Natural History of Photoreceptor Degeneration in USH1B: Clinical Parameters and Validation of Functional Vision Tests in MYO7A

Inherited retinal diseases (IRDs) are a heterogeneous group of disorders that gradually lead to severe visual impairment, with limited therapeutic options available. Rod dystrophy, also known as retinitis pigmentosa (RP), is the most common form of IRD, with an estimated global prevalence of 1 in 4,500. Approximately 20% to 30% of rod-cone dystrophy cases are syndromic, with Usher syndrome (USH) being the most frequent. USH has an estimated prevalence of 1 to 4 per 25,000 individuals and accounts for 50% of all cases of deafblindness and 3% to 6% of all cases of childhood deafness. Usher syndrome type 1 (USH1) is the most severe form of the disease. It typically presents with congenital severe-to-profound sensorineural hearing loss, vestibular areflexia, and early-onset rod-cone dystrophy, usually within the first decade of life. Mutations in nine different genes have been associated with USH1, among which biallelic mutations in the MYO7A gene account for approximately 70% of cases. This specific subtype is referred to as USH1B. There is currently no approved treatment for USH1B, representing a significant unmet medical need for this severe condition. Objectives: 1. To study the natural history of retinal degeneration in a large USH1B patient cohort. 2. To validate functional vision tests based on virtual reality, along with two patient-reported outcome questionnaires.