Corneal Confocal Microscopy: A novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

• Published in: Diabetes care Vol. 33; no. 8; pp. 1792 - 1797
• Main Authors: Tavakoli, Mitra, Quattrini, Cristian, Abbott, Caroline, Kallinikos, Panagiotis, Marshall, Andrew, Finnigan, Joanne, Morgan, Philip, Efron, Nathan, Boulton, Andrew J.M, Malik, Rayaz A
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.08.2010
• Subjects: Care and treatment; cornea; Cornea - innervation; Cornea - pathology; Diabetes; Diabetic Neuropathies; Diabetic Neuropathies - diagnosis; Diabetic neuropathy; Diagnosis; Female; Football (Professional); heat; Humans; innervation; Male; Medical research; Medicine, Experimental; methods; Microscope and microscopy; microscopy; Microscopy, Confocal; Microscopy, Confocal - methods; Middle Aged; nerve tissue; Original Research; pain; pathology; patients; risk; Statistical methods; Studies
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc10-0253

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = -0.475, P < 0.0001; NBD r = -0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm² with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm² with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74). CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity.