Choroideremia

Overview

Choroideremia is a rare genetic disorder that causes vision loss and leads to eventual blindness in all cases, usually over the course of several decades. The disease involves a mutation in the CHM gene, which is located on the X chromosome, one of the two sex chromosomes—males generally have two kinds of sex chromosomes (X and Y) while females have two of the same kind (XX). The disorder mainly affects men: those with XY chromosomes only have one copy of the gene located on the single X chromosome. As a result, a mutation of the single CHM gene will lead to the disease. Females with XX chromosomes, on the other hand, have an additional copy of CHM on the additional X chromosome: in this case, both copies of the gene must be mutated for the condition to manifest, which is significantly less likely. It is estimated that the disease affects 1 in 50,000 to 1 in 100,000 individuals (again, mostly men), though it is possible that it is underdiagnosed as a result of its similarity to other disorders.[1]

Before its identification as a distinct disease, choroideremia was believed to be a form of retinitis pigmentosa (RP). With choroideremia, the gradual loss of photoreceptors, the retinal cells responsible for converting light into visual signals for our brains, is the main driver of vision loss—this is the case with RP as well. And in both diseases, childhood onset is typical and the experience of gradual vision loss is quite similar: rod photoreceptors die off first, leading to an initial loss of peripheral and night vision. This is followed by the degeneration of cone photoreceptors, resulting in the loss of the central and high-acuity vision they are responsible for. The overall experience is often likened to a progressively worsening form of tunnel vision.

The underlying genetic and molecular causes of photoreceptor death are unique in choroideremia, however. The CHM gene that is mutated in choroideremia is responsible for producing a protein called REP-1, which serves the important function of “escorting” other proteins to their appropriate places within cells so that they can do their work. With an absence of REP-1, vital cell maintenance and production is inhibited in the retina, which is what triggers the death of photoreceptors. Other areas of the eye are damaged due to a lack of REP-1 as well: the choroid, a network of blood vessels that supply nutrients and oxygen to the retina, as well as the retinal pigment epithelium (RPE), a cell layer below the retina that nourishes the photoreceptors.

Content on this page was written by Dr. Chad Andrews and Dr. Mary Sunderland, and was edited and approved by Dr. Ian MacDonald. The information was most recently updated on August 23, 2018.

Symptoms and Diagnosis

As with RP, the most common early symptom of choroideremia is difficultly seeing at night and in low-light conditions—this is called nyctalopia or “night blindness.” Symptoms usually manifest around the time of grade school, which is also the case with RP, though in choroideremia it is predominantly boys who are affected. Most men with choroideremia will experience legal blindness by the age of 40 and complete blindness by age 70-80. Though it is mostly males who are affected, approximately 30% of women who have the mutation will also develop vision loss, though it is rarely as severe as a man’s.

Since choroideremia is difficult to distinguish from RP and other retinal diseases, a family history is often important for a diagnosis. Genetic testing can help with this; in fact, the genetic test for choroideremia was developed in 1998 by Dr. Ian MacDonald at the University of Alberta with the support of the Foundation Fighting Blindness. It involves testing a blood sample to confirm the disease and, in the case of women, determine if one is a carrier.

Read Our Guide to Genetic Testing

There are also eye tests that can bring patients closer to a final diagnosis, though they may not be able to pinpoint the exact nature of the disease itself. These are the same tests used for RP and many other inherited retinal diseases:

  • ERG (electroretinography): this is a test that measures the electrical responses of the retina to light, evaluating responses of both rod and cone photoreceptors. Although both rods and cones may be affected in people with RP, the most marked changes early in disease are in the rod cells; this characteristic pattern helps diagnose the condition. The ERG test involves staying in a darkened room for 30 minutes, with drops put into the eye or eyes being tested. A special contact lens or fine fibre electrode is then placed on the eye or lower eyelid, and the eye is exposed to flashes of light.
  • OCT (optical coherence tomography): this is an imaging technique that involves taking digital images of the various layers of the retina. The process is uses light rather than sound or radio waves, which is why the images are in high resolution.
  • Visual field test: this exam is designed to detect, measure, and monitor blind spots in vision. It involves looking into a device that emits flashes of light, with the patient asked to indicate which flashes can be seen. The flashes that are not seen are recorded. This gives a measure of how much vision is affected.

Existing Treatments

Currently, there is no existing treatment or cure for choroideremia. However, a gene therapy for a rare form of RP was approved by the FDA at the end of 2017 and is now on the market in the United States. Called Luxturna, it has the potential to halt vision loss and even restore some sight in individuals with a mutation of their RPE65 gene (manifesting as either RP or Leber congenital amaurosis). The approval and emergence of Luxturna shows that similar gene therapies could be used to treat other genetic disorders in the future, including choroideremia.

Read Our Story About The Approval of Luxturna

Clinical Trials

In November 2011, the first clinical trial of gene therapy for choroideremia began in the UK led by Dr. Robert MacLaren of Oxford University. The therapy aims to replace the mutated CHM gene with a healthy copy. This healthy gene will hopefully allow the retina to produce the missing protein.

With funding from the FFB and others, a team of scientists led by Dr. MacDonald at the University of Alberta, tested conducted a gene therapy trial for choroidermia in Canada. Thanks to FFB-donors, we were thrilled to help support Canada’s very first ocular gene therapy trial! The trial has been completed and the results have been reported – you can read more about them in the choroideremia news feed.

There are multiple gene therapy trials for choroideremia that are ongoing.

Clinical trials are essential to the scientific process of developing new treatments: they test the viability and safety of experimental drugs and techniques, called “interventions,” on human beings. While there is no guarantee that enrolling in a clinical trial will provide any medical benefit, some patients do experience positive results after receiving an experimental therapy.

Read Our Clinical Trials Guide

The website clinicaltrials.gov is a centralized database of clinical trials that are offered globally. But as the disclaimer on the site’s home page states, there is no guarantee that a listed trial has been evaluated or approved—the National Institutes of Health runs the site but does not vet its content. This means that there could be bogus or dangerous trials listed that are preying on patients. It is essential that you discuss a clinical trial with your ophthalmologist before enrolling, and that you pay close attention to enrollment criteria.

If you are interested in exploring what is available on the site you can click on the buttons below, which will take you to clinicaltrials.gov and initiate a search for trials relevant for patients living with choroideremia.

CLINICAL TRIALS FOR CHOROIDEREMIA

Patient Registry

For individuals living with an inherited retinal disease (a disease caused by a genetic mutation), participation in a clinical trial could be a logical next-step (for a description of clinical trials, see above). But in Canada there is no centralized, guided mechanism for enrolling in a trial; with this in mind, the Foundation Fighting Blindness has developed a secure medical database of Canadian patients living with inherited retinal diseases: we call it the Patient Registry.

By enrolling in the Patient Registry, your information will become a part of this essential Canadian database that can be used to help connect you to a relevant clinical trials. The availability of relevant trials depends on a number of factors, so this tool provides no guarantees, but signing onto it will put you in a position to be connected to something appropriate. It is also a way of standing up and being counted: the more individuals enrolled in the Patient Registry, the better our chances of showing policymakers that there is a significant need for new treatments for inherited retinal diseases. The Patient Registry also helps to drive more sight-saving research!

You can begin the process of enrolling in the Patient Registry by clicking the button below.

Patient Registry Enrollment

Research Developments and Health Policy

The Foundation Fighting Blindness is committed to advancing the most promising sight-saving research, and has invested over $33 million into cutting-edge science since the organization was founded. Recognizing that science is tied to policy frameworks, the Foundation is also actively involved in health policy activities across Canada.

Many research groups are working to develop treatments and cures for choroideremia. Experimental treatments can be divided into three broad categories:

  • Protective Therapies
  • Corrective Therapies
  • Sight-Restoring Therapies

Protective therapies aim to stop (or at least slow) the damage caused by genetic mutations. These include treatments to stop the process of photoreceptor death (apoptosis), as well as cell-derived therapies that aim to help photoreceptors survive.

Corrective therapies aim to reverse the underlying genetic defect that causes vision loss. If these therapies are successful they might prevent a person who is treated when first diagnosed, from ever developing vision loss. Corrective therapies might also help slow the disease in people whose vision has already been affected, especially in the earlier stages. Gene therapies, which replace a non-functioning gene, are one type of corrective therapy. Several clinical trials of gene therapies for choroideremia are underway.

Sight-restoring therapies are also a growing area of research success. These therapies are intended for people who have already lost all, or much, of their vision. Stem cell therapies aim to replace the retina’s lost photoreceptors. There are promising early results with stem cell trials involving other retinal degenerative diseases; trials with choroideremia are on the horizon. Retinal prosthetics, such as the Arugus II or “Bionic Eye,” use computer technology to generate vision. The Foundation Fighting Blindness helped to support the first Canadian trial of the Argus II and continues to work closely with health policy experts across Canada to ensure that patients who could benefit from the Argus II device have access to this innovative treatment. Drug and gene therapies are also being developed that may give non-photoreceptor nerve cells in the retina the capacity to sense light.

Thanks to our generous donors, we are funding ground-breaking research in these areas. Click on the button below to review the full list of FFB-funded projects:

FFB-FUNDED RESEARCH

At the bottom of this webpage, you will find an updating list of stories that detail new research and health policy developments relevant for individuals affected by choroideremia.

Educational Resources

The page you are now on provides information on achromatopsia, but the Foundation Fighting Blindness has developed additional resources that can be helpful in plotting an optimal path through vision care. Below is a link to our must-read resources, where you will find information on genetic testing, clinical trials, stem cell research, and more as well as a link to Vision Quest (the FFB’s in-person educational events). The list will update as new resources are added.

Must-Read Resources

Vision Quest Educational Series

References

[1] https://ghr.nlm.nih.gov/condition/choroideremia#statistics