Nicholas C. Sinclair

First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis

Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576

Factors affecting perceptual thresholds in a suprachoroidal retinal prosthesis.

PURPOSE The suprachoroidal location for a retinal prosthesis provides advantages over other locations in terms of a simplified surgical procedure and a potentially more stable electrode-neural interface. The aim of this study was to assess the factors affecting perceptual thresholds, and to optimize stimulus parameters to achieve the lowest thresholds in patients implanted with a suprachoroidal retinal prosthesis. METHODS Three patients with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal array. Perceptual thresholds measured on individual electrodes were analyzed as a function of stimulus (return configuration, pulse polarity, pulse width, interphase gap, and rate), electrode (area and number of ganged electrodes), and clinical (retinal thickness and electrode-retina distance) parameters. RESULTS A total of 92.8% of 904 measurements made up to 680 days post implantation yielded thresholds (range, 44-436 nanocoulombs [nC]) below the safe charge limit. Thresholds were found to vary between individuals and to depend significantly on electrode-retina distance, negligibly on retinal thickness, and not on electrode area or the number of ganged electrodes. Lowest thresholds were achieved when using a monopolar return, anodic-first polarity, short pulse widths (100 μs) combined with long interphase gaps (500 μs), and high stimulation rates (≥400 pulses per second [pps]). CONCLUSIONS With suprachoroidal stimulation, anodic-first pulses with a monopolar return are most efficacious. To enable high rates, an appropriate combination of pulse width and interphase gap must be chosen to ensure low thresholds and electrode voltages. Electrode-retina distance needs to be monitored carefully owing to its influence on thresholds. These results inform implantable stimulator specifications for a suprachoroidal retinal prosthesis. (ClinicalTrials.gov number, NCT01603576.).

Vision function testing for a suprachoroidal retinal prosthesis: effects of image filtering

OBJECTIVE One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results. APPROACH Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off. MAIN RESULTS Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP ([Formula: see text]) or with system off ([Formula: see text]). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance ([Formula: see text]) compared to WV, scrambled and system off on the grating acuity task. SIGNIFICANCE Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01503576.

neuroBi: A Highly Configurable Neurostimulator for a Retinal Prosthesis and Other Applications

To evaluate the efficacy of a suprachoroidal retinal prosthesis, a highly configurable external neurostimulator is required. In order to meet functional and safety specifications, it was necessary to develop a custom device. A system is presented which can deliver charge-balanced, constant-current biphasic pulses, with widely adjustable parameters, to arbitrary configurations of output electrodes. This system is shown to be effective in eliciting visual percepts in a patient with approximately 20 years of light perception vision only due to retinitis pigmentosa, using an electrode array implanted in the suprachoroidal space of the eye. The flexibility of the system also makes it suitable for use in a number of other emerging clinical neurostimulation applications, including epileptic seizure suppression and closed-loop deep brain stimulation. Clinical trial registration number NCT01603576 (www.clinicaltrials.gov).

Determining the Contribution of Retinotopic Discrimination to Localization Performance With a Suprachoroidal Retinal Prosthesis

Purpose With a retinal prosthesis connected to a head-mounted camera, subjects can perform low vision tasks using a combination of electrode discrimination and head-directed localization. The objective of the present study was to investigate the contribution of retinotopic electrode discrimination (perception corresponding to the arrangement of the implanted electrodes with respect to their position beneath the retina) to visual performance for three recipients of a 24-channel suprachoroidal retinal implant. Proficiency in retinotopic discrimination may allow good performance with smaller head movements, and identification of this ability would be useful for targeted rehabilitation. Methods Three participants with retinitis pigmentosa performed localization and grating acuity assessments using a suprachoroidal retinal prosthesis. We compared retinotopic and nonretinotopic electrode mapping and hypothesized that participants with measurable acuity in a normal retinotopic condition would be negatively impacted by the nonretinotopic condition. We also expected that participants without measurable acuity would preferentially use head movement over retinotopic information. Results Only one participant was able to complete the grating acuity task. In the localization task, this participant exhibited significantly greater head movements and significantly lower localization scores when using the nonretinotopic electrode mapping. There was no significant difference in localization performance or head movement for the remaining two subjects when comparing retinotopic to nonretinotopic electrode mapping. Conclusions Successful discrimination of retinotopic information is possible with a suprachoroidal retinal prosthesis. Head movement behavior during a localization task can be modified using a nonretinotopic mapping. Behavioral comparisons using retinotopic and nonretinotopic electrode mapping may be able to highlight deficiencies in retinotopic discrimination, with a view to address these deficiencies in a rehabilitation environment. (ClinicalTrials.gov number, NCT01603576).

Identification of Characters and Localization of Images Using Direct Multiple-Electrode Stimulation With a Suprachoroidal Retinal Prosthesis

Purpose Retinal prostheses provide vision to blind patients by eliciting phosphenes through electrical stimulation. This study explored whether character identification and image localization could be achieved through direct multiple-electrode stimulation with a suprachoroidal retinal prosthesis. Methods Two of three retinitis pigmentosa patients implanted with a suprachoroidal electrode array were tested on three psychophysical tasks. Electrode patterns were stimulated to elicit perception of simple characters, following which percept localization was tested using either static or dynamic images. Eye tracking was used to assess the association between accuracy and eye movements. Results In the character identification task, accuracy ranged from 2.7% to 93.3%, depending on the patient and character. In the static image localization task, accuracy decreased from near perfect to <20% with decreasing contrast (patient 1). Patient 2 scored up to 70% at 100% contrast. In the dynamic image localization task, patient 1 recognized the trajectory of the image up to speeds of 64 deg/s, whereas patient 2 scored just above chance. The degree of eye movement in both patients was related to accuracy and, to some extent, stimulus direction. Conclusions The ability to identify characters and localize percepts demonstrates the capacity of the suprachoroidal device to provide meaningful information to blind patients. The variation in scores across all tasks highlights the importance of using spatial cues from phosphenes, which becomes more difficult at low contrast. The use of spatial information from multiple electrodes and eye-movement compensation is expected to improve performance outcomes during real-world prosthesis use in a camera-based system. (ClinicalTrials.gov number, NCT01603576.).

Subthalamic nucleus deep brain stimulation evokes resonant neural activity.

Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target‐specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large‐amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027–1031