Electricity in the Rabbit Retina

PURPOSE: By recording the electrically evoked potential (EEP) we tried to verify that focal electrical stimulation of retina sends a signal to the cortex that is similar to that elicited by light and also to investigate optimal stimulus parameters. METHODS: Five New Zealand white rabbits were placed under anesthesia. A tungsten bipolar stimulating electrode (diameter: 250 um) was placed on the vitreal surface of the retina. Cutaneous Ag/AgCl patch electrodes of VEP were used to record EEP. EEP was recorded at each stimulation. Focal visual evoked potentials (VEPs) were also recorded and compared to the focal EEP to ascertain cortical origin of the EEP, and similarities of the EEP to the VEP were determined. RESULTS: EEP recordings were elicited in 8 eyes. Current amplitudes which produced detectable responses ranged from 100 to 5000 micro A. In our best series, EEP amplitudes increased by 8 to 119 micro V in response to the current increasing from 100 to 1000 micro A. In comparing latencies of the EEP and focal VEP, the EEP latencies were 12~16 ms faster, which supports our EEP recording was done properly. CONCLUSIONS: EEPs obtained using VEP setting with adequate parameters of current duration and threshold level for the retinal implant showed that use of the EEP response is a good way to monitor the proper functioning of the retinal implant.