Multifocal choroiditis: Clinical, immunologic and genetic aspects

Abstract

In this thesis we explored the clinical and genetic risk factors for idiopathic multifocal choroiditis (MFC). MFC is a rare ocular disease affecting the choroid in the posterior pole of the eye. This relapsing disease predominantly affects relatively young women with myopia. In the first part of this thesis, we explored clinical risk factors associated with an increased relapse rate and the efficacy of several treatment options. We discovered that the presence of the complication of choroidal neovascularization at the first presentation and the level of myopia were both significantly associated with the relapse rate. Moreover, we described that treatment with disease modifying rheumatic drugs (DMARDs) and/or adalimumab decreased the relapse rate in these patients. In the second part of this thesis, we discovered imaging characteristics that were associated with disease activity using a multimodal imaging approach. We found that an increased choroidal thickness on optical coherence tomography and increased area of hypoperfusion of the choriocapillaris visualized with indocyanine green angiography and optical coherence tomography angiography, were an indication for disease activity. In the third part of this thesis, we investigated immunological and genetic risk factors. In a genome-wide association study we discovered a genetic locus in the complement factor H gene, that was significantly associated with idiopathic MFC. Moreover, we demonstrated that the risk genotype of this locus significantly increased the concentrations of proteins in two biological pathways: the complement cascade and the activation of platelets. Lastly, we found that increased granularity of the platelets, measured with automated hematocytometry, was an independent risk factor for treatment with a DMARD.