Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Neurol. 2020 Dec;27(12):2635-2640. doi: 10.1111/ene.14507. Epub 2020 Oct 5.
Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers.
Twenty-one D-CAA mutation carriers (n = 8 presymptomatic, n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of ≥1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age.
The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) µm vs. 99 (87-108) µm; P = 0.006]. Both presymptomatic [111 (93-122) µm vs. 131 (123-143) µm; P < 0.001] and symptomatic carriers [119 (95-128) µm vs. 131 (123-143) µm; P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls.
Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression.
对荷兰型遗传性（D-）脑淀粉样血管病（CAA）的突变携带者进行研究，为 CAA 的早期和症状前阶段发现标志物提供了可能。光学相干断层扫描（OCT）已显示出在几种神经退行性疾病中检测视网膜变化的潜力。本探索性研究的目的是研究视网膜层变薄是否可作为 D-CAA 突变携带者的一种（早期）生物标志物。
对 21 名 D-CAA 突变携带者（无症状 8 名，有症状 13 名，中位年龄 50 岁）和 9 名对照者（中位年龄 53 岁）进行了频域 OCT 扫描。有症状的突变携带者被定义为有≥1 次症状性颅内出血史。D-CAA 突变携带者和对照者均来自我们的 D-CAA 队列和健康对照者队列。测量和分析了总视盘周围神经纤维层（pRNFL）厚度、pRNFL 的 6 个区域、全 macular 体积（TMV）和各 macular 区的厚度，这些都经过了年龄调整。
与对照组相比，症状性但无症状性 D-CAA 突变携带者的 pRNFL 整体中位（四分位间距）厚度较低[91（86-95）µm 比 99（87-108）µm；P=0.006]。与对照组相比，无症状携带者[111（93-122）µm 比 131（123-143）µm；P<0.001]和有症状携带者[119（95-128）µm 比 131（123-143）µm；P=0.034]的颞上方象限 pRNFL 更薄。携带者和对照组之间的 TMV 或各 macular 层厚度没有差异。
视网膜神经纤维层变薄可能是遗传性 CAA 疾病的候选标志物。需要进一步的研究来确定视网膜变薄是否存在于散发性 CAA 中，并评估其作为疾病进展标志物的价值。
