Neuro-Optical Diagnostic System for Macular Degeneration

老年性黄斑变性(AMD)导致进行性中央视力丧失，是主要的 在发达国家导致失明的原因。AMD患者表现出暗适应(DA)恢复延迟。 DA测试是FDA批准的诊断AMD的方法，在该方法中，闪光照射会使视杆和视锥细胞发生漂白 光感受器和随后的恢复是衡量视网膜新陈代谢应激反应的指标。那里 对快速、实用、灵敏和客观的测试的需求尚未得到满足，该测试将为 早期诊断和监测对新开发的治疗方法的反应。视觉诱发电位(VEP) 在对视觉刺激的反应中产生的，提供了神经-视觉通路的定量客观测量 以及不需要患者持续关注的视觉过程。NeuroFieldz已经开发出一种新的 一种名为NeuroDotVR的系统，它将高分辨率的头皮电位和电场传感器与 智能手机供电的头盔显示器，并在DA恢复期间客观测量VEP。 在第一阶段STTR项目1R41AG057250-01中，我们为黄斑DA和 验证了正常对照组和确诊为AMD的患者的VEP测量，范围为 年龄从18岁到88岁不等。在4个视网膜位置同时测量DA(每只眼2个)，在一个容易- 管理测试，总共持续约15分钟。第一阶段提案的结果确定 DAVEP可以在繁忙的诊所成功地应用于具有不同视觉水平的幼稚患者 损伤和测试的耐受性很好。达到了第一阶段的所有业绩里程碑。在此阶段II中 SBIR建议我们将进一步开发和验证DA-VEPF系统，以最终获得FDA的批准。 该项目的目标是：具体目标1：开发DA-VEPF多焦刺激的附加测试将进一步 DA-VEPF结果将与其他视觉生物标记物相关联。目标1.1研究合规性 监控。目的1.2采用自适应激发分支进行跨阈值刺激强度扫描。具体目标2： 在人体研究中验证DAEP系统将在100名受试者中进行验证，以建立 明确早期和晚期AMD的诊断标准。符合AIM 2.1标准的多焦点自适应DAVEP AMD分期的功能。目的2.2 AMD分期对DAVEP信度的重测。目标2.3 暗适应恢复的DAVEP和行为学估计的比较。目标2.4-高级信号 处理和分析算法开发。具体目标3：促进510(K)申请研究 为了准备FDA 510(K)批准上市应用，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)对510(K)申请进行监管评估。 3)扩大制造战略。

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.