Eye Diseases, Retinitis Pigmentosa
Conditions
Keywords
EYS mutation, Retinitis Pigmentosa
Brief summary
The overall goal of this project funded by the Foundation Fighting Blindness is to characterize the natural history of disease progression in patients with EYS mutations in order to accelerate the development of outcome measures for clinical trials.
Detailed description
This natural history study of patients with EYS mutations will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to EYS mutations. Together these approaches are expected to have an impact on understanding EYS-related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness. The goals and expected impact of this natural history study are to: 1. Describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene 2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration 3. Identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration Study Objectives The primary objectives of the natural history study are to: 1. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the EYS gene over 4 years, as measured using functional, structural, and patient-reported outcome measures 2. Investigate whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the EYS gene 3. Evaluate possible risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individual with biallelic pathogenic mutations in the EYS gene 4. Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene
Interventions
None listed
Sponsors
Jaeb Center for Health Research
Foundation Fighting Blindness
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing to participate in the study and able to communicate consent during the consent process 2. Ability to return for all study visits over 48 months 3. Age ≥ 18 years 4. Must meet one of the Genetic Screening Criteria, defined below: * Screening Group A: At least 2 disease-causing variants in the EYS gene which are homozygous or heterozygous in trans, based on a report from a clinically-certified lab (or a report from a research lab that has been pre- approved by the Genetics Committee) * Screening Group B: Only 1 disease-causing variant in the EYS gene, based on a report from a clinically-certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee) * Screening Group C: At least 2 disease-causing variants in the EYS gene which are unknown phase, based on a report from a clinically-certified lab (or a report from a research lab which has been pre-approved by the Genetics Committee) Note pertaining to all Screening Groups: if a participant has a variant(s) of unknown significance, he/she would still qualify as long as there is at least 1 disease-causing variant(s) on the EYS gene. Ocular Inclusion Criteria: Both eyes must meet all of the following: 1. Clinical diagnosis of retinal dystrophy 2. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging
Exclusion criteria
1. Mutations in genes that cause autosomal dominant retinitis pigmentosa (ADRP), X-linked retinitis pigmentosa (RP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than EYS 2. Expected to enter experimental treatment trial at any time during this study 3. History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy (including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine) Ocular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Field Sensitivity | Baseline and every year until study completion (4 years) | Measured by static perimetry with topographic analysis (Hill of Vision) and assessed by a central reading center for cohorts 1 and 2. |
| Change in Best Corrected Visual Acuity | Screening visit and every year until study completion (4 years) with the exception of baseline for cohorts 1 and 2. Screening visit and 48 month follow-up for cohort 3. | Measured on the Electronic Visual Acuity (EVA) system or ETDRS charts. Berkeley Rudimentary Vision Test (BRVT) will be used for patients unable to see letters. |
| Change in Mean Retinal Sensitivity | Baseline and every year until study completion (4 years). | Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment for cohorts 1 and 2. |
| Change in Full-field Retinal Sensitivity | Baseline and every year until study completion (4 years) for cohort 1 and 2. Baseline and 4 year follow-up for cohort 3. | Measured by full-field stimulus threshold (FST) testing to blue, white, and red stimuli |
| Change in Best Corrected Low Luminance visual acuity | Screening visit and every year until study completion (4 years) with the exception of baseline for cohorts 1 and 2. Screening visit and 48 month follow-up for cohort 3. | Measured by letter score |
| Change in Contrast Sensitivity Function | Baseline and every year until study completion (4 years). | Measured by the CSV-1000E VectorVision chart for cohorts 1 and 2. |
| Change in Retinal Function | Baseline and 4 year follow-up visit. | Measured by full-field electroretinogram (ERG) amplitudes and timing in response to rod- and cone-specific stimuli for cohorts 1 and 2. |
| Change in Ellipsoid zone (EZ) area | Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3. | Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Explore Qualitative categorization of Fundus Autofluorescence (FAF) pattern | Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3. | Assessed by a central reading center |
| Explore quantitative measures of FAF | Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3. | assessed by a central reading center |
Countries
Canada, Finland, France, Germany, Israel, Netherlands, United States
Contacts
STUDY_CHAIRMark Pennesi, MD, PhD
Retina Foundation of the Southwest
Outcome results
None listed