Preclinical investigation of electrical field shaping strategies for retinal prostheses

Abstract

Retinal prostheses are a promising technology aimed at restoring vision in people suffering severe retinal degenerative conditions such as retinitis pigmentosa (RP). Present-generation devices achieve this by electrically stimulating the residual neuronal population in the retina following degeneration in order to elicit the perception of light. At present, patients implanted with these devices are able to perceive multiple localised flashes of light, termed phosphenes, which are used to build up an artificial image of the patient's surroundings. However, present-generation retinal implants lack the spatial resolution to provide a suitable replacement for everyday visual tasks. While adequate for rudimentary tasks such as object recognition, motion detection, and pattern recognition, more complex tasks such as reading, facial recognition, and independent navigation are still not possible with modern prosthetic vision devices. Two major issues that affect retinal prostheses are: the large spread of electrical potential in the retina resulting in widespread activation of neurons, undesirable electrical field interaction and the elicitation of large phosphenes that patients find difficult to discriminate between; and that many devices are not able to elicit enough phosphenes to convey complex visual information to patients.

The studies presented in this thesis investigated the effectiveness of two multichannel electrical field shaping techniques: focused multipolar (FMP) stimulation and virtual electrode (VE) current steering. These techniques have shown considerable promise in studies conducted with one-dimensional neural prosthetic devices, such as cochlear and deep brain implants, as ways to restrict and `steer' electrical fields. In an effort to find new ways of improving spatial resolution, I have investigated whether these techniques can be adapted for use in a 2D retinal prosthesis. Using a normally-sighted cat model I have demonstrated that FMP stimulation is capable of restricting current spread in two dimensions and eliciting retinal and cortical response patterns with reduced spread compared with responses to the more conventional MP means of stimulation. I have also demonstrated that VE current steering between up to six electrodes can produce cortical activation patterns in predictable locations, with similar spread of neural activation as response patterns to physical electrode stimulation. By varying the proportions of charge applied to steering electrodes, it was also possible to shift the location of cortical activation in two dimensions in a predictable and intuitive fashion. To investigate the effectiveness of these techniques in a model more representative of patients, FMP stimulation and VE current steering were re-evaluated using a cat model of retinal degeneration. Unfortunately, many of the promising results from the normally-sighted cohort were not maintained when applied to degenerate retinae. While FMP stimulation still activated a localised population of retinal neurons, it was not found to elicit cortical response patterns with reduced spread compared to monopolar stimulation. The location of cortical response patterns elicited by VE stimulation were also found to be unpredictable. These results also show evidence of compressed retinotopy and increased spatial selectivity in the degenerate visual system, which significantly altered neural responses to electrical stimulation. These findings demonstrate that FMP stimulation and VE current steering, in their present form, may not be as effective in focusing and steering neural activation when applied to degenerate retinae. These results also provide a greater understanding of the differences between the responses of healthy and degenerate visual systems to electrical stimulation, which I hope will inform the further development and optimisation of these stimulation strategies.