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The treatment of patients with severe eosinophilic asthma has been transformed with the arrival of biological drugs targeting the type 2 cytokine pathway. One of these drugs is mepolizumab, a humanised monoclonal antibody against the eosinophil activating cytokine, interleukin (IL)-5, has consistently been shown to lead to a 50% reduction in exacerbation rate, when compared with placebo, and facilitates the weaning of maintenance oral corticosteroids (OCS) in patients with severe eosinophilic asthma. This works seeks to address two questions that arise from treatment with this novel monoclonal antibody: 1. What is the inflammatory phenotype and the physiological characteristics of the residual asthma exacerbations that occur in patients with severe eosinophilic asthma treated with anti-IL5 monoclonal antibodies? 2. To quantify toxicity associated with OCS treatment in severe eosinophilic asthmatics, and assess change in OCS-related toxicity after 1 year's treatment with mepolizumab and subsequent reduction in OCS, both through weaning of maintenance OCS and reduction in OCS for asthma exacerbations.

Amblyopia, a developmental disorder of the visual system, is widely known to cause a reduction in optotype acuity but it can also be associated with disrupted binocular vision, reduced contrast sensitivity and many other subtle high level visual processing deficits. The initial stages of the work presented in this thesis involved laboratory investigation of the functional visual deficit in global motion processing that has previously been reported abnormal in the presence of amblyopia. The key question is whether higher-levels of visual processing "inherit" abnormalities from lower levels, or whether additional developmental abnormalities arise in direct consequence of impoverished visual input. Overall, the results imply a far more complex perceptual change in amblyopia than would be predicted by the well -established losses in resolution and contrast sensitivity. The motivation behind Chapters 5 and 6 stems from the current observation that the recovery of visual function in amblyopia is contingent on even brief periods of correlated binocular vision, suggesting that amblyopia is intrinsically a binocular problem and that it is suppressive mechanisms that render the cortex, which is a structurally binocular system, functionally monocular. Research is now casting doubts on the idea that amblyopes do not possess cortical binocular connections, suggesting an active suppression rather than a deficit of cellular function. Interestingly, this is echoed in the clinical domain where, in cases of de-correlated visual input, strabismus clinical protocols have now established that the correction of refractive error alone can be sufficient to improve acuity, again implying incomplete inhibition mechanisms. The clinical investigations in this thesis have involved the validation of a series of psychophysical paradigms in cohorts of juvenile and adult amblyopes (as well as age-matched controls) to establish the degree of binocular interaction present and to explore the potential for treating amblyopia with prolonged viewing of a binocular stimulus adapted to correlate the visual imput from both eyes.