Age-related macular degeneration (AMD) causes progressive loss of central vision and is the leading cause of blindness in the developed world. A major challenge in the development of effective treatments for AMD is the lack of sensitive, practical visual function endpoints. People with AMD manifest delayed dark adaptation (DA) recovery, and DA tests are a FDA approved method for diagnosing AMD. Current DA tests measure psychophysical thresholds for the detection of visual stimuli following photobleaching to monitor the recovery of sensitivity over time. These tests typically last 20 minutes per eye, require sustained attention from the patient and dedicated light-proof test facilities, all of which are problematic for clinical testing. Rapid protocols address some of these issues, but test only the early stage of DA, test only a single retinal location and still require both eyes to be tested separately. There is therefore an unmet need for a rapid, practical, sensitive and objective test that will provide quantitative endpoints for early diagnosis and monitoring response to newly developed treatments. Visual evoked potentials (VEP) generated in response to visual stimuli, provide a quantitative objective measure of the neuro-optical pathways and visual processes that do not require sustained attention from the patient. Systematic use of this very attractive technique in the context of DA has been hampered by lack of easy- to-administer, affordable instrumentation. NeuroFieldz and Northeastern University have developed a new system called NeuroDotVR that combines a high-resolution sensor for scalp electric potentials and fields with a smartphone powered headset and have demonstrated superior sensitivity to visual responses to a variety of visual stimuli. Preliminary results are presented here with VEP responses under DA with healthy subjects. In this Phase I STTR project, we propose to optimize the NeuroDotVR product and to test the performance in patients. The project aims are: Specific Aim 1: Develop custom stimuli for Macular DA We will validate measurement approaches for photobleaches of the macula in healthy young eyes. VEPs will be measured with a scotopic flickering checkerboard stimulus that fills the macula. VEP Amplitude will be measured for a flickering checkerboard pattern of scotopic luminance contrast E1) binocularly and E2) dichoptically i.e. simultaneously and independently with a different temporal frequency in each eye for frequency tagging. We will estimate the time required for VEP amplitude and latencies to reach dark adapted levels as a function of temporal frequency. Specific Aim 2: Multi-focal Macular DA in AMD will validate dichoptic tests developed in Aims 1 and 2 in 10 patients with early stage AMD, 10 patients with intermediate stage AMD and 10 age matched controls. The multifocal stimuli will be divided into 16 locations (2 eyes * 2 eccentricities * 4 sectors) and DA times for each location will be compared with structural deficits in retinal fundus images.
Public Health Relevance Statement: PROJECT NARRATIVE TITLE: Neuro-Optical Diagnostic System for Macular Degeneration This project seeks to develop a new portable wireless system called NeuroDotVR that combines a sensor for measurement of scalp electric potentials and fields during recovery from dark adaptation using visual stimuli presented by a virtual reality headset powered by a smartphone, and to test them in patients with Age-related Macular Degeneration (AMD). NeuroDotVR will address an unmet need for a practical, sensitive test that will provide quantitative endpoints for early diagnosis and monitoring response to newly developed treatments for AMD.
Project Terms: Accident and Emergency department; Address; Affect; Age; Age related macular degeneration; aged; aging population; Algorithms; Ambulances; base; Behavioral; biological adaptation to stress; Blindness; Brain; Cellular Phone; Child; Clinic; Custom; Dark Adaptation; Darkness; Detection; Development; Devices; Diagnosis; Diagnostic; Early Diagnosis; effective therapy; electric field; Electrodes; Electroencephalography; encephalography; experience; Eye; FDA approved; Frequencies; Fundus; Gel; Hour; Image; instrumentation; Light; Lighting; Location; luminance; macula; Macular degeneration; Measurement; Measures; Metabolism; Methods; Monitor; multidisciplinary; nanostructured; Nanostructures; NGFRAP1 gene; operation; Ophthalmology; Optics; Paste substance; Pathway interactions; Patients; Pattern; Performance; performance tests; Phase; Photobleaching; portability; Preparation; Protocols documentation; Psychophysics; Recovery; research clinical testing; Resolution; response; Retinal; Retinal Cone; retinal rods; Scalp structure; Scientist; sensor; Skin; Small Business Technology Transfer Research; stereoscopic; Stimulus; sustained attention; System; Techniques; Testing; Time; trauma centers; Universities; Update; virtual reality; Vision; Visual; Visual Cortex; Visual evoked cortical potential; visual process; visual stimulus; Wireless Technology
