Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Acta Neuropathol Commun. 2021 Nov 18;9(1):184. doi: 10.1186/s40478-021-01290-8.
Alzheimer's disease (AD) is associated with inner retina (nerve fiber and ganglion cell layers) thinning. In contrast, we have seen outer retina thinning driven by photoreceptor outer nuclear layer (ONL) thinning with antemortem optical coherence tomography (OCT) among patients considered to have a frontotemporal degeneration tauopathy (FTLD-Tau). Our objective was to determine if postmortem retinal tissue from FTLD-Tau patients demonstrates ONL loss observed antemortem on OCT. Two probable FTLD-Tau patients that were deeply phenotyped by clinical and genetic testing were imaged with OCT and followed to autopsy. Postmortem brain and retinal tissue were evaluated by a neuropathologist and ocular pathologist, respectively, masked to diagnosis. OCT findings were correlated with retinal histology. The two patients had autopsy-confirmed FTLD-Tau neuropathology and had antemortem OCT measurements showing ONL thinning (66.9 μm, patient #1; 74.9 μm, patient #2) below the 95% confidence interval of normal limits (75.1-120.7 μm) in our healthy control cohort. Postmortem, retinal tissue from both patients demonstrated loss of nuclei in the ONL, matching ONL loss visualized on antemortem OCT. Nuclei counts from each area of ONL loss (2 - 3 nuclei per column) seen in patient eyes were below the 95% confidence interval (4 - 8 nuclei per column for ONL) of 3 normal control retinas analyzed at the same location. Our evaluation of retinal tissue from FTLD-Tau patients confirms ONL loss seen antemortem by OCT. Continued investigation of ONL thinning as a biomarker that may distinguish FTLD-Tau from other dementias is warranted.
阿尔茨海默病（AD）与内视网膜（神经纤维和节细胞层）变薄有关。相比之下，我们通过生前光学相干断层扫描（OCT）观察到，在被认为患有额颞叶变性tau 病（FTLD-Tau）的患者中，外视网膜变薄是由光感受器外核层（ONL）变薄驱动的。我们的目的是确定 FTLD-Tau 患者的死后视网膜组织是否表现出 OCT 上观察到的 ONL 丢失。两名经过临床和基因测试深度表型的可能 FTLD-Tau 患者接受了 OCT 成像，并在死后进行了随访。死后的大脑和视网膜组织分别由神经病理学家和眼病理学家进行评估，诊断结果被掩盖。OCT 结果与视网膜组织病理学相关。这两名患者均经尸检证实患有 FTLD-Tau 神经病理学，且生前 OCT 测量显示 ONL 变薄（患者 #1 为 66.9μm，患者 #2 为 74.9μm），低于我们健康对照组正常范围（75.1-120.7μm）的 95%置信区间。死后，两名患者的视网膜组织均显示 ONL 中的细胞核丢失，与生前 OCT 上观察到的 ONL 丢失相匹配。在患者眼中观察到的每个 ONL 丢失区域（每列 2-3 个核）的细胞核计数均低于分析的 3 个正常对照视网膜同一位置的 95%置信区间（ONL 每列 4-8 个核）。我们对 FTLD-Tau 患者的视网膜组织的评估证实了 OCT 生前观察到的 ONL 丢失。需要进一步研究 ONL 变薄作为一种生物标志物，以区分 FTLD-Tau 与其他痴呆症。
