Clinical Studies in Eye Health and Disease
The Clinical Studies Group comprises a close collaboration of University staff with clinicians based in the St Paul’s Eye Unit in the Royal Liverpool University Hospital. Together, we have a long history of performing original and novel clinical studies, both leading and contributing to national and international multicentre randomised controlled trials, observational studies and technology development. Between 30 and 40 clinical studies are running at any one time in age-related macular degeneration (AMD), diabetic retinopathy, retinal vascular diseases, ocular oncology, ocular surface disease and glaucoma.
Highlights include
• the Liverpool Diabetic Eye Study which led to the introduction of screening for diabetic eye disease in UK and worldwide
• the VPDT and IVAN studies which led to the introduction of current therapy for AMDy
The Group is engaged with all major pharmaceutical companies developing treatments for ocular disease.
We have an active diagnostics research programme in which new methods of electrophysiology, functional vision measures, and methods of structural measurement are being applied to better detect important causes of visual disability.
Our international programme is based around key partnerships. Research conducted in Malawi with colleagues in the Liverpool School of Tropical Medicine and the College of Medicine, University of Malawi, has led to major advances in understanding malarial retinopathy. The growing burden of diabetic eye disease in sub-Saharan Africa is also being investigated. We are researching and developing new tampenade agents with colleagues in the University of Hong Kong.
Projects
Comparative genomics of keratitis-causing bacterial organisms
Bacterial infections of the cornea are a major cause of visual loss world-wide. There are approximately 6000 cases of bacterial keratitis per year in the UK with 200 per year for a city the size of Liverpool or Manchester. P. aeruginosa accounts for approximately 25% of cases of severe bacterial keratitis. Although antimicrobial therapy is an essential part of treatment, bacterial and host factors are of major importance in determining clinical outcome. And dependence on antimicrobials has led to increasing antibiotic-resistant bacteria. New strategies are needed to identify and develop new drug targets.
We have shown using genotyping that P. aeruginosa isolates associated with keratitis tend to cluster as a distinct sub-population within the wider population structure of P. aeruginosa. However, so far our approach has been relatively crude. Recent advances in genotyping techniques offer improved resolution and we are investigating whether they could be used to offer more personalized and targeted treatment. This approach might be ideal in keratitis where treatments can be delivered topically and directly to the cornea.
As part of the ongoing UK Microbiology Ophthalmic Group we have isolates from 658 cases of P. aeruginosa keratitis together with antimicrobial susceptibility profiles, clinical outcome information, and associated risk factors such as contact lens wear. This is a unique collection, essentially representing a nation’s burden of disease for a specific infection type associated with a single pathogen.
We are genetically characterizing the entire collection of keratitis-associated isolates of P. aeruginosa using WGS. The datawill be linked to the P.aeruginosa 1000 Genomes Project which is aiming to define the diversity of the whole P.aeruginosa population worldwide from multiple clinical and environmental sources.
Early Functional Vision Biomarkers of Macular Disease
The macula is a highly sensitive area at the centre of the retina, where the light sensitive cells (the photoreceptors) are most densely packed. Although perhaps less than 1.5mm in diameter, this part of the retina provides the high acuity vision that allows us to read, drive, recognise faces, read signs – many of the things that are most important to us. Unfortunately a number of relatively common conditions (like age-related macular degeneration and diabetic macular oedema) affect the function of the cells at the macula, leading to visual disability.
The good news is that there are excellent new treatments for these conditions. The eventual outcome of these treatments is best if problems are detected early and treatment commenced as soon as possible. So we are investigating new ways of detecting diseases of the macula.
In the EDiMaD project we are investigating a shape discrimination test which runs on a small handheld device. We are following 200 patients being treated for wet AMD in one eye, and testing their other eye when they come for their treatment. We know that in a proportion of patients this other eye will develop the condition during the follow-up period. This will allow us to establish how good the new test is at detecting the development of the new disease. We are now extending investigations of the test to patients who are suspected of having diabetic macular oedema (EDDMO).
The stimulus used in the shape discrimination test being trialled in EDiMaD and EDDMO. Which circle is distorted?
Smartphone imaging of the Eye
The growing computing and optical capabilities of mobile devices provides a potentially inexpensive means of obtaining, analysing, storing and transmitting images of the retina at the back of the eye. We are investigating the images obtained with a number of smartphone-based devices.
Changes to the optic disc (the part of the retina where the optic nerve leaves the eye) are useful in detecting and monitoring glaucoma, a potentially blinding condition. We have been obtaining images of the optic disk in both dilated and undilated eyes of glaucoma patients, and comparing them to dilated images obtained with a standard fundus camera. We are currently grading a large set of images for quality. The next step is to experiment with automated analysis of gradable images.
By exploiting the computing power in smartphones, combining imaging with automatic image analysis, it might be possible to provide a quick, effective and inexpensive screening tool for glaucoma.
These three optic disc images are of the same eye, but obtained with three different devices
Individualised Screening for Diabetic Retinopathy (ISDR)
This five year research programme aims to develop a major enhancement to the existing screening process for sight threatening diabetic retinopathy (DR, STDR) for implementation in the NHS. Important evidence gaps in screening for DR will be tackled comprising collection of prospective patient centred data in a whole population cohort study and new knowledge produced on outcomes relevant to patients such as visual impairment (VI). An individual risk-based approach will be developed and evaluated based on evidence collected from a well-established diabetes eye care pathway in Liverpool. Safety, cost-effectiveness and acceptability to patients and staff will be assessed. Our mixed quantitative and qualitative approach has been piloted in a NIHR funded programme development grant (PDG) and barriers to success identified and overcome. Inter-linked workstreams (WS) will run in parallel, each informing the progress of others:
WS A. Systematic review
WS B. Establishment of a study data warehouse and observational cohort study
WS C. Risk calculation engine
WS D. Health economics
WS E. Randomised controlled trial, (ISDR RCT Protocol, SAP and HEAP)
WS F. Qualitative perceptions of changing screening intervals (patients and professionals)
WS G. Results dissemination and preparation for implementation
