3.1 Background

Disease affecting the retina causes the majority of the visual disability and blindness in the UK population. Although, retinal disease is mostly untreatable (vision can rarely be restored by clinical intervention once visual loss has occurred), it can sometimes be prevented, as in an effective screening strategy for diabetic patients. Inflammatory retinal disorders may also be improved with appropriate treatment. Through recent unprecedented advances in research into healthy and diseased retina, to which UK-based clinicians and scientists have made major contributions, real opportunities for the development of novel treatments now exist. The spectrum of disease includes the following classes of disorders.

  3.1.1 Age-related macular degeneration

The recent past has seen an upsurge of interest in the function and dysfunction of the macular retina. This small region of the retina centred around the visual axis is responsible for fine and discriminant vision encompassing the functions of resolution, colour perception, contrast sensitivity, scanning, reading and detection of motion. Diseases of the macula, which were previously under-researched are now the focus of attention particularly owing to the identification of degenerative age-related macular disease as the major visual public health problem of the 21st century. Age-related maculopathy (ARM) is a common disorder of the macular retina accounting for the majority of blindness and partial sight in the developed world. The disease is responsible for over 50% of all blind and partially-sighted registration in the UK and is estimated to affect over three million people in the UK. The magnitude of the problem will grow significantly as the number of elderly people increases; one study projects an increase of over 29% in the number of people over the age of 65 years in the next 20 years in the UK. Moreover, the disease may be increasing in prevalence in real terms over and above that due to changing demographics. The fact that the disease is untreatable and non-preventable increases the frequency of the contact of sufferers with the medical and social professional services. The resulting disability requires symptomatic amelioration of, and ongoing social support with. Although not life threatening, age-related macular degeneration (AMD) has been judged, on the basis of a spectrum of measures of patient disability, as the third most disabling disease in the US population after diabetes and cancer. For these reasons, funds into AMD research have been targeted recently as a high priority in the distribution of US NIH/NEI national funding. Clearly, the development of measures to prevent or a strategy to treat even a small proportion of sufferers of AMD, will produce a large saving in health care costs and a substantial reduction in disability of a large proportion of the population. Research into the genes and proteins underlying the disorder offers the most promising hope for the development of such novel treatment strategies.

  3.1.2 Vascular retinal disease

Disease of the retina due to complications arising secondary to retinal vascular disease include common disorders such as diabetic retinopathy and retinal vein occlusion. Diabetic retinopathy is the leading cause of blindness in the working population of the UK. Diabetes affects over 2% of the British population and, as with age-related macular degeneration, the prevalence of Type II disease is likely to increase in the future in the UK with the changing demographics of the population. It is estimated that a diabetic person has a 10-20 times greater likelihood to be registered blind than a non-diabetic person. Unlike AMD, clinical research has identified at least partially effective preventive treatments, including intensive diabetic control, control of hypertension and retinal laser photocoagulation for proliferative diabetic retinopathy and macular oedema (responsible for 70% of visual loss in diabetic patients). Secondly, vascular occlusion occurring in the venous and arterial retinal vasculature is also a common cause of visual loss in the Western population although it is rarely bilateral. Occlusion of the central retinal vein or a branch of the retinal venous system are the most common events, with the incidence of central retinal vein occlusion (CRVO) being approximately 30/100,000 persons/year. Only 6% of eyes with CRVO recover at least 3 lines of visual acuity at one year.

  3.1.3 Inherited retinal disease

Monogenic retinal disorders including retinal dystrophies, chorioretinal dystrophies and stationary retinopathies although less common than AMD and diabetic retinopathy, affect approximately 1 in 3000 persons. Because these disorders are untreatable and often severe, they place a high burden in terms of rehabilitation and care for those people affected. Over and above the direct burden of disease, these disorders also allow a special opportunity for the identification of key molecules in retinal biology and disease. Through the strategies of linkage analysis and physical mapping, many causative genes for retinal disease have been determined; each discovery elucidates a key molecule in retinal biology which directs further research into protein structure, interaction, function and pharmacology. To date, over 69 such genes have been characterised as causing retinal disease and a further 59 distinct chromosomal loci have also been identified. The impact of these discoveries on all retinal disease and the development of novel therapies is likely to be highly promising if funding is directed towards research programmes targeted at strategies that follow-on from gene discovery.

  3.1.4 Inflammatory retinal disease

This is a major cause of severe visual loss in patients of working age. Intraocular inflammation is largely an autoimmune condition, which may or may not be associated with systemic disease. Many types of intraocular inflammation can result in inflammation in the retina and cause breakdown of the blood-retinal barrier (BRB). This is normally very tight but when its integrity is breached due to active inflammation, retinal oedema can result and cause visual loss. The pathogenesis of these conditions is very similar to that of other autoimmune disorders such as thyroiditis and insulin dependent diabetes. It is unknown as to the initial stimulus but infection with an unknown agent may be implicated in triggering the immune response which affects the eye in individuals who may be genetically susceptible to this insult. CD4+ T-cells infiltrate all layers of the eye and secret cytokines which may recruit in other cell types as well as directly affecting the retinal tissues and disturbing function. Treatment is aimed at reducing the activity of these infiltrating cells and have to be given systemically in patients with bilateral disease. Although current immunosuppresive therapy may help many patients, the drugs themselves have many unpleasant side effects and in about 30 % of patients with severe inflammation they may be ineffective. The most common cause of visual loss, which responds poorly to treatment, is chronic macular oedema due to intractable BRB failure.

   3.2 Research Potential