Early detection of glaucoma is essential to prevent blindness, and appropriate strategies should be adopted to manage glaucoma once a diagnosis has been confirmed. The key areas of research are: diagnosis; monitoring and measuring disease progression; establishing risk factors for glaucoma; and evaluating the impact of disease on the individual.
The ultimate goal is to reduce the burden on the individual and on society of visual impairment and blindness from glaucoma, and to lessen the impact of the diagnosis of glaucoma and subsequent treatments on the patient’s quality of life. Worldwide, there are only a few centres with a comparable expertise in the study of this group of complex diseases and the molecular analysis of ophthalmic genetics.
Our objectives are:
- the identification of genetic and environmental susceptibility factors and biomarkers that predict patients at highest risk of visual loss, using modern psychophysical and imaging techniques,
- the identification of patients at risk of treatment failure after surgery by improving phenotyping using modern tissue and cellular imaging techniques and biomarkers, including genotyping,
- the development of a newer generation of more specific anti-scarring treatments to promote tissue regeneration. Our recent long-term MRC trial has shown that no disease worsened if post-operative scarring was minimised.
Corneal biomechanics and their influence on IOP measurement
Glaucoma is the leading cause of irreversible blindness in the developed world and increases in prevalence with advancing age. A core test used to detect and manage glaucoma is the measurement of eye pressure (intraocular pressure; IOP). However, the accuracy of IOP measurements is affected by the biomechanical properties of the cornea, the clear layer over the front of the eye. This research involves assessing the precision of new and established devices used to measure IOP as well as modelling the effects of the cornea on the accuracy of IOP measurements. This work involves collaboration with UK and international researchers.
The effect of visual impairment on day-to-day living
As clinicians, we undertake a variety of tests to detect glaucoma and monitor its progression. The results of these tests provide us with vital information to help us manage the disease, but they tell us very little about how it affects our patient’s ability to carry out the tasks of everyday living. This research involves quantifying the impact of visual impairment on functional ability by examining how glaucoma (and other eye diseases) affects the individual’s ability to reach out and pick up an object, as well as assessing how it affects their balance and mobility. By better understanding how the common eye diseases of the elderly affect their everyday lives, we can better inform them and their families on what to expect and how they might better adapt to their visual impairment.The equipment in the functional testing laboratory in the BRC was kindly donated by the Friends of Moorfields Eye Hospital
Visual fields (perimetry)
The current ‘gold standard’ test for detecting visual loss in glaucoma patients is visual field testing. This test involves measuring the sensitivity of the eye to a test object which may vary in brightness, size or movement. Current visual field testing techniques suffer from high variability (ie. tests can give different results when repeated on the same individual) and can sometimes poorly represent the severity of disease. Our research explores new techniques for measuring visual field that are less vairbale, that more precisely reflect the severity of the underlying disease process, and that detect glaucoma at an earlier stage in the disease. A major advance of the research group has been the development of the Moorfields Motion Displacement Test or MDT.
Diagnosis of glaucoma is dependent on reliable assessment of the optic nerve to distinguish between a healthy nerve and one that has been damaged by glaucoma. Imaging the optic nerve provides an objective and reproducible method of assessment, and various imaging techniques are available in clinical practice. The most widely used are: scanning laser ophthalmoscopy, scanning laser polarimetry and ocular coherence tomography. The main aim of our research is to improve the diagnostic ability and repeatability of current imaging techniques.
Research has shown that genetic factors play an important role in the development of glaucoma. One study suggests that the immediate members of a family in which one person has glaucoma may be as much as 10 times more likely to be affected by the condition than the general population. Three glaucoma associated genes have already been identified by studying a relatively small number of extended families with several affected members. However, the major genetic contribution to familial glaucoma is not explained by these 3 genes - other ways must therefore be found to advance our understanding of glaucoma genetics.
Identifying which genes are involved in the development of glaucoma would help us to better understand why it occurs and ultimately could lead to improved methods of treatment. A large number of patients are required in order to identify these genes and a collaboration with other European centres has therefore been initiated, named the European Glaucoma Society GlaucoGENE project. This project will create a resource for large-scale genetic studies into glaucoma. The pilot study, which aimed to test the feasibility of the setup, has completed recruitment and resulted in further protocol refinements which will be tested prior to the full-scale project going ahead.
Glaucoma Affected Sibling Pair Study (GASP)
Funding has recently been awarded for another genetic study into primary open angle glaucoma (POAG), called the Glaucoma Affected Sibling Pair study (GASP). This aim of this project is to recruit large numbers of sibling pairs, both of whom have been diagnosed with POAG. By using statistical techniques to study the distribution of genetic markers over a large number of such sibling pairs, it is possible to make inferences about the location of the genes responsible for glaucoma. This approach has been used successfully to identify the exact location of chromosomes in a number of other diseases including schizophrenia, type I diabetes and colon cancer.
Pigment Dispersion Syndrome (PDS) Genetics
Pigment Dispersion Syndrome is an eye disorder characterised by the presence of pigment underneath the cornea, defects of the iris, and increased pigmentation of the trabecular meshwork (the internal drainage tissue of the eye). In some patients the build up of pigment will affect the ability of the trabecular meshwork to drain fluid away from the eye causing a rise in eye pressure. This in turn may lead to pigmentary glaucoma, a potentially blinding condition that can affect patients at a relatively young age.
The present focus is on families with several affected members. Such families are particularly suitable for a form of genetic research known as ‘linkage analysis’ which works by studying the distribution of genetic markers across the family and uses statistical techniques to explore differences between affected and unaffected family members. Patients with PDS are being asked to invite immediate relatives to attend a PDS family clinic where they can be carefully examined for signs of the condition. The aim is to recruit 300 participants (comprising PDS patients and their relatives) in an effort to find as many families as possible that are suitable for linkage analysis.
Combining structural and functional measurements – GIFT
In the clinical setting, both structural and visual field (‘functional’) measurements are used to evaluate the likelihood of glaucoma or a change in disease state. The group developed and validated the first Glaucoma Information Fusion Technology (GIFT) software, based on specially designed statistical learning technology, namely Bayesian Radial Basis Function, to predict a patietn's visual field from the structure of their optic nerve. GIFT analysis therefore links the functional and structural measurements made in the clinical assessment of glaucoma, and has proved useful in undertadning any disrepacies between these test results. Preliminary work from this group also indicates that using GIFT to fuse structure and function measurements improves their reproducibility compared to standard visual field testing. This work is being undertaken in collaboration with City University.
The UKGTS (UK Glaucoma Treatment Study)
The UKGTS (UK Glaucoma Treatment Study) is a randomised, double-masked, placebo-controlled treatment study to demonstrate the effectiveness of latanoprost (xalatan) in reducing the frequency of glaucoma progression compared to placebo-treated eyes (primary outcome).
The main secondary outcomes of the study are the identification of risk factors for progressive glaucoma and an evaluation of the imaging technniquea currently used to measure the rate of progression of the disease. These techniques involve quantitative imaging technology to measure the optic nerve head (ONH) and retinal nerve fibre layer (RNFL), and conventional perimetry to measure visual field. It is anticipated that this data will enable improved study designs for subsequent clinical trials.
EAGLE is an international multi-centre pragmatic randomised controlled trial (RCT) funded by the Medical Research Council. It aims to establish whether removal of the lens of the eye (lens extraction) in patients newly diagnosed with Primary Angle Closure Glaucoma, results in better health (as reported by the patient), improved vision, lower intraocular pressure (IOP) and other improved outcomes, compared with standard management.
The Moorfields Motion Displacement Test (MDT)
This is a new test for glaucoma diagnosis that has been developed through 20 years of work. It is affordable, portable, easily understood by patients and is not affected by the presence of cataract and refractive error.
For more information visit the MDT website.
The EPIC Norfolk Study – eye and vision module
The European Prospective Investigation of Cancer (EPIC) investigates the effect of diet on long-term health and over 6,000 participants have been examined to date. The eye module is a key component of this study.
UK Biobank Eye Study
We are responsible for the eye component of the nationwide UK Biobank project, which aims to shed light on many of the most common debilitating diseases by studying genetic and molecular information from samples obtained from over 100,000 people around the UK.