Tavakoli Mitra, Ferdousi Maryam, Petropoulos Ioannis N, Morris Julie, Pritchard Nicola, Zhivov Andrey, Ziegler Dan, Pacaud Danièle, Romanchuk Kenneth, Perkins Bruce A, Lovblom Leif E, Bril Vera, Singleton J Robinson, Smith Gordon, Boulton Andrew J M, Efron Nathan, Malik Rayaz A
Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
Medical Statistics Unit, University of Manchester and University Hospital of South Manchester, Manchester, U.K.
Diabetes Care. 2015 May;38(5):838-43. doi: 10.2337/dc14-2311. Epub 2015 Jan 29.
Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters.
A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis.
There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm(2) per year for men, P < 0.01, and -0.161 no./mm(2) per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm(2) per year for men, P = 0.26, and -0.050 no./mm(2) per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm(2) per year, P = 0.07) and women (-0.060 mm/mm(2) per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter.
This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.
角膜共焦显微镜检查是一种新型诊断技术，可用于检测一系列周围神经病变，尤其是糖尿病性神经病变中的神经损伤和修复情况。需要规范的参考值，以便将该技术应用于临床并更广泛地使用。因此，我们开展了一项多中心合作研究，以提供全球范围内经年龄调整的角膜神经纤维参数规范值。
从六个临床学术中心收集了343名健康志愿者的总共1965张角膜神经图像。所有受试者均使用海德堡视网膜断层扫描角膜共焦显微镜进行检查。每个中心按照标准方案采集中央角膜基底膜下神经丛的图像，并由三名经过培训的检查人员使用手动追踪和半自动软件（CCMetrics）进行分析。使用简单线性回归确定年龄趋势，并使用分位数回归分析计算角膜神经纤维密度（CNFD）、角膜神经纤维分支密度（CNBD）、角膜神经纤维长度（CNFL）和角膜神经纤维弯曲度（CNFT）的规范参考值。
CNFD随年龄呈显著线性下降（男性每年下降-0.164条/mm²，P<0.01；女性每年下降-0.161条/mm²，P<0.01）。CNBD随年龄无变化（男性每年增加0.192条/mm²，P = 0.26；女性每年增加-0.050条/mm²，P = 0.78）。男性（每年下降-0.045 mm/mm²，P = 0.07）和女性（每年下降-0.060 mm/mm²，P = 0.02）的CNFL均下降。男性（每年增加0.044，P<0.01）和女性（每年增加0.046，P<0.01）的CNFT随年龄增加。身高、体重和BMI对任何角膜神经参数的第5百分位数规范值均无影响。
本研究为糖尿病及其他周围神经病变研究中的角膜神经参数提供了可靠的全球规范参考值，可用于研究和临床实践。
