A Multi-Domain Continuum Model of Electrical Stimulation of Healthy and Degenerate Retina

Abstract

Visual neuroprostheses aim to restore vision to patients suffering from degenerative retinal diseases such as retinitis pigmentosa and age-related macular degeneration. Development of visual implants faces a great number of challenges in both device design and stimulation strategy. Computational modelling is a powerful tool for exploring and testing new visual prostheses design and stimulation strategies. In this thesis, we have proposed and validated a new version of the classical cable equation valid for any fibre morphology, electrode configuration, or non-uniformity in ion channel expression, implemented using a finite element approach. Moreover, we developed the first continuum multi-domain model of retinal electrical stimulation to represent all main retinal ganglion cell (RGC) compartments. The continuum model was validated against discrete morphologicallyrealistic OFF and ON RGC models as well as RGC excitation thresholds reported in recently published in vitro experimental studies using intra- and extra-cellular electrical stimulation. The continuum model reproduced the same results as that of the discrete model and in vitro experimental studies. Furthermore, the first degenerate model of retinal electrical stimulation accounting for observed changes occurring in the whole retina was developed, using a detailed model of electrical stimulation of OFF and ON RGCs. Interestingly, the model predicted that suprachoroidal stimulation of the degenerate retina exhibited increased current thresholds, mainly due to the presence of the glial scar layer. In contrast, epiretinal stimulation thresholds were almost similar for both healthy and degenerate models, implying epiretinal prostheses can bypass the influence of the glial scar layer. Various stimulation strategies were examined for both healthy and degenerate retinal models. No significant difference among the three return electrode configurations (monopolar, quasi-monopolar and hexapolar) was found when the distance between electrodes and RGCs was less than the electrode diameter. Electrode spacing was the significant factor underlying increased current thresholds, where electrode size had a marginal impact among all three return electrode configurations. Stimulus pulse polarities and durations were found to have a significant impact on the localisation of evoked phosphenes. Moreover, virtual electrodes could be elicited by using an appropriate time shift between two stimulus waveforms applied to the active electrodes.