Department of Ophthalmology and Vision Science, Washington University in St Louis, St Louis, Missouri.
Department of Medicine, Washington University in St Louis, St Louis, Missouri.
JAMA Ophthalmol. 2018 Nov 1;136(11):1242-1248. doi: 10.1001/jamaophthalmol.2018.3556.
Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD.
To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017.
Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome.
Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] μm; P = .03).
This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.
无症状、临床前阿尔茨海默病（AD）的生物标志物检测具有侵入性且昂贵。光学相干断层血管造影（OCTA）是一种非侵入性技术，可分析视网膜和微血管解剖结构，这些结构在早期 AD 中发生改变。
确定 OCTA 是否可以检测到通过标准生物标志物检测诊断为临床前 AD 的认知正常研究参与者的早期视网膜改变。
设计、地点和参与者：这项病例对照研究纳入了 32 名参与者，他们均来自密苏里州圣路易斯市华盛顿大学查尔斯·F.和乔安妮·奈特阿尔茨海默病研究中心。广泛的神经心理测试结果确定所有参与者的认知均正常。参与者接受正电子发射断层扫描和/或脑脊液检测以确定生物标志物状态。排除有先前眼部疾病、眼部混浊、糖尿病或未控制的高血压的个体。数据于 2016 年 7 月 1 日至 2017 年 9 月 30 日采集，并于 2016 年 7 月 30 日至 2017 年 12 月 31 日进行分析。
使用 OCTA 系统从所有参与者的双眼收集视网膜神经纤维层厚度、神经节细胞层厚度、内和外中心凹厚度、血管密度、黄斑体积和中心凹无血管区的自动测量值。使用协方差的单独模型 III 分析来分析个体数据结果。
分析纳入了 30 名参与者的 58 只眼（53%为女性；平均[SD]年龄 74.5[5.6]岁；年龄范围 62-92 岁）。1 名参与者为非裔美国人，29 名为白人。14 名参与者的生物标志物阳性，因此诊断为临床前 AD（平均[SD]年龄 73.5[4.7]岁）；16 名无生物标志物的参与者作为对照组（平均[SD]年龄 75.4[6.6]岁）。与对照组相比，生物标志物阳性组的中心凹无血管区增加（平均[SD]，0.364[0.095]比 0.275[0.060]mm2；P=0.002）。生物标志物阳性组的内中心凹厚度降低（66.0[9.9]比 75.4[10.6]μm；P=0.03）。
本研究表明，除了结构改变外，具有临床前 AD 的认知正常个体还存在视网膜微血管异常，并且这些变化发生在 AD 的早期阶段，早于以前的研究结果。需要在更大的队列中进行纵向研究，以确定这一发现是否有助于识别临床前 AD。
