High Performance Multimodal Adaptive Optics Retinal Imaging

描述（由申请人提供）：物理科学公司（PSI）已经成功完成了一项I期项目，开发一种多模态自适应光学（AO）视网膜成像仪，用于诊断视网膜疾病，包括青光眼、糖尿病视网膜病变（DR）、年龄相关性黄斑变性（AMD）和视网膜色素变性（RP）。该开发代表了有史以来第一个将AO校正扫描激光检眼镜（SLO）和扫描源傅立叶域光学相干断层扫描（SSOCT）成像模式结合在一个紧凑的临床原型平台上的高性能AO系统。SSOCT通道在15m波长下工作，以增加对绒毛膜毛细血管和脉络膜的穿透和可视化，这是DR和湿性AMD的主要疾病活动部位。该系统设计用于广泛的临床人群，具有双变形镜（DM）配置，允许同时进行低阶和高阶像差校正。该系统还包括一个用于初始筛选、目标识别和全局定位的宽视场线扫描检眼镜（LSO）；集成视网膜跟踪器（RT），用于在眼球转动时稳定SLO、OCT和LSO成像场；以及基于lcd的高分辨率固定目标，用于向受试者呈现刺激和其他视觉线索。该系统在有限数量的没有视网膜疾病的人类受试者中进行了测试，以进行性能优化和验证。该系统能够分辨和量化黄斑中心凹~0.5度（~100-150米）范围内的锥状光感受器，成像和描绘视网膜10层，并穿透到脉络膜深处来分辨目标。除了仪器硬件开发之外，还开发了分析算法，用于从临床成像会议中有效地提取信息，其功能包括自动图像配位，光感受器计数，条带和蒙太奇拼接以及分割。我们与匹兹堡大学医学中心（UPMC）眼科中心的眼科医生和研究人员合作，建议在II期继续进行仪器开发和全面临床试验。多模态AO仪器将被改进和增强用于临床操作，包括视网膜跟踪器和同步硬件的升级。此外，我们将为仪器配备一个压电驱动的参考镜，用于测量精细视网膜毛细血管的功率多普勒信号。该系统将安装在UPMC进行两阶段的临床试验，包括在无视网膜疾病的受试者中进行初步验证，以及在青光眼、DR、AMD和RP患者中进行测试。该研究将证明，多模态AO系统提供了目前任何其他商用成像仪都无法提供的结构和流量信息。如果成功，II期项目和随后的III期商业开发将为临床医生提供高分辨率、高性能的自适应光学成像，以帮助指导治疗、开发新药和改善患者的预后。

DESCRIPTION (provided by applicant): Physical Sciences Inc. (PSI) has successfully completed a Phase I program to develop a multimodal adaptive optics (AO) retinal imager for diagnosis of retinal diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinitis pigmentosa (RP). The development represents the first ever high performance AO system constructed that combines AO- corrected scanning laser ophthalmoscopy (SLO) and swept source Fourier domain optical coherence tomography (SSOCT) imaging modes in a single compact clinical prototype platform. The SSOCT channel operates at a wavelength of 1 5m for increased penetration and visualization of the choriocapillaris and choroid, sites of major disease activity for DR and wet AMD. The system is designed to operate on a broad clinical population with a dual deformable mirror (DM) configuration that allows simultaneous low- and high- order aberration correction. The system also includes a wide field line scanning ophthalmoscope (LSO) for initial screening, target identification, and global orientation; an integrated retinal tracker (RT) to stabilize the SLO, OCT, and LSO imaging fields in the presence of rotational eye motion; and a high-resolution LCD-based fixation target for presentation to the subject of stimuli and other visual cues. The system was tested in a limited number of human subjects without retinal disease for performance optimization and validation. The system was able to resolve and quantify cone photoreceptors across the macula to within ~0.5 deg (~100-150 5m) of the fovea, image and delineate ten retinal layers, and penetrate to resolve targets deep into the choroid. In addition to instrument hardware development, analysis algorithms were developed for efficient information extraction from clinical imaging sessions, with functionality including automated image registration, photoreceptor counting, strip and montage stitching, and segmentation. In collaboration with ophthalmologists and researchers at University of Pittsburgh Medical Center (UPMC) Eye Center, we propose to continue instrument development and full clinical testing in Phase II. The multimodal AO instrument will be refined and enhanced for clinical operation, including upgrades of the retinal tracker and synchronization hardware. In addition, we will outfit the instrument with a piezo-driven reference mirror for measurement of power Doppler signals from fine retinal capillaries. The system will be installed at UPMC for a two-stage clinical trial including initial validation in subjects without retinal disease and tests in subjects with glaucoma, DR, AMD, and RP. The study will demonstrate that the multimodal AO system provides structural and flow information not currently available from any other commercially- available imager. If successful, the Phase II program and subsequent Phase III commercial development will provide clinicians with high-resolution, high performance adaptive optics imaging to help guide therapies, develop new drugs, and improve patient outcomes. PUBLIC HEALTH RELEVANCE: By making high-resolution ocular access more widespread, the proposed high performance multimodal AO instrument will bring adaptive optics technology into use by a greater number of clinicians and scientists. These researchers will, in turn, use this tool to increase our understanding of vision and its disruption by disease and to measure tissue effects of new drugs and therapies.