Advanced CLAD PERG system with minimal patient preparation for clinical settings (Phase II)

Abstract: Glaucoma is one of a number of optic nerve diseases which lead to retinal ganglion cells (RGC) degeneration, ultimately manifesting in a functional loss of vision if left untreated. There exist a number of therapeutic approaches to treat these conditions, but there are currently no clinical methods to detect the onset of RGC dysfunction. The Pattern Electroretinogram (PERG) is the only established tool to monitor RGC health in vivo in humans and experimental models of optic nerve diseases. The monitoring of PERG responses can potentially provide earlier detection of degenerative retinal disorders such as glaucoma, allowing for treatment paradigms to be initiated before irreversible functional vision loss has occurred. A critical barrier to the widespread adoption of PERG for research and clinical use involves suboptimal characteristics of conventionally available displays for eliciting visual responses. The goal of the proposed project is to produce commercially available device for use in both vision research and clinical applications, which is not only more compact, faster, cheaper and more user‐friendly, but also provides a higher quality of information through innovative display technology and processing techniques. As part of our Phase I efforts, we developed a miniaturized PERG visual display unit based on variable polarization. Additionally, we used the CLAD deconvolution technique to extract additional clinical information from the PERG response. Recording data from both glaucoma suspects and age matched controls, the CLAD extracted data was more significantly different between the two populations when compared to conventional techniques. Additionally, ROC curves generated from the CLAD data had higher AUC values than the conventional techniques (0.897 using CLAD, versus 0.74 and 0.683 for conventional transient and steady state PERG). During Phase II, the following specific aims will be pursued: 1) Refining the next generation PERG stimulator for humans. We will refine the prototype developed in the phase I effort into a head mounted, near eye display configuration. We will incorporate additional functionality, such as active fixation and pupil size monitoring and a disposable dry electrode interface (based on Phase I effort) which will minimize patient preparation and increase throughput and remove the need for sanitizing device between subjects. 2) Expanding CLAD in Glaucoma. As part of our phase I effort, we showed that the CLAD technique has the potential to increase the clinical utility of the well establish, but underutilized PERG response. In our Phase II effort, we will expand testing in glaucoma suspects, looking at the effects of temporal presentation rate, and the dynamic adaptation of the PERG response. Research has shown that both of these factors are affected in patients with retinal dysfunction. Looking at these additional applications of the CLAD analysis techniques in a larger patient pool will further expand on the work done in the Phase I effort and continue to expand on the clinical utility of the PERG response.