The overall goal of this project funded by the Foundation Fighting Blindness is to characterize the natural history of disease progression in patients with USH2A related retinal degeneration associated with congenital hearing loss (Usher syndrome type 2a) or non-syndromic retinitis pigmentosa (RP39).
This natural history study of patients with USH2A mutations will accelerate the development of outcome measures for clinical trials. Sensitive, objective outcome measures of retinal degeneration will greatly facilitate development of treatments for Usher syndrome patients. Together these approaches are expected to have an impact on understanding USH2A-related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness. The goals and expected impact of this natural history study are to: 1. Report the natural history of retinal degeneration in patients with biallelic mutations in the USH2A gene 2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in USH2A-related retinal degeneration 3. Identify well-defined subpopulations for future clinical trials of investigative treatments for USH2A-related retinal degeneration Study Objectives The primary objectives of the natural history study are to: 1. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using functional outcome measures (static perimetry, microperimetry, full-field stimulus threshold (FST), electroretinography (ERG), and visual acuity) 2. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using structural outcome measures (spectral-domain optical coherence tomography (SD-OCT) ellipsoid zone (EZ) area) 3. Investigate structure-function relationships for insights into the mechanisms of retinal degeneration by relating changes in SD-OCT EZ area to visual field progression in individuals with biallelic pathogenic mutations in the USH2A gene 4. Assess for possible genotype, phenotype, and environmental risk factors with progression of the outcome measures at 4 years in individuals with biallelic pathogenic mutations in the USH2A gene Some additional secondary objectives of this study include: 1. Characterize baseline cross-sectional retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene (as measured using the main outcome measures) 2. Investigate comorbidities associated with disease (baseline cross-sectional) and disease progression (longitudinal natural history study) in individuals with biallelic pathogenic mutations in the USH2A gene 3. Explore patient reported outcome (PRO) measures associated with disease (baseline cross-sectional) and disease progression (longitudinal natural history study) in individuals with biallelic pathogenic mutations in the USH2A gene 4. Evaluate variability and symmetry of left and right eye kinetic perimetry and SD-OCT outcomes at baseline and at 4 years in individuals with biallelic pathogenic mutations in the USH2A gene
