H. Benav

Subretinal electronic chips allow blind patients to read letters and combine them to words

A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes (‘chip’), each with its own amplifier and local stimulation electrode. At the implants tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron–electrode interface. Visual scenes are projected naturally through the eyes lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.

Spatial Resolution and Perception of Patterns Mediated by a Subretinal 16-Electrode Array in Patients Blinded by Hereditary Retinal Dystrophies

PURPOSE The perception of 11 persons blinded by hereditary retinal degeneration elicited by a subretinally implanted 16-electrode array used for light-independent direct stimulation of the retina is described. This device is part of the Tübingen retina implant, which also employs a light-sensitive, multiphotodiode array (MPDA). The ability to reliably recognize complex spatial percepts was investigated. METHODS Eleven blind volunteers received implants and participated in standardized psychophysical tests investigating the size and shape of perceptions elicited by single-electrode activation, multiple-electrode activation, and activation of compound patterns such as simplified letters. RESULTS Visual percepts were elicited reliably in 8 of 11 patients. On single-electrode activation, percepts were generally described as round spots of light of distinguishable localization in the visual field. On activation of a pattern of electrodes, percepts matched that pattern when electrodes were activated sequentially. Patterns such as horizontal or vertical bars were identified reliably; the most recent participant was able to recognize simplified letters presented on the 16-electrode array. The smallest distance between sites of concurrent retinal stimulation still yielding discernible spots of light was assessed to be 280 μm, corresponding to a logMAR of 1.78. CONCLUSIONS Subretinal electric stimulation can yield reliable, predictable percepts. Patterned perception is feasible, enabling blind persons to recognize shapes and discriminate different letters. Stimulation paradigms must be optimized, to further increase spatial resolution, demanding a better understanding of physical and biological effects of single versus repetitive stimulation (ClinicalTrials.gov number, NCT00515814).

Restoration of useful vision up to letter recognition capabilities using subretinal microphotodiodes

Our group has developed a subretinal microphotodiode array for restoration of vision. In a clinical pilot study the array has been implanted in 11 patients suffering from photoreceptor degenerations. Here we present promising results from some of those patients where the retinal tissue above the chip was functional and the implant fulfilled its expected function. A spatial resolution of approximately 0.3 cycles/degree could be achieved with fine stripe patterns. In one subject where the implant had been placed directly under the macular region of the retina a visual acuity of 20/1000 could be measured. Artificially restored visual acuity of this quality has not been reported previously. Finally, we present images illustrating an approximation of how the visual perceptions might have appeared to the subjects, based on a mathematical model and patient reports.

Subretinal Microelectrode Arrays Allow Blind Retinitis Pigmentosa Patients to Recognize Letters and Combine them to Words

Eleven patients received subretinal implants, powered and controlled via a subdermal cable ending in a thin intraocular foil, placed transsclerally between the retinal pigment epithelium and the neuroretina. The tip of this foil carries two distinct arrays, a Multiphotodiode Array (MPDA) with 1500 electrodes, each electrode being controlled by an adjacent photodiode and an amplifier within a 3x3x0.1 mm chip, as well as a second array with 16 electrodes, for direct stimulation (DS). Subretinal multielectrode implants with currents close to recognition threshold (10 to 27 nC/electrode) produce retinotopically correct patterns that allow for the first time recognition of individual letters (8 cm high, viewed in appr. 62 cm distance) even at low luminance levels. Stripe patterns of moderate luminance can be resolved up to 0.35 cycles/deg via the subretinal chip. This clearly supports the feasibility of light sensitive subretinal multielectrode devices for restoration of useful visual percepts in blind patients.

Modeling the response of ON and OFF retinal bipolar cells during electric stimulation

Highlights • Biphasic stimuli with opposed polarity activate ON and OFF BP cells differently.• Synaptic [Ca]i reaches levels to initiate synaptic activity during stimulation.• Axonal length influences de- and hyperpolarization of ON and OFF BP cell compartments.

Subretinal Microelectrode Arrays Implanted Into Blind Retinitis Pigmentosa Patients Allow Recognition of Letters and Direction of Thin Stripes

Eleven patients have received subretinal implants, powered and controlled via a subdermal cable that enters the body retroauricularly and ends in a thin intraocular foil, placed transsclerally between the retinal pigment epithelium and the neuroretina. The tip of this foil carries two distinct arrays, a Multiphotodiode Array (MPDA) with 1500 electrodes, each electrode being controlled by an adjacent photodiode and an amplifier within a 3x3x0.1 mm chip, as well as a second array (1.2x1.2 mm) with 16 electrodes, for direct stimulation (DS) controlled via wires from outside. Safety of the approach has been investigated by means of angiography, OCT and fundus photography. The implant was well tolerated in all patients. Efficacy has been investigated in terms of threshold voltages to elicit phosphenes and the ability to perceive visual information mediated by the MPDA. Patients were tested for 4 weeks and spatial as well as temporal characteristics of repetitive multielectrode-stimulation were investigated. Letters were presented to the 3 most recent patients either by stimulating retinal cells in 10 ms steps via individual electrodes in a sequence patients had learned to write such letters or - via the light sensitive chip - by individual bright letters or stripe patterns steadily presented at a screen in 62 cm distance.

Investigating the Influence of 3D Cell Morphology on Neural Response During Electrical Stimulation

Neuronal compartment models are a basic and often used method to investigate the effect of electrical stim- ulation on the cell. As the outcome of the model heavily de- pends on the cells morphology and its position relative to the electrode, a realistic representation of the cell structure and its variations is of great importance. A method is pre- sented which allows the quick and easy creation of a three dimensional neuron morphology on the basis of a single two dimensional image. Basic properties of this morphology like local diameters, cell size or the amount of branching can easily be changed.

Vision restoration with implants in retinal degenerations

Up until now there has been no available treatment for diseases causing the permanent impairment of retinal photoreceptors. Currently the development of the retinal prostheses is the earliest to promise a result that can be implemented in the clinical treatment of these patients. Implants with different operating principles and in various stages of progress are presented in details, highlighting the characteristics, as well as the Hungarian aspects of the development. This survey intends to provide an overview on retinal prostheses, implantable in case of degenerative diseases of the retina, by reviewing and assessing the papers published in relevant journals and based on personal experience. Developments in microelectronics in recent years made it possible and proved to be feasible to replace the degenerated elements in the retina with electrical stimulation. Multiple comparable approaches are running simultaneously. Two types of these implants are directly stimulating the remaining living cells in the retina. Hitherto the finest resolution has been achieved with the subretinal implants. Although the epiretinal implant offer lower resolution, but requires shorter surgery for implantation. Retinal implants in certain retinal diseases are proved to be capable of generating vision-like experiences. A number of types of retinal implants can be expected to appear in clinical practice a few years after the successful conclusion of clinical trials.