Structure and Function of the Chorioretinal Complex in Age-Related Macular Degene

描述（由申请人提供）：提出了三个目的来研究年龄相关性黄斑变性（AMD）中的脉络膜视网膜复合体（脉络膜、脉络膜毛细血管、布鲁赫膜、视网膜色素上皮、光感受器）。每个目标包括涉及光学成像的技术目标和与这种疾病的发病机制相关的假设的测试。目标1将使用连续光学相干断层扫描（OCT）B扫描（帧）之间的相位变化来可视化视网膜后面的血管层，特别是脉络膜的脉络膜毛细血管层、Sattler层和Haller层。使用1050 nm光源将提供通过视网膜色素上皮的深度穿透，以研究与非渗出性AMD相关的血管形成的变化，非渗出性AMD是目前没有有效治疗的病症。它还将允许在体内检查与新生血管性AMD的抗VEGF治疗相关的视网膜下血管形成的变化，这种治疗通常是有效的，但尚未完全理解。目标2将使用超高分辨率自适应光学（AO）与同时反射和荧光扫描激光检眼镜和OCT体积成像测量地图状萎缩中视网膜色素上皮的眼底自发荧光（FAF）和形态，以共同定位两种模式可视化的疾病相关变化。该目的将调查的假设，在FAF表征AMD的一些变化是次要的变化，在视紫红质色素筛选的激发和发射光。这一结果可能会改变对AMD和其他与视杆细胞损失相关的脉络膜视网膜复合体疾病中FAF变化的解释，并将在开发或评估新的治疗方法中发挥关键作用。目的3将使用新构建的无焦AO-OCT系统和相位恢复算法来测量正常视网膜和具有早期和中期AMD特征性玻璃疣的视网膜中光感受器外节的长度和更新率的变化。光感受器的变化将在短期和长期的时间尺度上进行表征。这些结果可以提供AMD进展的新的和敏感的功能指标，以及在生物老化和眼部疾病之间的交叉点处脉络膜视网膜复合体的健康变化的领先指标。

DESCRIPTION (provided by applicant): Three aims are proposed to study the chorioretinal complex (choroid, choriocapillaris, Bruch's membrane, retinal pigment epithelium, photoreceptors) in age-related macular degeneration (AMD). Each aim includes both technical goals involving optical imaging and tests of hypotheses related to the pathogenesis of this disease. Aim 1 will use phase changes between successive optical coherence tomography (OCT) B-scans (frames) to visualize the vascular layers behind the retina, specifically the choriocapillaris, Sattler's and Haller's layers of the choroid. Use of a 1050 nm light source will provide deep penetration through the retinal pigment epithelium to study changes in vascularization associated with nonexudative AMD, a condition for which there is currently no effective treatment. It will also permit in vivo examination of changes in subretinal vascularization associated with anti-VEGF treatment for neovascular AMD, a treatment that is generally effective but not completely understood. Aim 2 will measure fundus autofluorescence (FAF) and morphology of the retinal pigment epithelium in geographic atrophy using ultrahigh-resolution adaptive optics (AO) with simultaneous reflectance and fluorescent scanning laser ophthalmoscopy and OCT volumetric imaging to co- localize disease-related changes visualized with the two modalities. This aim will investigate the hypothesis that some of the changes in FAF characterizing AMD are secondary to changes in rhodopsin photopigment screening of the excitation and emitted light. This result may alter interpretations of FAF changes in AMD and other diseases of the chorioretinal complex associated with rod photoreceptor losses, and will be critical in developing or assessing new treatments. Aim 3 will use a newly constructed afocal AO-OCT system and phase retrieval algorithm to measure changes in length and renewal rates of the photoreceptor outer segments in normal retinae and those with drusen characteristic of early and intermediate stage AMD. Changes in photoreceptors will be characterized over short- and long-term time scales. These results may provide new and sensitive functional indicators of AMD progression and a leading indicator of changes in the health of the chorioretinal complex at the intersection between biological aging and eye disease.