Current Topics
Corneal confocal microscopy: New surrogate marker for Diabetic neuropathy and other small fibre neuropathies
The accurate detection and quantification of human diabetic neuropathy (DPN) are important to define at risk patients, anticipate deterioration, and assess new therapies. Current methods lack sensitivity (QST), require expert assessment (neurophysiology) or are invasive (skin/nerve biopsy). The focus of our work is to use Corneal confocal microscopy (CCM), a relatively new technique to examine small nerve fibres; in real-time and in a non-invasive means. We can image the sub-basal nerve plexus of the in vivo human cornea at 700X magnification. The primary hypothesis of our research is based on the assessment of corneal nerve morphology using corneal confocal microscopy as a valid surrogate end point for human diabetic neuropathy and in a range of other peripheral neuropathies. Our recent NIH (5RO1 NS46259-03 NINDS), JDRF (5-2002-185) and DUK (RD03/0002624) funded research using corneal confocal microscopy suggests that this non-invasive and hence reiterative test might be an ideal surrogate endpoint for human diabetic neuropathy.
Now, we are trying to establish whether corneal nerve fibre damage as assessed with CCM and corneal sensation is altered at early stages in patients with impaired glucose tolerance and diabetic patients with minimal neuropathy, thereby establishing its place in the diagnosis of DPN. We will also establish whether corneal nerve fibre damage as assessed with CCM and corneal sensation reflects progressive damage to nerves as assessed by clinical (NDS, QST, EMG) and laboratory (intra-epidermal nerve fibre density) markers of somatic nerve damage in diabetic neuropathy in a longitudinal study to enable assessment of progression or deterioration. Our studies also focus on the benefits of improved glycemic control by pancreas transplantation, as our preliminary study shows an improvement in corneal nerve fibre structure (CCM) and function (corneal sensation). This data may allow us to assess the potential of CCM to determine therapeutic efficacy for future trials in human diabetic neuropathy.
Myogenic Autoregulation
Myogenic autoregulation is the most basic and essential of the functions of the small artery. It is the capacity of the artery to respond to an increase in intraluminal pressure by vasoconstricting, or vasodilation to a decrease in pressure. This process enables small arteries to protect the organs that they supply from central pressures elevated by hypertension. We are engaged in the study of myogenic autoregulation in both Caucasian and Asian patients with obesity, hypertension and dysregulation of glucose and lipid metabolism: in other words, patients with the metabolic syndrome. Using isobaric myography, we have found that myogenic autoregulation is impaired in patients with the metabolic syndrome who have early renal disease. By contrast, those patients who do not have target organ damage have a comparable autoregulatory profile to control participants. We are now investigating the mechanisms by which myogenic autoregulation is damaged. To do this we assess levels of inflammation in fat which surrounds the small artery using immunohistochemistry and examine mechanical aspects of the arterial wall using immunoflorescence.