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

描述（由申请人提供）：提出了三个目标来研究年龄相关性黄斑变性（AMD）的绒毛膜视网膜复合体（脉络膜，绒毛膜，Bruch膜，视网膜色素上皮，光感受器）。每个目标都包括涉及光学成像的技术目标和与该疾病发病机制有关的假设测试。目的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，特别是脉络膜的毛毛层、Sattler’s层和Haller’s层。使用1050 nm的光源将提供穿透视网膜色素上皮的深度穿透，以研究与非渗出性AMD相关的血管化变化，目前尚无有效的治疗方法。它还将允许在体内检查与抗vegf治疗有关的视网膜下血管化的变化，这种治疗通常有效，但尚未完全了解。目的2将使用超高分辨率自适应光学（AO）测量眼底自身荧光（FAF）和地理萎缩视网膜色素上皮的形态学，同时使用反射和荧光扫描激光检眼镜和OCT体积成像来共同定位两种方式可视化的疾病相关变化。本研究将探讨一种假设，即表征AMD的FAF的一些变化是继发于紫红质光色素对激发光和发射光的筛选的变化。这一结果可能会改变对AMD和其他与杆状光感受器丧失相关的绒毛膜视网膜复合体疾病中FAF变化的解释，并将对开发或评估新的治疗方法至关重要。Aim 3将使用新构建的聚焦AO-OCT系统和相位检索算法来测量正常视网膜和早期和中期AMD患者视网膜光感受器外段长度和更新速率的变化。光感受器的变化将在短期和长期的时间尺度上被表征。这些结果可能为AMD的进展提供新的和敏感的功能指标，并在生物衰老和眼病之间的交叉点提供绒毛膜视网膜复合体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.