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

Abstract

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 curveTo 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 age-and 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

Diagnosis and management of sensory polyneuropathy

“…This technique has advantages over skin biopsy as it is rapid and non-invasive, but it is not yet widely available. There is only a modest correlation with disease stage in any patient and the correlation is of limited utility in clinical practice 183184185. A recent study of nearly 1000 patients with type 1 and type 2 diabetes demonstrated the diagnostic validity of corneal confocal microscopy using a 12.5 mm/mm 2 optimal threshold for automated corneal nerve fiber length in type 1 diabetes (73% sensitivity, 69% specificity) and a 12.3 mm/mm 2 optimal threshold in type 2 diabetes (69% sensitivity, 63% specificity) 176.…”

Evidence of small‐fiber neuropathy in neurofibromatosis type 1

“…Finally, the two patients with a history of MPNST had normal small-and large-fiber tests. 10,25 Our rate of abnormal NCS, indicating large-fiber neuropathy, was low. In addition, clinical findings of a length-dependent large-fiber neuropathy, such as symmetrical distal weakness, sensory loss, and abnormal distal reflexes, were also rare.…”

“…Thus, more studies are needed to determine whether this test is abnormal in a larger cohort of NF1 patients, as well as to determine how CNFL changes with time. For example, in diabetes, CNFL changes can predict the onset of clinically significant neuropathy …”

Risk factors for diabetic kidney disease in adults with longstanding type 1 diabetes: results from the Canadian Study of Longevity in Diabetes

“…This was a cross-sectional study of 75 people enrolled in the second phase of the Canadian Study of Longevity in T1D. Participants with T1D were recruited among the 300 participants who took part in the mail-based survey based on geographical proximity to Toronto General Hospital and willingness to participate [23][24][25].…”