Experimental choroidal surgery for age-related macular degeneration

Age-related macular degeneration is the commonest cause of blindness in the UK and most people have an elderly relative who is affected by the disease to some extent. Macular degeneration leads to a burning out of the central part of the vision, leaving patients unable to read or recognise people?s faces. The retina is made up of a thin delicate sensory layer that is easily damaged, lined and protected by a more robust layer known as the choroid. This is analogous to an inner tube inside a tyre. Macular degeneration begins in the choroid (tyre) layer, but over a period of years gradually erodes through to damage the retina (inner tube), at which point vision is lost. The aim of our research is to develop an operation to move the degenerating choroid away from the central retina before it is irreversibly damaged. We propose to do this by rotating a large disc of the choroid layer after lifting up the retina. This will move the diseased choroid away from the fovea (the sensitive central part of the retina) to another part in the peripheral retina where vision loss will be barely noticeable. The fovea will thus be provided with relatively healthy choroid, which may set the degeneration back many decades. The surgery is performed from within the eye and is extremely challenging, but instruments developed recently have made it easier. We have already completed one trial with patients in our hospital and showed that this technique works well in principle. We have however discovered that we need to slide a much larger choroid layer and in such a way that preserves a blood vessel underneath. We have devised a means of doing this, but the surgery is quite different to anything we have done before and we therefore need to validate its effects in an animal model before proceeding to another clinical trial. Ethically we must be sure that there are no unexpected problems with the surgery before recommending it to our patients.

Age-related macular degeneration (AMD) causes blindness in thousands of people in the UK and its prevalence is increasing. AMD is believed to represent a chronic inflammation in the retinal pigment epithelium (RPE) and choroid layers of the retina. The inflammation is focussed on the central macula area and, over time, the inflammation breaks through to destroy the fovea and surrounding neurosensory retina with haemorrhage and fibrosis. Generally only the central area of RPE-choroid is affected by AMD, but this is the most vital part for vision. New injectable antibody treatments are being developed, but these are not applicable to all AMD patients, only combat the late stages of the disease and require repeated administration. Our research is to develop an operation to replace the diseased subfoveal RPE-choroid in one go and before the fovea is irreversibly damaged. We recently completed a clinical trial in 12 patients and showed that RPE-choroid taken from the equator of the eye (where it is virtually unaffected by AMD) can support vision when slid under the fovea. In that study the RPE-choroid was a free tissue graft and re-establishment of blood supply was erratic. We therefore propose a second trial to transplant an RPE-choroid graft, but in this case pedicled on the lateral long posterior ciliary artery (LPCA). The graft would remain vascularised throughout the procedure. We are proposing to move a relatively large plate of tissue under the retina within the eye and this has never been done before. We therefore need first to be sure that the operation is safe before performing it on patients. In particular, we need to know if the blood supply within the graft can be sustained during the movement and whether or not the overlying retina is damaged by the surgery. We therefore propose to test the operation in an animal model with a similar LPCA choroidal vascular system to humans. We will assess blood flow through the graft by angiography and examine the overlying fovea anatomically and functionally. We believe this will provide us with the information we require in order to continue with the next step of our clinical trial.