Compact Line Scanning Adaptive Optics Retinal Imager

描述（由申请人提供）：物理科学公司（PSI）已经成功完成了一期项目，展示了将自适应光学（AO）集成到线扫描激光检眼镜（LSLO）中的可行性。台式AO-LSLO仪器显著降低了研究AOSLOs的尺寸、复杂性和成本，目的是将自适应光学成像更快地推向常规临床应用。AO-LSLO产生高分辨率的视网膜图像，只有一个移动部件，大大减少了仪器占地面积和光学元件的数量。AO-LSLO具有中等视场（5.5度），允许更快速有效地获得黄斑或其他目标的蒙太奇。在初步的人类受试者研究中，光感受器可以被分辨和计数到距中央凹0.5毫米的范围内。光感受器计数与先前报道的组织学密切匹配。围绕中央凹无血管区周围的毛细血管以及在其中流动的细胞都可以被分辨出来。单个神经纤维束可以被分解，特别是在视神经头附近，以及其他结构，如筛板。除了仪器设计、制造和测试之外，还开发了用于自动图像配准、锥体计数和蒙太奇拼接的软件算法。我们与杜克大学眼科中心的眼科医生合作，建议在二期继续进行仪器开发和全面临床试验。为了临床操作，AO-LSLO仪器将进行改进和增强，包括重新设计光学布局以减少占用空间，临床包装的光机械设计，修改扫描硬件以实现自动蒙太基，以及升级一些组件以提高性能。此外，我们将探索通过实现无波前传感器算法进一步降低硬件复杂性。杜克大学的试点临床研究将分三个阶段进行。第一阶段将在临床环境中完成初步测试。第二阶段将包括一项可重复性研究，对几种不同的视网膜疾病（Stargardt’s，视网膜色素变性等）进行成像，并将AO-LSLO与目前常规临床使用的其他成像方式进行比较。第三阶段将探索该仪器在地理萎缩（GA）边缘的干性年龄相关性黄斑变性（AMD）和先前激光治疗部位的糖尿病性黄斑水肿中成像光感受器的能力。特别是，我们将表征和量化光感受器损失在这些部位的疾病或激光治疗和其他内部视网膜成分。这项研究将确定AO-LSLO是否提供了其他成像模式目前无法获得的补充信息。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，其成本与其他视网膜成像仪相当，以帮助指导治疗并改善患者的预后。

DESCRIPTION (provided by applicant): Physical Sciences Inc. (PSI) has successfully completed a Phase I program demonstrating the feasibility of integrating adaptive optics (AO) into a line scanning laser ophthalmoscope (LSLO). The bench-top AO-LSLO instrument significantly reduces the size, complexity, and cost of research AOSLOs, for the purpose of moving adaptive optics imaging more quickly into routine clinical use. The AO-LSLO produces high resolution retinal images with only one moving part and a significantly reduced instrument footprint and number of optical components. The AO-LSLO has a moderate field of view (5.5 deg), which allows montages of the macula or other targets to be obtained more quickly and efficiently. In a preliminary human subjects investigation, photoreceptors could be resolved and counted to within ~0.5 mm of the fovea. Photoreceptor counts matched closely to previously reported histology. The capillaries surrounding the foveal avascular zone could be resolved, as well as cells flowing within them. Individual nerve fiber bundles could be resolved, especially near the optic nerve head, as well as other structures such as the lamina cribrosa. In addition to instrument design, fabrication, and testing, software algorithms were developed for automated image registration, cone counting, and montage stitching. In collaboration with ophthalmologists at Duke University Eye Center, we propose to continue instrument development and full clinical testing in Phase II. The AO-LSLO instrument will be refined and enhanced for clinical operation, including re-design of the optical layout for a smaller footprint, opto- mechanical design of a clinical package, modification of scanning hardware for automatic montaging, and upgrade of some components for improved performance. In addition, we will explore further reduction of hardware complexity with the implementation of wave front sensorless algorithms. The pilot clinical study at Duke will be conducted in three stages. The first stage will accomplish preliminary testing in a clinical environment. The second stage will include a repeatability study, image several different retinal diseases (Stargardt's, retinitis pigmentosa, etc.), and compare the AO-LSLO to other imaging modalities currently in routine clinical use. The third stage will explore the instrument's capabilities to image photoreceptors in dry age-related macular degeneration (AMD) at the margin of sites of geographic atrophy (GA) and in diabetic macula edema at sites of previous laser treatment. In particular we will characterize and quantify photoreceptor loss across these sites of disease or laser treatment and other inner retinal components. This study will determine if the AO-LSLO provides complementary information not currently available from other imaging modes. If successful, the Phase II program and subsequent Phase III commercial development will provide clinicians with high-resolution, high performance adaptive optics imaging at a cost comparable to other retinal imagers to help guide therapies and improve patient outcomes. PUBLIC HEALTH RELEVANCE: By making high-resolution ocular access more widespread, the proposed AO-LSLO 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.