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

Ostrovski I, Lovblom LE, Farooqi MA, Scarr D, Boulet G, Hertz P, Wu T, Halpern EM, Ngo M, Ng E, Orszag A, Bril V, Perkins BA - PLoS ONE (2015)

Bottom Line: 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-Automated compared to others).The other IVCCM parameters had substantially lower ICC compared to those for CNFL.Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.

View Article: PubMed Central - PubMed

Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

ABSTRACT

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 CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 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-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual 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.

No MeSH data available.


Related in: MedlinePlus

Agreement between CNFLManual and CNFLFully-Automated.In Panels A and B, the reference lines, from top to bottom, denote the 97.5th percentile, the mean, and the 2.5th percentile for the indicated differences.
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pone.0142309.g002: Agreement between CNFLManual and CNFLFully-Automated.In Panels A and B, the reference lines, from top to bottom, denote the 97.5th percentile, the mean, and the 2.5th percentile for the indicated differences.

Mentions: Bland-Altman plots of agreement between CNFLManual and CNFLFully-Automated are shown in Fig 2. There was excellent correlation between the protocols (Pearson r = 0.82), but Fig 2 Panel A shows that on average, CNFLFully-Automated underestimated CNFLManual by 3.4 [95% CI (-1.6, 7.8)] mm/mm2. Fig 2 Panel B shows that this was equivalent to a 21 [95% CI (-21.6, 46.1)] % underestimation.


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

Ostrovski I, Lovblom LE, Farooqi MA, Scarr D, Boulet G, Hertz P, Wu T, Halpern EM, Ngo M, Ng E, Orszag A, Bril V, Perkins BA - PLoS ONE (2015)

Agreement between CNFLManual and CNFLFully-Automated.In Panels A and B, the reference lines, from top to bottom, denote the 97.5th percentile, the mean, and the 2.5th percentile for the indicated differences.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634969&req=5

pone.0142309.g002: Agreement between CNFLManual and CNFLFully-Automated.In Panels A and B, the reference lines, from top to bottom, denote the 97.5th percentile, the mean, and the 2.5th percentile for the indicated differences.
Mentions: Bland-Altman plots of agreement between CNFLManual and CNFLFully-Automated are shown in Fig 2. There was excellent correlation between the protocols (Pearson r = 0.82), but Fig 2 Panel A shows that on average, CNFLFully-Automated underestimated CNFLManual by 3.4 [95% CI (-1.6, 7.8)] mm/mm2. Fig 2 Panel B shows that this was equivalent to a 21 [95% CI (-21.6, 46.1)] % underestimation.

Bottom Line: 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-Automated compared to others).The other IVCCM parameters had substantially lower ICC compared to those for CNFL.Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.

View Article: PubMed Central - PubMed

Affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

ABSTRACT

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 CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 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-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual 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.

No MeSH data available.


Related in: MedlinePlus