Age-related macular degeneration (AMD) is the leading cause of severe visual loss in Europe and North America and, with an ageing population, the burden of this disease is projected to increase dramatically.
As its name suggests AMD predominantly affects the macula, the centre of vision that is important for reading and detailed vision. It can be classified into early and late stages based on specific clinical features. Early AMD is characterised by the presence of drusen (tiny yellowish deposits under the retina) and is compatible with reasonable vision. However, many patients with early AMD progress to the vision-threatening late forms of AMD.
The late ‘wet’ or neovascular form is characterised by the growth and leak of abnormal blood vessels beneath the macula causing severe loss of vision.
Currently, we have treatments for late neovascular AMD but these involve an intensive intervention with frequent injections into the eye and long-term monthly follow-up of the patient, which is problematic to deliver, and only a third of patients recover some of their lost vision. We have no effective treatments for the late dry atrophic form of AMD, or effective interventions for early AMD.
The London Project to Cure Blindness (AMD)
One of our approaches to treating AMD is through the ground-breaking research of the London Project to Cure Blindness, which is led by Professor Pete Coffey at the UCL Institute of Ophthalmology. Pete and his team aim to replace the retinal pigment epithelium cells (RPE) at the back of the eye that are affected in AMD, using human embryonic stem cells (HES) that have been transformed into RPE cells. They seek to transplant these RPE cells into the patient on a specially engineered patch that will be inserted behind the retina.
Another important arm of the project is to develop the technology by which HES cells can be transformed into photoreceptors (lightdetecting
cells) and transplanted into patients. It is believed that the photoreceptors are lost after the RPE have degenerated. We are now ready to initiate the safety studies that we need to do prior to clinical trials, and are on track to begin human clinical trials during 2011. Considering that these will be the first human embryonic stem cell trials in the UK, the project really will be breaking new ground.
A novel intervention to treat geographic atrophy (late ‘dry’ AMD)
There is currently no effective therapy to prevent progressive vision loss in patients with atrophic AMD. In 2011 we will commence a pioneering clinical trial of a novel intervention that prevents the build-up of a key waste product that damages the cells under the retina. As precursor to this trial, the study team at Moorfields and the UCL Institute of Ophthalmology are developing new ways of assessing atrophy disease progression, and functional changes in patients with this disorder to allow for more effective clinical trial design.
The ABC trial for wet AMD
Current strategies for the use of drugs to treat neovascular AMD lead to gradual drop-off in vision, which means that the benefits of these intensive treatments are being lost with time. Moorfields was the lead and coordinating centre of an important randomised multi-centre trial of an anti-VEGF drug (a substance that prevents the formation or growth of new blood vessels) that resulted in not only the recovery of lost vision on average, but also the development of an individualised retreatment algorithm that maintained this benefit over time with a reduced treatment burden relative to current interventions.