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. 2025 Sep 4;15(9):e098294.
doi: 10.1136/bmjopen-2024-098294.

Methods for the evaluation of corneal nerve fibres in diabetes mellitus by in vivo confocal microscopy: a scoping review

Siv A Sandvik  1 , Tove Lise Morisbakk  2 , Eilin Lundanes  2 , Jorunn Lid  2 , Neil Lagali  3 , Vibeke Sundling  2
Affiliations

Methods for the evaluation of corneal nerve fibres in diabetes mellitus by in vivo confocal microscopy: a scoping review

Siv A Sandvik et al. BMJ Open. .

Abstract

Aim: To map, summarise and analyse the methodologies of corneal nerve fibre imaging in studies using in vivo confocal microscopy (IVCM) in diabetes and assess the potential for standardising methods and reporting.

Methods: A scoping review was conducted using five databases, MEDLINE, Embase, Cochrane, Web of Science and Scopus, with search terms related to IVCM, diabetes and corneal nerves. Two researchers independently screened the studies for eligibility. Relevant data were extracted and systematically analysed.

Results: Out of 1533 screened articles, 195 met the inclusion criteria. Spanning from 2000 to 2024, the studies showed high variability in image acquisition, image processing, image analysis and reporting detail. Most studies used laser scanning confocal microscopy, examining the central cornea in both eyes in patients with type 2 diabetes, manually selecting 3-6 images from each eye, and using ACCMetrics and CCMetrics for quantifying corneal nerve fibre length in mm/mm2. Many studies lacked sufficient methodological details for reproducibility.

Conclusion: IVCM studies of corneal nerve fibres in diabetes show substantial methodological heterogeneity and inconsistent reporting, limiting reproducibility. We propose a guideline to support standardisation and improve the reliability of future research.

Keywords: DIABETES & ENDOCRINOLOGY; Methods; Protocols & guidelines; Review.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. PRISMA flow diagram illustrating the search strategy.
Figure 2
Figure 2. Overview of studies with different imaging and selection criteria, % of studies. (a) Overview of studies imaging one, two or both eyes. (b) Corneal region for image acquisition (%). (c) Categorised image selection criteria, numbers not mutually exclusive (% of studies) representing different categories of selection criteria. (d) Number of images selected per eye for further analysis (% of studies). NA, not applicable; NI, no information; RF, refer further to other articles.
Figure 3
Figure 3. Overview of the analysis tools for quantification of the subbasal nerves. % of studies.
See this image and copyright information in PMC

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