Natural history of vision loss in USH1B (MYO7A) and validation of virtual-reality vision tests

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

This project tests how vision changes over time in people with USH1B caused by MYO7A mutations and whether virtual-reality mobility and visual-search tasks plus questionnaires can measure those changes.

Quick facts

• Study type: Observational
• Enrollment: 60 (estimated)
• Ages: 3 Years to 75 Years
• Sex: All
• Sponsor: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (Academic / other)
• Locations: 1 site (Paris, Île-de-France Region)
• Trial ID: NCT07278843 on ClinicalTrials.gov

What this trial studies

This is an observational natural-history project enrolling people with biallelic pathogenic or likely pathogenic MYO7A variants (USH1B) to document retinal degeneration over time using retinal imaging and standard clinical measures. The protocol also includes validation of functional-vision tests delivered in virtual reality (VR) and complementary patient-reported outcome questionnaires, including Streetlab mobility and visual-search tasks. Participants will undergo repeated imaging, vision testing, VR performance tasks, and questionnaires to map decline and determine which measures are reliable, sensitive, and practical for future interventional trials. Subsets performing VR tests must meet additional language and cochlear-implant criteria to ensure comprehension of instructions.

Who should consider this trial

Good fit: Ideal candidates are people aged 3 years or older with clinical USH1 and confirmed biallelic class 4 or 5 MYO7A variants who can attend visits at the coordinating center, with VR subsets limited to French-speaking adults (18–75) with a cochlear implant and MMSE ≥20/25.

Not a fit: Patients without confirmed biallelic pathogenic MYO7A variants, those with other ocular conditions that affect the retina, those unable to attend study visits, or those planning to start an experimental treatment during the observation period are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the project could identify reliable outcome measures and timelines that make future treatment trials for USH1B more feasible and informative for patients.

How similar studies have performed: Natural-history studies in inherited retinal diseases have successfully informed trial design and endpoints, while validation of VR-based functional-vision tests is relatively novel with limited but growing supportive data.

Eligibility criteria

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.

Where this trial is running

Paris, Île-de-France Region

• Centre National d'Ophtalmologie des Quinze-Vingts — Paris, Île-de-France Region, France (Recruiting)

Study contacts

• Principal investigator: Isabelle Audo, Pr — Centre National d'Ophtalmologie des Quinze-Vingts
• Study coordinator: Isabelle AUDO, Pr

Conditions Usher Syndrome; Retina; Genetic mutation; Inherited disease; Retinis pigmentosa; Usher syndrome