Scarr Daniel, Lovblom Leif E, Ostrovski Ilia, Kelly Dylan, Wu Tong, Farooqi Mohammed A, Halpern Elise M, Ngo Mylan, Ng Eduardo, Orszag Andrej, Bril Vera, Perkins Bruce A
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
J Diabetes Complications. 2017 Jun;31(6):1066-1073. doi: 10.1016/j.jdiacomp.2016.07.024. Epub 2016 Jul 26.
Quantification of corneal nerve fiber length (CNFL) by in vivo corneal confocal microscopy represents a promising diabetic neuropathy biomarker, but applicability is limited by resource-intensive image analysis. We aimed to evaluate, in cross-sectional analysis of non-diabetic controls and patients with type 1 and type 2 diabetes with and without neuropathy, the agreement between manual and automated analysis protocols.
Sixty-eight controls, 139 type 1 diabetes, and 249 type 2 diabetes participants underwent CNFL measurement (N=456). Neuropathy status was determined by clinical and electrophysiological criteria. CNFL was determined by manual (CNFL, reference standard) and automated (CNFL) protocols, and results were compared for correlation and agreement using Spearman coefficients and the method of Bland and Altman (CNFL subtracted from CNFL).
Participants demonstrated broad variability in clinical characteristics associated with neuropathy. The mean age, diabetes duration, and HbA1c were 53±18years, 15.9±12.6years, and 7.4±1.7%, respectively, and 218 (56%) individuals with diabetes had neuropathy. Mean CNFL was 15.1±4.9mm/mm, and mean CNFL was 10.5±3.7mm/mm (CNFL underestimation bias, -4.6±2.6mm/mm corresponding to -29±17%). Percent bias was similar across non-diabetic controls (-33±12%), type 1 (-30±20%), and type 2 diabetes (-28±16%) subgroups (ANOVA, p=0.068), and similarly in diabetes participants with and without neuropathy. Levels of CNFL and CNFL were both inversely associated with neuropathy status.
Although CNFL substantially underestimated CNFL, its bias was non-differential between diverse patient groups and its relationship with neuropathy status was preserved. Determination of diagnostic thresholds specific to CNFL should be pursued in diagnostic studies of diabetic neuropathy.
通过体内角膜共聚焦显微镜对角膜神经纤维长度（CNFL）进行定量分析是一种很有前景的糖尿病神经病变生物标志物，但由于图像分析资源密集，其适用性受到限制。我们旨在通过对非糖尿病对照组以及1型和2型糖尿病患者（有无神经病变）的横断面分析，评估手动和自动分析方案之间的一致性。
68名对照组、139名1型糖尿病患者和249名2型糖尿病参与者接受了CNFL测量（N = 456）。通过临床和电生理标准确定神经病变状态。通过手动（CNFL，参考标准）和自动（CNFL）方案确定CNFL，并使用Spearman系数以及Bland和Altman方法（从CNFL中减去CNFL）比较结果的相关性和一致性。
参与者在与神经病变相关的临床特征方面表现出广泛的变异性。平均年龄、糖尿病病程和糖化血红蛋白分别为53±18岁、15.9±12.6岁和7.4±1.7%，218名（56%）糖尿病患者患有神经病变。平均CNFL为15.1±4.9mm/mm，平均CNFL为10.5±3.7mm/mm（CNFL低估偏差，-4.6±2.6mm/mm，相当于-29±17%）。非糖尿病对照组（-33±12%）、1型糖尿病组（-30±20%）和2型糖尿病组（-28±16%）亚组的偏差百分比相似（方差分析，p = 0.068），在有和无神经病变的糖尿病参与者中也是如此。CNFL和CNFL水平均与神经病变状态呈负相关。
虽然CNFL大幅低估了CNFL，但其偏差在不同患者组之间无差异，且其与神经病变状态的关系得以保留。在糖尿病神经病变的诊断研究中应确定特定于CNFL的诊断阈值。
