Medical treatment of autoimmune uveitis : clinical and laboratory investigations into new therapies for non-infectious posterior segment intraocular inflammation
The studies in this thesis were aimed at developing new treatment concepts for PSII based on the understanding of the immunological mechanisms characterised in basic research. The intensity and prognosis of inflammatory disease determine the intensity of immunosuppressive therapy. In addition to clinical features, markers of effective immunosuppression are required to guide the immunosuppressive treatment in PSII patients, especially in those patients with opaque media. A secondary aim of this thesis was, hence, the evaluation of laboratory markers, notably CD4+ T cell phenotype markers, for their prognostic value in PSII. Chapter 1 provides an introduction into the cellular and molecular mechanisms of immunological self-tolerance and autoimmunity with a special focus on T cell activation and differentiation. Then, this section discusses the current knowledge of the processes leading to autoimmune disease, e.g. autoimmune uveitis, and outlines the foundations of immunosuppressive therapy. Chapter 2 presents on overview of the clinical features, diagnosis and current treatment of strategies for PSII. Characteristics of animal models of PSII, which represent a valuable tool in developing new therapies, are discussed as well as experimental treatment concepts in PSII patients. Chapter 3 describes the experimental methods applied in this thesis. This comprises the recruitment and clinical assessment of patients as well as methods for clinical and laboratory investigations. The flow cytometry analysis of peripheral blood T cell phenotype included cell surface markers (CD69, CD62L, chemokine receptors CXCR3, CCR4, CCR5), TCRzeta and intracellular cytokines (TNFalpha, IFNgamma, IL-10). Chapter 4 presents a randomised trial on the clinical and immunological effects of cyclosporin A (CSA) and tacrolimus in 37 patients with severe PSII requiring second line immunosuppression. Nine patients (50%) on CSA and 8 patients (42%) on tacrolimus showed an improvement of logMAR visual acuity of at least 0.2 within 3 months. CSA was found to be associated with a higher incidence of side effects, e.g. increase of mean arterial pressure and serum cholesterol.