Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study
Research Design and Methods: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 who were free of DPN at baseline and completed at least four 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: 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, had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and CCM parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve (AUC) 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 14.1mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard rate 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 approximately 6 years in the future.