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Andrey Zhivov, Dan Ziegler, Sabine Peschel, Stephan Allgeier, Karsten Winter, Bernd Koehler, Nikolaos Papanas, Oliver Stachs, Michael Roden, Rudolf Guthoff, GDC Study Group; Confocal Microscopy of Corneal Nerves for Early Detection of Diabetic Neuropathy in Recently Diagnosed Type 2 Diabetic Patients. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3577.
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© ARVO (1962-2015); The Authors (2016-present)
Detection of the earliest stage of diabetes at which neuropathy starts to develop is of major interest to prevent the feared sequelae of advanced neuropathy. In-vivo confocal laser scanning microscopy (CLSM) of the cornea enables nerve fiber quantification in the corneal sub-basal nerve plexus (SNP). The study was performed to determine whether SNP alterations may be detected in subjects with recently diagnosed type 2 diabetes in comparison to healthy volunteers.
86 recently diagnosed (duration 2.1±1.8 yrs., Hba1c 6.8+/-1.1) diabetic patients aged 57.8 ± 9.1 yrs. and 48 healthy volunteers aged 53.7±13.4 yrs. were enrolled in an observer masked study. Both groups underwent in-vivo CLSM in the central cornea unilaterally and assessment of corneal sensation. In-house developed automated algorithms for image reconstruction and analysis were used to quantify the morphological quantities of SNP. Intraepidermal nerve fiber density (IENFD) was evaluated in skin specimens gained with 3-mm punch biopsy from the distal leg using PGP 9.5 antibody immunohistochemistry. Peripheral and autonomic nerve function was evaluated.
CLSM parameters were reduced in the diabetic group as compared to the controls (nerve fiber density (p<0.001), number of branches (p=0.008), number of connecting points (p=0.005), and thickness of nerve fibers (p=0.032)). There was no difference in corneal sensation between diabetic patients and healthy volunteers. IENFD correlated with nerve fiber density of SNP (r=0.23; p=0.014) as well with the results of peripheral and autonomic nerve function tests. There was no correlation between SNP parameters and any nerve function tests.
This study demonstrated that corneal SNP parameters may be used as an early marker of small fiber neuropathy in recently diagnosed diabetes. The applied diagnostic technology has the potential to detect nerve damage at early stages of diabetes and to establish clinical end-user instrumentation for non-invasive diagnosis and follow-up.
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