Gilbert, Rose M.; (2018) A multifaceted approach to improving management of sight-threatening non-infectious uveitis: patient perspectives and disease phenotyping for individualised patient therapy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Non-infectious uveitis is a clinically heterogenous disease, which can cause chronic relapsing and remitting chorioretinal inflammation and vision loss. The disease is incurable but long-term clinical remission of inflammation may be induced with high dose ‘blockbuster’ systemic immunosuppression, which has multiple side effects. Personalised immunosuppressive therapy is currently not feasible, partly due to limitations in disease phenotyping. The aims of this thesis were to individualise management of patients with sight-threatening non-infectious uveitis by investigating: 1. Clinical phenotypes of two similar subtypes of sight-threatening non-infectious uveitis: multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC). 2. Immunological phenotypes of patients with sight-threatening non-infectious uveitis. 3. Perspectives of patients with sight-threatening retinal disease. Clinical and imaging data from 343 eyes of 185 subjects with MFC and PIC were found have some significant differences, with PIC showing a greater predilection for young, myopic women and tendency to secondary choroidal neovascularisation. Fifty patients with intermediate uveitis, posterior uveitis and panuveitis and 10 control subjects were prospectively recruited for immunological analysis of blood samples. Patients in clinical remission had significantly higher levels of Treg, polarised towards TIGIT and T-bet, associated with higher serum cytokine levels of IL-10 of TGF-β, and significantly lower methylation levels at key Treg epigenetic sites, compared to active patients and controls. Qualitative data was collected from patients with sight-threatening retinal disease and used to design a pilot intervention to increase subjects’ capability and opportunity for healthy lifestyle change. Results suggest that the phenotyping of non-infectious uveitis could be improved and that immunological biomarkers could assist in disease management. The visual and psychosocial consequences of sight-threatening retinal disease may also be addressed with tailored behavioural interventions. These findings could improve management of patients with uveitis by supporting the transition towards a more individualised therapeutic approach.

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