Small Nerve Fiber Quantification in the Diagnosis of Diabetic Sensorimotor Polyneuropathy: Comparing Corneal Confocal Microscopy With Intraepidermal Nerve Fiber Density

• DOI: 10.2337/dc14-2422
• Publication Date: 2015-03-21T03:31:35Z
• Authors: Xin Chen; Jim Graham; Mohammad A. Dabbah; Ioannis N. Petrop...; Georgios Ponirakis; Omar Asghar; Uazman Alam; Andrew Marshall; Hassan Fadavi; Maryam Ferdousi; Shazli Azmi; Mitra Tavakoli; Nathan Efron; Maria Jeziorska; Rayaz A. Malik
• Keywords: Adult; Male; Microscopy, Confocal; Biopsy; Neural Conduction; 3. Good health; Cornea; Polyneuropathies; 03 medical and health sciences; Diabetes Mellitus, Type 1; Early Diagnosis; Nerve Fibers; 0302 clinical medicine; Diabetic Neuropathies; ROC Curve; Case-Control Studies; Humans; Female; Biomarkers; Skin

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard.

RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy.

RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14).

CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.