Nicholas L. Opie

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

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

Development of a surgical procedure for implantation of a prototype suprachoroidal retinal prosthesis

Current surgical techniques for retinal prosthetic implantation require long and complicated surgery, which can increase the risk of complications and adverse outcomes.

Heating of the Eye by a Retinal Prosthesis: Modeling, Cadaver and In Vivo Study

In order to develop retinal implants with a large number of electrodes, it is necessary to ensure that they do not cause damage to the neural tissue by the heat that the electrical circuits generate. Knowledge of the amount of power that induces thermal damage will assist in development of power budgets for implants, which has a significant effect upon the design of the prostheses circuitry. In this study, temperatures were measured at multiple locations on the retina while the retina was heated in cadaver and in vivo preparations using a variety of prosthesis implantation sites. A finite element thermal model of the cat eye was also created and validated by the cadaver and in vivo tests, allowing for a much larger spectrum of thermal influences to be evaluated without additional animal experimentation. To ensure that retinal tissue temperatures are not increased by more than 2 °C, a 5 mm × 5 mm, suprachoroidally implanted heating element must not dissipate more than 135 mW (5.4 mW/mm2).

Retinal prosthesis safety: alterations in microglia morphology due to thermal damage and retinal implant contact.

PURPOSE In order to develop retinal implants with a large number of electrodes, it is necessary to ensure that they do not cause damage to the neural tissue by the heat that the electrical circuits generate. Knowledge about the threshold of the amount of power that induces damage will assist in developing power budgets for retinal implants. METHODS Heat-induced retinal damage was evaluated by measuring changes in the morphology of the resident immune cells, the microglia, which are the first cells to respond to retinal trauma. Microglial soma and arbor areas were assessed in rat retinal tissues in vitro to determine the effects of increasing temperatures, implant contact, and heating and implant contact combined. RESULTS In response to increasing incubation temperatures (no implant), microglial somas enlarged and arbor areas retracted, indicative of retinal stress. Thermal damage thresholds, defined as a significant change in microglial morphology from that observed at the upper limit of normal body temperature, occurred at a temperature of 38.7 °C. Implant contact, induced when a passive implant was placed on the retina, also caused similar morphological alterations in microglia, indicating retinal damage. Heated-implant contact exacerbated the effects of temperature alone but still resulted in a thermal damage threshold of 38.7 °C, the same as with heating alone. CONCLUSIONS Our conservative recommendations are that implanted retinal electronics keep power dissipations to less than 19 mW/mm(2) to stay below the microglial thermal damage threshold (2.1 °C) and to comply with international standards for implantable devices (2 °C).

A retinal neuroprosthesis design based on simultaneous current injection

We present an epiretinal neuroprosthesis design based on a hexagonally-latticed 98 electrode array and the capacity to multiplex up to 14 simultaneous current sources. The digital and analogue electronics required to perform this function and how this would be incorporated into an application specific integrated circuit (ASIC) are described. Simulation data and data from saline bath testing of a platinum/silicone electrode array (and associated driving electronics) are presented. Simulations were performed using a 2D computational model solved using a custom collocation method. The guarding affect of the hexagonal array is investigated and shown in simple simulations to be an approach worthy of further investigation.

The evolution of endovascular electroencephalography: historical perspective and future applications

Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings. The technical progress in device technology over time and the development of the ability to record chronic intravenous EEG from electrode arrays is described. Future applications for the use of endovascular EEG in the preoperative and operative management of epilepsy surgery are then discussed, followed by the possibility of the techniques future application in minimally invasive operative approaches to DBS and BMI.

Thermal heating of a retinal prosthesis: Thermal model and in-vitro study

In order to develop retinal implants with a large number of electrodes, it is necessary to ensure that they do not cause damage to the neural tissue by the heat that the electrical circuits generate. Knowledge about the threshold of the amount of power that induces thermal damage will greatly assist in development of power budgets for implants, which has a significant effect upon the design of implant circuitry. In this study, we developed and tested in-vitro equipment that can dissipate thermal energy in current prosthesis implantation sites while simultaneously measuring and recording temperature distributions at multiple locations along the retinal tissue. A finite element thermal model of the feline eye was also created and validated by the in-vitro tests allowing for a much larger spectrum of thermal influences to be evaluated without the additional cost of animal sacrifice.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution

&NA; Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T‐fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal‐to‐noise ratio (SNR) losses due to decreased net magnetization per voxel and T1‐relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI‐based BCI simulations. We compared temporal signal‐to‐noise ratio (tSNR), observed percent signal change (%&Dgr;S), volumes of significant activation, Z‐scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle‐tapping task. Our results revealed an average increase of 22% in %&Dgr;S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5 mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z‐scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500 ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor‐network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T‐fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs. Graphical abstract Figure. No caption available. HighlightsObserved BOLD contrast increases with shorter TR only at high spatial resolution.Decoding performance increases with shorter TR only at high spatial resolution.These occur despite the decrease in tSNR.Faster TRs reduce physiological noise, undersampling effect and increase SNR efficiency.Higher temporal resolution improves BOLD sensitivity, only at high spatial resolution.

Development of a Magnetic Attachment Method for Bionic Eye Applications

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.