Neuro-Optical Diagnostic System for Macular Degeneration

视网膜相关性黄斑变性（AMD）导致中心视力的进行性丧失，是导致视网膜病变的主要原因。 在发达国家是致盲的主要原因。AMD患者表现出延迟的暗适应（DA）恢复。 DA测试是FDA批准的用于诊断AMD的方法，其中闪光照明漂白杆和锥 光感受器和随后的恢复是视网膜代谢的应激反应的量度。那里 是一个未满足的需求，快速，实用，灵敏和客观的测试，将提供定量终点， 早期诊断和监测对新开发治疗的反应。视觉诱发电位（VEP） 产生的视觉刺激，提供了一个定量的客观测量的神经光学途径 以及不需要患者持续关注的视觉过程。NeuroFieldz开发了一种新的 一个名为NeuroDotVR的系统，将头皮电位和电场的高分辨率传感器与 智能手机供电的头戴式显示器，并在DA恢复期间客观地测量VEP。 在I期STTR项目1 R41 AG 057250 -01中，我们开发了黄斑DA的自定义刺激， 验证了正常对照组和确诊AMD患者的VEP测量结果，范围为 年龄从18岁到88岁。DA在4个视网膜位置（每只眼2个）同时测量， 进行总共持续约15分钟的测试。第一阶段提案的结果表明， DAVEP可以在忙碌的诊所中成功地对具有各种视觉水平的幼稚患者实施 测试结果是良好的，测试结果是良好的。所有第一阶段性能里程碑均已达到。在第二阶段 SBIR提案我们将进一步开发和验证DA-VEPF系统，以最终获得510（k）FDA批准。 具体目标1：开发DA-VEPF的额外测试多焦点刺激将进一步 DA-VEPF结果将与其他视觉生物标志物相关。目标1.1研究依从性 监测.目的1.2跨阈值刺激强度扫描与自适应挑战分支。具体目标二： DAVEP系统将在100名受试者的更大队列中进行验证， 早期和晚期AMD的明确诊断标准。符合Aim 2.1标准的多焦点自适应DAVEP AMD分期功能。目标2.2 DAVEP的测试-重新测试可靠性与AMD阶段的函数关系。目标2.3 DAVEP和暗适应恢复的行为估计的比较。目标2.4-高级信号 处理和分析算法开发。具体目标3：510（K）申请的支持性研究 在准备FDA 510（k）上市许可申请时，我们将研究：1）市场战略：客户 发现;报销概述;合作伙伴识别。2)510（k）申请的监管评估。 3)扩大生产战略。

Age-related macular degeneration (AMD) causes progressive loss of central vision and is the leading cause of blindness in the developed world. People with AMD manifest delayed dark adaptation (DA) recovery. DA tests are a FDA approved method for diagnosing AMD in which a flash illumination bleaches rod and cone photoreceptors and the subsequent recovery is a measure of the stress response of retinal metabolism. There is 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. NeuroFieldz has developed a new system called NeuroDotVR that combines a high-resolution sensor for scalp electric potentials and fields with a smartphone powered headmount display and measures VEP objectively during DA recovery. In the Phase I STTR project 1R41AG057250-01, we developed custom stimuli for macular DA and validated the VEP measurements in normal controls and patients with confirmed diagnosis of AMD, ranging in age from 18 to 88. DA was measured simultaneously in 4 retinal locations (2 per eye) in an easy-to- administer test lasting around 15 minutes in total. The results of the Phase I proposal establish that DAVEP can be successfully implemented in a busy clinic on naïve patients with various levels of visual impairment and the test is well tolerated. All Phase I performance milestones were met. In this Phase II SBIR proposal we will further develop and validate the DA-VEPF system toward eventual 510(k) FDA approval. The project aims are: Specific Aim 1: Develop additional tests of DA-VEPF Multi-focal stimuli will be further developed and the DA-VEPF results will be correlated with other visual biomarkers. Aim 1.1 Study Compliance Monitoring. Aim 1.2 Cross threshold stimulus intensity sweeps with adaptive challenge branch. Specific Aim 2: Validate in human studies The DAVEP system will be validated in a larger cohort of 100 subjects to establish definite diagnostic criteria for early and late stage AMD. Aim 2.1 Compliant Multi-Focal Adaptive DAVEP as a function of AMD stage. Aim 2.2 Test-Retest Reliability of DAVEP as a function of AMD stage. Aim 2.3 Comparison of DAVEP and Behavioral estimates of Dark Adaptation Recovery. Aim 2.4– Advanced Signal Processing and Analytical Algorithm Development. Specific Aim 3: Enabling studies for 510(K) application In preparation for an FDA 510(k) clearance to market application, we will research: 1) Market Strategy: Customer Discovery; Reimbursement Overview; Partner Identification. 2) Regulatory Assessment for 510(k) application. 3) Scale-up manufacturing strategy.