Dr Tom Margrain
Research Topics and Related Projects:
The primary focus of my research is macular disease. Accounting for 57% of all visual impairment in the UK, macular disease is responsible for significant individual suffering and places a heavy burden on society. My research revolves around two distinct areas of activity. The first is concerned with the development of biomarkers for macular disease that can be used to expedite the evaluation of novel therapeutic interventions. The second relates to the identification of effective rehabilitation interventions that can help people with advanced macular disease cope with vision loss.
Currently, there are no validated biomarkers for the commonest type of macular disease, age-related macular degeneration (AMD). Most clinical trials use the onset of advanced AMD, either neovascular AMD (nAMD) or geographic atrophy (GA), as disease end points. The use of such coarse end points, even for exploratory studies, dictates that trials must be large, long and expensive. To speed up the development of novel treatments for AMD, my research has evaluated the ability of electrophysiological, psychophysical and imaging biomarkers.
For example, by placing sensors around the eye it is possible to measure the tiny voltage produced by the retina known as the electroretinogram (ERG). By measuring the recovery of this signal following exposure of the eye to bright light we developed a sensitive objective test for early AMD called the ERG photostress test (see Fig 1).
Fig 1. Typical ERG photostress recovery data in two people with early AMD. Immediately after exposure to a bright light, that bleaches almost all cone photopigment the ERG is extinguished (upper traces). Over the following 5 minutes the signal, an index of disease status, recovers. The lower plots show how the amplitude of the signal increases over time (From Binns & Margrain. IOVS. 2007).
Results from our lab indicated that ‘dark adaptation’, the recovery of visual function in the dark following a period of light adaptation, is a sensitive candidate biomarker for AMD. Hence we have spent the last few years refining the test protocol i.e. examining the effect of stimulus location, bleach intensity and psychophysical methods on sensitivity and specificity.
Fig 2. Location of various annuli used to optimise dark adaptation parameters (A). The dark adaptation functions obtained from the central most to outermost annuli are shown going from top to bottom (B). (From Gaffney et al, 2011).
Right now we are collaborating with a team from the UK’s Astronomy Technology Centre to develop an imaging retinal densitometer that can measure the recovery of visual pigments directly. We can now evaluate the regeneration of rod or cone pigments on a point by point basis across the retina.
Fig. 3. The upper row shows a series of false colour retinal images. These are recorded continuously, at 5Hz, both before and immediately after exposure to intense illumination that ‘bleaches’ retinal photopigments. The images obtained at each wavelenght are initially used to quantify reflectance, then wavelenght dependent optical density and, via a pigment fitting routine, rod and cone photoreceptor signals. The lower right hand plot shows how the rod and cone signal varies as a function of time at the fovea. (Patent 2012 No. 1206174.3).
Rehabilitation research is my other passion. How can we help people with untreatable visual loss maintain their independence? My involvement in the establishment of the community based Welsh Low Vision Service was a great opportunity to evaluate a range of interventions and survey based outcome measures. The Low Vision Service Model Evaluation (LOVSME) project, supported by the RNIB, was another collaborative project examining the effectiveness of low vision services. And more recently, a group of us have begun to examine the impact of mental health status on rehabilitation outcomes. The Depression in Visual Impairment Trial (DEPVIT), funded by Guide Dogs, is evaluating 3 treatments for depression in a multicentre RCT. We hope the results will help shape future NICE guidance.
1. Melotte, Margrain, Binns, Henry, £844,000, “Imaging densitometry”, National Institute of Health Research i4i Programme, 2013-2016
2. Margrain & Gaffney, £5,642, “Net Mobility”, Guide Dogs, 2013-2015.
3. Margrain, £10,000, “Ophthalmology Research in Wales”, National Institute of Social Care and Health Research (NISCHR), 2012.
4. Margrain, Binns &Tucker, £52,254, “Imaging Densitometry” Cardiff President’s Studentship Award, 2013-2016.
5. Binns & Margrain, £52,254, “Night Lights for AMD: a randomised controlled trial”, College of Optometrists, 2012-2015.
6. Binns & Margrain, £52,254 “Hypoxia in age-related macular degeneration”, JE Williams Endowment Studentship, 2012-2015.
7. Binns & Margrain, £17,532, “Evaluating Eccentric Viewing and Steady Eye Technique Training”, Macular Disease Society, 2012.
8. Henry D, Margrain TH, Binns A. £86,600, “Development of an imaging retinal densitometer”, National Institute of Health Research (NIHR), 2010-2012.
9. Margrain TH, Smith DJ, Stanford M, Tudor-Edwards RT, Ryan B, Bunce C, Casten R, Hegel M. £207,000, “Depression in Visual Impairment Trial (DEPVIT), Guide Dogs, 2011-2014.
10. Binns AM, Margrain TH. £51,000, “Early detection of age-related macular degeneration”. College of Optometrists, 2008-2011.
11. Margrain TH, Bunce C, Dickinson C, Harper R, Tudor-Edwards R, Binns A, Woodhouse M, Link P, Jackson J, Massof R, Wolffsohn J, Stelmack J. £58, 000, “Low Vision Service Model Evaluation (LOVSME)”, Royal National Institute of Blind People, 2008-2009.
Macular Research Group
Clinical and Investigative Vision Sciences
Current research Associates / Assistants / Managers:
Allannah Gaffney, Research Assistant, “Net Mobility”, Guide Dogs, 2013-2015.
Claire Nollett, “DEPVIT Study Coordinator”, Guide Dogs, 2011-2014
Julia Shearn, “DEPVIT Psychological Therapist”, Guide Dogs, 2012-2014
Ryre Cornish, “DEPVIT Psychological Therapist”, Guide Dogs, 2013-2014.
Dr Danny Smith, University of Glasgow, Depression in Visual Impairment Trial.
Dr Catey Bunce, Moorfields Eye Hospital, Evaluating Eccentric Viewing and Steady Eye Technique Training.
Prof. Miles Stanford, St Thomas’ Hospital, Depression in Visual Impairment Trial.
Dr Ruth van Nispen, VU University Medical Center in Amsterdam. Stepped-care program in visual impairment.
Prof. Rhiannon Tudor Edwards, Bangor University, Depression in Visual Impairment Trial.
Dr Robin Casten, Jefferson Medical College, Depression in Visual Impairment Trial.
Dr Mark Hegel, Dartmouth-Hitchcock Medical Centre, Depression in Visual Impairment Trial.
Mr David Henry, UK Astronomy Technology Centre, Edinburgh, Imaging Densitometry.
Prof Chris Dickinson, The University of Manchester, Low Vision Service Model Evaluation.
Dr Robert Harper, Royal Manchester Eye Hospital, Low Vision Service Model Evaluation.
Dr Robert Massof, Wilmer Eye Institute, Low Vision Service Model Evaluation.
Dr Joan Stelmack, Edward Hines Jr VA Hospital, Low Vision Service Model Evaluation.
Mr Stephen Todd, UK Astronomy Technology Centre, Edinburgh, Imaging Densitometry.
Mr Dave Melotte, UK Astronomy Technology Centre, Edinburgh, Imaging Densitometry.
Mr David Atkinson, UK Astronomy Technology Centre, Edinburgh, Imaging Densitometry.
Dr Lorna Marquès-Brocksopp, Guide Dogs, Net Mobility.
Prof Gary Rubin, Institute of Ophthalmology, Depression in Visual Impairment Trial.
Prof Jonathan Jackson, Australian College of Optometry, Depression in Visual Impairment Trial.
Dr Helen Prance, University of Sussex, The Electroretinogram.
Prof Tom Freeman, Cardiff University, Eye movements and ageing.