Rate of Progression in EYS Related Retinal Degeneration

NCT ID: NCT04127006

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 103 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-02-25
• Study Completion Date: 2026-02-15

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

Conditions

Retinitis Pigmentosa; Eye Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

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)

No interventions assigned to this group

Vision Cohort 3

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

No interventions assigned to this group

Eligibility Criteria

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.

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)

If either eye has any of the following, the participant is not eligible:

1. Current vitreous hemorrhage

2. Current or any history of rhegmatogenous retinal detachment

3. 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

4. History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months

5. 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)

6. Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy

7. History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function

8. History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:

1. Any use of ocular stem cell or gene therapy

2. Any treatment with ocriplasmin

3. Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)

4. Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Screening Visit date is at least 5 times the half-life of the given product)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation Fighting Blindness

OTHER

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Pennesi, MD, PhD

Role: STUDY_CHAIR

Retina Foundation of the Southwest

Locations

University of California, San Francisco

San Francisco, California, United States

Colorado Retina Associates

Denver, Colorado, United States

Vitreo-Retinal Associates

Gainesville, Florida, United States

University of Miami: Neuro-ophthalmology Department

Miami, Florida, United States

Emory Eye Center

Atlanta, Georgia, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Massachusetts Eye and Ear

Boston, Massachusetts, United States

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, United States

Duke University Eye Center

Durham, North Carolina, United States

Oregon Health Science University Casey Eye Institute

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Retina Foundation of the Southwest

Dallas, Texas, United States

University of Wisconsin-Madison: McPherson Eye Research Institute

Madison, Wisconsin, United States

Hospital for Sick Children

Toronto, , Canada

Helsinki University Hospital

Helsinki, , Finland

Centre hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, , France

University of Tubingen

Tübingen, , Germany

Hadassah Medical Center

Jerusalem, , Israel

Radboud University

Nijmegen, , Netherlands

Countries

United States; Canada; Finland; France; Germany; Israel; Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Related Links

https://public.jaeb.org/ffb

Foundation Fighting Blindness Public Website

Other Identifiers

Pro-EYS

Identifier Type: -

Identifier Source: org_study_id