Cabrera DeBuc Delia, Somfai Gabor Mark, Arthur Edmund, Kostic Maja, Oropesa Susel, Mendoza Santiesteban Carlos
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, FL, United States.
Retinology Unit, Pallas Kliniken, Olten, Switzerland.
Front Physiol. 2018 Dec 6;9:1721. doi: 10.3389/fphys.2018.01721. eCollection 2018.
Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with CI using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject ( = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 ± 0.2) compared with controls (0.6 ± 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D, D and D (mean ± SD): 1.57 ± 0.06; 1.56 ± 0.06; 1.55 ± 0.06; age 81 ± 6years) vs. controls (1.61 ± 0.03; 1.59 ± 0.03; 1.58 ± 0.03; age: 80 ± 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D, D, D and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.
以往研究表明，认知障碍（CI）并不局限于大脑，还会影响视网膜。在这项初步研究中，我们采用低成本多模态方法，调查了CI患者视网膜血管复杂性与神经退行性变之间的相关性。使用先进的视网膜成像、全视野视网膜电图（ERG）和视觉性能检查，对每位受试者（n = 69）的视网膜结构和功能进行了量化。使用新加坡国立眼科中心血管评估软件计算视网膜血管参数。采用蒙特利尔认知评估量表来测量CI。对各变量进行Pearson积矩相关分析。69名参与者中，32人患有CI（46%）。我们发现，与对照组（0.6±0.2）相比，CI患者的微血管网络有显著改变（较大的静脉不对称因子：0.7±0.2）。CI患者的血管分形维数较低（容量维、信息维和关联维：D0、D1和D2（均值±标准差）：1.57±0.06；1.56±0.06；1.55±0.06；年龄81±6岁），而对照组为（1.61±0.03；1.59±0.03；1.58±0.03；年龄：80±7岁）。此外，轻度CI患者的周边视网膜出现了类玻璃膜疣区域以及色素分散。CI患者出现了色觉功能丧失，以及较小的ERG振幅和较长的峰值时间。Pearson积矩相关分析显示，血管参数（动静脉比、总长度直径比、D0、D1、D2和闪烁反应的隐含时间（IT））之间存在显著关联，但这些关联在偏相关分析中并不显著。本研究表明，存在多种可能对CI衰退敏感的视网膜标志物，并进一步证明存在一种统计趋势，表明视网膜神经元功能障碍与微血管变化之间存在相关性，提示视网膜几何血管和功能参数可能与CI导致的视网膜生理变化有关。我们推测，对结构 - 功能参数进行综合分析，而非单个生物标志物，可能会提供一种有用的CI临床标志物，也可能提高CI鉴别诊断的敏感性和特异性。然而，由于我们的研究样本量较小，我们方法的临床应用的全面程度仍有待探讨和确定。
