Choroideremia is a rare, inherited disorder that causes progressive vision loss, primarily affecting males. The condition impacts an estimated 1 in 50,000 to 100,000 people and is characterized by the gradual deterioration of the choroid and retina. These layers in the back of the eye are responsible for sensing light and providing nutrients to light-sensitive cells, and their degeneration leads to a steady decline in vision.
Symptoms and Progression of Vision Loss
The initial symptom of choroideremia is difficulty seeing in dim light or at night (nyctalopia), which becomes noticeable in early childhood. This occurs because the disease first impacts the rod photoreceptor cells in the retina, which are responsible for low-light vision. As the disease advances, the damage extends beyond these specialized cells.
Following the onset of night blindness, individuals experience a progressive loss of peripheral vision, resulting in “tunnel vision” as their field of view narrows. This stage occurs as the degeneration of the choroid and retinal pigment epithelium (RPE) spreads from the outer edges of the retina toward the center. The rate of progression varies significantly among individuals.
In later stages, the disease affects central vision as it damages the macula, the area responsible for sharp, detailed sight. Many people maintain good visual acuity into their 40s but may become legally blind around this age, with some eventually losing all sight. Color perception can also decline as the cone photoreceptor cells in the macula deteriorate.
The Genetic Basis of Choroideremia
Choroideremia is caused by mutations in the CHM gene, located on the X chromosome. This gene provides instructions for making Rab escort protein-1 (REP-1). The REP-1 protein is part of intracellular trafficking, which moves materials within cells. Without functional REP-1, this transport system fails, leading to the death of cells in the retina and choroid.
The inheritance pattern is X-linked, which is why the disorder predominantly affects males. Since males have only one X chromosome, a single mutated CHM gene is enough to cause the disease. Females have two X chromosomes and are carriers; if one CHM gene is mutated, the healthy copy can produce enough REP-1 protein to prevent severe vision loss.
While most female carriers do not experience severe vision loss, some may develop mild symptoms like light sensitivity or patchy vision loss later in life. An eye examination can reveal signs of their carrier status, such as pigmentary changes in the retina, even without symptoms. A female carrier has a 50% chance of passing the mutated gene to her children.
How Choroideremia Is Diagnosed
Diagnosis begins when an individual seeks an eye exam for symptoms like night blindness or peripheral vision loss. An ophthalmologist performs a fundus exam to inspect the retina, RPE, and choroid for signs of degeneration. In early stages, this may reveal “salt and pepper” pigment mottling in the fundus.
Functional tests are used to quantify vision loss. Visual field testing measures the scope of peripheral vision to document the progression of tunnel vision. An electroretinogram (ERG) measures the electrical response of the retina’s light-sensing cells, providing data on photoreceptor function.
While clinical findings strongly suggest choroideremia, a definitive diagnosis requires genetic testing to identify a mutation in the CHM gene. This confirmation distinguishes it from other inherited retinal diseases, like retinitis pigmentosa. It also allows for accurate genetic counseling for the individual and their family.
Management and Emerging Treatments
There is no cure for choroideremia, so management focuses on supportive care and adapting to vision loss. Regular monitoring by an ophthalmologist tracks the disease’s progression. Patients can benefit from low-vision aids, such as magnifiers and specialized lighting, to maximize remaining sight. Wearing sunglasses with UV protection is also recommended to reduce light sensitivity.
Significant advancements in treating choroideremia are in gene therapy. This approach aims to correct the genetic defect by delivering a healthy copy of the CHM gene to retinal cells. A harmless, deactivated virus acts as a vehicle to transport the functional gene into the target cells, allowing them to produce the REP-1 protein and halt the degenerative process.
Clinical trials for choroideremia gene therapy have shown promise in slowing or stopping vision loss in some patients, and research is ongoing to optimize its long-term effectiveness and safety. Patient advocacy organizations and foundations are a resource for the most current information on treatment developments and clinical trials. These groups provide support, education, and access to the latest research.