Retinitis PigmentosaPro-EYSNCT04127006
Rate of Progression in EYS Related Retinal Degeneration
An observational study of Retinitis Pigmentosa and Eye Diseases, run by Jaeb Center for Health Research at 19 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Retinitis Pigmentosa, Eye Diseases
- How many people
- 103 participants
- Where
- 19 sitesin 7 countries
- Study dates
- 25 Feb 2020to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
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- 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:
- Clinical diagnosis of retinal dystrophy
- Clear ocular media and adequate pupil dilation to permit good quality photographic imaging
Who cannot join
- 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)
- Ocular exclusion Criteria:
- If either eye has any of the following, the participant is not eligible:
- Current vitreous hemorrhage
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- 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)
- 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)
Trial locations and contacts
19 sites in 7 countries.
19 sites in 7 countries
United States13 sites
Kellogg Eye Center, University of Michigan
Ann Arbor, Michigan, 48105
Emory Eye Center
Atlanta, Georgia, 30322
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, 21287-9277
Massachusetts Eye and Ear
Boston, Massachusetts, 02114
Retina Foundation of the Southwest
Dallas, Texas, 75231
Colorado Retina Associates
Denver, Colorado, 80230
Duke University Eye Center
Durham, North Carolina, 27710
Vitreo-Retinal Associates
Gainesville, Florida, 32607
University of Wisconsin-Madison: McPherson Eye Research Institute
Madison, Wisconsin, 53705
University of Miami: Neuro-ophthalmology Department
Miami, Florida, 33136
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Oregon Health Science University Casey Eye Institute
Portland, Oregon, 97239
University of California, San Francisco
San Francisco, California, 94143-0344
France1 site
Centre hospitalier National d'Ophtalmologie des Quinze-Vingts
Paris, 75012
About this study
Official title: Rate of Progression in EYS Related Retinal Degeneration (Pro-EYS)
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.
Read the 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:
- Describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene
- Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration
- 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:
- 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
- Investigate whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the EYS gene
- 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
- Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene
Extension Study Objectives:
Objectives of the Pro-EYS Extension Study include evaluating the original study objectives over the longer term (progression on structural and functional outcomes, correlation of progression among outcomes, and factors related to progression) as well as correlating early changes of microperimetry slope, static perimetry slope, full-field stimulus threshold with longer term clinically meaningful outcomes (possible design of early endpoint / late endpoint proposal for FDA).
- Conditions
- Retinitis Pigmentosa, Eye Diseases
- Keywords
- EYS mutation, Retinitis Pigmentosa
- Medical subject headings
- Retinitis Pigmentosa, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Assessed by a central reading center
Measured: 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
assessed by a central reading center
Measured: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2019
- Study start25 Feb 2020
- Primary completion9 Feb 2026
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation Fighting Blindness
- Responsible party
- Sponsor
- Investigators
- Mark Pennesi, MD, PhD, Study chair, Retina Foundation of the Southwest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04127006
- Sponsor's protocol ID
- Pro-EYS
- Acronym
- Pro-EYS
- Status last verified
- Oct 2026
- First submitted
- 11 Oct 2019
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: A de-identified database is placed in the public domain on the FFB/Jaeb public website after the completion of each protocol and publication of the manuscript.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rate of Progression in EYS Related Retinal Degeneration (Pro-EYS)
- ClinicalTrials.gov ID
- NCT04127006
- Acronym / sponsor ID
- Pro-EYS / Pro-EYS
- Conditions
- Retinitis Pigmentosa, Eye Diseases
- Keywords
- EYS mutation, Retinitis Pigmentosa
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- Foundation Fighting Blindness
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 9 Feb 2026 (actual)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 15 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene
- Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration
- 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:
- 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
- Investigate whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the EYS gene
- 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
- Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene
Extension Study Objectives:
Objectives of the Pro-EYS Extension Study include evaluating the original study objectives over the longer term (progression on structural and functional outcomes, correlation of progression among outcomes, and factors related to progression) as well as correlating early changes of microperimetry slope, static perimetry slope, full-field stimulus threshold with longer term clinically meaningful outcomes (possible design of early endpoint / late endpoint proposal for FDA).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (17 listed)
- 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)
- Current vitreous hemorrhage
- Current or any history of rhegmatogenous retinal detachment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Visual Field Sensitivity
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
2 secondary outcomes
Explore Qualitative categorization of Fundus Autofluorescence (FAF) pattern
Time frame: 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
Time frame: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Foundation Fighting Blindness Public WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. A de-identified database is placed in the public domain on the FFB/Jaeb public website after the completion of each protocol and publication of the manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Pennesi, MD, PhD study chair
Retina Foundation of the Southwest
19 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Retinitis Pigmentosa and Eye Diseases, run by Jaeb Center for Health Research at 19 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Canada, Finland, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Visual Field Sensitivity (time frame: Baseline and every year until study completion (4 years)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.