Chen Siyu, Abu-Qamar Omar, Kar Deepayan, Messinger Jeffrey D, Hwang Yunchan, Moult Eric M, Lin Junhong, Baumal Caroline R, Witkin Andre, Liang Michelle C, Waheed Nadia K, Curcio Christine A, Fujimoto James G
Department of Electrical Engineering and Computer Science, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
New England Eye Center, School of Medicine, Tufts University, Boston, Massachusetts.
Ophthalmol Sci. 2023 Feb 2;3(3):100277. doi: 10.1016/j.xops.2023.100277. eCollection 2023 Sep.
Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging.
Prospective cross-sectional study.
A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects.
Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band.
Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (μm).
In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls.
Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times.
Proprietary or commercial disclosure may be found after the references.
超高分辨率光谱域光学相干断层扫描(UHR SD-OCT)能够在体内可视化微米级结构标记物,这些标记物与正常衰老和年龄相关性黄斑变性(AMD)存在差异关联。本研究探讨了UHR SD-OCT能够检测和量化早期AMD中视网膜色素上皮(RPE)下沉积物,从而将AMD病理与正常衰老区分开来的假设。
前瞻性横断面研究。
来自39名患者的53只非渗出性(干性)AMD眼,以及来自39名受试者的63只正常眼。
使用高密度方案进行临床UHR SD-OCT扫描。从存档的供体眼中获取示例性高分辨率组织学和透射电子显微镜图像。三名经过培训的阅片者评估并标记外层视网膜形态特征,包括在UHR亮度(B)扫描中RPE-RPE基膜(RPE-BL)-布鲁赫膜(BrM)复合体中低反射裂隙的外观。一种半自动分割算法测量RPE-BL-BrM裂隙/低反射带的厚度。
UHR SD-OCT B扫描中外层视网膜形态变化的定性描述;可见裂隙的RPE-BL-BrM复合体的比例(%)以及由此产生的低反射带的厚度(μm)。
在年轻正常眼中,UHR SD-OCT始终显示出RPE-BL-BrM裂隙/低反射带。在高龄眼中,其可见性和厚度较小。然而,在早期AMD眼中再次可见裂隙/低反射带。定性阅片和定量厚度测量均显示,与年龄匹配的对照组相比,早期AMD眼中RPE-BL-BrM裂隙/低反射带的可见性和厚度显著增加。
我们的成像结果有力支持了以下假设:老年受试者中RPE-BL-BrM裂隙/低反射带的出现主要由BL沉积物主导,BL沉积物是组织学中众所周知的早期AMD指标。超高分辨率SD-OCT可用于临床成像研究中研究生理衰老以及早期AMD病理。开发与疾病发病机制和进展相关的可量化标记物有助于药物研发,并减少临床试验时间。
专有或商业披露信息可在参考文献之后找到。