Natural History of Photoreceptor Degeneration Related to USH1B: Clinical Parameters and Validation of Functional Vision Tests in MYO7A
Conditions: Usher Syndrome
Sponsor: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Protocol Summary 
CRMR – MYO7A – Protocole Summary– 2025-A00690-49 - V.1 of 14.04.2025  
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Title 
Natural History of Photoreceptor Degeneration Related to USH1b, Clinical 
Parameters, and Validation of Functional Vision Tests 
 
Acronyme 
MYO7A 
 
Principal Investigator 
Pr. Isabelle AUDO 
 
Sponsor 
Hôpital National de la Vision des Quinze-Vingts, Paris (France) 
 
Justification for the Study 
nherited retinal diseases (IRD) are a heterogeneous group of disorders that 
progressively lead to severe visual impairments with limited therapeutic options. 
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 forms, among which Usher 
syndrome (USH) is the most frequent (estimated prevalence of 1 to 4 in 25,000), 
accounting for 50% of cases of combined deafness and blindness in males and 3 
to 6% of all childhood deafness cases. 
 
Type 1 Usher syndrome (USH1) is the most severe form of USH and typically 
presents with severe to profound congenital sensorineural deafness, vestibular 
areflexia, and early-onset rod-cone dystrophy (i.e., during the first decade of life). 
Mutations in nine genes have been associated with USH1, among which biallelic 
mutations in MYO7A represent 70% of cases. These specific mutations are known 
as USH1B syndrome. 
 
Currently, there is no treatment available for USH1B, representing a significant 
unmet medical need for this severe form of USH. 
 
Study Objectives 
1. Study of the natural history of retinal degeneration in a large USH1B 
cohort 
2. Validation of functional vision tests based on virtual reality and two 
patient-reported questionnaires 
 
Study Category and Type 
Research with minimal risks and constraints, Category 2 
This is a prospective and longitudinal study focusing on the natural history and 
progression of inherited retinal diseases related to USH1b, as well as the 
validation of clinical parameters and functional vision tests. 
 
Evaluation Criteria and 
Parameters 
Functional Tests: 
• 
Letter score from Best-Corrected Visual Acuity (BCVA) using the Early 
Treatment Diabetic Retinopathy Study (ETDRS) scale 
• 
In case of very low visual acuity: Berkeley Rudimentary Vision Test 
(BRVT) 
• 
Low Luminance Visual Acuity (LLVA) using ETDRS or HOTV charts 
• 
Color Contrast Sensitivity using the Lanthony 15-HUE test and 
Cambridge Colour Test 
• 
Contrast Sensitivity with the backlit Pelli-Robson chart 
• 
Mesopic Microperimetry (MAIA) 
• 
Kinetic Visual Field testing (Octopus 900) 
• 
Static Visual Field testing (Octopus 900) 
 

Protocol Summary 
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• 
Retinal Function evaluated by Full-Field Stimulus Threshold (FST) 
testing (global photoreceptor sensitivity) 
• 
Retinal Function assessed by full-field electroretinogram (ERG) 
responses to rod- and cone-specific stimuli (measuring amplitude and 
peak time) 
 
Structural Tests: 
• 
Retinography (Clarus) 
• 
Fundus Autofluorescence (FAF) imaging using both short-wavelength 
autofluorescence (SWAF) and near-infrared autofluorescence (NIRAF) 
(HRA2) 
• 
Spectral Domain Optical Coherence Tomography (SD-OCT) 
• 
Optical Coherence Tomography Angiography (OCT-A) 
• 
Axial Length Measurements 
• 
Objective Refraction and Non-contact Tonometry 
 
Quality of Life: 
• 
Responses to the two patient-reported outcome questionnaires: 
o 
The Michigan Vision-Related Anxiety Questionnaire (MAVQ): A 
Psychosocial 
Outcomes 
Measure 
for 
Inherited 
Retinal 
Degenerations 
o 
The Michigan Retinal Degeneration Questionnaire (MRDQ): A 
Patient-Reported Outcome Instrument for Inherited Retinal 
Degenerations 
- 
 
Inclusion Criteria 
- 
Age ≥ 3 years 
- 
Clinical diagnosis of Usher Syndrome Type 1 (USH1) in both eyes, defined 
as profound congenital deafness, vestibular dysfunction, and rod-cone 
dystrophy, with biallelic class 4 or 5 variants in the MYO7A gene 
- 
Affiliation with, or beneficiary of, a social security system (according to 
article L1121-8-1 of the French Public Health Code) 
- 
Additional Inclusion Criteria for Participants in the MOST-VR and VR-ViSA 
(Streetlab) Tests: 
- 
Sufficient understanding of spoken and signed French to ensure proper 
comprehension of the tasks and instructions 
- 
Presence of a cochlear implant allowing for comprehension of auditory 
instructions during the virtual reality mobility test, with a Mini-Mental 
State Examination (MMSE) score ≥ 20/25 
- 
Age between 18 and 75 years 
 
Exclusion Criteria 
- 
Inability to attend or complete all study visits 
- 
Anticipated participation in an experimental treatment trial at any point 
during the study 
- 
Presence of ocular conditions that could impact retinal status other than 
retinitis pigmentosa (e.g., history of retinal detachment, glaucoma, vein 
occlusion, diabetic retinopathy, etc.) 
- 
Prior participation in the USH1B gene therapy trial (USHSTAT, NCT01505062) 
- 
Pregnant, postpartum, or breastfeeding women (according to article L1121-
5 of the French Public Health Code) 
 

Protocol Summary 
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- 
Individuals deprived of liberty by judicial or administrative decision 
(according to article L1121-6 of the French Public Health Code) 
- 
Adults under legal protection or unable to provide informed consent 
(according to article L1121-8 of the French Public Health Code) 
- 
Additional Exclusion Criteria for Participants in the MOST-VR and VR-ViSA 
Tests: 
- 
MMSE score (visual items excluded) ≤ 20/25 
- 
Physical or cognitive impairment likely to interfere with mobility 
- 
Ongoing treatment with medications that may affect motor, visual, or 
cognitive function (e.g., antipsychotics, neuroleptics) or that may interfere 
with study assessments 
Criteria for Early 
Discontinuation or Study 
Withdrawal 
- 
Occurrence of other medical conditions or treatments likely to interfere with 
the assessments planned during the study. 
- 
Voluntary withdrawal: A participant may decide to discontinue participation 
at any time, without justification and without affecting their future medical 
care. 
- 
Investigator decision: A participant may also be withdrawn from the study 
at the discretion of the investigator, for reasons such as safety concerns, 
protocol non-compliance, or any other reason deemed appropriate. 
 
Constraints and Risks 
The procedures involved in this study may expose participants to the following 
medical risks: 
 
- 
Pupil dilation, performed as part of the ophthalmologic evaluation, may 
cause side effects, with a risk of acute angle-closure glaucoma estimated at 
less than 1 in 5000 cases. Risk factors will be systematically screened during 
the ophthalmologic examination, particularly through slit-lamp evaluation. 
 
- 
Placement of corneal electrodes for the full-field electroretinogram (ERG), 
as well as the instillation of topical anesthetic eye drops (oxybuprocaine), 
may occasionally cause corneal erosion or corneal edema, resulting in pain 
lasting 24 to 48 hours after the examination. This rare complication will be 
systematically assessed during the fundus examination, and a healing eye 
drop will be prescribed if necessary. 
 
- 
 Completion of patient-reported questionnaires may induce psychological 
side effects, such as increased anxiety or emotional stress. However, such 
reactions are typically transient, and participants are free to discontinue at 
any time if needed. 
 
Population 
A total of 60 participants are expected to be recruited for this study. The study is 
divided into three sub-cohorts: two pediatric cohorts (n=10 patients, ages 3–5 
and 6–13 years) and one mixed adolescent and adult cohort (aged 14 and older, 
n=50). 
 
Research Procedure 
See Tables 1, 2, and 3 
The following procedures are not part of routine care and are therefore added 
specifically for the research: 
 
- 
    MOST-VR and VR-ViSA tests (Streetlab) 
 

Protocol Summary 
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Projected Research 
Timeline 
- 
Planned Study Start Date: June 2025 
- 
Duration of Participation per Participant: 4 years (48 months) 
- 
Visit Frequency: 6 visits in total (initial visit, reproducibility visit, and 4 
follow-up visits) 
- 
Planned Enrollment Period: 6 months. If recruitment goals are not met 
within this timeframe, the enrollment period may be extended up to a 
total of 24 months. 
- 
Total Study Duration: 72 months (48 months participation + up to 24 
months enrollment extension) 
 
Funding Source 
Foundation Fighting Blindness 
Reimbursement of 
Expenses 
The study will cover the costs of all examinations beyond standard care, 
including contrast sensitivity, color contrast vision, mesopic microperimetry, 
FST, and SS-OCT-A. Additionally, travel and accommodation expenses related 
to these visits will be reimbursed upon presentation of receipts and prior 
approval for each evaluation visit. 
 
 
 

Protocol Summary 
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Table 1. Test Protocol for the Pediatric Cohort Aged 3 to 5 Years 
Visits 
Initial 
visit 
(D+0) 
Reproductibility 
visit (D+1 à D+30) 
M12  
± 3M 
M24  
± 3M 
M36  
± 3M 
M48  
± 3M 
Duration 
of the 
examinati
on 
(minutes) 
Procedures and tests 
Informed Consent 
X 
- 
- 
- 
- 
- 
15 
Demographics / Medical History 
X 
- 
X 
X 
X 
X 
10 
Concomitant Medications / 
Adverse Events 
X 
- 
X 
X 
X 
X 
5 
Objective Refraction + Air 
Tonometry 
X 
- 
X 
X 
X 
X 
5 
Axial Length Measurement 
X 
- 
X 
X 
X 
X 
5 
Visual Acuity Measurement 
X 
- 
X 
X 
X 
X 
15 
Full-Field Electroretinogram 
(ERG) 
X 
- 
X 
X 
X 
X 
60 
Ophthalmological Examination 
X 
- 
X 
X 
X 
X 
5 
Retinal Photography 
X 
 
X 
X 
X 
X 
10 
Blue and Near-Infrared Fundus 
Autofluorescence Imaging 
(HRA2, 30° and 50°) 
X 
- 
X 
X 
X 
X 
15 
Spectral-Domain and Swept-
Source Optical Coherence 
Tomography (SD-OCT and OCT-
Angiography) 
X 
- 
X 
X 
X 
X 
25 
1 The full-field electroretinogram (ERG) will not be performed if previous data showed no detectable response. 
2 Axial length measurement may be difficult to perform in some subjects depending on their level of 
concentration. 
 
 
 

Protocol Summary 
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Table 2. Testing protocol for the pediatric cohort aged 6 to 13 years 
Visits 
Initial 
visit 
(D+0) 
Reproductibility 
visit (D+1 à D+30) 
M12  
± 3M 
M24  
± 3M 
M36  
± 3M 
M48  
± 3M 
Duration 
of the 
examinati
on 
(minutes) 
Procedures and tests 
Informed Consent 
X 
- 
- 
- 
- 
- 
15 
Demographics / Medical History 
X 
- 
X 
X 
X 
X 
10 
Concomitant Medications / 
Adverse Events 
X 
- 
X 
X 
X 
X 
5 
Objective Refraction + Air 
Tonometry 
X 
- 
X 
X 
X 
X 
5 
Axial Length Measurement² 
X 
- 
X 
X 
X 
X 
5 
Best Corrected Visual Acuity 
(ETDRS or BRVT) 
X 
- 
X 
X 
X 
X 
15 
Low Luminance Best Corrected 
Visual Acuity (LLVA) 
X 
- 
X 
X 
X 
X 
10 
Color Contrast Sensitivity (15 
HUE Lanthony Test) 
X 
- 
X 
X 
X 
X 
30 
Contrast Sensitivity (Pelli-
Robson) 
X 
- 
X 
X 
X 
X 
15 
Kinetic Visual Field (Octopus 
900) 
X 
- 
X 
X 
X 
X 
45 
Full-field Electroretinogram 
(ERG)¹ 
X 
- 
X 
X 
X 
X 
60 
Ophthalmological Examination 
X 
- 
X 
X 
X 
X 
5 
Retinophotography 
X 
- 
X 
X 
X 
X 
10 
Blue and Near-Infrared Fundus 
Autofluorescence (HRA2, 30° 
and 50°) 
X 
- 
X 
X 
X 
X 
15 
Spectral-Domain and Swept-
Source Optical Coherence 
Tomography (SD-OCT and SS-
OCT-A) 
X 
- 
X 
X 
X 
X 
25 
1 L'électrorétinogramme plein champ ne sera pas effectué si les données antécédentes n'ont montré aucune 
réponse détectable. 
2 La mesure de la longueur axiale peut être difficilement réalisée chez certains sujets en fonction de leur 
concentration 
 
 

Protocol Summary 
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Table3. Test Protocol for the Adolescent (≥14 years) and Adult Cohort 
Visits 
Initial visit 
(D+0) 
Reproductibility 
visit (D+1 à D+30) 
M12  
± 3M 
M24  
± 3M 
M36  
± 3M 
M48  
± 3M 
Duration of 
the 
examination 
(minutes) 
Procedures and tests 
Informed Consent 
X  
-  
-  
-  
-  
-  
15  
Demographics / Medical History 
X  
-  
X  
X  
X  
X  
10  
Concomitant Medications / 
Adverse Events 
X  
-  
X  
X  
X  
X  
5  
Objective Refraction + Air 
Tonometry 
X  
-  
X  
X  
X  
X  
5  
Axial Length Measurement 
X  
-  
X  
X  
X  
X  
5  
Best Corrected Visual Acuity 
(ETDRS or BRVT) 
X  
-  
X  
X  
X  
X  
15  
Low Luminance Best Corrected 
Visual Acuity (LLVA) 
X  
-  
X  
X  
X  
X  
10  
Color Contrast Sensitivity 
(Cambridge Color Test, Triverctor 
protocol) 
X  
-  
X  
X  
X  
X  
30  
Contrast Sensitivity (Pelli-Robson) 
X  
-  
X  
X  
X  
X  
15  
Mesopic Microperimetry (MAIA) 
X  
X  
X  
X  
X  
X  
30  
Static Visual Field (Octopus 900) 
X  
-  
X  
X  
X  
X  
60  
Kinetic Visual Field (Octopus 900) 
X  
-  
X  
X  
X  
X  
45  
Full-field Stimulus Threshold (FST) 
X  
-  
X  
X  
X  
X  
90  
Full-field Electroretinogram (ERG)¹ 
X  
-  
X  
X  
X  
X  
60  
Ophthalmological Examination 
X  
-  
X  
X  
X  
X  
5  
Retinophotography 
X  
  
X  
X  
X  
X  
10  
Blue and Near-Infrared Fundus 
Autofluorescence (HRA2, 30° and 
50°) 
X  
-  
X  
X  
X  
X  
15  
Spectral-Domain and Swept-
Source Optical Coherence 
Tomography (OCT and OCT-A) 
X  
-  
X  
X  
X  
X  
25  
Patient-Reported Outcome 
Questionnaires (MVAQ and 
MRDQ) 
X  
-  
X  
X  
X  
X  
30  
Streetlab Tests (MOST-VR, VR-
ViSA)² 
X  
X  
  
X  
  
  
150  
1.  The full-field electroretinogram (ERG) will not be performed if prior data showed no detectable response. 
2. MOST-VR and VR-ViSA tests will only be conducted in participants aged 18 years and older who meet the inclusion criteria specified in the table 
"Inclusion Criteria for MOST-VR and VR-ViSA Tests."