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Fully Automated, Semiautomated, and Manual Morphometric Analysis of Corneal Subbasal Nerve Plexus in Individuals With and Without Diabetes

Dehghani, Cirous MSc; Pritchard, Nicola PhD; Edwards, Katie PhD; Russell, Anthony W. MBBS, PhD; Malik, Rayaz A. MBChB, PhD; Efron, Nathan PhD, DSc

doi: 10.1097/ICO.0000000000000152
Clinical Science

Purpose: The aim of the study was to determine the association, agreement, and detection capability of manual, semiautomated, and fully automated methods of corneal nerve fiber length (CNFL) quantification of the human corneal subbasal nerve plexus (SNP).

Methods: Thirty-three participants with diabetes and 17 healthy controls underwent laser scanning corneal confocal microscopy. Eight central images of the SNP were selected for each participant and analyzed using manual (CCMetrics), semiautomated (NeuronJ), and fully automated (ACCMetrics) software to quantify the CNFL.

Results: For the entire cohort, mean CNFL values quantified by CCMetrics, NeuronJ, and ACCMetrics were 17.4 ± 4.3 mm/mm2, 16.0 ± 3.9 mm/mm2, and 16.5 ± 3.6 mm/mm2, respectively (P < 0.01). CNFL quantified using CCMetrics was significantly higher than those obtained by NeuronJ and ACCMetrics (P < 0.05). The 3 methods were highly correlated (correlation coefficients 0.87–0.98, P < 0.01). The intraclass correlation coefficients were 0.87 for ACCMetrics versus NeuronJ and 0.86 for ACCMetrics versus CCMetrics. Bland–Altman plots showed good agreement between the manual, semiautomated, and fully automated analyses of CNFL. A small underestimation of CNFL was observed using ACCMetrics with increasing the amount of nerve tissue. All 3 methods were able to detect CNFL depletion in diabetic participants (P < 0.05) and in those with peripheral neuropathy as defined by the Toronto criteria, compared with healthy controls (P < 0.05).

Conclusions: Automated quantification of CNFL provides comparable neuropathy detection ability to manual and semiautomated methods. Because of its speed, objectivity, and consistency, fully automated analysis of CNFL might be advantageous in studies of diabetic neuropathy.

*Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia;

Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia;

School of Medicine, University of Queensland, Brisbane, Australia; and

§Center for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, United Kingdom.

Reprints: Nathan Efron, PhD, DSc, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia (e-mail:

The authors have no conflicts of interest to disclose.

Supported by grants from the National Health and Medical Research Council (Australia) (497230) and the JDRF International (27-2007-878 and 8-2008-362).

Received October 31, 2013

Accepted April 10, 2014

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.