1.1 Ocular Inflammation

1.1.1 Ocular inflammatory disease is one of the major causes of significant visual loss in patients of working age. Its causes are varied and include immune related diseases as well as infection by a variety of organisms including bacteria, viruses, fungi and parasites.

1.1.2 Over the last few years, we have been working towards the above objectives and results to date have been published in peer-reviewed journals. In ocular inflammation we have shown that T-lymphocytes are responsible for the intraocular damage and that they do this by secreting different patterns of cytokines. In severe disease where the eye undergoes most damage, there is low amounts of interleukin IL-10 (IL-10) in the ocular fluids whereas in the less damaging types, levels of IL-10 are higher. This applies to both the aqueous and the vitreous fluids. Clinical trials in patients with ocular inflammation have shown that mycophenolate and methotrexate are useful immunosuppressive agents to use in severe ocular inflammation and that intravitreal triamcinolone can reverse cystoid macular oedema with severe visual loss and significantly improve vision in eyes that were refractory to treatment with any other therapy.

1.1.3 PCR techniques with specific primers have been adapted to use on ocular fluids to detect bacterial, viral, fungal and protozoal DNA. The culture positive rate for clinically diagnosed intraocular infection is about 40% and with these PCR techniques is 100% with a less than 5% false positive rate. In addition, we can determine whether the organism is gram positive or negative and its species thus allowing appropriate antibiotic treatment to be instituted. A standardised therapeutic regime for first line management of acute bacterial endophthalmitis was carried out and showed that most of the common organisms found in these patients were sensitive to this. Clarithromycin is an antibiotic that penetrates the eye with the additional property of breaking up biofilm formation which is thought to limit antibiotic penetration in infected eyes. A clinical trial showed that the addition of this to the standardised regime significantly improved the visual prognosis of patients who were culture negative.

1.2 Ocular Oncology - Ocular melanoma is rare but potentially devastating. The focus of recent research has been on the molecular pathogenesis of ocular melanoma and the development of effective chemotherapy for metastatic disease and adjuvant therapy for patients with high risk of developing metastatic disease. Recent achievements include:

1.2.1 Development of the ATP-based chemosensitivity assay.

1.2.2 The demonstration that uveal melanoma is susceptible to chemotherapy.

1.2.3 Development of the combination of treosulfan + gemcitabine chemotherapy for metastatic uveal melanoma, now proven to be active in more common tumours, including breast and ovarian cancer.

1.2.4 Demonstration that loss of the TGFbeta pathway control of melanoma cell growth is a common event, and may be involved in the formation of the tumour.

1.2.5 Demonstration of the role of angiogenic factors in uveal melanoma and in iris neovascularisation in these patients. Our work is performed in the context of a collaborative research effort with a number of associated laboratories in Germany and the USA.