Quantitative Evaluation of Electrical Stimulation Therapy for Eye Disease

Electrical stimulation therapy (EST) is an emerging treatment for degenerative diseases of the retina. There is great variety in EST protocol parameters (e.g.: electrode configuration, stimulus strength, waveform, treatment schedule) that have been reported by different labs in literature. Thus there is a need for a way to objectively compare the different protocols and to correlate the protocol parameters with treatment effects (e.g.: functional and histological measures of structure and function). Towards this end, the focus of this work was to develop and validate finite element (FE) models that provide spatial maps of current density distribution in retinal tissue afforded by different EST electrode configurations, and to evaluate possible functional effects of EST on retinal tissues via electroretinogram (ERG) analysis. The FE simulation environment creates a “level playing field” in which different protocol parameters can be evaluated. A base geometry of the rat head was developed in Solidworks and imported to ANSYS for FE electrostatic simulations. Measurements for validation and optimization of the model were taken from rat specimens undergoing EST. Three representative electrode configurations were applied to the base geometry for comparison of the current density distribution given by each: whole-eye electrical stimulation (WES), transcorneal electrical stimulation (TES) and subretinal electrical stimulation (SES). Similarly, simulations were carried out on a base geometry of the human head with representative electrode configurations applied. Spatial profiles of current density from the different electrode configurations were plotted for comparison. The results show distinct current density distribution profiles afforded by the different electrode configurations. Notably, the distribution from the SES configuration in the rat model appears to be affected by the altered conductivity approximation of a degenerated retina, while distributions from the TES and WES configurations remained unchanged. Also noteworthy is the effect of changing the position of the reference electrode in the human model, although there is a lack of validation data from human subjects to support generalized claims. Analysis of ERG waveforms was conducted on data collected in the Hetling lab at the University of Illinois at Chicago as well as data collected at the Pardue lab in the Center for Visual and Neurocognitive Rehabilitation, VA Medical Center, Atlanta. Trends in a-wave amplitude, b-wave amplitude, half-saturation (I1/2) and amplification (α) between treated and control groups of P23H rats are reported, yielding insight into functional preservation in the retina when exposed to EST, despite a lack of structural preservation in the photoreceptor layer. Further analysis on these rats undergoing EST is reported elsewhere. The methods demonstrated herein provide a means for objective, quantitative prediction and comparison of current density distribution in subjects undergoing EST in existing and future protocols. These methods may inform interpretation of the effects of existing EST protocols and the design of future clinical protocols.