© 2015 Ostrovski et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective In vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis. Methods In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols. Results Mean CNFLManualwas 16.7±4.0, 13.9±4.2 mm/mm2for non-diabetes controls and diabetes participants, while CNFLSemi-Automatedwas 10.2±3.3, 8.6±3.0 mm/mm2and CNFLFully-Automatedwas 12.5±2.8, 10.9 ± 2.9 mm/mm2. Inter-observer ICC and 95%confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFLFully-Automatedcompared to others). The other IVCCMparameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automatedand CNFLFully-Automatedunderestimated CNFLManualby mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively. Conclusions Despite an apparent measurement (underestimation) bias in comparison to the manual strategy of image analysis, fully-automated analysis preserves CNFL reproducibility. Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.
Ostrovski, I., Lovblom, L. E., Farooqi, M. A., Scarr, D., Boulet, G., Hertz, P., … Perkins, B. A. (2015). Reproducibility of in vivo Corneal Confocal Microscopy using an automated analysis program for detection of diabetic sensorimotor polyneuropathy. PLoS ONE, 10(11). https://doi.org/10.1371/journal.pone.0142309