Inherited Retinal Degeneration, Retinitis Pigmentosa
Conditions
Keywords
Inherited Retinal Degeneration
Brief summary
This is an international, multicenter study with two components: Registry * A standardized genetic screening and a prospective, standardized, cross-sectional clinical data collection * Enrollment is open to all genes on the RD Rare Gene List Natural History Study * A prospective, standardized, longitudinal Natural History Study * Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment The study objectives are as follows. Registry Objectives 1. Genotype Characterization 2. Cross-Sectional Phenotype Characterization (within gene) 3. Establish a Link to My Retina Tracker Registry (MRTR) 4. Ancillary Exploratory Studies - Pooling of Genes Natural History Study Objectives 1. Natural History (within gene) 2. Structure-Function Relationship (within gene) 3. Risk Factors for Progression (within gene) 4. Ancillary Exploratory Studies - Pooling of Genes
Detailed description
This study includes multiple phases. 1. Screening Phase The patient's current genetic report will be reviewed. Genetic testing will not be performed in this study. A prior conclusive genetic test will be assessed for screening analysis. Having at least one gene on the RD Rare Gene List meets one of the eligible Genetic Screening Criteria and other eligibility criteria can be evaluated based on medical history. 2. Genetic Screening Phase: Genetic reports for participants enrolled into the genetic screening phase will be uploaded to study website for review and confirmation by Central Genetics Auditor (CGA) as meeting Genetic Screening Criteria.Participants confirmed as meeting those criteria will be considered enrolled into the Registry. 3. Registry Phase: The flow of participants who are enrolled into the Registry depends on whether their causal gene is designated as a Natural History Study (NHS) Target Gene. If they are not Designated as NHS Target Gene, they will receive annual phone calls up to 48 months from the Registry/Screening visit or until the gene is designated as NHS Target Gene. If they are Designated as NHS Target Gene participants will be considered pending enrollment into the NHS. The Registry will establish genetically and clinically well-characterized cohorts of patients across hundreds of genetic variants associated with retinal dystrophy (RD). Characterization of these patients will accelerate eligibility screening for the Natural History Study, provide cross-sectional data on phenotype-genotype associations, and contribute to our knowledge of pathogenicity of these rare disease-causing variants. 4. Natural History Study (NHS) Phase Participants pending enrollment will return to the clinic for the NHS Enrollment/Baseline Visit and return to the clinic for follow-up visits. The Natural History Study will accelerate the identification and development of sensitive, reliable outcome measures for clinical trials, which will facilitate development of treatments for retinal dystrophies due to disease-causing genetic variants. The expected impact of the Natural History Study is as follows: 1. Describe the natural history of retinal degeneration in patients with rare disease-causing genetic variants 2. Identify sensitive structural and functional outcome 3. Identify well-defined subpopulations for future clinical trials of investigative treatments for rare inherited retinal degeneration
Interventions
None listed
Sponsors
Jaeb Center for Health Research
Foundation Fighting Blindness
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all the following inclusion criteria at the Registry/Screening Visit to be eligible to enroll into the genetic screening phase: 1. Willing to participate in the study and able to communicate consent during the consent process 2. Willing and able to complete all applicable Registry/Screening Visit assessments 3. Age ≥ 4 years 4. Must have a single gene on the RD Rare Gene List which meets one of the Genetic Screening Criteria below based on a genetic report\* from a clinically certified lab (or from a research lab which has been approved by the study Genetics Committee): Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are homozygous or heterozygous in trans OR Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and meets all the following additional informatic criteria that is consistent with likely segregation in trans: 1. Investigator confirms genotype and phenotype are consistent with autosomal recessive inheritance 2. The 2 disease-causing variants have not been reported in cis in variant databases 3. No additional potentially pathogenic variants were found on the gene (and the sequencing data for the gene were sufficiently robust to detect any additional potentially pathogenic variants) 4. No potentially pathogenic variants were found in other common, likely candidate genes for the proposed condition OR Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1 disease-causing variant Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into the genetic screening phase: 1. Both eyes must have a clinical diagnosis of retinal dystrophy 2. Both eyes must permit good quality photographic imaging (e.g., but not limited to, clear ocular media, adequate pupil dilation, stable fixation)
Exclusion criteria
Participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome: Characterize change using Visual field sensitivity measured with quantitative topographic analysis (hill of vision [HOV]) | Baseline and every year until study completion (4 years) | Measured by Static Perimetry (SP) using Octopus 900 Pro |
| Functional Outcome: Characterize Change Using Early Treatment of Diabetic Retinopathy Study (ETDRS) / HOTV Best Corrected Visual Acuity (BCVA) letter score | Baseline and every year until study completion (4 years) | Measured by Electronic Visual Acuity (EVA) system or ETDRS/HOTV charts |
| Functional Outcome: Characterize Change Using Low visual acuity test - for participants unable to see ETDRS letters | Baseline and every year until study completion (4 years) | Measured by Berkeley Rudimentary Vision Test (BRVT) for Low Visual Acuity |
| Functional Outcome: Characterize Change Using ETDRS/HOTV best corrected low luminance visual acuity letter score | Baseline and every year until study completion (4 years) | Measured by Electronic Visual Acuity (EVA) system or ETDRS/HOTV charts |
| Functional Outcome: Characterize Change in Mean retinal sensitivity | Baseline and every year until study completion (4 years) | Measured by Fundus guided Microperimetry (MP) using MAIA |
| Functional Outcome: Characterize Change in Contrast sensitivity function | Baseline and every year until study completion (4 years) | Measured by Contrast sensitivity CSV-1000E chart |
| Functional Outcome: Characterize Change in Retinal function using amplitudes and timing in response to rod- and cone-specific stimuli | Baseline and at study completion (4 years) | Measured by Full-field Electroretinogram (ffERG) Diagnosys Espion |
| Functional Outcome: Characterize Change in Full-field retinal sensitivity | Baseline and every year until study completion (4 years) | Measured by Full-field stimulus threshold (FST) testing to blue, white, and red stimuli using Diagnosys Espion |
| Functional Outcome: Characterize Change in Color vision function | Baseline and every year until study completion (4 years) | Measured by Color vision testing using Lanthony D15 |
| Structural Outcome: Characterize Change in Ellipsoid zone (EZ) area; outer nuclear layer and ganglion cell layer thicknesses | Baseline and every year until study completion (4 years) | Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) using Heidelberg Spectralis |
| Structural Outcome: Characterize Change Using Qualitative and quantitative assessments of autofluorescence pattern | Baseline and every year until study completion (4 years) | Measured by Fundus Autofluorescence (FAF) using Optos |
Countries
Australia, Belgium, Brazil, Canada, Finland, France, Israel, Italy, Mexico, Netherlands, Norway, Switzerland, United Kingdom, United States
Contacts
CONTACTCoordinating Center
STUDY_CHAIRJosé-Alain Sahel, MD
Director, UPMC Eye Center University of Pittsburgh School of Medicine
Outcome results
None listed