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Updated: Apr 4, 2026
Corneal Confocal Microscopy: A Novel Non-invasive Technique to Quantify Small Fibre Pathology in Peripheral Neuropathies
Published on: January 3, 2011
The Reliability and Reproducibility of Corneal Confocal Microscopy in Children
Danièle Pacaud1, Kenneth G Romanchuk2, Mitra Tavakoli3
1Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 2Alberta Children's Hospital, Calgary, Alberta, Canada 3Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
Insights
In vivo corneal confocal microscopy (IVCCM) shows good reproducibility for measuring corneal nerve fiber length in children. Refinements in image selection can further enhance this noninvasive method for early neuropathy detection.
Area of Science:
- Ophthalmology
- Neurology
- Pediatrics
Background:
- Diabetic neuropathy can affect children, necessitating early detection methods.
- In vivo corneal confocal microscopy (IVCCM) offers a noninvasive approach to assess corneal nerves.
Purpose of the Study:
- To evaluate the interrater agreement and 1-month repeatability of corneal nerve fiber length (CNFL) measurements in children using IVCCM.
- To compare manual and automated image analysis for CNFL quantification in pediatric subjects.
Main Methods:
- Seventy-one children (8-18 years), including 44 with type 1 diabetes, underwent IVCCM.
- Manual analysis of 547 corneal images by two masked observers; 1-month repeat assessment in 21 patients.
- Automated image analysis using specialized software (ACCMetrics).
Main Results:
- Excellent image-level (ICC 0.94) and good patient-level (ICC 0.86) reproducibility for CNFL.
- High agreement between manual and automated analysis (ICC 0.89), with manual measurements yielding higher values.
- Minimal bias observed between observers in Bland-Altman analysis.
Conclusions:
- IVCCM demonstrates good reproducibility for CNFL assessment in pediatric subjects.
- Image-level reproducibility surpasses patient-level, suggesting image selection refinement is key.
- IVCCM is a promising tool for early, noninvasive detection of neuropathy in children, particularly those with diabetes.
Purpose:
To assess the image and patient level interrater agreement and repeatability within 1 month for corneal nerve fiber length (CNFL) measured using in vivo corneal confocal microscopy (IVCCM) in children.
Methods:
Seventy-one subjects (mean [SD] age 14.3 [2.6] years, range 8-18 years; 44 with type 1 diabetes and 27 controls; 36 males and 35 females) were included. 547 images (∼6 images per subject) were analyzed manually by two independent and masked observers. One-month repeat visit images were analyzed by a single masked observer in 21 patients. Automated image analysis was then performed using a specialized computerized software (ACCMetrics).
Results:
For CNFL, the ICC (95% CI) were 0.94 (0.93-0.95) for image-level, 0.86 (0.78-0.91) for patient-level, and 0.88 (0.72-0.95) for the 1-month repeat assessment, and the Bland-Altman plots showed minimal bias between observers. Although there was excellent agreement between manual and automated analysis according to an ICC 0.89 (0.82-0.93), the Bland-Altman plot showed a consistent bias with manual measurements providing higher readings.
Conclusions:
In vivo corneal confocal microscopy image analysis shows good reproducibility with excellent intraindividual and interindividual variability in pediatric subjects. Since the image-level reproducibility is stronger than the patient-level reproducibility, refinement of the method for image selection will likely further increase the robustness of this novel, rapid, and noninvasive approach to detect early neuropathy in children with diabetes. Further studies on the use of IVCCM to identify early subclinical neuropathy in children are indicated.
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