EYS

The EYS gene provides instructions for a protein made in the photoreceptor (definition: A light-sensing cell in the retina. Rods (used for night and peripheral vision) and cones (used for color and detail) are the two types.) layer of the retina, the part of the eye that captures light. Its full name, EGF-like photoreceptor maintenance factor, reflects its role in supporting the ongoing health and structure of these light-sensing cells. When both copies of the gene carry disease-causing changes, the photoreceptors gradually stop working properly and degenerate, leading to progressive vision loss. You may see EYS referred to by older names such as RP25, EGFL10, or EGFL11; these all point to the same gene. EYS is a very large gene, and its full coding sequence is roughly 11.6 thousand base pairs long, which has important consequences for how researchers approach potential gene therapies.

In most people described in the available studies, EYS causes a rod-cone dystrophy, a pattern of retinitis pigmentosa in which the rod cells that handle dim and peripheral vision are affected first. The most common first symptom reported is night blindness, followed over time by narrowing of the side (peripheral) vision. In one large Japanese group of patients, the average age when symptoms began was about 25 to 26 years, though this ranged widely. Progression of central vision loss tends to be gradual, with studies reporting a slow average decline in visual acuity per year. EYS does not always cause classic retinitis pigmentosa; researchers have also described people with cone-rod dystrophy and, less commonly, a macular dystrophy affecting central vision. Some people have an atypical form of retinitis pigmentosa that appears to progress more slowly and to preserve better central vision, so prognosis differs from one person to another. Cataract has been reported as a common accompanying eye finding in people with EYS-related disease. Some people develop cystoid macular edema, a build-up of fluid in the central retina that can further affect central vision.

The link between EYS and autosomal recessive (definition: An inheritance pattern where a person needs an altered copy of a gene from both parents to be affected. Parents with only one copy are usually unaffected carriers.) retinitis pigmentosa is firmly established and appears consistently across large patient studies from many countries. EYS is a rare cause of inherited retinal disease overall, but how often it appears varies markedly across populations. In Japanese cohorts it is repeatedly reported as the most common cause of autosomal recessive retinitis pigmentosa, and it is also a leading cause in Korean patients. In some other populations, such as Poland, EYS accounts for a smaller share of cases than in East Asia. In East Asian patients, a small number of recurring EYS variants account for a large proportion of cases, and different variants have been linked to somewhat different ages of onset and rates of progression. This growing genotype (definition: A person's specific genetic makeup — which gene and which variant is causing their condition — as opposed to the phenotype, the symptoms it produces.)-phenotype (definition: The observable traits or symptoms a condition actually produces in a person — as opposed to the genotype, the underlying genetic cause.) information supports the value of genetic testing in understanding an individual's likely disease pattern. Several studies have carefully measured how EYS-related disease changes over time using retinal imaging, giving researchers reliable ways to track progression.

Because onset, severity, and progression differ so much between people, a genetic result alone cannot predict exactly how one person's vision will change. The reasons some people have typical retinitis pigmentosa while others have an atypical, milder, or macula-focused form are not fully understood. In rare cases, people carry disease-causing changes in more than one retinal gene, which can complicate diagnosis and prognosis; one report noted that EYS tended to dominate the resulting picture. Some laboratory measures, such as retinal blood-flow patterns seen on specialized imaging, differ by gene, but their long-term usefulness for predicting outcomes is still being explored.

As of the date of this review, the supplied evidence does not identify a treatment approved specifically for EYS-related retinal disease. A major research challenge is the large size of the EYS gene, which does not fit into the viral vectors commonly used to deliver gene therapy (definition: A treatment that delivers a working copy of a gene into cells to take over for a copy that isn't functioning properly.). In laboratory and animal-tissue experiments, researchers recently used lipid nanoparticles, tiny fat-based carriers, to deliver a full-length EYS DNA construct into retinal cells; this is early preclinical (definition: Research done in cells or animals, before a treatment is considered ready to be studied in people.) work, not an available therapy. Scientists have also created stem cell lines from EYS patients to study the disease and test potential treatments in the laboratory. For complications, a small case series reported that the drug tocilizumab reduced macular fluid in retinitis pigmentosa, including one EYS patient, but this involved only two people and its effect on long-term prognosis is unknown. An older randomized trial and later genetic analysis found that vitamin E supplementation should be avoided in retinitis pigmentosa and did not support a general benefit of vitamin A across all genetic subtypes.

• Broadening the range of EYS-related disease

  Observational human study with supporting laboratory splicing experiments.

  What was found:

  Most had retinitis pigmentosa, but one had cone-rod dystrophy and two siblings had a macular dystrophy; identical variants sometimes produced different diagnoses.

  Why it matters:

  It suggests EYS should be considered even in people whose diagnosis is not typical retinitis pigmentosa.

  Limitation: The number of non-RP cases was very small.

• A non-viral way to deliver the large EYS gene

  Preclinical laboratory and tissue research.

  What was found:

  The carriers delivered and expressed the large EYS construct, which is too big for standard viral gene-therapy vectors.

  Why it matters:

  It addresses a key obstacle to future EYS gene therapy, namely the gene's size.

  Limitation: This is early-stage work in cells and animal tissue, not a tested or available treatment in people.

• Natural history of EYS disease in a large Japanese group

  Observational human study (retrospective multicenter cohort).

  What was found:

  Average onset was about 26 years, night blindness was the most common first symptom, and nearly all had a rod-cone pattern; three East Asian-specific variants accounted for most cases, with one linked to the earliest onset.

  Why it matters:

  It gives patients and clinicians realistic expectations of how EYS disease typically behaves and shows how a specific variant can shape the disease course.

  Limitation: The findings come from one population and may not fully apply to people of other ancestries.

• Natural history and phenotype spectrum in a Portuguese cohort

  Observational human study (single-center cohort with cross-sectional exam).

  What was found:

  Most had typical retinitis pigmentosa but a substantial minority had an atypical form with better preserved central vision and slower decline; eight new EYS variants were identified.

  Why it matters:

  It shows that prognosis varies and that some people have a milder course, which matters for counseling.

  Limitation: It is a single referral center in one country and cannot predict any individual's outcome.

• EYS as a leading cause across large genetic studies

  Observational human genetic study (large cohort).

  What was found:

  EYS was the most frequently mutated gene, driven largely by a few recurring founder variants.

  Why it matters:

  It confirms how common and clinically important EYS is, especially in East Asian populations.

  Limitation: Gene frequencies are population-specific and differ elsewhere in the world.

Because EYS-related disease is autosomal recessive (definition: An inheritance pattern where a person needs an altered copy of a gene from both parents to be affected. Parents with only one copy are usually unaffected carriers.), both parents of an affected person are typically unaffected carriers, and siblings each have a chance of being affected or of being carriers, which a genetic counselor can explain for your family. One study noted that daughters of an affected patient were carriers but had no symptoms, illustrating that carrying a single EYS change does not usually cause disease. Beyond this inheritance point, the general caregiver guidance shown on every gene page applies here.

• Which specific EYS variants were found, and is there published information about how they typically behave?
• Is my retinal disease best described as typical retinitis pigmentosa, an atypical form, or a cone-rod or macular pattern?
• How often should my vision and retina be monitored, and with which tests?
• Am I showing any treatable complications such as cataract or macular edema?
• What does autosomal recessive inheritance mean for my children, siblings, and other relatives?
• Are there natural-history studies or registries relevant to EYS that I could consider joining?

If an EYS result is new to you, confirming the specific variants and how they were inherited with a genetics professional can help clarify what is known for your situation. A retinal specialist can document your current vision and use imaging and other tests to monitor change over time. Because cataract and macular fluid can occur alongside EYS-related disease, asking your eye care team to watch for treatable complications may be worthwhile. You can also explore whether any current studies fit your situation using RP Hope's Clinical Trials Finder, which lets you screen with EYS preselected. RP Hope's genetic testing resources explain what testing involves and what questions to bring to a genetic counselor.