title: Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy.
abstract: OBJECTIVE
  We have assessed whether corneal confocal microscopy can be used to detect alterations in nerve morphology following an improvement in risk factors associated with diabetic neuropathy.
  
  
  METHODS
  Twenty-five patients with diabetes with mild to moderate neuropathy and 18 control subjects underwent corneal confocal microscopy to quantify corneal nerve fibre (density, branch density, length and tortuosity) at baseline and after 24 months from first visit. This was not planned as an intervention trial and was simply an observational follow-up.
  
  
  RESULTS
  At baseline, nerve fibre density (18.8 ± 2.1 vs. 46.0 ± 3.8 number/mm(2), P = 0.001), nerve branch density (6.9 ± 1.5 vs. 35.6 ± 6.7 number/mm(2), P < 0.0001), nerve fibre length (8.3 ± 0.9 vs. 13.5 ± 0.8 mm/mm(2), P < 0.0001) and nerve fibre tortuosity (19.8 ± 1.6 vs. 22.7 ± 2.2, P < 0.05) were significantly lower in patients with diabetes than in control subjects. At follow-up, glycaemic control (HbA(1c) 64 ± 3 to 58 ± 2 mmol/mol, P = 0.08), total cholesterol (4.9 ± 0.2 to 4.2 ± 0.2 mmol/l, P = 0.01), systolic blood pressure (145.8 ± 4.9 to 135.9 ± 3.7 mmHg, P = 0.09) and diastolic blood pressure (77.8 ± 2.7 to 70.8 ± 2.5, P = 0.03) improved. Nerve fibre density (24.1 ± 2.0, P = 0.05), nerve branch density (11.1 ± 1.3, P < 0.01) and nerve fibre tortuosity (22.6 ± 1.5, P = 0.05) increased significantly, with no change in nerve fibre length (8.4 ± 0.5). Improvement in nerve fibre density correlated significantly with the improvement in HbA(1c) (r = -0.51, P = 0.008). Via four multifactorial regressions, this confirms the negative association between HbA(1c) and nerve fibre density (P = 0.02).
  
  
  CONCLUSIONS
  This study shows that corneal confocal microscopy may be employed in longitudinal studies to assess progression of human diabetic neuropathy and also supports the hypothesis that improvements in risk factors for diabetic neuropathy, in particular HbA(1c) , may lead to morphological repair of nerve fibres.
authors.affiliation: Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tavakoli
authors.forename: P
authors.initials: P
authors.lastname: Kallinikos
authors.forename: A
authors.initials: A
authors.lastname: Iqbal
authors.forename: A
authors.initials: A
authors.lastname: Herbert
authors.forename: H
authors.initials: H
authors.lastname: Fadavi
authors.forename: N
authors.initials: N
authors.lastname: Efron
authors.forename: A J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: R
authors.initials: R
authors.lastname: A Malik
mesh_terms: D003315:Cornea / Q000294:innervation / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000473:pathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D012307:Risk Factors
chemical_list: D006442:Glycated Hemoglobin