What is Fuchs Uveitis Syndrome?

Fuchs uveitis syndrome (FUS) is a long-term, usually one-sided, mild inflammation of the front part of the uvea, which is the middle layer of the eye. Ernst Fuchs was the first to describe this condition in 1906. It’s also known by other names, such as Fuchs heterochromic uveitis and Fuchs heterochromic iridocyclitis. What exactly causes FUS is still unclear. Despite Ernst Fuchs proposing several ideas, none have been confirmed, with the possibility of an infection causing this condition regarded as the most likely.

Who gets affected by FUS, at what age symptoms appear, as well as rates of occurrence and complications seem to vary depending on where patients live and the specific group that is studied. Most people living with FUS experience vision changes mainly because of secondary problems like cataracts and glaucoma, which develop as a result of the disease. These problems can be treated effectively, leading to a good prognosis, meaning most people have a favourable outcome.

Around 13.9% of FUS patients have nonhereditary heterochromia. This is a condition where the color of one iris is different from the other and is caused by the thinning of the front part of the iris. As a result, patients may notice that the affected eye has lightened in color. This is mainly seen in patients who have light-colored irises. Darker-colored irises have more pigment cells, which makes the thinning of the iris less noticeable, thus these patients are less likely to develop heterochromia.

This piece will discuss the cause, how common the disease is, potential reasons for its development, how it presents itself, and how FUS and related problems are managed.

What Causes Fuchs Uveitis Syndrome?

Early research on FUS (Fuchs’ Uveitis Syndrome) suggested that it could be caused by different things, such as nerve damage (like in Horner Syndrome), or infections like herpes virus and Toxoplasma gondii. An important study by scientists named Quentin and Reiber came up with the main theory we use today: FUS is caused by inflammation related to rubella, which is also known as German measles.

The scientists looked for antibodies (proteins your body makes to fight infections) related to various infections, including rubella, herpes, chickenpox, measles, and toxoplasmosis in the fluid inside the eye. The results showed that every sample from a FUS patient contained rubella antibodies, so this became an important marker for diagnosing FUS.

Later studies confirmed the finding. They found that FUS patients consistently have rubella antibodies in the affected eye, but presence of rubella virus itself in the eye fluid does not contribute to FUS getting worse.

Initial theories about how FUS happens included nerve dysfunction, genetics, eye toxoplasmosis (an infection caused by a parasite), blood vessels, and immune system theories, but these have largely fallen out of favor. Other diseases, like retinitis pigmentosa, Usher syndrome, and chikungunya have been suggested to present with FUS, but there’s little evidence to support these theories, as eye fluid antibody analysis is missing in these disease diagnosis. Also, there’s no specific HLA (Human Leukocyte Antigen, which are proteins on your cells that play a crucial role in the immune system) associated with FUS.

Risk Factors and Frequency for Fuchs Uveitis Syndrome

Several research studies globally have found that the typical age for diagnosis of FUS, a type of eye condition, ranges from 27 to 44.5 years. Both men and women are diagnosed at a similar rate. In a group of 131 patients at the University of Illinois Eye and Ear Infirmary, the average age of patients diagnosed with FUS was around 43.9.

From 1919 to 1958, 4.48% of patients attending the clinic had experienced FUS before and after getting their rubella vaccination.
In the decade after the rubella vaccine was introduced in 1969, just 1.18% of patients had FUS.
While FUS rates continued to fall in the following years, the proportion of patients with FUS not born in the U.S. has risen despite the overall drop in patients with FUS since the introduction of the rubella vaccine.

Signs and Symptoms of Fuchs Uveitis Syndrome

Fuchs’ Uveitis Syndrome (FUS) typically starts to show in a person’s thirties or forties. Many people may not notice the slow, subtle changes in their eyes due to the quiet nature of this condition. Most patients do not experience any symptoms, and FUS is often found during a regular eye exam. Some may notice a lightening of the color of the affected eye. Sometimes, both eyes can be affected. Some people may find that their vision starts to deteriorate, mostly due to the formation of a cataract. They may also report seeing “floaters,” or small objects appearing to drift across their vision, which is a common symptom. Other symptoms to look out for include blurriness, mild eye pain, and seeing colored rings around lights, which could indicate increasing eye pressure.

In an eye exam using a slit lamp, there would be little to no visible signs of inflammation. The color difference between eyes, known as heterochromia, is a distinguishing feature of FUS, but there are several factors like forward eye tissue atrophy, natural iris color, and the pigmentation of the iris that can affect this. This color change happens due to irreversible tissue degeneration. In some people, especially those with dark-colored eyes, heterochromia may not be apparent while others might see a lightening of the iris color. However, people with a lighter iris may notice their iris color becoming deeper. What is more consistently observed are white, star-like deposits distributed throughout the inner layer of the eye.

The drainage area of the eye and the iris may show abnormal blood vessels, and there can sometimes be variable amounts of inflammation in the gel-like material in the back of the eye. Some patients may develop small bumps at the edge of the pupil (known as Koeppe’s nodules) or on the iris surface (known as Busacca nodules). The muscle in the iris that controls the size of the pupil can also degenerate, causing the pupil to have an irregular shape and respond poorly to light. Since the condition develops slowly, many face advanced disease by the time they seek medical help. These patients may have a form of cataract that presents as a cloudy area at the back of the lens, which can eventually lead to a completely opaque lens and increased eye pressure.

Testing for Fuchs Uveitis Syndrome

The diagnosis of Fuchs Uveitis Syndrome (FUS), a type of inflammation of the eye, is mainly made based on your medical history and a thorough eye examination. Sometimes, if your doctor is not able to determine the cause of your symptoms from a basic eye exam, they might use some other methods.

One such method is anterior chamber paracentesis, a procedure where a small amount of fluid (called aqueous humor) is removed from the eye and analysed in a lab. Detecting specific antibodies related to the rubella virus in this fluid doesn’t necessarily confirm FUS, but not finding them can lower the chances that you have FUS.

In vivo confocal microscopy (IVCM) is another non-invasive technique which allows doctors to see the cells in your eye in great detail. A study published in 2009 used IVCM to take detailed images of the innermost layer of the cornea (the clear outer layer of the eye) and another eye condition called keratic precipitates, that often occur in people with FUS. Notably, these images were similar to those found in people with uveitis caused by infection, suggesting FUS might also be caused by infection. However, despite its potential benefits, IVCM is not routinely used.

Enhanced depth imaging optical coherence tomography (EDI-OCT) is another imaging technique used to study the changes in the eye structure associated with FUS. Comparisons between healthy eyes and those with FUS showed that the eyes with FUS had a thinner iris (the colored part of the eye), as well as significant thinning in certain regions of the choroid (the layer under the retina at the back of the eye). While these various imaging techniques provide valuable insights into FUS, none of them have resulted in changes to the standard criteria for diagnosing the condition.

Treatment Options for Fuchs Uveitis Syndrome

In Fuchs’ Uveitis Syndrome (FUS), a type of eye inflammation, doctors can use corticosteroids for a short time to reduce symptoms. Corticosteroids are drugs that lower inflammation in the body. They come in different forms and, for FUS, the most useful kind is often a topical one, like an eye drop. This is especially true for flare-ups of anterior uveitis, which affects the front part of the eye. The drops can’t penetrate to the back of the eye, but they work directly on the front part where the inflammation is.

When the whole eye, including the optic nerve at the back, is inflamed, systemic corticosteroids can be useful. Systemic means they work throughout the body; these might be pills or injections.

However, it’s important to know that corticosteroids typically aren’t a long-term solution in FUS. Continuous use can lead to eye issues like cataracts, which cloud your vision, and glaucoma, which can cause damage to your optic nerve. Also, even with ongoing use of these medications, flare-ups can still occur.

In cases where the cause of eye inflammation isn’t clear, a short trial of corticosteroids could help doctors figure out the source of the problem. With FUS, other symptoms may develop over time like cataracts or glaucoma. It’s necessary to treat these to prevent long-term vision problems.

Fuchs Uveitis Syndrome (FUS), Posner-Schlossman Syndrome (PSS), and Herpes Keratouveitis (HKU) are three conditions that can show similar symptoms, making it challenging for healthcare providers to correctly diagnose them. The symptoms of these conditions often include eye discomfort, pain, blurred vision, or even no symptoms at all. Some shared features between FUS and PSS include an atrophic iris and heterochromia, characterized by different eye colors. PSS and FUS can often be differentiated by evaluating the patient’s medical history, physical exam, and the results of steroid medication trials.

HKU, another possible diagnosis, shows signs similar to those seen in FUS, with the addition of stromal edema, pigmented keratic precipitates, and endotheliitis. Distinguishing features of HKU include typical herpetic lesions and additional diagnostic tests that can detect HSV-1 or HSV-2 in the eye fluids.

Patients with VZV and CMV infections may also present with symptoms of chronic uveitis.
Increased intraocular pressure (IOP) is another condition that can be confused with FUS. Acute angle-closure glaucoma, which is a common cause of increased IOP, tends to have unique symptoms such as a fixed and dilated pupil, severe pain, nausea, and vomiting, which are not usually seen in FUS.

As a result, medical professionals must consider all these possibilities and perform detailed evaluations to attain an accurate diagnosis.

What to expect with Fuchs Uveitis Syndrome

Patients who undergo cataract surgery generally have a good outcome, with about 85% of them experiencing significantly improved vision. These success rates are even more promising than other similar eye conditions. According to an Italian study, about a third of patients that had cataract surgery eventually developed a condition which causes clouding behind the lens (posterior capsule opacification), which then required further treatment with a type of laser surgery (YAG laser capsulotomy). This occurrence of clouding after surgery happens roughly between 20% to 40% of the time. However, it is believed that this can be reduced with a more aggressive method of removing all the cortex.

Regarding glaucoma, a condition that causes damage to the eye’s optic nerve, data shows varied results with medical treatments. In one report, as many as 73% of patients did not respond well to the maximum medical therapy for glaucoma. However, other studies have shown better outcomes, with one researcher named Jones revealing that only 37% of patients did not respond to treatment. It’s estimated that 47% to 66% of patients with glaucoma will need to undergo surgery, with most of them regaining their original level of vision after the procedure.

In another study, patients diagnosed with Fuchs Uveitis Syndrome (FUS), an inflammation in the eye, only had worsened vision in 10% of the cases during the follow-up period. This suggests that in most cases, their vision either improved or remained the same after being diagnosed.

Possible Complications When Diagnosed with Fuchs Uveitis Syndrome

A severe complication of FUS (Fuchs Uveitis Syndrome) is secondary glaucoma, which can cause lasting damage to vision. Secondary glaucoma affects 15% to 59% of FUS patients. Unfortunately, typical medical treatments often fail to control the increased pressure in the eye that comes with this condition. When this happens, a surgical procedure known as trabeculectomy is usually required.

Trabeculectomy has proven to be the most successful surgical treatment. In some cases, an additional treatment with a drug called mitomycin C can help lower eye pressure after the surgery. A study showed that another medication, bevacizumab, wasn’t as successful when used in the same way.

Poor vision in FUS patients is most commonly due to cataract formation, affecting 23% to 90.7% of individuals with FUS. However, the visual outcomes are generally positive for patients who undergo cataract removal surgeries, specifically phacoemulsification and small-incision cataract surgery. Both these surgical techniques are generally safer and result in fewer complications than another method known as extracapsular cataract extraction.

Key Complications and Treatments:

Secondary glaucoma – potentially leading to vision loss
Trabeculectomy – the most successful surgical procedure for glaucoma
Mitomycin C – a supplementary treatment for lowering eye pressure post-surgery
Cataract formation – the main reason for poor vision among FUS patients
Phacoemulsification and small-incision cataract surgery – effective procedures for cataract removal with lower complication rates.

Preventing Fuchs Uveitis Syndrome

If you have Fuchs’ uveitis syndrome (FUS), it’s important to be aware of certain warning signs which may indicate a sudden increase in the pressure inside your eye, known as intraocular pressure (IOP). Severe pain and a sudden decrease in your ability to see clearly are serious symptoms, and if you experience them you should seek medical attention right away to prevent permanent loss of vision. If you’re diagnosed with FUS early on, you should understand that you have a high chance of developing a clouding of the lens in your eye, known as a cataract, which may require surgery to remove it. In some cases, you may also need immediate surgery if you develop a condition called refractory glaucoma, a form of glaucoma that is resistant to treatment.