What is Kayser-Fleischer Ring?
Kayser-Fleischer rings are a common eye-related sign found in people suffering from Wilson disease, a genetic condition affecting how copper is processed in the body. These rings usually appear in late childhood or early teenage years due to an excess of copper being deposited on the inner part of the eye (cornea’s) surface. This happens within the Descemet membrane – a thin layer on the inner part of the cornea. Sometimes, these rings can also be found in people with other health issues like primary biliary cholangitis (a disease damaging the bile ducts in the liver), neonatal cholestasis (a liver disease in newborns), and general liver disease. Other complications from Wilson disease include mental health disorders, neurological symptoms, heart muscle disease, fertility problems, and a type of anemia where the body destroys its own red blood cells. If Wilson disease doesn’t get the necessary treatment, it can worsen to liver cirrhosis and liver failure, which could lead to death.
It’s important to note that Kayser-Fleischer rings aren’t just seen in Wilson disease patients; they can occur in people with primary biliary cholangitis and infants with neonatal cholestasis as well. Originally, these rings were thought to be caused by a buildup of silver, but researchers in 1934 found that copper was the main component. These rings don’t generally affect vision and can be eliminated with appropriate treatment. However, they may reappear if the disease progresses, which serves as an important sign of how well the treatment is working and whether the patient is sticking to their treatment plan. To diagnose Kayser-Fleischer rings, especially in the early stages, an eye examination using a slit lamp (an instrument used by ophthalmologists) is essential unless these rings are clearly visible without such equipment in severe cases of copper overload.
Recognizing Kayser-Fleischer rings promptly, evaluating their root cause, and managing excessive copper levels in the body are key to reducing the chances of severe illness and death in patients.
What Causes Kayser-Fleischer Ring?
Kayser-Fleischer rings are brown or grayish-green rings that can be seen around the edge of the cornea, which is the clear, front surface of the eye. These rings sit over the colored part of your eye known as the iris. They form because of copper building up in a part of the cornea known as the Descemet membrane.
This excessive copper buildup can occur because of issues with the flow of bile (cholestasis), liver disease or because your body is making mistakes in how it handles copper.
Risk Factors and Frequency for Kayser-Fleischer Ring
Wilson disease is a condition that is found worldwide, affecting about 1 in every 30,000 newborns. Almost 95% of those who show neurological symptoms of the disease have something called Kayser-Fleischer rings. These rings also appear in about half of the people with the disease who don’t have neurological symptoms. Even those who don’t show any symptoms at all can have these rings, with 10% to 40% of such individuals displaying them. In children with Wilson disease, 63% have these rings. It’s important to note that while it’s possible for Kayser-Fleischer rings to appear in individuals with other health conditions, this is quite unusual.
Signs and Symptoms of Kayser-Fleischer Ring
Kayser-Fleischer rings, a sign of Wilson disease, are usually symptom-free. They appear in both eyes and initially affect the top part of the cornea. Gradually, these rings spread around the entire edge of the cornea. First visible at the Schwalbe line – the boundary where the cornea meets the sclera of the eye, they extend less than 5 mm onto the cornea (see Image. Schwalbe Line). These rings can take on various colors, including greenish-yellow, ruby red, bright green, or ultramarine blue.
Wilson disease should be considered as a possible diagnosis if individuals show certain signs:
- Kayser-Fleischer rings noticed during a routine eye examination
- A family history of Wilson disease, particularly if a sibling or parent was diagnosed
- Anemia that’s not caused by Rh blood incompatibility (also known as Coombs-negative hemolytic anemia)
- Neurological symptoms that can’t be explained by other conditions
- Mental health issues accompanied by signs of liver or neurological disease
- People aged between 3 and 55 showing unexplained high levels of aminotransferase, a liver enzyme, or having chronic hepatitis with fatty deposits in the liver, autoimmune hepatitis that doesn’t respond well to treatment, cirrhosis, or sudden liver failure
Keep in mind that we shouldn’t rule out Wilson disease just based on a person’s age. Some patients older than 55 first show neurological symptoms of Wilson disease, primarily if previous symptoms went unnoticed.
Testing for Kayser-Fleischer Ring
Kaiser-Fleischer rings are distinct markings that may indicate certain eye conditions, but they are not always easy to spot with a naked eye, especially at the early stages of the disease. As such, a careful examination with a specialized microscope called a slit lamp is recommended to detect these rings. As the disease progresses, the rings may start to become visible without the need for equipment, especially in those with light-colored eyes and a severe overload of copper within their bodies.
The use of a technique called gonioscopy is also widely acknowledged as the best method for diagnosing a condition known as angle-closure glaucoma. Using a special lens attached to the slit lamp, this method makes it possible to see and analyze the angle in the eye where the iris meets the cornea. Interestingly, this test may also reveal the presence of Kaiser-Fleischer rings at their early stages.
When testing for Wilson’s disease – a condition characterized by an abnormal buildup of copper in the body, a series of tests may be required. They may include an ocular examination using a slit lamp or an imaging technique called anterior segment optical tomography, checking copper levels in a 24-hour urine sample, looking at levels of a protein called ceruloplasmin in the blood, checking blood copper concentration, and evaluating liver enzymes through a blood test. If neurological symptoms are present, an MRI scan of the brain might be needed. Additionally, if the diagnosis is still unclear, a liver biopsy might be recommended. If this isn’t possible or doesn’t provide clear results, genetic testing may be performed.
Treatment Options for Kayser-Fleischer Ring
Wilson’s disease is a condition that causes a dangerous build-up of copper in your body. So, the main focus of treatment is to safely reduce this copper level and manage symptoms. Doctors often prescribe oral medications like penicillamine and trientine, which work by binding to the excess copper in your body and helping you pee it out.
Zinc acetate is another medication used to help manage Wilson’s disease. It works a bit differently — instead of removing copper from your body, it reduces the amount of copper you absorb from your food. During pregnancy, doctors may recommend taking zinc acetate alongside either penicillamine or trientine as a kind of maintenance therapy to ensure copper levels stay under control.
Patients will also be advised to adjust their diet, especially early on in the treatment process. Certain foods like shellfish, nuts, chocolate, mushrooms, and organ meats can be high in copper, so they should be avoided initially. Once treatment is well underway and copper levels have stabilized, it may be possible to start eating some of these foods again, but in moderation. It’s important to remember, though, that while diet changes can help support treatment, they’re not enough to manage Wilson’s disease on their own.
For individuals who experience severe liver damage due to Wilson’s disease, like acute liver failure, a liver transplant might be required. This is because medications alone are often not enough to manage the condition effectively in these severe cases.
Kayser-Fleischer rings, which are dark rings around the iris of the eye, are a common feature of Wilson’s disease. These rings often disappear once treatment starts, but they can reappear if the disease progresses. These rings can provide a useful way for doctors to check whether treatment is working and whether the patient is taking their medication as prescribed. In fact, “chelation” therapy—the use of medications like penicillamine to bind excess copper and help the body get rid of it— leads to the disappearance of the rings in around 80% of patients over 3 to 5 years. It’s also worth noting that a liver transplant, which might be necessary in severe cases, represents a complete cure for Wilson’s disease.
What else can Kayser-Fleischer Ring be?
Kayser-Fleischer rings are most commonly linked with a condition known as Wilson disease. However, they can also appear in a range of other diseases. These include primary biliary cholangitis, multiple myeloma, chronic cholestasis (bile flow reduction), neonatal cholestasis (a liver disease in newborns), autoimmune hepatitis, chronic lymphocytic leukemia, liver failure, and long-term liver disease.
When diagnosing Wilson disease, doctors have to rule out several other conditions that can show similar symptoms. These conditions can include:
- Chronic liver disease caused by issues like viral hepatitis, alcohol use disorder, autoimmune hepatitis, drug-induced liver injury, hereditary hemochromatosis, and alpha-1 antitrypsin deficiency.
- Chronic hypertensive encephalopathy (a brain disorder resulting from consistently high blood pressure)
- Glioma (a type of brain tumor)
- Japanese encephalitis (a brain infection)
- Primary central nervous system (CNS) lymphoma (a type of cancer in the brain or spinal cord)
- Tuberculosis meningoencephalitis (a bacterial brain infection)
- West Nile encephalitis (a viral brain infection)
- Primary biliary cholangitis (a liver disease)
- Psychiatric illness
- Fleischer ring of keratoconus (a non-inflammatory eye condition that results in progressive thinning of the cornea)
To narrow down the diagnosis, certain key factors can help. People with Wilson disease who also have acute liver failure are often found to have a type of anemia. Those with chronic liver disease resulting from Wilson disease usually show low levels of ceruloplasmin (a protein in the blood), and nearly all patients with neurological symptoms related to Wilson disease display Kayser-Fleischer rings. These specific findings help set Wilson disease apart from other possible causes.
What to expect with Kayser-Fleischer Ring
Wilson disease can become life-threatening if not treated in time. It can lead to severe liver disease, like cirrhosis, and complications related to increased pressure in the liver’s blood vessels, including fluid accumulation in the stomach (ascites) and bleeding. If not promptly addressed, the neurological symptoms associated with Wilson disease, such as abnormal body movements (dystonia), loss of voluntary movement (akinesia), and inability to speak (mutism), can worsen.
However, early treatment can result in a good outcome. Starting therapy before liver cirrhosis develops and keeping copper levels normal allows patients to have a normal life expectancy. While liver functions typically return to normal within a year of starting treatment, the scarring of the liver (cirrhosis) cannot be reversed. Neurological symptoms may take up to 18 months to improve and some lingering symptoms might become permanent. Luckily, any psychiatric symptoms generally improve along with the neurological symptoms.
Possible Complications When Diagnosed with Kayser-Fleischer Ring
Accumulation of copper in the body can lead to various health problems. The main impact of Wilson disease, which is a condition of excess copper in the body, is usually on the liver and the nervous system. However, excessive copper can also affect other parts of the body. This can result in a range of health issues such as liver cirrhosis, liver cancer due to cirrhosis, mood disorders, psychological disorders, sleeping troubles, heart muscle disease, bone disease, muscle weakness, joint diseases, overactivity of parathyroid glands, infertility, sexual problems, extra tall stature, nonimmune destruction of red blood cells, accumulation of fluid in the abdomen, and dilated veins (especially in the esophagus and stomach).
Effects of Copper Accumulation:
- Liver cirrhosis
- Liver cancer due to cirrhosis
- Mood disorders
- Psychological disorders
- Sleeping troubles
- Heart muscle disease
- Fanconi syndrome (a type of bone disease)
- Muscle weakness
- Joint diseases
- Overactive parathyroid glands
- Infertility and sexual problems
- Gigantism (extra tall stature)
- Nonimmune destruction of red blood cells
- Fluid accumulation in the abdomen
- Dilated veins (especially in the esophagus and stomach)
Preventing Kayser-Fleischer Ring
Kayser-Fleischer rings are unusual amounts of copper that are found in the eye. Although you may be able to see these rings without any aid, they usually need a specific eye check-up known as a slit-lamp examination to be detected early. These rings are often linked with a condition called Wilson disease and can be a sign of an underlying health issue. While these rings don’t affect your sight, they do indicate that there’s too much copper in your body. Too much copper can lead to serious health conditions such as cirrhosis (a liver disease), mental health illnesses, and symptoms impacting the nervous system and other body organs.
To find out if the rings are due to Wilson disease or another health problem, doctors will examine blood and urine samples. If these initial tests don’t provide enough information, you may need further evaluations such as a liver biopsy (taking a small tissue sample from the liver for testing), genetic testing, or a brain scan using magnetic resonance imaging.
Oral medicines and adjustments to diet can help manage excess copper in people with Wilson disease. However, changing just the diet is not enough. If people with Wilson disease get treatment early and maintain normal copper levels, they can expect to live a normal lifespan. If Wilson disease is not treated properly, it can cause death, mostly due to liver failure. In such cases, a liver transplant may be needed. Also, if you have relatives with Wilson disease, it’s important to tell your healthcare provider. They can help explore the option of getting tested.