What is Amantadine Keratopathy?
Amantadine was first found as a drug to treat flu in the 1950s. Later, in the late 1960s, it was discovered to be effective in managing tremors and awkward, often involuntary movements (dyskinesia) related to Parkinson’s disease, and it started to be largely used for this. These days, doctors often prescribe amantadine for certain long-term neurodegenerative conditions and diseases affecting brain functions such as thinking, memory, etc.
However, the exact way how amantadine works remains largely a mystery. Amantadine keratopathy is a medical term to describe a condition in which the cornea, the front surface of the eye, swells (corneal edema) and leads to reduced vision quality. Doctors think this condition might be caused by the drug. In most situations, the swelling in the cornea goes away when the drug use is stopped. However, in some cases, people might need a corneal transplant when the condition gets serious.
What Causes Amantadine Keratopathy?
Acute corneal edema, which is sudden swelling of the cornea in the eye, has been associated with using a medication called amantadine. It has been observed that this swelling occurs as soon as the medication is started and disappears once the medication is discontinued, indicating a direct link between the two. Studies have also found that this condition, known as amantadine keratopathy, can develop gradually over time and depends on the dosage of the medication.
Further research has suggested that the longer a patient takes amantadine, the greater the decrease in the density of endothelial cells, these cells line the inside of our blood vessels, in the cornea. Patients who were given a large dose of the medication, for example, 2000 mg within 30 days, had an increased risk of corneal swelling. If a person took a massive dose of 4000mg within 30 days, the risk of swelling was three times higher.
It’s important to note that amantadine could interact negatively with other medicines that are harmful to the cornea, thereby increasing the risk of permanent damage and corneal swelling.
Although ECD isn’t always a surefire indication of how a condition might turn out, patients with a lower initial ECD could be more at risk of developing amantadine keratopathy. As we age, we naturally lose ECD which can result in greater variation in ECD in our later years. According to one study using corneas from a large cornea donor database, the presence of ECD less than 2000 was much higher in patients who were aged over 75, those aged between 65-74 years, and those who had previously had a cataract surgery.
Risk Factors and Frequency for Amantadine Keratopathy
It’s uncertain how common amantadine keratopathy is in the general population because most studies don’t include people with eye-related issues like glaucoma or a history of corneal swelling, where amantadine keratopathy could be more common. This condition seems to affect both males and females equally.
In a research study conducted after the drug was approved for marketing, it was found that over two years, people taking amantadine had a 1.79 times higher risk of developing corneal swelling or Fuchs dystrophy compared to the general population. During this time, out of 13,137 patients using amantadine (almost all of whom were taking 100 mg twice a day), 36 (or 0.27%) were diagnosed with Fuchs dystrophy or corneal swelling.
The chance of developing amantadine keratopathy increased within months of starting treatment. However, some cases occurred as late as six years after starting medication, suggesting the risk could be higher. One large study looking back at the medical history of patients with amantadine keratopathy found that those taking amantadine for Parkinson’s disease specifically had a higher risk of developing the condition compared to those taking the drug for other reasons (the risk was 1.97 times higher). The higher risk was likely because they were using the treatment for a long time. This study also found that over a 15-year period, Parkinson’s patients taking amantadine had a risk of 1.97 times higher than healthy people not taking the drug.
Signs and Symptoms of Amantadine Keratopathy
Amantadine keratopathy is a rare eye condition that usually manifests as sudden, painless blurring of vision in both eyes, which gets progressively worse over the following months. Many patients may have a visual acuity of 20/200 or worse by the time they see an eye specialist. The occurrence of these symptoms in patients with no history of eye disease, and no relatives with eye disease, should lead to a detailed review of their medical background and any medications they’re taking. If a patient is on amantadine, it’s important to know how long they’ve been taking it and the amount they’re taking, to understand their risk of developing amantadine keratopathy. It’s crucial to consider the possibility of other eye conditions that may be contributing to the vision loss, as amantadine keratopathy is very rare and presents in a nonspecific way.
In people experiencing vision loss and are taking amantadine, extensive eye examinations should be performed to rule out other possible eye conditions. This examination can include a detailed exploration of the anterior segment, retina, and optic nerve through a slit lamp examination. During this examination, there may be findings of diffuse stromal edema with Descemet’s folds and absent guttae on the cornea. Other findings may include microcystic epithelial edema and loosened epithelia.
Testing for Amantadine Keratopathy
If your doctor suspects that you have corneal edema, a condition where excess fluid swells your cornea, they might order additional tests. One of these tests is pachymetry, which measures the thickness of your cornea. This test not only can confirm the presence of corneal edema but can also help track how the condition progresses and if it improves after stopping certain medications like amantadine.
Another test that can be done is specular microscopy. This test looks at the cells in the back part of your cornea, called the endothelium. It’s useful for assessing the degree of damage to these cells and the number of cells per square millimeter, often referred to as Endothelial Cell Density (ECD). ECD can give your doctor more information about the health of your cornea since these cells are vital for keeping it clear and vision sharp.
Treatment Options for Amantadine Keratopathy
Amantadine keratopathy affects the eye by causing corneal edema, a swelling that can affect vision. In most cases, when patients stopped taking the drug amantadine, this condition improved and their vision returned to normal. However, a few instances have been reported when the corneal swelling did not decrease even after stopping the drug. In these situations, vision was usually restored after undergoing corneal transplant surgery. It is also possible that other eye diseases could have further damaged the cornea and stopped the problem from improving when the drug was discontinued.
Newly emerging findings suggest that a patient who had previously had amantadine keratopathy was able to continue using the drug with the help of topical steroids, without any recurrence of the swelling or reduction in endothelial cell density (cells that line the inner part of the cornea). While there isn’t any significant evidence showing topical steroids reduce corneal swelling, they could serve as a preventive measure to protect those susceptible to developing amantadine keratopathy.
Currently, there isn’t sufficient evidence to predict who might develop amantadine keratopathy. Any loss of vision following the start of treatment should be assessed by an eye doctor right away. It might be prudent to have patients with a history of eye injury, eye surgery, or corneal disease, and possibly those of a certain age, consult a specialist before beginning amantadine therapy. However, more research is needed to better guide this practice. Standard tests used today have shown limited ability to predict the outcome of Fuchs endothelial corneal dystrophy (FECD), a condition that damages the innermost layer of cells in the cornea. This indicates these tests might not be helpful in evaluating patients before starting amantadine therapy.
On the brighter side, recent development with newer screening methods, like Scheimpflug tomography (an advanced imaging technique), shows promise for predicting the requirement for interventions in FECD before vision loss occurs. This could be a potentially effective way to screen for amantadine keratopathy, although no specific research has been done as of yet.
What else can Amantadine Keratopathy be?
Amantadine keratopathy, which is a condition of the eyes, can sometimes be confused with other eye diseases due to similar symptoms. These conditions include the following:
- Fuchs endothelial dystrophy (FECD): FECD is quite like amantadine keratopathy in terms of how it develops and its symptoms. One way to tell the difference is by observing specific formations in the eye called “guttata” using a device called a slit-lamp. Also, unlike amantadine keratopathy, Fuchs endothelial dystrophy doesn’t get better even after stopping the use of the drug amantadine.
- Band keratopathy: This condition involves the build-up of calcium in the front part of the eye and can look like the swellings seen in amantadine keratopathy. It’s likely to be confused with amantadine keratopathy because it also worsens with age and is associated with chronic diseases. However, with band keratopathy, the clouding over of the eyes develops slowly over a long time, unlike in amantadine keratopathy. Plus, this condition is more likely to be seen together with other eye diseases. Again, stopping the use of amantadine won’t make band keratopathy better.
Reach out to your doctor for proper testing and diagnosis if experiencing eye symptoms, as these conditions can appear similar.
What to expect with Amantadine Keratopathy
Most recorded cases have seen complete recovery from corneal edema (swelling in the clear tissue at the front of your eye) and restoration of vision or visual sharpness to its initial level when they stopped using amantadine, especially in those who have no previous eye condition history.
However, in patients who already have a lower density of the endothelial cells (cells that form a thin layer at the back of the cornea), they might need a corneal transplant or a specific surgical procedure known as Descemet Membrane Endothelial Keratoplasty.
Possible Complications When Diagnosed with Amantadine Keratopathy
Misdiagnosing conditions can sometimes lead to procedures and treatments that might not be needed, causing a lot of unnecessary stress, especially when the patients don’t feel better afterward. A medical condition called amantadine keratopathy is known to cause permanent damage to the corneal endothelium, which is part of our eyes. If not properly diagnosed or if people susceptible to the disease are not identified, it could result in a lifelong loss of vision.
Key Facts to Remember:
- Misdiagnosis can lead to unnecessary treatments, operation, and distress for patients.
- Amantadine keratopathy is a disease that causes permanent damage to the corneal endothelium, a part of the eye.
- Failure to identify susceptible individuals or this disease could potentially cause permanent vision loss.
Preventing Amantadine Keratopathy
Amantadine keratopathy refers to the swelling of the clear surface of the eye, known as the cornea. This swelling is caused by the damage of certain cells that normally keep the cornea clear and unswollen. The harm done to these cells is, sadly, permanent. However, the swelling itself usually goes away when the medication causing it, amantadine, is stopped.
If the symptoms the medication was treating get worse after it is stopped, the patient’s brain specialist (neurologist) and eye doctor (ophthalmologist) will need to have a conversation. They need to figure out the best way to manage the patient’s treatment, balancing the need to control their symptoms with avoiding damage to the eyes.
