Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes

Diabetes Care. 2015 Apr;38(4):671-5. doi: 10.2337/dc14-2114. Epub 2015 Jan 8.

Abstract

Objective: This study determined if deficits in corneal nerve fiber length (CNFL) assessed using corneal confocal microscopy (CCM) can predict future onset of diabetic peripheral neuropathy (DPN).

Research design and methods: CNFL and a range of other baseline measures were compared between 90 nonneuropathic patients with type 1 diabetes who did or did not develop DPN after 4 years. The receiver operator characteristic (ROC) curve was used to determine the capability of single and combined measures of neuropathy to predict DPN.

Results: DPN developed in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-to-creatinine ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds; impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff of 14.1 mm/mm(2) (area under ROC curve = 0.66, P = 0.041). Combining neuropathy measures did not improve predictive capability.

Conclusions: DPN can be predicted by various demographic, metabolic, and conventional neuropathy measures. The ability of CCM to predict DPN broadens the already impressive diagnostic capabilities of this novel ophthalmic marker.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Size
  • Cornea / innervation
  • Cornea / pathology
  • Cornea / ultrastructure*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Neuropathies / diagnosis*
  • Diabetic Neuropathies / epidemiology
  • Diabetic Retinopathy / diagnosis*
  • Diabetic Retinopathy / epidemiology
  • Diagnostic Techniques, Ophthalmological*
  • Female
  • Humans
  • Incidence
  • Male
  • Microscopy, Confocal / methods
  • Middle Aged
  • Nerve Fibers / pathology
  • Prognosis
  • Sensitivity and Specificity
  • Young Adult