True Sub-Micron Ocular Diagnostics with Visible Light Optical Coherence Tomography

摘要： 光学相干断层扫描(OCT)极大地提高了许多视网膜的诊断和治疗水平 通过使视网膜的体积结构成像成为可能，我们可以治疗各种疾病。通常情况下，视网膜OCT是在近- 红外(NIR)波长，限制了对视觉起作用的分子的轴向分辨率和对比度。 尽管近红外OCT定义了量化干性老年性黄斑变性(AMD)进展的生物标志物， NIR OCT还不能描绘出定义早期AMD的最精细的结构和功能变化，也不能预测 AMD的终末期--地理萎缩。可见光OCT有望实现前所未有的轴向分辨率 和分子对比度，但可见光OCT系统到目前为止还没有兑现这一承诺。 最近，我们的小组在可见光下发现了许多技术障碍，其中一些是社区所不知道的。 有了我们的创新解决方案，我们现在可以直接成像并单独量化Bruchs膜，视网膜 无临床表现的形态正常视网膜中的色素上皮(RPE)和细光感受器层 可检测的病理，达到近红外OCT系统无法达到的详细程度。这些成像功能包括 通过可见光提供的定量分子信息进一步增强。 在这项提案中，我们将开发基于光纤的可见光OCT仪器和协议来评估亚微米 随着人眼的衰老和黄斑变性而变化。采用了一系列的体外和体内研究 在啮齿动物和人类身上，我们建议验证从地形图上测量外部视网膜、RPE、 以及骨髓形态、光色素和黑色素密度、光感受器功能。我们将进行验证和测试 这些结构和功能测量的重复性，并将其应用于研究与年龄相关的变化 在正常受试者的横截面上。最后，我们将进行初步的临床影像研究，首先，比较 从衰老到早期AMD，其次，确定玻璃体向萎缩发展的候选早期生物标记物。如果 这一提议的成功将为更广泛的AMD纵向研究奠定基础 人类视网膜的进展，以及将新的生物标记物纳入临床试验。

Abstract: Optical Coherence Tomography (OCT) has greatly advanced the diagnosis and management of many retinal diseases by enabling volumetric structural imaging of the retina. Usually, retinal OCT is performed at near- infrared (NIR) wavelengths, limiting both axial resolution and contrast for molecules that play a role in vision. Though NIR OCT defines biomarkers that quantify progression of dry age-related macular degeneration (AMD), NIR OCT cannot yet delineate the finest structural and functional changes that define incipient AMD, or predict geographic atrophy, an end stage of AMD. Visible light OCT holds the promise of unprecedented axial resolution and molecular contrast, but visible light OCT systems to date have not delivered on this promise. Recently, our group identified numerous technical barriers, some unknown to the community, in visible light OCT. With our innovative solutions, we can now directly image and individually quantify Bruch’s membrane, the retinal pigment epithelium (RPE), and fine photoreceptor layers in morphologically normal retina without clinically detectable pathology, at a level of detail not attained by NIR OCT systems. These imaging capabilities are further enhanced by quantitative molecular information provided by visible light. In this proposal, we will develop fiber-based visible light OCT instrumentation and protocols to assess sub-micron changes with aging and macular degeneration in human eyes. Employing a range of in vitro and in vivo studies in rodents and humans, we propose to validate protocols that topographically measure the outer retina, RPE, and BM morphology, photopigment and melanin density, and photoreceptor function. We will validate and test the reproducibility of these structural and functional measurements, and apply them to study age-related changes in a cross-section of normal subjects. Finally, we will perform pilot clinical imaging studies to firstly, compare aging to early AMD, and secondly, identify candidate early biomarkers for progression of drusen to atrophy. If successful, this proposal will lay the groundwork for more extended longitudinal studies to study AMD progression in the human retina, and incorporation of new biomarkers into clinical trials.