1. Summary of programme area and objectives

1.1 Priorities in the national plan are determined by gaps in the current knowledge base, including disease prevalence, the evidence base for clinical practice and feasibility in the light of scientific developments. Research on interventions needs to be directed at both the primary care level, in order to impact on the majority of patients with minor problems, and at the tertiary level to improve treatment strategies for those with blinding disease. The latter requires collaboration with a range of other disciplines to investigate pathogenesis and develop more effective treatments.

1.2 This research programme will focus on the further investigation of bacterial biofilms in ocular infection. The initial focus will be on the factors influencing the development of biofilms and those underlying their resistance to both antibiotics and disinfectants. The long term aim will be to develop clinical strategies to prevent the development of biofilms and eliminate established biofilms. Clinical studies will continue on the management of ocular surface diseases, evaluating new treatment strategies as they are introduced, coordinating and contributing to trials as needed, and using laboratory resources to investigate pathogenesis and evaluate treatment mechanisms where appropriate.

  2. Programme plan

2.1 Incidence, prevalence and morbidity - The morbidity and burden on the population of some of the corneal & external eye disorders has been the subject of few studies. Studies that have been performed include the impact of this group of disorders in general practice, the incidence of corneal infection in contact lens wearers, and the prevalence of dry eye disease. Disease quantification is, however, lacking in many disorders.

2.2 Healthcare delivery - Support by ophthalmologists for delivery of primary eye care in the community, by optometrists and general practitioners, has been to shown in pilot studies to be effective and accessible. A priority of the research programme is to evaluate whether introduction of this service on a wider scale, with audit of costs and outcomes, shows both cost benefit and clinical effectiveness. Examples of conditions that are amenable to this approach are conjunctivitis and blepharitis.

2.3 Prevention - Identification of risk factors for iatrogenic disease such as contact lens wear, refractive surgery and inappropriate use of topical therapy are likely to have the greatest impact on prevention of corneal disease and toxic keratoconjunctivitis.

2.4 Pathogenesis, treatment & management strategies - These areas, in particular, require an integrated clinical and laboratory approach. Some of the most accessible, in view of the availability of current opportunities, are described here.

2.4.1 Continuing research is required into the pathogenesis of many corneal & external eye disorders leading to new treatment strategies. Investigations of pathogenesis at the cell biology level are leading to the introduction of new anti-inflammatory therapies that hold
substantial promise for an improvement in treatment. These surface disorders also lead to ocular surface failure which is the factor that results in blindness. New therapies are being developed such as in vitro amplification of corneal epithelial stem cells. Amniotic membrane is now freely available in the UK which is also linked to evaluation of the technique.

2.4.2 Corneal wound healing is critical to ocular surface disease and also to refractive surgery and corneal graft surgery. New strategies involve advances in understanding of the biology of this area, facilitated by the ability to develop micro-array technology to measure multiple relevant factors ie growth factors and proteases simultaneously. We need more specific corneal wound healing studies.

2.4.3 Management of ocular infections has now achieved an evidence base with the recent completion of some randomised controlled trials of therapy for severe corneal infection. However it has been shown outside the UK that antibiotic resistance patterns are constantly changing and that these need to be monitored. Rapid diagnosis of ocular infections is being developed and is needed to improve rational prescribing by targeting therapy appropriately.

2.4.4 Storage of donor corneas prior to transplantation is currently undertaken by various methods, but discard rates from eye banks using unselected donors indicate that major improvements might be made (approximately one third of corneas may be discarded because of poor endothelial function). This is especially necessary if the rates of donation of tissues for transplantation continue to decline. Research is therefore needed to improve or enhance survival rates in corneal graft material, not only for endothelium but also for the limbal tissue required for surface reconstruction techniques.

2.4.5 Corneal graft survival and rejection. Research in this area can be expected to bring improvements into corneal graft technique and outcomes for the first time in four decades. Complementary to this and to the problems of severe corneal disease is the development of the artificial cornea with bio-integratable devices that have the potential to circumvent the problems of graft failure and supply. The potential threat of prion diseases to corneal graft recipients, and the potential for transmission of these diseases from corneal graft recipients by instrument contamination is being evaluated.

2.4.6 Advances in molecular genetics facilitate research on the pathogenesis of corneal dystrophies and degenerations ranging from monogenic recessive disorders (such as stromal dystrophy) to polygenic disorders with an environmental component (keratoconus is probably such a disorder). Such research will not lead to new interventions for patients within five years. However such research is significantly facilitated both by publication of the human genome sequence in 2001 and also the superficial position of the cornea and external eye. The latter makes gene-based approaches to treatment an order of magnitude more feasible than 'gene therapy' initiatives for other ocular tissues.

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

Research priorities

3.1 Epidemiological and Service Issues

· Identification of risk factors for iatrogenic disease such as refractive surgery, contact lens wear and inappropriate use of topical medications.
· Rapid diagnosis and improved treatment strategies for ocular infections.

3.2 Clinical and Laboratory Issues

· Corneal wound healing mechanisms
· Factors affecting corneal graft survival and strategies to prevent rejection
· Molecular genetic analysis of the corneal dystrophies and degenerations