Choroideremia: Understanding This Inherited Retinal Condition
Understanding Choroideremia
Choroideremia is an inherited retinal dystrophy. This means it is a genetic condition that causes the light-sensing tissue at the back of the eye to break down over time. It affects three layers in the back of the eye: the retinal pigment epithelium (RPE, a supportive layer behind the retina), the photoreceptors (the cells that detect light), and the choriocapillaris (a network of tiny blood vessels that nourish the retina).
The condition leads to gradual loss of these tissues, starting at the outer edges of the retina and slowly working inward toward the center. This pattern of degeneration is why people with choroideremia typically lose peripheral (side) vision first and central vision later in life.
Choroideremia is caused by mutations in the CHM gene, located on the X chromosome at position Xq21.2. This gene provides instructions for making a protein called Rab escort protein-1 (REP1). REP1 plays an important role in vesicular trafficking, the process by which cells move materials in small packages between locations.
When the CHM gene is mutated, REP1 does not function properly. Without working REP1, the RPE cells, photoreceptors, and choriocapillaris gradually deteriorate. Scientists believe this disruption in cellular transport is the root cause of the progressive tissue loss seen in choroideremia.
Choroideremia shares some features with retinitis pigmentosa (RP), another group of inherited retinal diseases. Both conditions cause night blindness and progressive loss of peripheral vision. However, choroideremia has a distinct appearance on retinal imaging. Areas of atrophy (tissue loss) are sharply defined, and the white sclera (the outer wall of the eye) becomes visible through the thinned retina.
The pattern of inheritance also differs. Choroideremia follows an X-linked recessive pattern, while RP can be inherited in several different ways. Genetic testing is the most reliable method to distinguish between these conditions.
Who Is Affected and Risk Factors
Choroideremia is rare. The estimated prevalence ranges from 0.5 to 2 per 100,000 people worldwide (Nature Medicine, 2023). In the United States, an estimated 3,400 people are affected (Research and Markets, 2024). The condition occurs across all ethnic groups (Expert Market Research, 2024).
Choroideremia primarily affects males. The CHM gene sits on the X chromosome. Males have only one X chromosome paired with a Y chromosome. A single mutation in the CHM gene is enough to cause the full disease. Females have two X chromosomes, so even if one carries the mutation, the other typically provides a working copy. As a result, female carriers usually have milder or no symptoms, though some do experience subtle retinal changes.
The strongest risk factor for choroideremia is having a family history of the condition. A mother who carries the CHM mutation has a 50 percent chance of passing it to each son, who would then be affected. She also has a 50 percent chance of passing carrier status to each daughter. An affected father will pass the mutation to all daughters (who become carriers) but to none of his sons.
Genetic counseling is recommended for families with a history of choroideremia. Understanding the inheritance pattern helps family members make informed decisions. It also ensures that at-risk children receive early screening.
Signs and Symptoms
Night blindness is typically the first symptom of choroideremia. It often appears in the first or second decade of life. Children may have difficulty seeing in dim lighting, struggle to navigate dark rooms, or have trouble adjusting from bright to dark environments. These early signs can sometimes be mistaken for clumsiness or inattention, which may delay diagnosis.
Parents or caregivers may also notice that a child has difficulty with activities requiring good peripheral vision, such as sports or walking in unfamiliar places.
As the condition advances, the visual field progressively narrows. People with choroideremia develop ring-shaped blind spots (ring scotomata) in their mid-peripheral vision. Over time, these blind spots expand and merge, creating a tunnel-like visual field. This progression can span decades.
Central vision, used for reading and recognizing faces, is often preserved until later in adulthood. Many individuals retain useful central vision into their 40s, 50s, or beyond, though the degree of preservation varies.
On eye examination, a retina specialist can observe characteristic changes. Early on, there is widespread pigment clumping at the level of the RPE. As the disease progresses, well-defined areas of atrophy develop. These usually start just outside the major blood vessel arches of the retina. Through these atrophic zones, the white sclera and large choroidal vessels become visible.
These areas of atrophy advance inward toward the center of the retina. Advanced imaging using adaptive optics (AO) technology has shown that even in areas appearing normal on standard imaging, RPE cells may be enlarged and structurally abnormal (National Eye Institute).
Diagnosis and Testing
A retina specialist can often suspect choroideremia based on the retina's characteristic appearance during a dilated eye examination. The pattern of sharply defined atrophic areas, visible choroidal vessels, and pigment changes is distinctive. A family history consistent with X-linked inheritance further supports the clinical suspicion.
Visual field testing documents the extent of peripheral vision loss. This test maps areas where vision is present or absent and helps track progression over time.
Genetic testing is the definitive way to confirm a diagnosis of choroideremia. A blood sample or cheek swab can be analyzed to identify mutations in the CHM gene. Confirming the specific mutation is important for several reasons. It distinguishes choroideremia from other similar-looking retinal dystrophies. It also determines whether a person may be eligible for clinical trials.
Genetic testing can also identify female carriers who may not have obvious symptoms but could pass the condition to their children.
Several imaging techniques help retina specialists evaluate retinal damage and monitor progression. Optical coherence tomography (OCT) provides detailed cross-sectional images of the retina. It shows the thickness and structure of retinal layers. Fundus autofluorescence imaging highlights areas of healthy and damaged RPE cells.
Researchers at the National Eye Institute (NEI) have combined traditional imaging with adaptive optics, a technology that greatly enhances resolution. Studies using adaptive optics found that all subjects with pathogenic CHM mutations had subclinical structural changes and widespread enlarged RPE cells, even in areas appearing healthy on standard imaging (NEI).
Treatment Options
There is currently no FDA-approved treatment that stops or reverses choroideremia. Management focuses on supportive care to help individuals make the most of their remaining vision. This includes low-vision aids such as magnifying devices, specialized glasses, electronic readers, and screen-reading software.
Mobility training and orientation services help people with significant peripheral vision loss navigate safely. Occupational therapy can assist with adapting daily tasks. Regular monitoring by a retina specialist is important to track progression and adjust strategies.
Choroideremia has features that make it a strong candidate for gene therapy. The responsible gene (CHM) is small, the disease progresses slowly, and a single gene defect causes the condition. These factors have motivated significant research into gene replacement therapy.
Timrepigene emparvovec, developed by Biogen, is a gene therapy designed to deliver a working copy of the CHM gene directly into the eye. It reached phase 3 clinical trials. However, the trial did not meet its primary endpoint of improvement in best-corrected visual acuity. Researchers continue to study choroideremia as a viable target for gene therapy.
More recent studies have explored higher doses of gene therapy for choroideremia. These investigations have demonstrated that high-dose treatment appears safe and potentially effective. Researchers also found that best-corrected visual acuity may be appropriate for monitoring disease progression. This is an important finding for designing future clinical trials.
It is important to approach gene therapy news with both hope and realism. No gene therapy for choroideremia has yet received FDA approval. Individuals interested in clinical trials should discuss eligibility with their retina specialist.
Luxturna (voretigene neparvovec) is an FDA-approved gene therapy for a different inherited retinal condition caused by mutations in the RPE65 gene. While Luxturna does not treat choroideremia, its approval in 2017 showed that gene therapy for inherited retinal diseases is achievable. This milestone has provided a framework for choroideremia-specific therapies.
What to Expect
Choroideremia progresses slowly in most individuals. Night blindness and peripheral vision loss usually begin in childhood or adolescence. Useful central vision is often retained for decades. Some individuals maintain reading vision into their 50s or 60s. However, the rate varies, and there is no reliable way to predict how quickly vision will change for any given person.
Regular monitoring with a retina specialist helps track changes. Imaging tests such as OCT and fundus autofluorescence can detect subtle progression before a person notices changes in day-to-day vision.
Receiving a diagnosis of choroideremia can be emotionally overwhelming. The knowledge that vision loss is progressive and currently without an approved treatment carries significant weight. Feelings of grief, anxiety, frustration, and uncertainty are common and valid.
Connecting with support organizations such as the Choroideremia Research Foundation or the Foundation Fighting Blindness can provide community and emotional support. Mental health support through counseling or therapy can also be valuable.
Ongoing follow-up with a retina specialist is a critical part of managing choroideremia. Regular examinations allow the specialist to document changes, update low-vision strategies, and evaluate eligibility for emerging clinical trials. Visits typically include visual acuity testing, visual field assessment, and OCT imaging.
Living With Choroideremia
Many people with choroideremia lead full, active lives by adapting their environment and using available tools. Low-vision specialists can recommend devices tailored to specific needs. These may include handheld or stand magnifiers, telescopic lenses, large-print materials, and high-contrast screen settings.
Good lighting is especially important. Bright, even lighting in living and work spaces reduces the impact of night blindness. Anti-glare lenses and wide-brimmed hats can help manage light sensitivity outdoors.
Children and young adults with choroideremia benefit from early involvement with vision rehabilitation professionals. Individualized education plans (IEPs) or 504 plans can ensure appropriate classroom accommodations. Career planning that accounts for future vision changes allows individuals to build accessible skills early.
Assistive technology is advancing rapidly. Screen readers, voice-activated devices, and smartphone accessibility features make it possible for people with significant vision loss to work in a wide range of fields.
Genetic counseling is an important resource for families affected by choroideremia. A genetic counselor can explain the inheritance pattern and help family members understand their risk. For couples planning children, counselors can discuss reproductive options including preimplantation genetic testing.
Knowing the specific genetic mutation in a family also helps ensure that affected members are considered for relevant clinical trials as new therapies become available.
When to See a Retina Specialist
Any child or young person who has difficulty seeing at night or in dim lighting should be evaluated by an eye care professional. If choroideremia or another inherited retinal condition is suspected, a referral to a retina specialist is appropriate. Adults with a family history of choroideremia who have not been evaluated should also seek an examination.
Sudden changes in vision require immediate attention. A noticeable increase in floaters, flashes of light, or a curtain or shadow over any part of the visual field may indicate a separate urgent problem such as a retinal detachment. See a retina specialist or go to the emergency room right away if any of these symptoms occur.
Retina specialists (vitreoretinal surgeons) have specialized training in conditions affecting the retina. They are best equipped to diagnose, monitor, and manage choroideremia. They have access to advanced imaging technologies and are connected to the research community developing new treatments. Optometrists and primary care doctors play an important role in initial screening and referral.
For individuals with a confirmed diagnosis, maintaining a relationship with a retina specialist ensures continuity of care and timely access to emerging treatment options.
Questions and Answers
Because choroideremia follows an X-linked recessive inheritance pattern, females who carry one copy of the mutated CHM gene typically do not develop the full disease. Their second X chromosome usually provides enough working REP1 protein to maintain retinal function. However, some female carriers do show mild retinal changes on examination. In rare cases, carriers may experience some degree of vision loss. Female relatives of affected males should consider genetic testing and periodic retinal examinations with a retina specialist.
As of now, no gene therapy for choroideremia has received FDA approval. The most advanced candidate, timrepigene emparvovec, reached phase 3 clinical trials but did not meet its primary endpoint. Research continues, and high-dose studies have shown promising safety results. Individuals interested in clinical trials should speak with their retina specialist about current opportunities and eligibility criteria.
Choroideremia and retinitis pigmentosa (RP) share some symptoms, including night blindness and progressive peripheral vision loss. However, they differ in important ways. Choroideremia is caused by mutations in the CHM gene and follows an X-linked inheritance pattern. RP can result from mutations in many different genes (AAO, 2024) and can be inherited in multiple patterns. On retinal imaging, choroideremia shows sharply defined areas of atrophy with visible underlying sclera. This differs from the bone spicule pigment patterns typically seen in RP. Genetic testing is the most reliable way to tell them apart.
A diagnosis of choroideremia in a child can be difficult for the whole family. Starting with a thorough evaluation by a retina specialist helps establish a baseline and monitoring plan. Connecting with the Choroideremia Research Foundation provides access to educational resources and community support. Working with the child's school ensures appropriate accommodations. Genetic counseling helps the family understand the inheritance pattern and plan for the future. Encouraging the child to develop adaptive skills and use assistive technology early builds confidence.
In most cases, choroideremia progresses slowly over many years to decades. Night blindness and peripheral vision changes usually begin in childhood or adolescence. Many individuals retain functional central vision well into adulthood. The exact pace varies from person to person. Regular follow-up with a retina specialist, including imaging tests, is the best way to track your progression and adapt your care plan accordingly.