Rate of Progression in EYS Related Retinal Degeneration

NCT04127006 | Active Not Recruiting DMC

• 1 other identifier: Pro-EYS
• Study Type: observational
• Target: 103
• Locations: 7 countries
• Sites: 19

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.

Conditions

Eye Diseases; Retinitis Pigmentosa

Keywords

EYS mutation; Retinitis Pigmentosa

Outcome Measures

Primary Outcomes (8)

• Change in Visual Field Sensitivity

  Measured by static perimetry with topographic analysis (Hill of Vision) and assessed by a central reading center for cohorts 1 and 2.

  Baseline and every year until study completion (4 years)

• Change in Best Corrected Visual Acuity

  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.

  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.

• Change in Mean Retinal Sensitivity

  Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment for cohorts 1 and 2.

  Baseline and every year until study completion (4 years).

• Change in Full-field Retinal Sensitivity

  Measured by full-field stimulus threshold (FST) testing to blue, white, and red stimuli

  Baseline and every year until study completion (4 years) for cohort 1 and 2. Baseline and 4 year follow-up for cohort 3.

• Change in Best Corrected Low Luminance visual acuity

  Measured by letter score

  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.

• Change in Contrast Sensitivity Function

  Measured by the CSV-1000E VectorVision chart for cohorts 1 and 2.

  Baseline and every year until study completion (4 years).

• Change in Retinal Function

  Measured by full-field electroretinogram (ERG) amplitudes and timing in response to rod- and cone-specific stimuli for cohorts 1 and 2.

  Baseline and 4 year follow-up visit.

• Change in Ellipsoid zone (EZ) area

  Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center

  Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.

Secondary Outcomes (2)

• 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.

• 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.

Other Outcomes (4)

• Patient Reported Outcomes for Vision Cohorts 1 and 2 (Vision Visual Functioning)

  Baseline, 2 year follow-up, and 4 year follow-up visit

• Patient Reported Outcomes for Vision Cohorts 1 and 2

  Baseline, 2 year follow-up, and 4 year follow-up visit

• Patient Reported Outcomes for Vision Cohort 3 (Vision Visual Functioning)

  Baseline and 4 year follow-up visit

Study Arms (3)

Vision Cohort 1

Participants with the better eye Screening Visit visual acuity ETDRS letter score of 54 or more \[approximate Snellen equivalent 20/80 or better\] and visual field diameter 10 degrees or more in every meridian of the central field

Vision Cohort 2

Participants with the better eye Screening Visit visual acuity ETDRS letter score of 19-53 \[approximate Snellen equivalent 20/100 - 20/400\] or (visual acuity ETDRS letter score of 54 or more \[approximate Snellen equivalent 20/80 or better\] and visual field diameter less than 10 degrees in any meridian of the central field)

Vision Cohort 3

Participants with the better eye Screening Visit visual acuity ETDRS letter score of 18 or less \[approximate Snellen equivalent 20/500 or worse\]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Potential eligibility may be assessed as part of a routine care examination by an investigator prior to obtaining informed consent, as part of usual care, by referral from another physician, or self-referral.

You may qualify if:

• Willing to participate in the study and able to communicate consent during the consent process
• Ability to return for all study visits over 48 months
• Age ≥ 18 years
• 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.
• Both eyes must meet all of the following:
• Clinical diagnosis of retinal dystrophy
• Clear ocular media and adequate pupil dilation to permit good quality photographic imaging

You may not qualify if:

• 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
• Expected to enter experimental treatment trial at any time during this study
• 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)
• If either eye has any of the following, the participant is not eligible:
• Current vitreous hemorrhage
• Current or any history of rhegmatogenous retinal detachment
• Current or any history of (e.g., prior to cataract or refractive surgery) spherical equivalent of the refractive error worse than -8 Diopters of myopia
• History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months
• Current or any history of confirmed diagnosis of glaucoma (e.g., based on glaucomatous VF changes or nerve changes, or history of glaucoma filtering surgery)
• Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
• History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function
• History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:
• Any use of ocular stem cell or gene therapy
• Any treatment with ocriplasmin
• Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Foundation Fighting Blindness: collaborator

Study Sites (19)

University of California, San Francisco

San Francisco, California, 94143-0344, United States

Location

Colorado Retina Associates

Denver, Colorado, 80230, United States

Location

Vitreo-Retinal Associates

Gainesville, Florida, 32607, United States

Location

University of Miami: Neuro-ophthalmology Department

Miami, Florida, 33136, United States

Location

Emory Eye Center

Atlanta, Georgia, 30322, United States

Location

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, 21287-9277, United States

Location

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Duke University Eye Center

Durham, North Carolina, 27710, United States

Location

Oregon Health Science University Casey Eye Institute

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

University of Wisconsin-Madison: McPherson Eye Research Institute

Madison, Wisconsin, 53705, United States

Location

Hospital for Sick Children

Toronto, Canada

Location

Helsinki University Hospital

Helsinki, Finland

Location

Centre hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, 75012, France

Location

University of Tubingen

Tübingen, Germany

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Radboud University

Nijmegen, Netherlands

Location

Related Links

• Foundation Fighting Blindness Public Website

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples

MeSH Terms

Conditions

Retinitis Pigmentosa; Eye Diseases

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Mark Pennesi, MD, PhD

  Retina Foundation of the Southwest

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 15, 2019
• Study Start: February 25, 2020
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After manuscript is published
• Access Criteria: Users accessing data must enter an email address

Locations

IL (1); FI (1); US (13); CA (1); FR (1); DE (1); NL (1)