Course of EYS-associated retinitis pigmentosa in adults from Russia and former CIS

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

We will follow adults with pathogenic EYS gene variants from Russia and former CIS for four years to try to find reliable vision and retinal measures for future treatments.

Quick facts

• Study type: Observational
• Enrollment: 45 (estimated)
• Ages: 14 Years to 100 Years
• Sex: All
• Sponsor: Sensor Technology for Deafblind (Industry-sponsored)
• Locations: 1 site (Moscow)
• Trial ID: NCT07228793 on ClinicalTrials.gov

What this trial studies

This is a four-year observational natural history program enrolling adults with pathogenic EYS variants to collect functional, structural, and patient-reported outcomes. Participants will undergo genetic confirmation (whole exome/genome sequencing where needed), retinal imaging, visual field testing, electrophysiology, visual acuity measures, and standardized questionnaires at planned visits. Data will be analyzed for progression rates, left-right eye symmetry, genotype-phenotype correlations, and environmental or comorbidity risk factors for decline. The primary aim is to identify sensitive, reliable outcome measures and well-defined subgroups to enable future multicenter therapeutic trials for EYS-related retinal degeneration.

Who should consider this trial

Good fit: Ideal participants are adults (≥18) from Russia or former CIS with clinically confirmed pathogenic variants in the EYS gene who can consent and attend all study visits over 48 months.

Not a fit: Patients without EYS mutations, those under 18, or individuals unable to complete regular follow-up over four years are unlikely to benefit from this natural history program.

Why it matters

Potential benefit: If successful, the study could provide validated outcome measures and clearly defined patient groups that speed development and testing of treatments for EYS-related retinitis pigmentosa.

How similar studies have performed: Natural history studies in other genetic forms of retinitis pigmentosa have helped identify trial outcome measures, but long-term, EYS-specific natural history data are limited.

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 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)

Where this trial is running

Moscow

• Oftalmic Clinical Research Center — Moscow, Russia (Recruiting)

Study contacts

• Principal investigator: Marianna Weener, MD, PhD — Oftalmic
• Study coordinator: Olga Luneva

Conditions Retinitis Pigmentosa; Eye Diseases; EYS mutation; RP; Retinitis pigmentosa