Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study.
OBJECTIVE
We aimed to determine the corneal confocal microscopy (CCM) parameter that best identifies diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes and to describe its performance characteristics.


METHODS
Concurrent with clinical and electrophysiological examination for classification of DSP, CCM was performed on 89 type 1 diabetic and 64 healthy subjects to determine corneal nerve fiber length (CNFL), density, tortuosity, and branch density. Area under the curve (AUC) and optimal thresholds for DSP identification in those with diabetes were determined by receiver operating characteristic (ROC) curve analysis.


RESULTS
DSP was present in 33 (37%) subjects. With the exception of tortuosity, CCM parameters were significantly lower in DSP case subjects. In ROC curve analysis, AUC was greatest for CNFL (0.88) compared with fiber density (0.84, P = 0.0001), branch density (0.73, P < 0.0001), and tortuosity (0.55, P < 0.0001). The threshold value that optimized sensitivity and specificity for ruling in DSP was a CNFL of ≤14.0 mm/mm(2) (sensitivity 85%, specificity 84%), associated with positive and negative likelihood ratios of 5.3 and 0.18. An alternate approach that used separate threshold values maximized sensitivity (threshold value ≥15.8 mm/mm(2), sensitivity 91%, negative likelihood ratio 0.16) and specificity (≤11.5 mm/mm(2), specificity 93%, positive likelihood ratio 8.5).


CONCLUSIONS
Among CCM parameters, CNFL best discriminated DSP cases from control subjects. A single threshold offers clinically acceptable operating characteristics, although a strategy that uses separate thresholds to respectively rule in and rule out DSP has excellent performance while minimizing unclassified subjects. We hypothesize that values between these thresholds indicate incipient nerve injury that represents those individuals at future neuropathy risk.
Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ausma
A
Ahmed
Vera
V
Bril
Andrej
A
Orszag
Jenna
J
Paulson
Emily
E
Yeung
Mylan
M
Ngo
Steven
S
Orlov
Bruce A
BA
Perkins
D000328:Adult; D003315:Cornea / Q000473:pathology / Q000648:ultrastructure*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000175:diagnosis; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000209:etiology; D003941:Diagnostic Techniques, Ophthalmological; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D015840:Oculomotor Nerve Diseases / Q000175:diagnosis* / Q000209:etiology; D009900:Optic Nerve / Q000473:pathology / Q000648:ultrastructure; D009929:Organ Size; D010775:Photic Stimulation / Q000379:methods; D055815:Young Adult