Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study

Abstract

OBJECTIVE Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN. RESEARCH DESIGN AND METHODS From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves. RESULTS A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2–7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1–5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70–5.11; P < 0.001) for new-onset DPN. CONCLUSIONS CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.

BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy

“…The primary endpoint will be the difference between the change over 12 months in corneal nerve fibre length (CNFL) determined using corneal confocal microscopy (CCM) in the benfotiamine group and the placebo group. CCM is currently the most suitable non-invasive instrument to assess early changes in small nerve fibre morphology in DSPN trials 20 21. A recent meta-analysis confirmed a reduction of CCM indices in patients with DSPN compared with individuals without DSPN 22.…”

“…CCM is currently the most suitable non-invasive instrument to assess early changes in small nerve fibre morphology in DSPN trials. 20…”

Corneal Confocal Microscopy and the Nervous System: Introduction to the Special Issue

“…Subsequent funding from the NIDDK enabled the establishment of an international consortium, which combined data from ~1000 patients with type 1 and type 2 diabetes and impaired glucose tolerance and showed that CCM has excellent diagnostic [ 12 , 13 ] and prognostic [ 14 ] value and could detect early nerve regeneration after simultaneous pancreas and kidney transplantation in patients with type 1 diabetes [ 15 , 16 ]. Age-adjusted normative values for CCM were established [ 17 ], and we showed that the severity of corneal nerve loss and associated risk factors are different for type 1 and type 2 diabetic patients [ 18 ].…”

Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

“…Corneal nerve loss also occurs in patients with painful sarcoid neuropathy [ 44 ], painful human immunodeficiency virus (HIV) neuropathy [ 45 ], chemotherapy-induced peripheral neuropathy, and fibromyalgia [ 46 ].…”