1. Background to Programme Area and Objectives

1.1 Disease of the retina due to complications arising secondary to retinal vascular disease include common disorders such as diabetic retinopathy and retinal vein occlusion.

1.2 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).

1.3 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.

  2. Programme plan

2.1 Clinical research in diabetic retinopathy has identified at least partially effective preventive treatments, including intensive diabetic control, control of hypertension and retinal laser photocoagulation for proliferative diabetic retinopathy and to a lesser extent macular oedema (responsible for 70% of visual loss in diabetic patients).

2.2 The National Screening Guidelines for Diabetic Retinopathy will lay down, for the first time, countrywide targets for screening and treatment but implementation and optimisation of the proposals remains a major objective. The UK is well placed to investigate screening strategies. Topics of investigation include validation (grading strategies, training), incidence and prevalence (establishing optimum screening intervals, NSF targets), cost-effectiveness, detection systems and automated grading.

2.3 Diabetic macular oedema, even with timely laser treatment, often leads to a poor visual outcome. The effectiveness of alternative treatments such as vitrectomy/membrane peel will require careful assessment.

2.4 Continued investigation of the molecular mechanisms and the role of growth factors such as VEGF and the angiopoietins in diabetic retinal angiogenesis and macular oedema will suggest key molecular targets for pharmacological therapeutic intervention. Inhibition of intracellular molecules upregulated by VEGF, such as Protein Kinase C, will undergo more investigation and clinical trial appraisal before introduction as medical treatments. Finally viral vector introduction of VEGF receptors and other growth factor antagonist genes into the retina provides a method of long term prevention of retinopathy progression.

2.5 Treatment of vein occlusion is currently limited to the use of scatter retinal photocoagulation to prevent neovascularisation, and macular laser treatment has some bearing on visual outcome in branch retinal vein occlusion. The pathogenesis of CRVO remains obscure and future research will continue to examine patients for prothrombotic tendencies and systemic risk factors, in an attempt to develop strategies that will reduce disease incidence. VEGF has been implicated in the occurrence of neovascular complications and inhibitors will likely be used to prevent this. Chorio-retinal anastomosis, either by laser or surgical means to bypass CRVO will be further examined and systemic and intravitreal clot lysis agents refined and reassessed.

2.6 Epidemiological and Service Issues

· Assessment of most efficient delivery of diabetic screening and ophthalmic management in the UK diabetic population.

2.7 Clinical and Laboratory Issues

· Elucidation of novel genes and chromosomal loci causing monogenic retinal disease.
· Elucidation of population genetic polymorphisms influencing the susceptibility to diabetic retinopathy.
· Evaluation of gene function, protein structure, chemistry and interaction in cell systems and animal models.
· Elucidation of novel therapies including gene replacement therapy, modulation of retinal cell apoptosis, catalysis of harmful gene mutations in vivo (ribozymes) and retinal cell transplantation.
· Characterisation of molecules involved in neovascularisation occurring in diabetic retinopathy and vein occlusion (e.g. vascular endothelial growth factor).
· Phenotype-genotype characterisation of monogenic retinal disorders
· Elucidation of genes conferring susceptibility of diabetics to sight-threatening retinopathy.
· Evaluation of the use of anti-angiogenic agents to improve the outcomes of vitreoretinal surgery
· Development of surgical approach to cannulation of retinal vessels and delivery of new agents to them.

  3. Future development work in the programme during 2002/3

3.1 Genetics, genotyping and risk factors

· Molecular targets for pharmacological therapeutic intervention.
· Inhibition of intracellular molecules upregulated by VEGF, such as Protein Kinase C, will undergo more investigation before introduction as medical treatments.
· Viral vector introduction of VEGF receptors and other growth factor antagonist genes.

3.2 Prevention and surveillance

· Within the next year we intend to focus on the issues raised in the National Service Framework for diabetes and take forward evaluation studies of screening for diabetic retinopathy

3.3 Symptoms, presentation and referral - as above

3.4 Phenotyping, information and communication

· Develop services within the Phenotyping Unit including the Image Grading Centre, work towards automated grading.

3.5 Diagnosis, investigations and pathology

3.6 Interventions -surgery, medical, radiological

· prospective trials on the use of anti-angiogenic agents as adjuncts to vitreoretinal surgery (which is usually performed on eyes with severe diabetic retinopathy)
· randomised, controlled trial on the role of vitrectomy in the treatment of diabetic macular oedema

3.7 Follow-up

· optimum screening intervals

3.8 Nursing, community care, rehabilitation

· NSF targets and health promotion for diabetics