Retinal dystrophies comprise relatively rare but devastating causes of progressive vision loss. They represent a spectrum of diseases with marked genetic and clinical heterogeneity. Mutations in... Show moreRetinal dystrophies comprise relatively rare but devastating causes of progressive vision loss. They represent a spectrum of diseases with marked genetic and clinical heterogeneity. Mutations in the same gene may lead to different diagnoses, e.g. retinitis pigmentosa or cone dystrophy. Conversely, mutations in different genes may lead to the same phenotype. The age at symptom onset, as well as the rate of vision decline, may vary widely per disease group and even within families. For most IRD cases, no effective treatment is currently available. However, preclinical studies and phase I/II/III gene therapy trials are ongoing for several IRD subtypes, and recently the first retinal gene therapy has been approved by the United States Food and Drug Administration for RPE65-associated IRDs: voretigene neparvovec-rzyl (Luxturna®). With these rapid advances in gene therapy studies, insight into the phenotypic spectrum and long-term disease course becomes crucial. The vast clinical heterogeneity presents an important challenge in the evaluation of potential efficacy in future treatment trials, and in establishing treatment candidacy criteria. This thesis responds to these challenges, providing detailed clinical descriptions of several forms of IRD that are caused by genes of interest for ongoing and future gene or cell-based therapy trials. Show less
