Adaptive optics scanning laser ophthalmoscope-based microperimetry: establishing

描述（由申请人提供）：自适应光学扫描激光检眼镜（AOSLO）是一种定制的工具，用于克服眼睛光学不完美所带来的限制，使研究人员能够对活体人类视网膜中的单个锥体光感受器进行无创成像。除了具有高分辨率成像的能力外，AOSLO还可以用于在微观尺度上进行无像差的视觉灵敏度测量。将高速眼动追踪整合到AOSLO中，可以使视觉刺激以单锥体精度瞄准视网膜感兴趣的区域。因此，AOSLO提供了对视觉刺激的最佳控制水平，允许在视网膜结构和功能之间建立高度精确的相关性。该项目的目的是开发工具，即基于aoso的微周测量，以提高我们对aoso图像中可用的高分辨率结构信息的理解，并将这些工具应用于遗传性视网膜变性患者的结构-功能关系的纵向研究。最近，在评估视网膜外变性及其治疗的临床试验中，基于aoslo的视网膜成像显示出作为一种高度敏感的疾病进展指标的潜力

DESCRIPTION (provided by applicant): The adaptive optics scanning laser ophthalmoscope (AOSLO) is a custom-built tool used to overcome the limitations imposed by the eye's imperfect optics, allowing the researcher to noninvasively image individual cone photoreceptors in the living human retina. In addition to its capacity for high-resolution imaging, AOSLO can be employed to conduct aberration-free measures of visual sensitivity on a microscopic scale. Incorporating high-speed eye tracking into the AOSLO allows the visual stimulus to be targeted to retinal regions of interest with single cone precision. As a result, the AOSLO affords the best possible level of control over the visual stimulus, allowing highly precise correlations between retinal structure and function to be established. The aim of this project is to develop tools-namely, AOSLO-based microperimetry-to enhance our understanding of the high-resolution structural information available in AOSLO images, and to apply these tools to the longitudinal study of structure-function relationships in patients with inherited retinal degenerations. AOSLO-based retinal imaging has shown potential as a highly-sensitive measure for disease progression in clinical trials evaluating outer retinal degenerations and their treatments A recent study from our group that included AOSLO imaging in a subset of three retinitis pigmentosa (RP) patients demonstrated that treatment with ciliary neurotrophic factor (CNTF) prevents photoreceptor loss relative to untreated eyes; however, the standard functional outcome measures used in the trial indicated no significant difference in visual performance between treated and untreated eyes. Because of its unprecedented ability to test visual sensitivity with high retinotopic precision, AOSLO-based microperimetry is uniquely suited to better elucidate the functional status of these CNTF-preserved cones. The proposed research aims to establish AOSLO-based microperimetry as a means to measure visual function on a microscopic scale. Once our optical set-up is optimized (Aim 1) and a normative database of AOSLO-based microperimetry values is established (Aim 2), we plan to apply these tools to examine the relationship between high-resolution retinal structure and function in patients with RP, including those undergoing CNTF treatment (Aims 3 and 4). The proposed project encompasses aspects of my previous research experiences, and has been designed to leave me with a unique set of skills that will put me on track to achieve my long-term goal of becoming an independent clinician-scientist conducting meaningful patient-based research. My mentor, Austin Roorda, offers expertise in developing advanced ophthalmic imaging systems, and my co-mentor, Jacque Duncan, brings experience in conducting patient-based research in patients with retinal degenerations. Their mentorship, combined with my career development plan and the support and facilities provided by UC Berkeley and UCSF, will position me to succeed in completing this project and achieving my career objectives.