Adaptive optics scanning laser ophthalmoscope-based microperimetry: establishing

描述(申请人提供)：自适应光学扫描激光眼底镜(AOSLO)是一种定制的工具，用于克服眼睛不完美的光学造成的限制，使研究人员能够非侵入性地成像活体人类视网膜中的单个视锥感光细胞。除了高分辨率成像的能力外，AOSLO还可以用于在微观范围内进行视觉灵敏度的无像差测量。在AOSLO中加入高速眼球跟踪功能，使视觉刺激能够以单一视锥精度瞄准感兴趣的视网膜区域。因此，AOSLO提供了对视觉刺激的最好水平的控制，允许建立视网膜结构和功能之间的高度精确的相关性。这个项目的目的是开发工具，即基于AOSLO的微视野检查，以增强我们对AOSLO图像中可用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结构-功能关系的纵向研究。基于AOSLO的视网膜成像在评估视网膜外层变性及其治疗的临床试验中显示出作为疾病进展高度敏感指标的潜力 我们小组的研究包括对三名视网膜色素变性(RP)患者的AOSLO成像，研究表明，与未治疗的眼睛相比，睫状神经营养因子(CNTF)治疗可以防止光感受器丢失；然而，试验中使用的标准功能结果测量表明，治疗和未治疗的眼睛的视觉表现没有显著差异。由于其前所未有的能力，测试视觉灵敏度和高精度的视网膜，基于AOSLO的微视野计是唯一适合于更好地阐明这些CNTF保存的视锥细胞的功能状态。这项拟议的研究旨在建立基于AOSLO的微视野检查，作为在微观尺度上测量视觉功能的一种手段。一旦我们的光学设置得到优化(目标1)，并建立了基于AOSLO的微视野测量值的标准数据库(目标2)，我们计划应用这些工具来检查RP患者高分辨率视网膜结构和功能之间的关系，包括接受CNTF治疗的患者(目标3和4)。这个拟议的项目包含了我以前研究经验的一些方面，并旨在让我拥有一套独特的技能，这些技能将使我走上正轨，实现我的长期目标，即成为一名独立的临床医生-科学家，进行有意义的以患者为基础的研究。我的导师奥斯汀·罗达提供了开发先进眼科成像系统的专业知识，我的共同导师雅克·邓肯则提供了在视网膜变性患者中进行以患者为基础的研究的经验。他们的指导，再加上我的职业发展计划，以及加州大学伯克利分校和加州大学旧金山分校提供的支持和设施，将使我能够成功完成这个项目并实现我的职业目标。

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.