Glaucoma

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.

We aim to concentrate on two main programmes of investigation:

• 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, and
• the identification of patients at risk of treatment failure after surgery by improving phenotyping using modern tissue and cellular imaging and biomarkers, including genotyping, and 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 window 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 every-day living. This research involves quantifying the impact of visual impairment on functional ability. This includes examining how glaucoma (as well as other eye diseases) affects the individual’s ability to reach out and pick up an object, as well as assessing the how it affects their balance and mobility. By better understanding how the common eye diseases of the elderly affect their every day lives, we can better inform them and their families of 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 testing the light 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 (test result can give different results when repeated in the same individual) and poorly represent the severity of disease. Our research focuses on improving on current visual field tests which can reduce the variability of tests and can detect glaucoma at an earlier stage in the disease, with measurements that precisely reflect the severity of the underlying disease process. In this regard, a major advance of the research group has been the development of the Moorfields MDT. (www.moorfieldsmdt.co.uk).

Imaging

Diagnosis of glaucoma is dependent on reliable assessment of the optic nerve to distinguish a nerve which has been damaged by glaucoma from a healthy optic nerve. Imaging of the optic nerve provides an objective and reproducible method of optic nerve assessment. Various imaging modalities 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. 

Glaucoma Genetics

Research has shown that genetic factors play an important role in the development of glaucoma with one study suggesting that first degree family members may have as much as a 10 fold risk compared with the general population. Three glaucoma associated genes have already been identified by studying a relatively small number of extended families with multiple affected members. However, the major genetic contribution to familial glaucoma is not explained by these 3 genes - other strategies must therefore be used in order 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, the European Glaucoma Society GlaucoGENE project, has therefore been initiated. 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.

Funding has recently been awarded for another genetic study into primary open angle glaucoma (POAG), 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 disease causing genes. This approach has been used successfully to identify chromosomal loci 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 pigment deposition on the interior of the cornea, spoke-like iris defects and increased pigmentation of the trabecular meshwork (the internal drainage tissue of the eye). In a proportion of patients, the build up of pigment will affect the ability of the trabecular meshwork to drain the fluid 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 multiple affected members. Such families are amenable to a form of genetic study known as ‘linkage analysis’ which works by studying the distribution of genetic markers across the family and using statistical techniques to explore differences between affected and unaffected family members. Patients with PDS are being asked to invite first degree 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 and 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 the visual field from the structure of the optic nerve. This GIFT quantitatively bridges the structural and functional measurement in the clinical assessment of glaucoma, and has demonstrated clinical application in quantification of discordance between structural and functional tests. Preliminary study from the group also indicated that using GIFT to fuse structure and function measurement improved measurement reproducibility compared to standard visual field testing. This work is being undertaken in collaboration with City University.

UKGTS

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 measurements of the rate of progression of glaucoma by measurement of optic nerve head (ONH) and retinal nerve fibre layer (RNFL) structure with quantitative imaging technology, and of visual function with conventional perimetry. It is anticipated that the use of rates of progression will enable improved study designs for subsequent clinical trials.

EAGLE Study

EAGLE is an international multi-centre pragmatic randomised controlled trial (RCT) funded by the Medical Research Council to establish whether removal of the lens of the eye (lens extraction) for newly diagnosed Primary Angle Closure Glaucoma results in better patient reported health, vision, lower IOP and other outcomes compared with standard management.

Form more information please visit viis.abdn.ac.uk/HSRU/eagle/

The Moorfields Motion Displacement Test (MDT)

This is a new test for glaucoma diagnosis that has arisen as a result of 20 years’ 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 www.moorfieldsmdt.co.uk

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.