Research Optometrist
Nicola Pritchard
Postgraduate Research Students
Munira Al-Dossari (Masters)
Ayda Moaven Shahidi (Masters)
Australian Collaborators
Adjunct Professor Noel Brennan (Brennan Consultants, Melbourne)
Professor John Prins (School of Medicine, UQ)
Dr Tony Russell (School of Medicine, UQ)
Associate Professor Philip Walker (School of Medicine, UQ)
International Collaborators
Dr Philip Morgan (University of Manchester, UK)
Professor Andrew Boulton (University of Manchester, UK)
Dr Rayaz Malik (University of Manchester, UK)
Dr Craig Woods (University of Waterloo, Canada)
The Anterior Eye Laboratory (AEL) conducts a broad array of research on topics related to the anterior eye. This research relates not only to the health of the eye itself, but also to general systemic health problems that can be detected and monitored as a result of changes occurring in the anterior eye. Much of this work at the present time revolves around the use of the corneal confocal microscope (CCM) – a relatively new instrument that is capable of imaging the anterior ocular structures at a cellular level in the living human eye.
The effects of contact lens wear on the anterior ocular structures is an important aspect of the research efforts of the AEL. The CCM is being used to assess changes in the bulbar and palpebral conjunctiva resulting from contact lens wear. This work may help solve the problem of ocular discomfort – especially towards the end of the day – suffered by most contact lens wearers, by documenting changes to various cell types on the ocular surface during lens wear.
A layer of the cornea of particular interest to diabetic physicians is the epithelial sub-basal nerve plexus. Researchers at the AEL have demonstrated that this layer shows evidence of degeneration in diabetic patients suffering from neuropathy, making CCM a potentially useful instrument for monitoring such patients.
Eye temperature is being measured using special infra-red ocular thermographic equipment in patients suffering from carotid artery stenosis. In such patients, there is a partial or complete blockage of blood flow through the neck to the eye. Reduced blood flow in the eye will lead to reduced eye temperature. Thus, ocular thermography is being tested for its potential to serve as a screening test for patients with carotid artery stenosis, a condition that is often a precursor to stroke.
Research Program 1: Novel Ophthalmic Markers of Diabetic Neuropathy
Principal Researcher
Professor Nathan Efron
Research Optometrist
Nicola Pritchard
Graduate Student
Ayda Moaven Shahidi
Funding
George Weaber Foundation Trust
Juvenile Diabetes Research Foundation International
National Health and Medical Research Council
The overall aim of this work is to employ two novel non-invasive ophthalmic markers of peripheral nerve dysfunction – corneal confocal microscopy (CCM) and non-contact corneal aesthesiometry (NCCA) – to investigate longitudinal changes in peripheral nerve morphology and function in Type 1 and Type 2 diabetic patients with neuropathy. 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 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. 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 and NCCA 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.
Key References
- 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.
- 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.
- 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.
- 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.
- 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.
Figure 1: Composite map of the corneal sub-basal nerve plexus in a non-diabetic subject
Research Program 2: Ocular Thermographic Assessment of Internal Carotid Artery Stenosis
Principal Researcher
Professor Nathan Efron
Research Optometrist
Nicola Pritchard
The primary aim of this research is to assess the utility of ocular thermography (OT) as a simple, operator-independent, inexpensive, rapid and non-invasive screening tool for the identification of haemodynamically significant (≥ 50% artery diameter reduction) internal carotid artery stenosis (ICAS) in comparison to the ‘gold standard’ technique of carotid duplex ultrasound (CDUS). ICAS is a major risk factor for ischemic stroke. Once ICAS is detected, therapeutic and surgical measures are available to lessen the risk of stroke. Stroke is a significant health problem: each year there are about 40,000 – 48,000 stroke events among Australians. Although it is effective in diagnosing ICAS, CDUS is relatively expensive in terms of equipment and the operator dependence of this technique demands the employment of highly trained operators. Clearly, the development of new, effective and inexpensive methodologies to screen for ICAS could have a significant impact on the detection of carotid artery disease and the prevention of stroke. As the vascular supply to the eye is the dominant feature in the determination of its temperature, it might be supposed that a total or partial occlusion of the internal carotid artery system would cause a reduction in temperature on the affected side, notwithstanding compensatory collateral blood flow via the circle of Willis. OT can accurately measure eye temperature and in that way has the potential to serve as a simple screening tool for the identification of haemodynamically significant ICAS. The intended outcome of this work will be to define the sensitivity and specificity of OT as a screening test for haemodynamically significant ICAS when compared with the assessment of ICAS using CDUS and MRA. This work will also reveal the effect of collateral circulation in the circle of Willis upon eye temperature in patients with unilateral ICAS. A clear demonstration of the associations between ocular temperature, patterns of compensatory flow in the circle of Willis, and the extent of ICAS, could pave the way for a better understanding of ICAS and the causation of stroke, and validate OT as a simple, operator-independent, inexpensive, rapid and non-invasive adjunct to CDUS in the clinical evaluation and diagnosis of ICAS.
Key References
- Morgan PB, Soh MP, Efron N, Tullo AB. Potential applications of ocular thermography. Optom Vis Sci 1993; 70: 568-576.
- Morgan PB, Smyth JV, Tullo AB, Efron N. Ocular temperature in carotid artery stenosis. Optom Vis Sci 1999; 76: 850-854.
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| Figure 2: Hand held ocular thermographic camera for measurement of the temperature of the surface of the eye (Image courtesy of FLIR Systems) | Figure 3: Ocular thermogram showing the temperature profile of the normal eye |
Research Program 3: Confocal Microscopic Examination of the Conjunctiva in Contact Lens Wear
Principal Researcher
Professor Nathan Efron
Research Optometrist
Nicola Pritchard
Graduate Student
Munira Aldossari
Funding
Saudi Arabian Research Student Scholarship
The object of the research program is to make a detailed examination of the bulbar and superior palpebral conjunctiva in contact lens wearers using a Heidelberg Laser Scanning Confocal Microscope. A number of previous studies have reported compromise of the conjunctiva during contact lens wear, presumably as a result of the direct mechanical effects of lens wear; these include conjunctival staining, hyperaemia, chemosis and folding, and an apparent depletion of the number of conjunctival goblet cells (inferred from impression cytology studies). Direct in vivo observation of the conjunctiva at a cellular level using the confocal microscope is likely to provide important new insights into the impact of contact lens wear on the ocular surface. Qualitative observations of the bulbar and superior palpebral conjunctiva of contact lens wearers are being made using the confocal microscope, and we are attempting to quantify superficial conjunctival epithelial cell density and superficial conjunctival epithelial goblet density. This research will lead to a better understanding of the ocular response to contact lens wear, and may assist in developing superior contact lens materials and designs.
Key References
- Kallinikos P, Efron N. On the etiology of keratocyte loss during contact lens wear. Invest Ophthalmol Vis Sci 2004; 45: 3011-3020.
- Efron N. Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope. Prog Retin Eye Res 2007; 26: 398-436.
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| Figure 4: Adenoid structures in the tarsal conjunctiva of a normal subject |