A Comparative Study on the Diagnostic Utility of Corneal Confocal Microscopy and Tear Neuromediator Levels in Diabetic Peripheral Neuropathy

ABSTRACT

Aims

To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes.

Methods

Seventy individuals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve; TNS ≥ 2; T1D, n = 19; T2D, n = 16) and without DPN (DPN–ve; TNS ≤ 1; T1D, n = 19; T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN.

Results

In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced (P < .010) in DPN+ve. Also, for the nerve excitability measures, mean peak response, percentage of threshold electrotonus at peak and after 90-100 ms, superexcitability and subexcitability were significantly reduced (P < .050) in DPN+ve. In T2D, except for inferior whorl length (P = .190), all other corneal confocal microscopy measures were significantly reduced (P < .010) in DPN+ve, but there was no difference in substance P concentration. For the diagnosis of DPN in T1D, the AUC for inferior whorl length (0.910), mean peak response (0.800) and concentration of substance P (0.770) were high and in T2D, the AUC for corneal nerve fiber length (0.809) and nerve fractal dimension (0.777) were high.

Conclusion

Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.

KEYWORDS:

• Diabetic peripheral neuropathy
• Corneal confocal microscopy
• Substance P
• Calcitonin gene-related peptide
• Nerve excitability studies
• Tear neuromediators

Acknowledgments

The Total Neuropathy Score was provided to Professor Arun Krishnan by Professor David Cornblath and Johns Hopkins University.