Data_Sheet_1_Investigating Vascular Complexity and Neurogenic Alterations in Sectoral Regions of the Retina in Patients With Cognitive Impairment.PDF

Evidence is accumulating that cognitive function, and visual impairment may be related. In this pilot study, we investigated whether multifractal dimension and lacunarity analyses performed in sectoral regions of the retina may reveal changes in patients with cognitive impairment (CI) that may be masked in the study considering the whole retinal branching pattern. Prospective age-matched subjects (n = 69) with and with no CI and without the presence of any ophthalmic history were recruited (age > 55+ years). The Montreal Cognitive Assessment (MoCA) was used to measure CI, and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Quantification of the retinal structure was performed in retinal fundus images [45o field of view (FOV), optic disk centered] with excellent quality for all individuals [19 healthy controls (HC) and 20 patients with CI] after evaluating the inclusion and exclusion criteria in all study participants recruited (n = 69). The skeletonized vasculature network that comprised the whole branching pattern observable in the full 45° FOV was obtained for each image and divided into nine equal regions (superotemporal, superior, superonasal, macular, optic disk, nasal, inferotemporal, inferior, and inferonasal). The multifractal behavior was analyzed by calculating the generalized dimension Dq (Do, D1, and D2), the lacunarity parameter (Λ), and singularity spectrum f(α) in the nine sectoral skeletonized images as well as in the skeletons that comprised the whole branching pattern observable in the full 45° FOV. The analyses were performed using the ImageJ program together with the FracLac plug-in. Independent sample t-tests or Mann Whitney U test and Pearson correlation coefficient were used to find associations between all parameters in both groups. The effect size (Cohen’s d) of the difference between both groups was also assessed. A p-value < 0.05 was considered statistically significant. Significant correlations between multifractal and Λ parameters with the MoCA and implicit time ERG-parameter were observed in the regional analysis. In contrast, no trend was found when considering the whole retinal branching pattern. Analysis of combined structural-functional parameters in sectoral regions of the retina, instead of individual retinal biomarkers, may provide a useful clinical marker of CI.

越来越多的证据表明，认知功能与视力损害可能存在关联。本先导性研究旨在探讨在视网膜扇形区域开展的多重分形维数（multifractal dimension）与空缺度分析（lacunarity analysis），是否能够识别出认知损害（cognitive impairment, CI）患者的特征变化——这类变化在基于全视网膜分支模式的整体研究中可能被掩盖。本研究招募了69名年龄匹配的前瞻性受试者，年龄均大于55岁，分为认知损害组与非认知损害组，所有受试者均无眼部病史。采用蒙特利尔认知评估量表（Montreal Cognitive Assessment, MoCA）评估受试者的认知损害情况，并实施全视野视网膜电图（full-field electroretinogram, ERG）检查。此外，通过拉宾视锥对比度测试（Rabbin cone contrast test, CCT）开展视觉功能检测。研究人员对所有招募的69名研究参与者的纳入排除标准进行评估后，选取了图像质量优异的视网膜眼底图像（retinal fundus images）进行视网膜结构量化分析，这些图像均为45°视野（field of view, FOV）、以视盘为中心的眼底图，涵盖19名健康对照（healthy controls, HC）与20名认知损害患者。针对每张图像，提取覆盖完整45°视野内全部可见分支模式的骨架化血管网络（skeletonized vasculature network），并将其划分为9个均等区域：颞上区、上区、鼻上区、黄斑区、视盘区、鼻区、颞下区、下区及鼻下区。通过计算广义维数Dq（包含D0、D1与D2）、空缺度参数（lacunarity parameter, Λ）以及奇异谱f(α)，对9个扇形区域的骨架化图像以及覆盖完整45°视野全部可见分支模式的整体骨架化图像开展多重分形特征分析。本研究采用ImageJ软件（ImageJ）搭配FracLac插件（FracLac plug-in）完成上述分析。使用独立样本t检验或曼-惠特尼U检验（Mann Whitney U test）以及皮尔逊相关系数（Pearson correlation coefficient）分析两组间所有参数的关联，并评估两组差异的效应量（Cohen’s d）。以p值＜0.05作为具有统计学显著性的判定标准。区域层面分析结果显示，多重分形参数与空缺度参数与MoCA评分及视网膜电图隐时间参数存在显著相关性；与之相反，当采用全视网膜分支模式进行整体分析时，未发现类似趋势。相较于单一视网膜生物标志物（retinal biomarkers），对视网膜扇形区域的结构-功能参数进行联合分析，或可成为认知损害的潜在有效临床标志物。