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Abbreviations CNBD Corneal nerve branch density CNFD Corneal nerve fibre density CNFL Corneal nerve fibre length IVCCM In vivo corneal confocal microscopy ROC Receiver operating characteristic ROC-AUC Area under the ROC curve To the Editor: There exists an urgent need to better characterise and identify the presence of early-stage diabetic neuropathy when therapy is most likely to be effective. The lack of an objective endpoint for early neuropathy has seriously hindered the evaluation of disease-modifying therapies in clinical research and the prediction of neuropathy progression in clinical care [1, 2]. There is considerable evidence that injury to small, thinly myelinated and unmyelinated nerve fibres precedes injury to large myelinated fibres in individuals with diabetic neuropathy [3]. Morphological examination of the small nerve fibres of the cornea by in vivo corneal confocal microscopy (IVCCM) has emerged as an objective and non-invasive imaging technique for identifying diabetic neuropathy. Specifically, lower corneal nerve fibre length (CNFL) has been confirmed as a valid biomarker for neuropathy identification in younger adults with type 1 diabetes [4, 5] and may represent a surrogate endpoint for trials of disease-modifying therapies for neuropathy. However, CNFL’s diagnostic performance may be impaired with advanced age and diabetes duration owing to ageand extensive disease-related changes in corneal nerve morphology [6]. We aimed to determine whether CNFL retains its diagnostic validity in a unique cohort of older adults who have lived with type 1 diabetes for over 50 years. As part of the second phase of the Canadian Study of Longevity in Type 1 Diabetes [7], 67/75 (89%) participants with type 1 diabetes and 69/75 (92%) participants forming a non-diabetic control group from age/sex-matched subgroups underwent electrophysiology-based procedures to define neuropathy (reference standard) and evaluation of corneal morphology by IVCCM (index test) in a cross-sectional analysis of the baseline evaluation. All participants provided written informed consent and the study and its procedures were approved by the institutional ethics board at the University * Bruce A. Perkins bruce.perkins@sinaihealthsystem.ca

diabetologia

Lower corneal nerve fibre length identifies diabetic neuropathy in older adults with diabetes: results from the Canadian Study of Longevity in Type 1 Diabetes