Detection of Diabetic Sensorimotor Polyneuropathy by Corneal Confocal Microscopy in Type 1 Diabetes: A concurrent validity study

• Published in: Diabetes care Vol. 35; no. 4; pp. 821 - 828
• Main Authors: Ahmed, Ausma, Bril, Vera, Orszag, Andrej, Paulson, Jenna, Yeung, Emily, Ngo, Mylan, Orlov, Steven, Perkins, Bruce A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2012
• Subjects: Accuracy; Adult; Biological and medical sciences; Clinical medicine; complications; Complications and side effects; Confocal microscopy; cornea; Cornea - pathology; Cornea - ultrastructure; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - diagnosis; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies; Diabetic Neuropathies - diagnosis; Diabetic Neuropathies - etiology; Diabetic neuropathy; Diagnosis; Diagnostic Techniques, Ophthalmological; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; etiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; insulin-dependent diabetes mellitus; Male; Medical sciences; Metabolic diseases; methods; microscopy; Microscopy, Confocal; Microscopy, Confocal - methods; Middle Aged; Miscellaneous; nerve tissue; Neuropathies, Hereditary motor and sensory; Oculomotor Nerve Diseases; Oculomotor Nerve Diseases - diagnosis; Oculomotor Nerve Diseases - etiology; Optic Nerve; Optic Nerve - pathology; Optic Nerve - ultrastructure; Organ Size; Original Research; pathology; peripheral nervous system diseases; Photic Stimulation; Photic Stimulation - methods; Public health. Hygiene; Public health. Hygiene-occupational medicine; risk; Risk factors; Studies; Type 1 diabetes; ultrastructure; Young Adult; Canada; Endocrinopathy; Human; Immunopathology; Nervous system diseases; Cornea; Nutrition; Concurrent; Autoimmune disease; Metabolic diseases; Confocal microscopy; Polyneuropathy; Eye; Visual system; Validity; Concomitant disease; Type 1 diabetes; Peripheral nerve disease; Detection; Endocrinology
• DOI: 10.2337/dc11-1396
• ISSN: 0149-5992; 1935-5548

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. RESEARCH DESIGN AND 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/mm2 (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/mm2, sensitivity 91%, negative likelihood ratio 0.16) and specificity (≤11.5 mm/mm2, 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.