Litts Katie M, Cooper Robert F, Duncan Jacque L, Carroll Joseph
Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Invest Ophthalmol Vis Sci. 2017 May 1;58(6):BIO255-BIO267. doi: 10.1167/iovs.17-21868.
Improved understanding of the mechanisms underlying inherited retinal degenerations has created the possibility of developing much needed treatments for these relentless, blinding diseases. However, standard clinical indicators of retinal health (such as visual acuity and visual field sensitivity) are insensitive measures of photoreceptor survival. In many retinal degenerations, significant photoreceptor loss must occur before measurable differences in visual function are observed. Thus, there is a recognized need for more sensitive outcome measures to assess therapeutic efficacy as numerous clinical trials are getting underway. Adaptive optics (AO) retinal imaging techniques correct for the monochromatic aberrations of the eye and can be used to provide nearly diffraction-limited images of the retina. Many groups routinely are using AO imaging tools to obtain in vivo images of the rod and cone photoreceptor mosaic, and it now is possible to monitor photoreceptor structure over time with single cell resolution. Highlighting recent work using AO scanning light ophthalmoscopy (AOSLO) across a range of patient populations, we review the development of photoreceptor-based metrics (e.g., density/geometry, reflectivity, and size) as candidate biomarkers. Going forward, there is a need for further development of automated tools and normative databases, with the latter facilitating the comparison of data sets across research groups and devices. Ongoing and future clinical trials for inherited retinal diseases will benefit from the improved resolution and sensitivity that multimodal AO retinal imaging affords to evaluate safety and efficacy of emerging therapies.
对遗传性视网膜变性潜在机制的深入了解，为开发针对这些无情致盲疾病急需的治疗方法创造了可能性。然而，视网膜健康的标准临床指标（如视力和视野敏感度）对光感受器存活情况的检测并不敏感。在许多视网膜变性中，在观察到视觉功能出现可测量差异之前，必须有大量光感受器发生损失。因此，随着众多临床试验的开展，人们认识到需要更敏感的结果指标来评估治疗效果。自适应光学（AO）视网膜成像技术可校正眼睛的单色像差，可用于提供近乎衍射极限的视网膜图像。许多研究小组经常使用AO成像工具获取视杆和视锥光感受器镶嵌的体内图像，现在能够以单细胞分辨率随时间监测光感受器结构。我们重点介绍了近期在一系列患者群体中使用AO扫描激光检眼镜（AOSLO）的研究工作，回顾了基于光感受器的指标（如密度/几何形状、反射率和大小）作为候选生物标志物的发展情况。展望未来，需要进一步开发自动化工具和标准化数据库，后者有助于跨研究小组和设备比较数据集。遗传性视网膜疾病正在进行的和未来的临床试验将受益于多模态AO视网膜成像提供的更高分辨率和敏感度，以评估新出现疗法的安全性和疗效。
