Corneal Confocal Microscopy Predicts Cardiovascular and Cerebrovascular Events and Demonstrates Greater Peripheral Neuropathy in Patients with Type 1 Diabetes and Foot Ulcers

Abstract

Objective: In this study, we evaluate small and large nerve fibre pathology in relation to diabetic foot ulceration (DFU) and incident cardiovascular and cerebrovascular events in type 1 diabetes (T1D). Methods: A prospective observational study was conducted on people with T1D without diabetic peripheral neuropathy (DPN) (n = 25), T1D with DPN (n = 28), T1D with DFU (n = 25) and 32 healthy volunteers. ROC analysis of parameters was conducted to diagnose DPN and DFU, and multivariate Cox regression analysis was performed to evaluate the predictive ability of corneal nerves for cardiac and cerebrovascular events over 3 years. Results: Corneal nerve fibre length (CNFL), fibre density (CNFD) and branch density (CNBD) were lower in T1D-DPN and T1D-DFU vs. T1D (all p < 0.001). In ROC analysis, CNFD (sensitivity 88%, specificity 87%; AUC 0.93; p < 0.001; optimal cut-off 7.35 no/mm2) and CNFL (sensitivity 76%, specificity 77%; AUC 0.90; p < 0.001; optimal cut-off 7.01 mm/mm2) had good ability to differentiate T1D with and without DFU. Incident cardiovascular events (p < 0.001) and cerebrovascular events (p < 0.001) were significantly higher in T1D-DPN and T1D-DFU. Corneal nerve loss, specifically CNFD predicted incident cardiovascular (HR 1.67, 95% CI 1.12 to 2.50, p = 0.01) and cerebrovascular (HR 1.55, 95% CI 1.06 to 2.26, p = 0.02) events. Conclusions: Our study provides threshold values for corneal nerve fibre metrics for neuropathic foot at risk of DFU and further demonstrates that lower CNFD predicts incident cardiovascular and cerebrovascular events in T1D.

Corneal neuropathy in central serous chorioretinopathy

“…Similar findings have been repeatedly reported in patients suffering from autonomic diabetic neuropathy 37 and in which the cornea has served as a sensor of the severity and the risk of cardiovascular events. In diabetic type 1, corneal nerve fibre metrics predicted incident cardiovascular and cerebrovascular events 38 , though mechanisms involving neuroimmune inflammation related to increased sympathetic activity within the vascular wall. In diabetic patients, corneal confocal imaging has been considered as a rapid, non-invasive, but also highly sensitive and specific for the diagnostic of autonomic diabetic neuropathy.…”

Is the 10 g monofilament fit for purpose for diagnosing DPN?

“…11 It also identifies subclinical DPN 12 and predicts the development of clinical DPN 13 and DFU. 14 A one-stop-shop model which uses artificial intelligence-driven analysis of digital retinal fundus and corneal confocal microscopy images may enable rapid diagnosis of early diabetic retinopathy and neuropathy, respectively. In a pilot study in Manchester, 427 of 450 (94.9%) consecutive subjects with type 1 or type 2 diabetes attending for annual eye screening in primary care optometry settings successfully underwent CCM for the early diagnosis of DPN.…”