The immunopathogenesis and treatment of chronic allergic eye disease

The pathogenesis of the potentially blinding chronic ocular allergies is poorly understood, and current therapy relies on topical steroids which have vision-reducing side-effects. This thesis aimed to elucidate this pathogenesis, particularly of sight-damaging corneal involvement, and to evaluate therapeutic topical cyclosporin A in atopic keratoconjunctivitis (AKC). The techniques employed were conjunctival biopsy, immunohistochemistry, in situ hybridisation and a randomised, placebo-controlled clinical trial. An initial examination of normal conjunctival leukocytes showed the relative frequencies of different leukocytes and that lymphocytes had features of mucosal-associated lymphoid tissue but organised conjunctival-associated lymphoid tissue was infrequent. An examination of T cells, eosinophils and epithelial cells was conducted. Vernal keratoconjunctivitis and giant papillary conjunctivitis had predominantly Th2-like cells (resembling asthma) but AKC resembled atopic dermatitis with a shift towards a Th1-pattern. There was greater expression of eosinophil surface antigens (and possibly activation) associated with corneal disease and variations in patterns of eosinophil-cytokine localisation occurred between individual disorders. Epithelial cell expression of pro-inflammatory surface antigens was particularly upregulated in disorders with keratopathy and there were different patterns of cytokine co-localisation in the various diseases. A trial of topical cyclosporin A demonstrated clinical improvement and reduced steroid requirement in AKC associated with reductions in leukocyte numbers and T cell cytokine expression not seen with placebo. The drops were difficult to tolerate. These results show a complex pathogenesis of cellular and cytokine interactions underlying chronic allergic eye disease with certain parallels to systemic allergic disorders. These results may allow future therapeutic developments with greater specificity and fewer side-effects than topical steroids.