What is Gyrate Atrophy of the Choroid and Retina?
Gyrate atrophy (GA) of the choroid and retina is a rare inherited eye condition. Basically, it’s a genetic disease that affects the eyes and is passed down through families. This usually happens when someone lacks or has insufficient quantities of an enzyme called ornithine aminotransferase (OAT). This enzyme’s shortfall causes the buildup of an amino acid, ornithine, in the blood, about 10 to 20 times higher than normal levels. This unusual excess is believed to cause the eye problems related to this condition.
The lack or absence of this enzyme is caused by changes or mutations in the OAT gene located on chromosome 10. As for what the condition looks like, it is marked by the formation of thinning patches within the back of the eye that begin in the outer part of the retina in the first 10 years of life and gradually spread to the central part, the macular area. It might also cause nearsightedness, changes in the macula, which include cyst-like changes appearing within the first two decades of life, and the development of cataracts at the back of the lens.
Persons affected by this condition typically start experiencing night blindness, which later advances to a narrowing of the visual field, and finally a reduction of central vision leading to blindness. Doctors diagnose this condition by looking for characteristic signs in the eye, high levels of ornithine in the blood, and by finding mutations in the OAT gene. The main methods of managing this condition include altering the patient’s diet and managing any complications that might arise.
What Causes Gyrate Atrophy of the Choroid and Retina?
Gyrate atrophy of the choroid and retina is a rare genetic disorder passed down through families. This occurs when there are defects or mutations in the OAT gene located on chromosome 10q26. These mutations cause a lack of an enzyme called OAT, which plays a significant role in our body by helping to break down a specific amino acid called ornithine. When the OAT enzyme is damaged or missing, ornithine isn’t processed as it should, resulting in an excessive amount of this substance building up in various body fluids including blood, urine, spinal fluid, and a fluid in the eye called aqueous humor.
Presently, more than 60 different types of mutations in the OAT gene have been found to cause this condition. The build-up of extra ornithine is thought to lead to the physical symptoms of this disorder, likely due to the harmful effects of the extra ornithine, especially on certain eye cells responsible for our vision.
Other anomalies linked to this condition include abnormal levels of several other substances in the urine and blood such as lysine and cystine – substances excreted in the urine in large quantities, and lysine, glutamine, glutamic acid, ammonia, and creatine – substances that appear to be lower than usual in the blood. Although the OAT enzyme is present in most body tissues, the primary harmful effects of the condition are noticeable in the eye.
Risk Factors and Frequency for Gyrate Atrophy of the Choroid and Retina
Gyrate atrophy is a relatively rare condition. Even though the reasons aren’t clear, it seems to be especially common in Finland. That said, it has been found in many other parts of the world like the USA, Japan, Germany, UK, India, China, Australia, France, Tunisia, Egypt, Korea, Brazil, Nepal, and Turkey. In Finland, about 1 in 50,000 people have this condition.
- Vision problems linked to gyrate atrophy usually begin in early childhood. These can include nearsightedness, night blindness, and visual field defects.
- Loss of vision due to damage to the macula and the formation of cataracts typically happens more in the second decade of life. However, the age at which central vision loss begins can vary widely.
- Some studies suggest that females may keep larger visual fields and better night vision than males. Other research, though, finds that males and females are equally affected.
- A study comparing Japanese to Finnish patient data found that Japanese patients tend to have worse visual function. This suggests that the condition’s progression could vary among patients from different populations.
- Patients usually end up with vision that’s worse than 20/200 between the ages of 40 and 55.
Signs and Symptoms of Gyrate Atrophy of the Choroid and Retina
Gyrate atrophy of the choroid and retina is a condition that first affects patients during early childhood by causing night blindness and reducing their field of vision. This happens because the outer edges of the retina start to degenerate over time. Sometimes, a family history of the disease aids in detecting it early. As the condition progresses, patients may also experience a gradual decrease in sharpness of central vision due to changes in the macula (the central part of the retina) and the development of a type of cataract known as posterior subcapsular cataracts. In addition, patients may develop conditions such as intraretinal cystic spaces, cystoid macular edema, foveoschisis, epiretinal membrane, and atrophy. Short-sightedness, or myopia, is another common symptom linked with the condition.
More severe complications can occur, like a hole in the macula or abnormal blood vessels under the retina which can lead to a sudden severe decrease in central vision. By the age of 40 to 55, most patients become legally blind due to the later-stage effects of the condition.
Typically, on eye examination, the doctor might see well-defined areas of retinal degeneration that over time join together. These have pigmented edges with big choroidal vessels visible underneath. The atrophy usually starts in the middle of the retina but spreads to the center and outer edges of the retina over time, further deteriorating the field of vision. Some patients may also display peripheral nervous system abnormalities and may occasionally experience muscle weakness.
Although the decline in vision is the main effect of Gyrate Atrophy, it can also manifest in other ways:
- Affects the central nervous system leading to aggressive behavior
- Can cause intellectual disabilities
- Some patients may develop epilepsy
Testing for Gyrate Atrophy of the Choroid and Retina
Gyrate atrophy of the choroid and retina is a condition that can be identified based on a few key signs and a rise in plasma ornithine levels, typically 10 to 20 times higher than normal. Scientists have found over 60 mutations in the OAT gene that cause gyrate atrophy. Additionally, high levels of lysine and cystine found in urine, alongside decreased levels of lysine, glutamine, and creatine, can suggest potential gyrate atrophy.
An enzyme deficiency in OAT can also be confirmed in a lab using skin cells from patients. It’s important to test siblings of current patients, since early detection can lead to better visual outcomes in the long-term.
Patients with this condition typically show slower brain activity with possible epilepsy, aggressive behavior, or mental retardation. An MRI of the brain may reveal degenerative changes, while patients can also show muscle weakness, or even atrophy, related to creatine deficiency.
Concerning the health of your eyes, some patients also have macular edema—which is fluid retention in the retina. Others do not show signs of leaking at the macula, yet later show impact on this area of the eye. Tests such as fluorescein angiography, which allows doctors to look at blood flow in the retina, can demonstrate leakage for those with choroidal neovascularization, a condition that develops new blood vessels and tissue in the part of the eye responsible for central vision.
Electroretinography (ERG)—a test to measure the electrical responses of various cells in the eyes—reveals decreased response from rods and cones (cells in our eyes that help us see), which can eventually become unnoticeable with disease progression.
The size of your field of vision and its sensitivity can often be decreased, yet this can be decelerated with suitable treatment. Noticeable changes are typically made visible through regular visual field testing, while microperimetry—a test to detect central vision changes—can help doctors evaluate macular sensitivity and function.
Your doctor may also use methods like optical coherence tomography—a noninvasive imaging test that uses light to capture micrometer-resolution pictures from within biological structures. This may reveal features like cystoid macular edema, choroidal thinning, or even a macular hole. Other tests like fundus autofluorescence—an imaging technique used to evaluate the health of the retina and the underlying choroid—and optical coherence tomography angiography—a non-invasive diagnostic technique that reveals depth-resolved images of blood flow in the retina and choroid—can assist in further evaluation and monitoring of the disease.
Treatment Options for Gyrate Atrophy of the Choroid and Retina
Gyrate atrophy is a condition that can be primarily managed through changes in diet to reduce high levels of a chemical called ornithine in the body. This can be achieved by reducing the intake of arginine, a substance ornithine is derived from. Restricting arginine can effectively lower ornithine levels in both humans and mice and slow down chorioretinal degeneration, a condition where the back of the eye deteriorates. However, this is not always successful in all patients due to genetic differences.
Arginine-rich foods such as nuts, seeds, cereal, dairy products, seafood, meat, chicken, watermelon, and chocolate should be avoided or reduced in the patient’s diet.
Some patients may also show improvements after taking vitamin B6 supplements. This works by increasing the activity of a certain enzyme, thereby lowering their ornithine levels. Despite this, some patients may not respond to vitamin B6 supplementation because of genetic differences.
Creatine, a chemical found in the body, can also be taken as a supplement to slow the degeneration of the back of the eye and improve neurological and muscular symptoms. Other dietary changes like consuming more proline and lysine, types of amino acids, could also prove beneficial.
To catch the disease early, it’s vital to regularly examine the retina, which is at the back of the eyes, of family members of those diagnosed with gyrate atrophy. Low vision aid could play a crucial part in the treatment and may help to improve the patient’s quality of life.
Cystoid macular edema and intraretinal cystic spaces, which are types of eye conditions associated with gyrate atrophy, can also be managed by a restricted diet, vitamin B6 supplements, and various types of medication and treatments. However, some treatment options like steroid injections can carry risks such as progression of cataracts and elevation of intraocular pressure.
For those who suffer from complications related to gyrate atrophy, options include cataract surgery for significant vision loss, vitrectomy for macular holes, and injections for choroidal neovascularization, a condition where unwanted blood vessels grow beneath the retina.
What else can Gyrate Atrophy of the Choroid and Retina be?
When a doctor is trying to diagnose gyrate atrophy, a condition that affects the eyes, they consider a number of other conditions that have similar symptoms. These include:
- Choroideremia
- Retinitis pigmentosa
- Congenital stationary night blindness
- X-linked retinoschisis
- Bietti crystalline dystrophy
- Pigmented paravenous retinochoroidal atrophy
- Bifocal chorioretinal atrophy
- Pathological myopia
- Choroidal sclerosis
- Gyrate atrophy-like symptoms with normal blood ornithine
- Extensive paving stone (cobblestone) degeneration, but only in the peripheral area
To distinguish between these conditions, doctors will look at the patient’s medical history, how the disease is inherited, the symptoms, results from laboratory tests, genetic analysis, electrophysiology (a test that measures the electrical activity in the eyes), and using multimodal imaging analysis which combines different techniques to give a more detailed view of the eyes.
What to expect with Gyrate Atrophy of the Choroid and Retina
Patients with GA usually experience worsening night blindness and a reduced field of vision, starting from their early years. This is because of the steady deterioration of the choroid and retina, which are the layers at the back of the eye. This deterioration can usually be decelerated by limiting intake of a protein building-block, arginine, in your diet and taking vitamin B6 supplements. This can sometimes lead to a picture that looks like early retinitis pigmentosa, which is another eye condition.
This is then followed by a reduction in sharpness of central vision, which generally occurs in their early years or teens. This is due to progressive changes in the macula (an area at the back of your eye that helps you see details) and the formation of cataracts, which are cloudy areas in the eye’s lens. Treatment can often help manage these conditions and potentially improve visual clarity.
Complete vision loss and blindness (when vision is worse than 20/200) happens when this eye-layer deterioration affects the central macular area. This usually occurs between the ages of 40 and 55. However, this can vary greatly based on several factors, including the treatments received. Certain complications associated with GA, such as the creation of small holes in the macula, growth of new blood vessels beneath the macula (subfoveal choroidal neovascularization), and the retina becoming detached from the back of the eye can lead to an earlier and more serious loss of vision.
Possible Complications When Diagnosed with Gyrate Atrophy of the Choroid and Retina
Some potential complications that can affect the macula, the central part of your retina responsible for sharp vision, include:
- Cystoid macular edema, a type of fluid buildup in the eye.
- Foveal thinning, a condition where the central area of your retina becomes thinner.
- Epiretinal membrane, a thin layer of tissue that forms over the retina.
- Intraretinal cystic spaces, small fluid-filled spaces within the retina.
- Foveoschisis, a splitting of the layers of the retina.
- Macular hole, a tear in the macula.
- Choroidal neovascularization, where blood vessels grow under the retina and leak.
Complications affecting the area where the retina and vitreous, a jelly-like substance in your eye, meet can include:
- Vitreous hemorrhage, bleeding into the vitreous.
- Intraocular lens dislocation, where the artificial lens inserted during cataract surgery moves out of place.
- Rhegmatogenous retinal detachment, a serious condition where the retina detaches from the back of the eye.
Lastly, certain complications can affect the nervous system and lead to conditions such as:
- Mental retardation.
- Speech defects.
- Epilepsy, a condition characterized by repeated seizures.
- Peripheral neuropathy, damage to the nerves outside the brain and spinal cord.
- Muscular weakness.
Preventing Gyrate Atrophy of the Choroid and Retina
It’s crucial for patients and their parents to understand the nature of the illness and the necessity of sticking to diet changes over a long period of time. These changes involve reducing the amount of arginine, a kind of protein, in their diet. Studies have shown that this can have a significant impact on the patient’s vision. It’s also very important to have the patient’s family members checked for the condition so that if needed, these dietary adjustments can be made early on in life. This early action has been shown to make a big difference in the future vision health of the patient.
