Cottrell Paul, Ahmed Sohail, James Catherine, Hodson James, McDonnell Peter J, Rauz Saaeha, Williams Geraint P
Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, School of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom Department of Optometry, Birmingham and Midland Eye Centre, City Hospital, Birmingham, United Kingdom.
Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, School of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom.
Invest Ophthalmol Vis Sci. 2014 Oct 16;55(11):7312-20. doi: 10.1167/iovs.14-15140.
In vivo confocal microscopy (IVCM) demonstrates reduction in corneal sub-basal nerve density in herpes simplex keratitis (HSK). Image J is an open source image-analysis platform that can be combined with a nerve tracer, Neuron J. We sought to compare the reliability and speed of corneal nerve density quantification between these modalities and their relation to clinical damage.
A total of 16 eyes (14 patients) with chronic HSK was assessed clinically and by IVCM. Randomly ordered triplicate, representative images from the central cornea were presented to two masked observers and corneal sub-basal nerve density was measured using Image J/Neuron J. Agreement was quantified using intraclass correlation coefficients (ICC), Bland-Altman plots together with mean difference, and level of agreement (LoA).
The median nerve density was measured at 7.1 mm/mm(2) (quartiles, 3.3-11.2), with Neuron-J demonstrating good intra-/interobserver agreement (ICC, 0.96-0.99; P < 0.001; mean difference, 0.1-1.4; LoA, <±3.3). Intraeye reliability was less consistent (mean difference, 1.7-2.3; LoA, ±8.8-9.8). Neuron J was highly comparable to Image J for both observers (ICC, 1.0; P < 0.001; mean difference, <0.2; LoA, ±<1.2) and significantly faster than Image J (median, 49 vs. 102 seconds, P < 0.001). Diminished nerve density was associated with corneal opacification and reduction in visual acuity (both P = 0.03).
The IVCM combined with Neuron J affords objective, user-friendly, and fast quantification of corneal nerve damage in HSK. It provides semiobjective phenotyping of the sequelae of neurotrophic corneal damage and offers a potential tool for measuring vulnerability to relapse or additional infections. Further exploration in a larger longitudinal cohort is warranted.
体内共聚焦显微镜检查（IVCM）显示单纯疱疹性角膜炎（HSK）患者角膜基底膜下神经密度降低。Image J是一个开源图像分析平台，可与神经追踪软件Neuron J结合使用。我们试图比较这两种方法在角膜神经密度定量方面的可靠性和速度，以及它们与临床损伤的关系。
对16只眼（14例患者）的慢性HSK进行临床评估和IVCM检查。将来自中央角膜的随机排序的一式三份代表性图像呈现给两名不知情的观察者，并使用Image J/Neuron J测量角膜基底膜下神经密度。使用组内相关系数（ICC）、Bland-Altman图以及平均差异和一致性水平（LoA）对一致性进行量化。
神经密度中位数为7.1 mm/mm²（四分位数，3.3 - 11.2），Neuron-J显示观察者内/间一致性良好（ICC，0.96 - 0.99；P < 0.001；平均差异，0.1 - 1.4；LoA，<±3.3）。眼内可靠性不太一致（平均差异，1.7 - 2.3；LoA，±8.8 - 9.8）。对于两名观察者，Neuron J与Image J具有高度可比性（ICC，1.0；P < 0.001；平均差异，<0.2；LoA，±<1.2），并且比Image J快得多（中位数，49秒对102秒，P < 0.001）。神经密度降低与角膜混浊和视力下降相关（P均 = 0.03）。
IVCM联合Neuron J可对HSK患者的角膜神经损伤进行客观、用户友好且快速的定量分析。它为神经营养性角膜损伤后遗症提供了半客观的表型分析，并为测量复发或额外感染的易感性提供了一种潜在工具。有必要在更大的纵向队列中进行进一步探索。
