Natural History Study in Subjects With Usher Syndrome

A Multicentre Longitudinal, Observational Natural History Study to Evaluate Disease Progression in Subjects With Usher Syndrome Type 1B (USH1B)

Natural History Study in Subjects With Usher Syndrome ((USH1B) is a multi-centre, longitudinal, observational study designed to evaluate disease progression in subjects with USH1B by several vision-related assessments.

Natural History Study in Subjects With Usher Syndrome (USH1B) is being conducted to understand the progression of disease in USH1B patients as measured by visual acuity and visual field testing and a number of other vision-related assessments. Disease progression will be evaluated as change over time in these measures and associations between the endpoints will be examined.

The primary objective of this study is to evaluate the natural progression of disease over time in USHIB patients using visual field testing and best corrected visual acuity.

The secondary objectives of this study are to evaluate the progression of disease over time in USHIB patients through additional assessments:

• Microperimetry (only in selected centres)
• Fundus autofluorescence (FAF)
• Optical Coherence Tomography (OCT)
• Full-field Electroretinogram (ERG),
• Multifocal Electroretinogram,
• Vision-related function and quality of life, as measured by the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25)

Inclusion Criteria:

1. Must be willing to adhere to protocol for long-term follow-up as evidenced by written informed consent or parental permission and subject assent.
2. Subjects diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations (homozygotes or compound heterozygotes).
4. Age eight years old or older at the time of baseline.
5. Visual acuity ≥ 20/640 in at least one eye

Exclusion Criteria:

1. Unable or unwilling to meet requirements of the study.
2. Unable to communicate with suitable verbal/auditory and/or tactile sign language (in the opinion of the investigator)
3. Participation in a clinical study with an investigational drug in the past six months.
4. Pre-existing eye conditions that would interfere with the interpretation of study endpoints (for example, glaucoma, corneal or significant lenticular opacities, cystoid macular oedema, macular hole).
5. Complicating systemic diseases in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example, radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Also excluded would be subjects with immuno- compromising diseases, as there could be susceptibility to opportunistic infection [such as cytomegalovirus (CMV) retinitis].
6. Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes).
7. Prior ocular surgery within three months.
8. Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.