Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study

Bruce A. Perkins, Leif E. Lovblom, Vera Bril, Daniel Scarr, Ilia Ostrovski, Andrej Orszag, Katie Edwards, Nicola Pritchard, Anthony Russell, Cirous Dehghani, Danièle Pacaud, Kenneth Romanchuk, Jean K. Mah, Maria Jeziorska, Andrew Marshall, Roni M. Shtein, Rodica Pop-Busui, Stephen I. Lentz, Andrew J.M. Boulton, Mitra TavakoliNathan Efron, Rayaz A. Malik

Research output: Contribution to journalReview articlepeer-review

103 Citations (Scopus)
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Aims/hypothesis: Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods: Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results: Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88% specificity and 88% sensitivity. Conclusions/interpretation: We established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.

Original languageEnglish
Pages (from-to)1856-1861
Number of pages6
Issue number8
Publication statusPublished - 1 Aug 2018
Externally publishedYes


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