Natural History Study of Patients With EYS-Associated RP (RUS_EYS)

Natural History Prospective Open Clinical and Genetic Study of Patients With EYS-Associated Retinitis Pigmentosa

This natural history study of patients with EYS mutations from Russia and former CIS (Commonwealth of Independent States) territories 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. This approach helps to develop experimental treatment protocol, and assessing its 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 EYS gene in Russia and former CIS territories.
2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration in Russia and former CIS territories.
3. Identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration in Russia and former CIS territories.

Study Overview

• Status: Recruiting
• Conditions: Eye Diseases; Retinitis Pigmentosa
• Intervention / Treatment: Diagnostic test: Whole exome/genome sequencing

Detailed Description

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 risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individuals 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

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Olga Luneva; Phone Number: +7 9629412912; Email: info@oftalmic.com

Study Locations

• Russia
  • Moscow, Russia, 125167
    • Recruiting
    • Oftalmic Clinical Research Center
    • Contact: Marianna E Weener, MD, PhD; Phone Number: +7 903 758 66 19; Email: info@oftalmic.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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 Study 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 Study 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 Study 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 exclusion Criteria:

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 visual functions 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
• 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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vision Cohort 1; Participants with the better eye Screening Visit decimal visual acuity of 0.4 or more and visual field diameter 10 degrees or more in every meridian of the central field.	Diagnostic test: Whole exome/genome sequencing; Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)
Vision Cohort 2; Participants with the better eye Screening Visit decimal visual acuity 0.15 - 0.35 and visual field diameter less than 10 degrees in any meridian of the central field)	Diagnostic test: Whole exome/genome sequencing; Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)
Vision Cohort 3; Participants with the better eye Screening Visit decimal visual acuity 0.14 or less.	Diagnostic test: Whole exome/genome sequencing; Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Visual Field Sensitivity	Measured by static perimetry with topographic analysis and assessed by a certified reading center for cohorts 1 and 2.	Baseline and every year until study completion (4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best Corrected Visual Acuity	Measured on Golovina-Sivtsev charts	Screening visit and every year until study completion (4 years) for cohort 1&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 certified reading center for cohorts 1 and 2.	Baseline and every year until study completion (4 years)
Change in Best Corrected Low Luminance visual acuity	Measured by letter score	Screening visit and every year until study completion (4 years) for cohort 1&2. Screening visit and 48 month follow-up for cohort 3.
Change in Contrast Sensitivity Function	Measured by Zebra software for cohorts 1 and 2.	Baseline and every year until study completion (4 years).
Change in Ellipsoid zone (EZ) area	Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a certified expert	Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Explore qualitative and quantitative categorization of Fundus Autofluorescence (FAF) pattern	Assessed by a certified expert	Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcomes for Vision Cohorts 1, 2 and 3	Measured by modified MRDQ (Michigan Retinal Degeneration Questionnaire)	Baseline and 4 year follow-up visit

Collaborators and Investigators

• Sponsor: Sensor Technology for Deafblind
• Collaborators: Russian RetinaFond
• Investigators: Principal Investigator: Marianna Weener, MD, PhD, Oftalmic

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2025
• Primary Completion (Estimated): December 15, 2029
• Study Completion (Estimated): March 30, 2030

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 14, 2025

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: RP; Retinitis pigmentosa; EYS mutation
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Eye Diseases; Retinitis Pigmentosa
• Other Study ID Numbers: EYS_RUS_2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A de-identified database will be placed in the public domain on the Oftalmic public website after the completion of each protocol and publication of the manuscript.
• IPD Sharing Time Frame: After manuscript is published
• IPD Sharing Access Criteria: Users accessing data must enter an email address
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No