Corneal confocal microscopy detects improvements in nerve morphology after simultaneous Pancreas and Kidney transplantation (SPK) in type 1 diabetic patients

Abstract

Purpose: : Tests which assess diabetic neuropathy focus primarily on large nerve fiber dysfunction. Whilst small fibres are the earliest to be damaged and demonstrate repair even in advanced neuropathy, skin and nerve biopsy, which allow assessment of small fibre morphology are invasive procedures. Corneal confocal microscopy represents a rapid, non invasive clinical examination technique which quantifies small nerve fiber pathology.

Methods: : 15 Type 1 diabetic patients (age: 47±3 yrs, duration of diabetes: 27±3.5 yrs) undergoing simultaneous pancreas-kidney transplantation (SPK) were studied at baseline, 6 and 12 months after SPK transplantation and compared with 10 non-diabetic healthy subjects. All subjects underwent assessment of electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy at baseline, 6 and 12 months after successful SPK.

Results: : CCM demonstrated a significant reduction in Nerve fibre density (NFD) (P<0.0001), nerve branch density (NBD) (P<0.0001) and nerve fibre length (NFL) (P<0.0001) at baseline in diabetic patients compare to control subjects. 6 months after SPK transplantation, HbA1c normalized (5.93±0.35 v 7.38 ± 0.80, P=0.1), confirming successful pancreas transplantation and NBD showed a significant improvement (36.85±6.04 v 21.46±3.78, P=0.03). At 12 months peroneal nerve conduction velocity (P=0.3), amplitude (P=0.2) and vibration perception (P=0.6) failed to show a significant improvement. However, NFD (19.27±1.57 v 14.44±1.20, P= 0.02), NBD (43.02±6.48 v 21.46±3.78, P=0.008) and NFL (15.63±1.56 v 11.35±1.04, P=0.03) demonstrated a significant improvement.

Conclusions: : Despite marked nerve fiber damage in Type 1 diabetic patients before undergoing SPK, small fiber repair begins within 6 months of transplantation and continues at 12 months. Corneal confocal microscopy provides a non-invasive clinical technique to assess early nerve fibre repair which cannot be detected using electrophysiology or QST. We suggest that CCM may provide an important means to assess the benefits of therapeutic intervention in human diabetic neuropathy.

Keywords: cornea: clinical science • diabetes • clinical (human) or epidemiologic studies: outcomes/complications