Alex Harscher

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).

A CMOS Chip With Active Pixel Array and Specific Test Features for Subretinal Implantation

This paper presents a CMOS imager chip that is aimed at subretinal implantation for partially restoring human vision. It has low supply voltage (plusmn 2 V) and all DC free terminals for long life wired operation. Stimulation voltage is increased to approximately 4 Vpp by low voltage drop design. 40 x 40 pixel cells including light sensors, amplifiers, control logic and electrode drivers are addressed sequentially to improve power consumption and spatial resolution of perception. Pad count is limited to 6, which requires a specific test procedure. The 3 x 3 mm2 design is fabricated in a 0.35 mum CMOS technology optimized for optical performance.

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.

Design and Performance of an improved active subretinal chip

The aim of the subretinal implant is to restore visual perception in blind patients suffering from retinitis pigmentosa (RP) and - at a later stage - age-related macular degeneration (AMD). Electrical stimulation of the remaining retinal neurons can restore meaningful visual perceptions [1, 2]. Our retina implant, consisting of a light sensitive CMOS chip (1,500 pixels) and 16 separate direct stimulation electrodes, is presently being tested successfully in a clinical pilot study with 12 patients. A detailed analysis of the data obtained sofar led to a redesign of the CMOS chip [4]. Results of the technical characteristics of this next generation retina chip are presented here. The chip was designed in cooperation with the Institute of Microelectronics at the University of Ulm. Tests in vitro show that the chip performs according to its specifications. Implants with an inductively coupled power supply equipped with the novel chip are in production and will soon be ready for extensive testing in vivo.