Longitudinal Assessment of Novel Ophthalmic Diabetic Markers (LANDMark Study)

Overview

Project status: In progress

The overall aim of this work is to employ novel non-invasive ophthalmic markers of peripheral nerve dysfunction - corneal confocal microscopy (CCM), non-contact corneal aesthesiometry (NCCA), ocular coherence tomography (OCT) and flicker perimetry (FP) - to investigate longitudinal changes in peripheral nerve morphology and function in Type 1 and Type 2 diabetic patients with neuropathy.

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Grantor
  • Juvenile Diabetes Research Foundation International
  • National Health and Medical Research Council
  • George Weaber Foundation Trust
  • American Optometric Foundation/Vision Service Plan
Research leader
Research team
QUT External collaborators

Australian Collaborators

  • Dr Anthony Russell (School of Medicine, UQ)
  • Associate Professor Andrew Cotterill (Mater Children's Hospital)

International Collaborators

  • Professor Rayaz Malik (University of Manchester, UK)
  • Professor Andrew Boulton (University of Manchester, UK)
Organisational unit
Lead unit Faculty of Health Other units
Research area
Vision Improvement
 

Details

Longitudinal assessment

Figure 1: Composite map of the corneal sub-basal nerve plexus in a non-diabetic subject

Advanced diabetic neuropathy is a major cause of morbidity and mortality worldwide. The late sequelae of diabetic neuropathy include foot ulceration and lower extremity amputation. Therefore, the accurate early detection, characterization and quantification of diabetic neuropathy are important to define at risk patients, anticipate and monitor deterioration, and assess new therapies.

The extent to which nerve electrophysiology and quantitative sensory testing (QST) indicate small fibre pathology is not known. Nerve and skin biopsy methods allow detailed pathological assessment but are invasive and cannot be performed in routine clinical practice. CCM is a relatively new technique and can be used to examine small nerve fibres; it is a real-time, non-invasive means of imaging the sub-basal nerve plexus of the in vivo human cornea at 700X magnification, and has been shown to be capable of accurate diagnosis and stratification of diabetic patients with neuropathy. Thus, the advent of CCM means that longitudinal studies of nerve degeneration can be studies in patients with diabetic neuropathy.

In addition, NCCA is a novel new form of QST whereby corneal sensitivity can be monitored non-invasively. OCT and FP will allow investigation of anatomical and functional correlates of diabetic neuropathy. The primary intended outcome of this work is that it will be possible to define, for the first time, longitudinal morphological changes in peripheral nerves in patients suffering from diabetic neuropathy, and determine the extent to which these changes correlate with clinical signs and symptoms. The significance of this work is that it will reveal the potential for CCM, NCCA, OCT and FP to serve as sensitive, rapid, reiterative, non-invasive ophthalmic markers for the detection, quantification and monitoring of the progression of diabetic neuropathy.

This information will provide a robust basis for the design of therapeutic trials taking into account the natural history of diabetic neuropathy. This research will reveal the importance (or otherwise) of glycaemic control and other metabolic abnormalities and demographic factors which may impact on the progression of neuropathy in diabetic patients.


Publications and output

  1. Malik RA, Kallinikos P, Abbott CA, vanSchie CHM, Morgan PB, Efron N, Boulton AJM. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia 2003; 46: 683-88.
  2. Kallinikos P, Berhanu M, O'Donnell C, Boulton AJ, Efron N, Malik RA. Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci 2004; 45: 418-422.
  3. Tavakoli M, Kallinikos P, Efron N, Boulton AJ, Malik RA. Corneal sensitivity is reduced and relates to the severity of neuropathy in patients with diabetes. Diabetes Care 2007; 30(7): 1895-1897.
  4. Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, Marshall A, Boulton AJM, Efron N, Malik RA. Surrogate markers of small fibre damage in human diabetic neuropathy. Diabetes 2007; 56(8): 2148-2154.
  5. Mehra S, Tavakoli M, Kallinikos PA, Efron N, Boulton AJ, Augustine T, Malik RA. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care 2007; 30(10): 2608-2612.
  6. Moavenshahidi A, Sampson GP, Pritchard N, Edwards K, Russell A, Malik RA, Efron N. Exploring retinal and functional markers of diabetic neuropath. Clin Exp Optom 2010; 93: 5: 309-323.
  7. Efron N, Edwards K, Roper N, Pritchard N, Sampson GP, Shahidi A, Vagenas D, Russell AW, Graham J, Dabbah MA, Malik RA. Repeatability of measuring corneal subbasal nerve fibre length in individuals with type 2 diabetes. Eye & Contact Lens 2010; 36(5): 245-248.
  8. Pritchard N, Edwards K, Vagenas D, Moavenshahidi A, Sampson GP, Russell AW, Malik RA, Efron N. Corneal sensitivity as an ophthalmic marker of diabetic neuropathy. Optom Vis Sci 2010; 67:1003-1008.
  9. Pritchard N, Edwards K, Moavenshahidi A, et al. Corneal markers of diabetic neuropathy. Ocul Surf 2011;9(1): 17-28.