Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

Mitra Tavakoli, Cristian Quattrini, Caroline Abbott, Panagiotis Kallinikos, Andrew Marshall, Joanne Finnigan, Philip Morgan, Nathan Efron, Andrew J M Boulton, Rayaz A Malik, Mitra Tavakoli, Cristian Quattrini, Caroline Abbott, Panagiotis Kallinikos, Andrew Marshall, Joanne Finnigan, Philip Morgan, Nathan Efron, Andrew J M Boulton, Rayaz A Malik

Abstract

Objective: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.

Research design and methods: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).

Results: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = -0.475, P < 0.0001; NBD r = -0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm(2) with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm(2) with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74).

Conclusions: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity.

Figures

Figure 1
Figure 1
Images of corneal nerves in Bowman layer, showing abundant nerve fibers and adequate branching in a control subject (A) with a typical image from a diabetic patient with mild (B), moderate (C), and severe (D) neuropathy showing a progressive loss of nerve fibers.
Figure 2
Figure 2
Corneal nerve morphology in control subjects and diabetic patients with increasing neuropathic severity: A: NFD (P < 0.0001); B: NBD (P < 0.0001); C: NFL (P < 0.0001).
Figure 3
Figure 3
ROC curves for NFD, NBD, and NFL for (A) NDS >3 and (B) NDS >6. Diagonal segments are produced by ties.

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Source: PubMed

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