RECRUITINGOBSERVATIONAL

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

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

About This Trial

Inherited retinal diseases (IRDs) are a group of degenerative disorders that cause progressive vision loss. Retinitis pigmentosa (RP) is the most common form, with a global prevalence of approximately 1 in 4,500. About 20-30% of these cases are syndromic, most notably Usher syndrome (USH), which combines hearing loss with visual impairment. Usher syndrome type 1 (USH1), the most severe form, presents at birth with profound sensorineural hearing loss, vestibular areflexia, and early-onset retinal degeneration. Biallelic mutations in the MYO7A gene, which define the USH1B subtype, account for 70% of USH1 cases. There is currently no treatment available for this serious condition. The objective of the study is to characterize the natural history of retinal degeneration in USH1B patients and to validate functional vision tests using virtual reality and patient-reported outcome questionnaires.

Who May Be Eligible (Plain English)

Who May Qualify: - Be at least 3 years old; - Have a clinical diagnosis of USH1 in both eyes, meaning subjects with congenital profound deafness, vestibular dysfunction, and rod dystrophy, carrying biallelic class 4 or 5 variants in the MYO7A gene; - Be affiliated with or beneficiary of a social security system (according to article L1121-8-1 of the French Public Health Code); For participants in the MOST-VR mobility test and VR-ViSA visual search test (Streetlab), additional criteria apply: - Sufficient knowledge of spoken and signed French to ensure understanding of tasks and instructions; - Have a cochlear implant allowing comprehension of auditory instructions for the virtual reality mobility test and a MMSE score ≥ 20/25; - Age between 18 and 75 years. Who Should NOT Join This Trial: - Unable to participate in all study visits; - Expected to enter an experimental treatment trial at any time during this study; - Presence of ocular conditions that may affect eye status other than retinitis pigmentosa (e.g., history of retinal detachment, glaucoma, vein occlusion, diabetic retinopathy, etc.); - Participation in the previous gene replacement trial (USHSTAT, NCT01505062); - Pregnant, delivering, or breastfeeding women (according to article L1121-5 of the French Public Health Code); - Persons deprived of liberty by judicial or administrative decision (article L1121-6 of the French Public Health Code); - Adults under legal protection measures or unable to provide consent (article L1121-8 of the French Public Health Code). For participants in the MOST-VR mobility and VR-ViSA visual search tests, the following non-inclusion criteria apply: - MMSE score without visual items ≤ 20/25; - Physical or cognitive impairment that could interfere with mobility; - Medication that may cause motor, visual, or cognitive disorders (e.g., APS, neuroleptics) or interfere with study assessments. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Be at least 3 years old; * Have a clinical diagnosis of USH1 in both eyes, meaning subjects with congenital profound deafness, vestibular dysfunction, and rod dystrophy, carrying biallelic class 4 or 5 variants in the MYO7A gene; * Be affiliated with or beneficiary of a social security system (according to article L1121-8-1 of the French Public Health Code); For participants in the MOST-VR mobility test and VR-ViSA visual search test (Streetlab), additional criteria apply: * Sufficient knowledge of spoken and signed French to ensure understanding of tasks and instructions; * Have a cochlear implant allowing comprehension of auditory instructions for the virtual reality mobility test and a MMSE score ≥ 20/25; * Age between 18 and 75 years. Exclusion Criteria: * Unable to participate in all study visits; * Expected to enter an experimental treatment trial at any time during this study; * Presence of ocular conditions that may affect eye status other than retinitis pigmentosa (e.g., history of retinal detachment, glaucoma, vein occlusion, diabetic retinopathy, etc.); * Participation in the previous gene replacement trial (USHSTAT, NCT01505062); * Pregnant, delivering, or breastfeeding women (according to article L1121-5 of the French Public Health Code); * Persons deprived of liberty by judicial or administrative decision (article L1121-6 of the French Public Health Code); * Adults under legal protection measures or unable to provide consent (article L1121-8 of the French Public Health Code). For participants in the MOST-VR mobility and VR-ViSA visual search tests, the following non-inclusion criteria apply: * MMSE score without visual items ≤ 20/25; * Physical or cognitive impairment that could interfere with mobility; * Medication that may cause motor, visual, or cognitive disorders (e.g., APS, neuroleptics) or interfere with study assessments.

Treatments Being Tested

DIAGNOSTIC_TEST

Vision tests

Standardized assessments of visual function including best corrected visual acuity (BCVA), low vision acuity (BRVT), low luminance visual acuity (LLVA), color and contrast sensitivity tests, visual field measurements, and electroretinography (ERG) to evaluate retinal function.

DIAGNOSTIC_TEST

Retinal imaging

Advanced imaging techniques such as optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCT-A) are used to visualize retinal structure and detect abnormalities.

DIAGNOSTIC_TEST

Questionnaires

Patient-reported outcome measures including the Michigan Vision-Related Anxiety Questionnaire (MAVQ) and the Michigan Retinal Degeneration Questionnaire (MRDQ) assess the psychological and quality-of-life impacts of retinal degeneration.

DIAGNOSTIC_TEST

Streetlab performance tests

Virtual reality-based functional tests evaluating mobility (MOST-VR) and visual search performance (VR-ViSA) to assess real-world vision-related abilities.

Locations (1)

Centre National d'Ophtalmologie des Quinze-Vingts

Paris, Île-de-France Region, France