Choroideremia

When a diagnosis of choroideremia has been made in family member, certain relatives should be examined by an ophthalmologist for signs of the condition.

Since choroideremia is an X-linked condition, the mother should have a dilated eye examination for subtle signs of choroideremia. This examination will help determine whether the CHM gene change was inherited or occurred as a spontaneous event. If the condition is suspected to be inherited, either due to a family history or carrier signs in the mother’s eyes, the brothers and sisters of an individual with choroideremia should have an eye examination. Other family members at risk to have choroideremia, especially male relatives, could consider having an eye examination.

You can use the Find a Genetic Counselor search tool on the National Society of Genetic Counselors’ website to find a genetic counselor near you who can help to determine if other people in your family should be tested for choroideremia.

You may be able to connect with other individuals or families with choroideremia through email or online groups.

There is an email-based support group which can be joined by emailing the following address: [email protected]

If you have a Facebook profile, you can request to be a member of a choroideremia group: https://www.facebook.com/groups/Choroideremia/

The Foundation Fighting Blindness is a non-profit organization supporting patients and families with retinal conditions and also raises and donates money to research about retinal disorders. This foundation has an online presence as well as local chapters in cities across the United States. To learn more about the Foundation Fighting Blindness and to see whether there is a chapter near to your home, visit their website at http://blindness.org/.

Legal blindness is used by the United States government to determine eligibility for different services and programs. There are two criteria for legal blindness. A person is legally blind when they meet one or both of the criteria.

Individuals with choroideremia should have regular appointments with an ophthalmologist who specializes in retinal conditions. These appointments should occur at least once per year to evaluate the overall health of the eyes, monitor the progression of the condition, and assess for any rare complications of choroideremia.

Individuals with choroideremia may also benefit from an evaluation with an optometrist or ophthalmologist that specializes in low vision. A low vision evaluation focuses on maximizing vision through obtaining the best corrected vision with glasses, modifications to glasses, and recommendations for low vision devices.

There are several ophthalmic instruments and tests that can support a clinical diagnosis of choroideremia including electroretinography (ERG), optical coherence tomography (OCT), fundus autofluoresence (FAF), and fluorescein angiography (FA). The equipment used to perform these tests is highly specialized and may only be available in certain offices and clinics.

Electroretinography (ERG) is a specialized test designed to measure the function of the retinal cells. In choroideremia, the ERG reveals decreased responses from the rod and cone cells of the retina. The rod cells tend to be more affected than the cone cells, producing a weaker response. Over time, no responses are obtained from the retinal cells. This is referred to as non-recordable or extinguished ERG.

Optical coherence tomography (OCT) is a non-invasive test that can image other layers of the retina that are not visible on an eye examination. In choroideremia, the OCT may reveal abnormal thickening of the retinal tissue in and around the central seeing part of the eye (macula). It may also reveal abnormal thinning in areas of the retina that are deteriorating.

Fundus autofluoresence (FAF) is a non-invasive test that assesses the natural fluorescent properties of the pigment of the retina. In choroideremia, FAF may reveal "scalloped lesions" and a scattered appearance of pigment.

Fluorescein angiography (FA) involves an injection of dye into a vein in the arm, where the dye flows throughout the body and into the blood vessels of the retina. A specialized camera takes pictures of the circulation of blood in the retina and choroid. In choroideremia, patches of atrophy appear hypofluoresent (dark) with hyperfluorescent (bright) lines. The bright lines represent the remaining blood vessels of the choroid.

For more information about testing for choroideremia, talk to your doctor or ophthalmologist.

Optical devices are tools used to increase the magnification and clarity of objects both near and far. These devices allow individuals with low vision to perform near and distance vision tasks more easily.

Some examples of optical devices include:

The first symptom of choroideremia in males is difficulty seeing in the dark (nyctalopia). This vision change is most often noticed in the first ten years of life or in the early teenage years.

Choroideremia is a genetic disease of the eye. This condition results in degeneration, or loss of function, of the light-sensing tissue (retina) and the vascular layer (choroid) of the eyes. The degeneration is progressive, meaning that it worsens over time, and results in vision loss.

Choroideremia is most often diagnosed in males. Some females may have mild symptoms of choroideremia in late adulthood and, only in rare cases, are females as severely affected as males.

Choroideremia is most often called by its full name by doctors. If an eye doctor is speaking more generally about choroideremia, it may be referred to as a retinal degeneration or retinal disorder.

In nearly all cases of choroideremia, the primary symptom is vision loss. The initial visual changes associated with choroideremia are night vision difficulty and peripheral (side-to-side and up-and-down) vision loss.

In the early stages of choroideremia, there may be no obvious changes to the retina. Over time, there are changes to the pigment of the retina. At first, these pigment changes are very small and are not found at the center of the retina. These changes may be described as "salt and pepper" pigment mottling. As the condition progresses, large patches of atrophy (lost retinal tissue) appear around the retina and eventually merge. These patches correspond with the peripheral visual field loss the "tunnel vision" effect. In the late stages of the disease, the retinal tissue including the central seeing part of the retina (macula) begins to degenerate, resulting in central vision loss.

Choroideremia is caused by mutations in the CHM gene. Over 140 unique genetic changes have been identified within this gene in individuals with choroideremia.

The CHM gene provides the code to build a protein called Rab escort-1 (REP-1). REP-1 connects to Rab proteins and moves them between structures inside the cells of the body. Once Rab proteins are transported to their destination by REP-1, the proteins play a role in moving other proteins and substances (a process called intracellular trafficking).

When the CHM gene is mutated, the REP-1 protein is limited in its function or is completely absent. This prevents Rab proteins from reaching their destination and from assisting the movement in other cellular materials and causes the cell to die prematurely.

The classic signs and symptoms of choroideremia affect males and, only in rare cases, affect females. One of the first symptoms of choroideremia is difficulty seeing in the dark, referred to as night blindness or nyctalopia. This symptom may begin in childhood or the teenage years. Following this, the peripheral (side-to-side and up-and-down) visual field becomes restricted and the vision in these areas is lost. The peripheral field changes are progressive and eventually result in "tunnel vision" by age 40 years. The central seeing part of the retina (macula) remains intact until the degeneration becomes more advanced, typically between ages 50 to 70 years. At that point, the central vision becomes progressively blurred and can be severely reduced. Central vision may also be impacted by cataracts (progressive clouding of the lens of the eye) or cystoid macular edema (accumulation of fluid under the macula).

After receiving a diagnosis of choroideremia from a clinical eye examination or genetic testing, specialized eye testing may be recommended. The purpose of these tests is to determine how choroideremia is currently affecting the eyes. These tests will also be a reference point for future visits, allowing the progression of the condition to be determined.

Prenatal genetic testing for choroideremia is available, but is not commonly performed. In order to pursue prenatal diagnosis for choroideremia, there must be a family history of the condition and the CHM gene change must be known. This will allow the developing baby to be tested for the exact cause of choroideremia in the family.

Choroideremia is not tested for by newborn screening. There are no signs of choroideremia at birth or in infancy, meaning that an eye examination of a newborn would not be able to diagnose a child with this condition.

If you are concerned that your newborn may have an eye condition, talk with your child’s pediatrician about your concerns and whether seeing an eye doctor is necessary.

The genetic cause of choroideremia can be determined with a genetic test that analyzes the CHM gene. A genetic test is most often performed on DNA obtained from a blood sample or from cells gathered by a cheek swab.

Genetic analysis of the CHM gene includes sequencing, or reading through the gene letter-by-letter looking for genetic changes associated with choroideremia. As many as 95% of males with choroideremia will have a CHM gene change detected by sequencing. If this test does not find a genetic reason for choroideremia, the CHM gene can be analyzed for deleted (missing) or duplicated (extra) pieces.

For people from Finland or with Finnish ancestry, genetic testing for choroideremia may be targeted to a single CHM gene change. This gene change, notated c.1609+2dupT, is the most common cause for choroideremia in this population.

If you wish to obtain more information about genetic testing for choroideremia, consider making an appointment with a genetic counselor. To find a local genetic counselor, you can use the Find a Genetic Counselor search tool on the National Society of Genetic Counselors’ website.

Clinical research can be found at the following:
https://clinicaltrials.gov/ These are studies receiving US government funding. Some studies are supported by private industries.
In Europe, the EU Clinical Trial Register performs a similar service.
To learn about clinical trials sponsored by private sources, you can contact www.centerwatch.com

Type choroideremia in the search bar on each page to find current research.

There is no treatment for choroideremia. Rather, the care and management of individuals with choroideremia is focused on monitoring the progression of choroideremia, promoting overall eye health, and maximizing remaining vision through low vision services and support. Recently, phase I and II clinical trials for gene therapy for choroideremia have been completed. Before treatment is available widely on a clinical basis, further research is required. However, gene therapy may prove effective in the future.

All cases of choroideremia are the result of a CHM gene change. Gene changes may be inherited from a family member or occur for the first time in a person with the condition.

In cases where there is no family history of choroideremia and eye examinations or genetic testing reveal that no other family members have choroideremia, the CHM gene mutation may have occurred spontaneously (de novo genetic event). A person with a CHM gene change can still pass it on to their children, even if it was a spontaneous event.

All males with a CHM gene change develop choroideremia. In the earliest stages of the condition, the visual changes may not be obvious and the retina may appear normal. However, as choroideremia is a progressive condition, the visual symptoms will become more obvious and changes to the retina will occur with time.

The exact number of people diagnosed with choroideremia is unknown. It is estimated that 1 in 50,000 to 1 in 100,000 males has choroideremia.

Individuals with choroideremia should have regular appointments with an ophthalmologist who specializes in retinal conditions. At first, these appointments should occur at least once per year, or more often if you have sudden vision changes or have new concerns about your vision or eye health. With time, these appointments may become less frequent; however, it is important to stay in contact with your eye doctor to discuss any concerns or questions you have about choroideremia and your vision.

Choroideremia is inherited in an X-linked recessive manner, as the CHM gene is located on the X chromosome. The X chromosome is one of two chromosomes that determine a person’s gender. Females have two X chromosomes and males have one X and one Y chromosome. Unlike other pairs of chromosomes, the X and Y chromosomes do not carry the same genetic instructions, which means traits on these chromosomes are may be expressed differently in males and females. For this reason, all males with a CHM gene change will have choroideremia and females with a CHM gene change will have little to no symptoms because their other X chromosome has a normal, working copy of the CHM gene.

When a person with a CHM mutation has children, the risk for a child to inherit the mutation and have symptoms is dependent on the gender of both the parent and the child.

When a female with a CHM gene change has a child, she has a 50% (1 in 2) chance to pass on the CHM gene change and a 50% (1 in 2) chance to not pass on the CHM gene change. These chances are the same whether the child is a boy or a girl; however, a boy inheriting the CHM gene change will have choroideremia while a girl inheriting the CHM gene change will be a carrier. If the gender of the child is not determined during a pregnancy, there is a 25% (1 in 4) chance to have a boy with the CHM gene change and choroideremia, a 25% (1 in 4) chance to have a boy without the CHM gene change and without choroideremia, a 25% (1 in 4) chance to have a girl with the CHM gene change and a carrier of choroideremia, and a 25% (1 in 4) chance to have a girl without the CHM gene change and not a carrier of choroideremia.

When a male with a CHM gene and choroideremia has a child, he will not pass on the CHM gene change to his sons but he will pass on the CHM gene change to all of his daughters. This means that none of his sons will have choroideremia and all of his daughters will be carriers for choroideremia.

To discuss your reproductive risks and options, you can contact a genetic counselor. The Find a Genetic Counselor tool on the National Society of Genetic Counselors website can help you to find a genetic counselor in your area.

Choroideremia can be diagnosed by a clinical eye examination, performed by an ophthalmologist. This examination will measure the vision and assess the appearance of the retina through a dilated pupil. If the examination reveals decreased vision and retinal signs of choroideremia, the diagnosis can be confirmed with genetic testing.

If you wish to obtain more information about the specific testing used to diagnose choroideremia, consider making an appointment with an ophthalmologist. It is especially important to find an ophthalmologist with experience in diagnosing retinal conditions.

The Choroideremia Research Foundation provides several opportunities donations and fundraising, including ways to actively participate and become involved in ways that benefit choroideremia research.

The Foundation Fighting Blindness also accepts donations and holds fundraising events nationwide to benefit research for retinal degenerations, including choroideremia.

To find clinical research about choroideremia, visit the following websites and type "choroideremia" into the search bar:

The CHM gene encodes the REP-1 protein, which is present in the entire body. A similar protein, called REP-2, is present in most of the body and can help transport Rab proteins when REP-1 is not functioning properly or absent. However, the REP-2 protein is not found in high levels in the retina and cannot assist in the transport of Rab proteins enough to prevent early cell death. Therefore, the lack of functional REP-1 protein and lack of proper Rab protein transport within the retina results in early cell death and vision loss.

Orientation and mobility (O&M) services are designed to help people with low vision to be confident and safe in their surroundings. O&M training focuses on:

Since choroideremia is a rare condition, it can be difficult to find a specialist in this condition. At a minimum, it is important to find an eye doctor that can examine your eyes on a yearly basis. If possible, try to see a retina specialist on a regular basis. Certain hospitals and clinics may have access to specialized technologies and tests used to diagnose and monitor the progression of choroideremia, and these centers may have additional resources or recommendations for retinal specialists.

The Choroideremia Research Foundation maintains a list of eye doctors who have identified themselves as retinal specialists with expertise in choroideremia. To review this list, visit the Choroideremia Research Foundation website.

In some cases of choroideremia, the remaining vision may be threatened by additional complications including cataracts (progressive clouding of the lens), cystoid macular edema (fluid accumulation under the central seeing part of the retina), and neovascularization (growth of new blood vessels).

Each of these conditions may be treatable by an eye doctor. If cataracts are interfering with central vision, they can be removed surgically. Cystoid macular edema can be detected on a special imaging test called optical coherence tomography (OCT). An medicated eye drop called dorzolamide has been successful in treating cystoid macular edema in some individuals with choroideremia and other retinal conditions. Neovascularization is a rare complication of choroideremia and, if it occurs, may be treatable by bevacizumab injections to prevent the growth of additional vessels.

As of October 1, 2016, vitamin A supplementation is not known to help the symptoms of choroideremia. Although a long-term research study focused on the possible effects of vitamin A supplementation on the progression of vision loss related to retinal degeneration, the study only included individuals with retinitis pigmentosa. Retinitis pigmentosa is a distinct condition from choroideremia. Therefore, it cannot be assumed that vitamin A supplementation could have the same effect.

An individual with choroideremia may qualify for Social Security disability benefits. Qualification for these benefits is based on either meeting the criteria for legal blindness or if the vision loss or other health problems prevent you from working. The Social Security Administration (SSA) considers a person legally blind if one or both of the following criteria are met:

In most cases, choroideremia only involves the eyes, but in rare cases choroideremia is one part of a larger condition. This occurs when the CHM gene and other nearby genes on the X chromosome are disrupted.

In cases where a piece of the X chromosome, including the CHM gene, is deleted, choroideremia is associated with intellectual disabilities, underdevelopment of a brain tissue called the corpus callosum, hearing loss, and a cleft lip and palate. This condition is referred to by its clinical findings – choroideremia, deafness, and mental retardation – or it may be referred to as chromosome Xq21 deletion syndrome.

There are no known factors that can make choroideremia worse; however, overexposure to UV light has the potential to damage the retina.

Ultraviolet (UV) light and radiation are high-energy waves emitted by the sun. Although most UV rays are unable to reach the back of the eye, research has revealed that these powerful waves have the potential to damage the retina. These waves can be even more powerful when they are reflected off certain surfaces like water, sand, and snow. Since the retinal tissue is compromised in choroideremia, it may not be able to tolerate normal levels of UV rays and precautions including wearing a hat and UV-absorbing lenses should be considered. When purchasing UV-absorbent sunglasses, look for lenses that can absorb 99-100% of both UV-A and UV-B waves.

Since choroideremia affects both the peripheral and central vision, an individual with choroideremia will develop low vision as the condition progresses. The term "low vision" is used to described a reduced level of vision that cannot be corrected by eyeglasses. In general, low vision affects a person’s ability to perform their typical daily tasks such as reading, writing, seeing details in objects near or far, recognizing faces or places, or getting from place to place.

Females who carry a CHM gene change typically have no vision changes, but a dilated eye examination may reveal subtle pigment changes of the retina. These changes may become more obvious in the teenage years and beyond. In adulthood, some females may have patchy areas of retinal tissue loss and this may cause some night vision difficulty or peripheral vision loss if these areas expand. In other cases, the naturally occurring blind spot may be slightly enlarged but is not associated with progressive vision loss.

Individuals with choroideremia may be able to obtain a driver’s permit and license if their condition has not yet affected their peripheral vision. Each state has different vision requirements for driving and this may affect your ability to obtain a driver’s permit or a license.

To learn more about the driving requirements in your state and whether it is safe to begin or continue driving, speak with your eye doctor and contact your local licensing agency.

The vision loss associated with choroideremia is progressive and, once lost, it cannot be regained. This is because certain retinal tissues that play a role in creating vision deteriorate over time. As of October 1, 2016, there is no way of regrowing or replacing retinal tissues or restoring sight that is lost from choroideremia.

The degree and rate of vision loss due to choroideremia varies from person to person. Although peripheral vision loss occurs in the earlier stages of the condition, the central vision often remains clear into adulthood. Central vision becomes affected as the condition progresses and the retinal cells deteriorate. A majority of men with choroideremia who are under age 60 years have a visual acuity of 20/40 or better. Where as many as 35% of men with choroideremia over the age of 60 years have a vision that qualifies as legal blindness. With age, the central vision may continue to worsen and may be reduced to only hand motions or light perception at age 70 years and beyond.

Since choroideremia is a progressive condition that is caused by deterioration of retinal cells, the effect on vision is happening at a cellular level. This deterioration cannot be compensated for with glasses. Modifications to glasses by a low vision specialist may allow a temporary increase in visual field, improve contrast, or decrease glare, each of which can maximize the remaining vision. However, these modifications cannot reverse vision loss or improve vision to 20/20.

the vision lost due to the conditoin cannot be regained.
peripheral and central vision, an individual with choroideremia will develop low vision as the condition progresses.

Typically, females who are carriers of a CHM gene change have little to no visual symptoms. It is very rare for a female to have a severe case of choroideremia. This is only possible if the X chromosome carrying the CHM gene change is overly expressed in the retina or if two CHM gene changes are present.

The CHM gene is on the X chromosome and one CHM gene change is not sufficient to cause a disease in a female. This is because females have two X chromosomes and

In some cases of choroideremia, other eye conditions develop and can further compromise the vision including:

Choroideremia is the most common name for the condition. Rarely, choroideremia may also be referred to as progressive tapetochoroidal dystrophy (TCD) or choroidal sclerosis.

There are several different eye conditions that have similar symptoms to the early stages of choroideremia, including:

Although the early symptoms of choroideremia may be easily confused with other retinal conditions, there are features of the retina that are unique to choroideremia. A dilated eye examination will reveal patchy areas of retinal tissue loss (referred to as chorioretinal degeneration or atrophy) at the edges of the retina but do not initially involve the central seeing part of the eye (macula).

Low vision services provide opportunities to maximize vision and independence with daily tasks. Low vision services can be tailored to your needs and may include:

There are a few online support groups for individuals with choroideremia and their family members.

There is an email-based support group which can be joined by emailing the following address: [email protected]

If you have a Facebook profile, you can request to be a member of a choroideremia group: https://www.facebook.com/groups/Choroideremia/

There are not different types of choroideremia. Rather, choroideremia is a condition that affects males while females often have no symptoms.

The relationship between overall nutrition and ocular health has yet to be determined and research is ongoing. General guidelines for healthy diets that can benefit eyes and vision include eating fresh fruits and leafy green vegetables for antioxidant benefits and fish for omega-3 very long chain fatty acids. Supplements that include antioxidants, omega-3 oils, or docosahexaenoic acid (DHA) may be used, but there is no evidence that these supplements delay or reverse the symptoms of choroideremia.

Choroideremia may be abbreviated as CHM.