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M. Tavakoli, C. Quattrini, A. Boulton, N. Efron, R.A. Malik, Diabetic Research Centre, Eurolens Research; Corneal Confocal Microscopy Is Superior to Skin Biopsy in Detection of Diabetic Neuropathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1366.
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There is an urgent need to develop surrogate markers to aid in the diagnosis and assessment of treatment efficacy in human diabetic neuropathy.
22 diabetic patients underwent detailed assessment of Neuropathy Impairment Score in the lower limbs (NIS–LL), electrophysiology (EMG), quantitative sensory testing (QST), corneal confocal microscopy (CCFM) and skin biopsy. On the basis of NIS–LL, EMG and QST assessment 11 patients were classed to have no neuropathy, and 11 had neuropathy. CCFM was performed to quantify corneal nerve morphology: nerve fibre density (NFD), tortuosity (NFT), and branch density (NBD) were compared with normative values from healthy control group.
3 mm punch skin biopsies were performed from the dorsum of the foot and immunohistochemical staining was performed with PGP 9.5 to quantify dermal nerve fibre density (DNFD) and compared with normative values from 23 volunteers (aged sex matched)
1) CCFM demonstrated differences between non neuropathic diabetic, neuropathic diabetic and control groups. Respective results are given as mean ± SD: NFD 29±10, 35±13, and 46±16 nerves/mm2 (P=0.02); NFT 8±8, 19 ±14, 24±10 (tortuosity index, P=0.002), NFBD 6±2, 6±3, 33±26 branches/mm2 (p<0.001). 2) DNFD was reduced in all diabetic patients, non neuropathic and neuropathic, compared to controls (respectively 203±114, 190±58, and 414±196 fibres/mm2 (P<0.001). No differences between the two patient groups were showed by post–hoc analysis.
Whilst both CCFM and DNFD were more reduced in diabetic patients with compared to those without neuropathy this did not reach significance. Corneal nerve morphology and skin DNFD correlated with electrophysiological parameters. However they did not correlate to each other. This preliminary study demonstrates significant associations between corneal nerve morphology, ENFD and conventional measures of neuropathic severity suggesting that they may be reliable surrogate measures of human diabetic neuropathy.
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