Progression of Visual Pathway Degeneration in Primary Open-Angle Glaucoma: A Longitudinal Study.
Progression of Visual Pathway Degeneration in Primary Open-Angle Glaucoma: A Longitudinal Study.
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DOI：
10.3389/fnhum.2021.630898
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发表时间：
2021
影响因子：
2.9
通讯作者：
Cornelissen FW
中科院分区：
文献类型：
--
作者：
Haykal S;Jansonius NM;Cornelissen FW
背景：原发性开角型青光眼（POAG）患者在其视觉通路中表现出广泛的白质（WM）变性。这种退行性变是从膝曲前通路还是膝曲后通路开始的尚不清楚。在这项纵向研究中，我们评估了POAG患者膝前视束（OTs）和膝后视束辐射（ORs）随时间的进展，旨在确定这种变性的来源和扩散模式。方法：在相隔5.4±2.1年的两个时间点对12例POAG患者和14例对照组进行弥散加权MRI扫描。纤维密度（FD）， WM轴突密度的估计，计算所有参与者的OTs和ORs在一个无偏的纵向人口模板空间。首先，分别比较POAG患者和对照组在时间点1 （TP1）和时间点2 （TP2）的FD。其次，对两个时间点之间POAG患者FD变化进行重复测量分析。最后，我们比较了两组之间FD随时间的变化率。结果：与对照组相比，POAG患者在TP1的左侧OT以及TP2的左侧OT和左侧OR均表现出明显较低的FD。POAG患者在右侧OT和两个手术室的时间点之间表现出明显的FD损失，而左侧手术室中POAG患者的FD损失率明显高于对照组。结论：我们发现POAG患者膝前和膝后视觉通路的神经退行性WM变化的纵向进展。变化模式提示青光眼WM变性始于膝状前通路，然后扩散到膝状后通路。此外，我们发现证据表明青光眼变性向膝状后通路的跨突触扩散是一个长期的过程，在没有可检测的膝状前退行性进展的情况下继续进行。这表明保存完整膝后神经通路的时间窗口存在，这可能被证明是未来可行的治疗靶点。
Background: Primary open-angle glaucoma (POAG) patients exhibit widespread white matter (WM) degeneration throughout their visual pathways. Whether this degeneration starts at the pre- or post-geniculate pathways remains unclear. In this longitudinal study, we assess the progression of WM degeneration exhibited by the pre-geniculate optic tracts (OTs) and the post-geniculate optic radiations (ORs) of POAG patients over time, aiming to determine the source and pattern of spread of this degeneration. Methods: Diffusion-weighted MRI scans were acquired for 12 POAG patients and 14 controls at two time-points 5.4 ± 2.1 years apart. Fiber density (FD), an estimate of WM axonal density, was computed for the OTs and ORs of all participants in an unbiased longitudinal population template space. First, FD was compared between POAG patients and the controls at time-point 1 (TP1) and time-point 2 (TP2) independently. Secondly, repeated measures analysis was performed for FD change in POAG patients between the two time-points. Finally, we compared the rate of FD change over time between the two groups. Results: Compared to the controls, POAG patients exhibited significantly lower FD in the left OT at TP1 and in both OTs and the left OR at TP2. POAG patients showed a significant loss of FD between the time-points in the right OT and both ORs, while the left OR showed a significantly higher rate of FD loss in POAG patients compared to the controls. Conclusions: We find longitudinal progression of neurodegenerative WM changes in both the pre- and post-geniculate visual pathways of POAG patients. The pattern of changes suggests that glaucomatous WM degeneration starts at the pre-geniculate pathways and then spreads to the post-geniculate pathways. Furthermore, we find evidence that the trans-synaptic spread of glaucomatous degeneration to the post-geniculate pathways is a prolonged process which continues in the absence of detectable pre-geniculate degenerative progression. This suggests the presence of a time window for salvaging intact post-geniculate pathways, which could prove to be a viable therapeutic target in the future.
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