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Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy

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 no...

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Autores principales: Ostrovski, Ilia, Lovblom, Leif E., Farooqi, Mohammed A., Scarr, Daniel, Boulet, Genevieve, Hertz, Paul, Wu, Tong, Halpern, Elise M., Ngo, Mylan, Ng, Eduardo, Orszag, Andrej, Bril, Vera, Perkins, Bruce A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634969/
https://www.ncbi.nlm.nih.gov/pubmed/26539984
http://dx.doi.org/10.1371/journal.pone.0142309
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author Ostrovski, Ilia
Lovblom, Leif E.
Farooqi, Mohammed A.
Scarr, Daniel
Boulet, Genevieve
Hertz, Paul
Wu, Tong
Halpern, Elise M.
Ngo, Mylan
Ng, Eduardo
Orszag, Andrej
Bril, Vera
Perkins, Bruce A.
author_facet Ostrovski, Ilia
Lovblom, Leif E.
Farooqi, Mohammed A.
Scarr, Daniel
Boulet, Genevieve
Hertz, Paul
Wu, Tong
Halpern, Elise M.
Ngo, Mylan
Ng, Eduardo
Orszag, Andrej
Bril, Vera
Perkins, Bruce A.
author_sort Ostrovski, Ilia
collection PubMed
description 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 (CNFL(MANUAL)), a protocol in which images were manually selected for automated analysis (CNFL(SEMI-AUTOMATED)), and one in which selection and analysis were performed electronically (CNFL(FULLY-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 CNFL(Manual) was 16.7±4.0, 13.9±4.2 mm/mm(2) for non-diabetes controls and diabetes participants, while CNFL(Semi-Automated) was 10.2±3.3, 8.6±3.0 mm/mm(2) and CNFL(Fully-Automated) was 12.5±2.8, 10.9 ± 2.9 mm/mm(2). 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 CNFL(Fully-Automated) compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFL(Semi-Automated) and CNFL(Fully-Automated) underestimated CNFL(Manual) by 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.
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spelling pubmed-46349692015-11-13 Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy Ostrovski, Ilia Lovblom, Leif E. Farooqi, Mohammed A. Scarr, Daniel Boulet, Genevieve Hertz, Paul Wu, Tong Halpern, Elise M. Ngo, Mylan Ng, Eduardo Orszag, Andrej Bril, Vera Perkins, Bruce A. PLoS One Research Article 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 (CNFL(MANUAL)), a protocol in which images were manually selected for automated analysis (CNFL(SEMI-AUTOMATED)), and one in which selection and analysis were performed electronically (CNFL(FULLY-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 CNFL(Manual) was 16.7±4.0, 13.9±4.2 mm/mm(2) for non-diabetes controls and diabetes participants, while CNFL(Semi-Automated) was 10.2±3.3, 8.6±3.0 mm/mm(2) and CNFL(Fully-Automated) was 12.5±2.8, 10.9 ± 2.9 mm/mm(2). 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 CNFL(Fully-Automated) compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFL(Semi-Automated) and CNFL(Fully-Automated) underestimated CNFL(Manual) by 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. Public Library of Science 2015-11-05 /pmc/articles/PMC4634969/ /pubmed/26539984 http://dx.doi.org/10.1371/journal.pone.0142309 Text en © 2015 Ostrovski et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Ostrovski, Ilia
Lovblom, Leif E.
Farooqi, Mohammed A.
Scarr, Daniel
Boulet, Genevieve
Hertz, Paul
Wu, Tong
Halpern, Elise M.
Ngo, Mylan
Ng, Eduardo
Orszag, Andrej
Bril, Vera
Perkins, Bruce A.
Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title_full Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title_fullStr Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title_full_unstemmed Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title_short Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy
title_sort reproducibility of in vivo corneal confocal microscopy using an automated analysis program for detection of diabetic sensorimotor polyneuropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634969/
https://www.ncbi.nlm.nih.gov/pubmed/26539984
http://dx.doi.org/10.1371/journal.pone.0142309
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