Nonspecific Orbital Inflammation

What is Nonspecific Orbital Inflammation?

Orbital pseudotumor is a condition where a harmless mass causes inflammation in the eye socket, often expanding into the surrounding areas. It has many different names including orbital inflammatory pseudotumors (OIP), idiopathic orbital inflammation (IOI), idiopathic orbital inflammatory syndrome (IOIS), idiopathic orbital inflammatory pseudotumor (IOIP), and nonspecific orbital inflammation (NSOI). Despite its serious name, it’s not caused by infection or related to any identified sickness or cancer-related condition. It ranks as the third most common eye socket disorder in adults, right after thyroid-related issues and diseases involving an abnormal growth of lymph cells, which are components of the immune system.

Different types of orbital inflammations might be linked to general health issues or problems with distant organs. These types of orbital pseudotumors can occur in different areas in and around the eye socket and are classified based on their location— front of the eye socket, throughout the socket, at the back, or at the tip of the socket. They can also be classified by their characteristics such as whether they’re targeting eye muscles (myositis), tear gland (dacryoadenitis), surrounding the white part of the eye (periscleritis), surrounding a nerve (perineuritis), or forming a localized lump (focal mass).

Orbital pseudotumor is a rare condition in children. Symptoms can include swelling around the eye and drooping of the eyelids. In some cases, a lump might be felt. Eye-related scans may reveal issues with the tear gland, show the mass in the socket, or indicate inflammation of the muscles. Up to half of the kids with this condition might also have whole-body symptoms like headaches, vomiting, loss of appetite, fatigue, and fever. Additionally, this disorder may come with eye inflammation (either iritis or uveitis), swelling of the optic nerve (disc edema), and increased levels of eosinophils— a type of white blood cell— in the blood.

Despite being identified over hundred years ago, the exact cause of orbital pseudotumor remains unknown, making diagnosis and treatment quite challenging. However, advancements in medical imaging, tissue examination techniques (histology), and study of the immune system (immunology) have allowed us to understand some key factors. It is believed that eye inflammation is caused by a combination of imbalances in the immune system, viral agents, and inherent genetic factors.

Knowing how to identify different types of symptoms and conditions, and understanding the diagnostic criteria for orbital pseudotumor, is very important for the correct identification and treatment of this disease. Patients often show symptoms like one-sided bulging of their eye, discomfort, double vision, and vision abnormalities. These symptoms can come on suddenly or gradually. The tricky part is that these symptoms can also be caused by other eye socket diseases like cancer, infections, or thyroid eye disease. Therefore, doctors use tools like CT scans and MRI scans, and in some cases, removing a small piece of tissue for examination (biopsy), to specifically diagnose orbital pseudotumor.

What Causes Nonspecific Orbital Inflammation?

Orbital pseudotumor is a term that refers to different inflammatory conditions that affect the eye socket. Despite lots of research, we still don’t know exactly what causes it. It’s likely due to a combination of factors like genetics, environmental triggers, and issues with the immune system.

For a long time, experts have suspected that various microbes, such as viruses, bacteria, and other unusual organisms, might start the process of orbital pseudotumor. However, no single microbe has been definitively identified. More recent research has shown a possible link between the condition and certain viral infections, including types of herpes, SARS-CoV-2 (the virus that causes COVID-19), and Epstein-Barr virus.

In people who are at risk, HIV can cause a condition called orbital myositis, which leads to inflammation in the eye socket. Other infections, like those of the upper respiratory tract, sinuses, and tear gland, have also been linked to orbital pseudotumor. The presence of Streptococcal throat infection or a viral upper respiratory infection might correlate with the onset of orbital pseudotumor. One theory suggests that this could be due to the body confusing its own proteins with those of the invading organism, leading to inflammation.

Orbital pseudotumor is also associated with various conditions that affect the whole body, such as granulomatosis with polyangiitis (previously known as Wegener granulomatosis), thyroid eye disease, giant cell arteritis, systemic lupus erythematosus (SLE), discoid lupus, Behcet’s disease, sarcoidosis, Churg-Stauss syndrome, rheumatoid arthritis, polyarteritis nodosa, multifocal fibrosclerosis (now considered part of IgG4-related disease), Crohn’s disease, psoriasis, and ulcerative colitis. These diseases can present varied symptoms, making diagnosis complex.

Several theories have been put forward to explain the inflammation related to orbital pseudotumor, including issues with the immune system. The inflammation in the eye socket has been linked to problems in how both the innate and adaptive immune responses are regulated. Many types of immune cells, such as T and B lymphocytes, macrophages, eosinophil granulocytes, neutrophils, and dendritic cells, are thought to contribute to this inflammation. Inflammation-promoting compounds such as interleukins, interferon, and tumor necrosis factor have been found to be abundant in samples from people with the condition, along with extra expression of CD20 and CD25.

Environmental factors, such as obesity, may also contribute to orbital pseudotumor, but we don’t yet know how. Studies have shown that people with a high body mass index (a measure of obesity) are more likely to experience orbital inflammation. One theory is that the chronic, low-level inflammation seen in obesity, due to an excess of immune cells in fat tissue, might disturb the immune balance and lead to inflammation in the eye socket.

Some medications like lithium, bisphosphonates, and chemotherapy treatments might affect inflammatory responses and lead to increased cytokine production and activation of T-cells. This could potentially trigger orbital inflammation.

Risk Factors and Frequency for Nonspecific Orbital Inflammation

Orbital pseudotumor is a type of eye disorder that is more common in adults, particularly middle-aged women, however, it can occur in people of every ethnicity worldwide. Usually, this condition affects the lacrimal gland, which is part of the eye. It typically shows up between the ages of 30 and 60, and it’s rare to have it in both eyes at the same time, especially in adults. However, it’s more common for children to have it in both eyes. In children, the condition often comes back, with recurrence rates as high as 76%. For a specific type of orbital pseudotumor known as NSOI, recurrence rates range from 33% to 58%, after the condition has initially cleared up.

• Orbital pseudotumor makes up about 8% to 11% of all orbital disorders.
• 6% to 16% of patients who are suspected of having orbital tumors are found to have orbital pseudotumors.
• In a study at an eye hospital in India, out of over 6000 patients with orbital diseases over 10 years, 23% had orbital pseudotumor.
• A study in Tokyo found that 27% of 1000 patients with primary orbital tumors had benign orbital tumors.

Signs and Symptoms of Nonspecific Orbital Inflammation

Orbital pseudotumor, an eye condition with diverse and sometimes ambiguous symptoms, can be challenging to diagnose. A doctor needs to conduct a detailed patient history, physical examination, and identify common signs and symptoms. The symptoms vary greatly, depending on which parts of the eye are affected and how severe the inflammation is.

This ailment is diagnosed by ruling out other eye diseases with similar symptoms. These can include systemic diseases, such as sarcoidosis, granulomatosis with polyangiitis, Sjogren syndrome, IgG4-related disease, lymphoproliferative and histiocytic disorder, xanthogranulomatous disease, or metastatic disease. If a patient doesn’t have a history of these conditions, additional lab tests may be needed.

When getting the patient’s history, a doctor needs to understand the onset, duration, progression, and related systemic symptoms of orbital pseudotumor. The doctor will also ask when symptoms occur and how long they last. Symptoms usually start subtly and develop over a few days to weeks but sometimes can be more gradual or sudden.

Patients should be asked about discomfort, redness, swelling, or pain around the eyes. Other symptoms to look for include diminished eyesight, double vision or blurring. Sometimes, patients may exhibit fever, fatigue, weight loss, or joint pain along with eye symptoms. In addition, patients should also be questioned about any recent viral infections, autoimmune diseases, eye injuries, surgeries, or radiation therapies.

The clinical features of orbital pseudotumor, which may target the tear gland and extraocular muscles, can greatly vary, appearing acute, subacute, insidious, chronic, and relapsing. Redness and swelling are common symptoms. Acute proptosis, a forward displacement of the eye due to intraorbital tissue swelling, often prompts an emergency visit. Gradual proptosis, swollen eyelids and restricted eye movement may lead to double vision.

Patients may report a dull, intense pain around the eyes, which is worsened by eye movement or palpation of the orbit. Involvement of the extraocular muscle can cause double vision, impairing binocular vision and eye alignment. Decreased visual acuity can range from slight blurring to severe vision loss, depending on whether the optic nerve is involved or compressed.

Some patients can show systemic symptoms, such as joint pain, fever, fatigue, or weight loss, especially when autoimmune disorders or systemic inflammation are present. Some adult patients may report orbital pain and headache. For adults, symptoms may include eyelid and periorbital redness and swelling, conjunctival congestion, and discomfort with eye movement.

In children, periorbital swelling, ptosis, pain, and decreased extraocular muscle movements are more common. Symptoms are usually one-sided in adults but can involve both eyes in children. Dacryoadenitis, the inflammation of the tear gland, accounts for 50% of all orbital pseudotumor cases.

Orbital pseudotumor is associated with several systemic disorders. Examples include rheumatoid arthritis, Crohn’s disease, lupus, and scleritis. Other concurrent conditions such as the flu, asthma, colitis, and severe anemia have also been associated with this eye condition.

A thorough physical examination is necessary for proper identification of orbital pseudotumor. The following steps should be included in the examination:

• Check each eye separately for visual acuity and look for any abnormalities in the visual fields
• Check for swelling, redness, or swelling around the eye
• Examine the posture of the eyelids and assess for sinking or bulging of the eye
• Assess the function and movement of the extraocular muscles
• Look for signs of inflammation in the conjunctiva, cornea, anterior eye chamber, and iris
• Perform a dilated examination of the back of the eye to check the optic nerve head, retina, and macula.

Testing for Nonspecific Orbital Inflammation

If your doctor suspects you might have an orbital pseudotumor, a type of inflammation in the eye area, several tests might be carried out. These can aid in confirming the diagnosis, assessing the condition, and ruling out other potential causes. The tests could include blood tests, checks for inflammation, and screenings for autoimmune diseases. Blood tests can also identify any abnormalities like high sedimentation rates, which is a sign of inflammation, and changes in thyroid function.

Other tests and measurements such as antinuclear antibodies, antineutrophil cytoplasmic antibodies and the angiotensin-converting enzyme level can help detect specific conditions. Although normal results won’t necessarily confirm the disease, these tests can help rule out other issues.

In addition to these, you might also undergo imaging procedures like an ultrasound, computed tomography (CT) scan, or a magnetic resonance imaging (MRI) scan. These techniques can provide detailed pictures of the structures within and around your eye, and help to identify the extent of any inflammation.

An MRI scan is very good at showing changes in the soft tissues around the eye and detecting any related inflammation. CT scans are helpful in examining bone structure and distinguishing between inflammatory and growth-related changes. The ultrasound can be used to assess the condition of the eye, such as the occurrence of retinal or choroidal detachments which are layers in the back of the eye.

Recently, advancements in technology such as artificial intelligence and deep learning have been employed to improve the diagnosis of orbital pseudotumors. These techniques can use clinical data along with imaging data to provide a more accurate diagnosis. Other emerging biomarkers, like microRNA, a type of molecule, have shown potential in diagnosing and evaluating treatment responses.

Treatment Options for Nonspecific Orbital Inflammation

Idiopathic orbital inflammation, also known as ocular pseudotumor, can be treated with different types of medicines. Some people with this condition get better without any treatment, but certain medications can potentially resolve the symptoms more quickly.

One commonly used treatment for ocular pseudotumor is a group of medicines known as corticosteroids, which help to reduce inflammation. Among these, prednisone and methylprednisolone are primarily used. They work fast and are readily available and affordable, making them an attractive first-line treatment. However, long-term use of corticosteroids can lead to side effects like immune suppression (weakening of the immune system), diabetes, high blood pressure, and osteoporosis (weak and brittle bones). That’s why doctors carefully monitor patients on corticosteroids and may consider alternative medications if needed.

If the inflammation doesn’t improve with corticosteroids, or if the patient experiences a relapse, other treatments may be used. These include:

• Immunomodulatory drugs like methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine – these reduce inflammation by modulating (changing) the immune response
• Biologic agents like infliximab and adalimumab – these target specific inflammatory molecules to reduce inflammation
• Radiation therapy – a type of therapy that uses radiation to control inflammation
• Surgery – used for patients who do not respond to medication therapy or whose vision is seriously threatened by the inflammation

Choosing the right treatment for ocular pseudotumor can depend on a variety of factors, including the patient’s overall health, the specifics of their condition, and how well they tolerate certain medications. Therefore, it’s important for patients to have ongoing discussions with their healthcare provider to find the treatment strategy that works best for them.

What else can Nonspecific Orbital Inflammation be?

Diagnosing orbital pseudotumor, a condition affecting the eye, is not straightforward because its symptoms can be similar to those of both benign and malignant diseases. Doctors use a careful and orderly method to distinguish orbital pseudotumor from other conditions, using factors such as clinical features, imaging results, laboratory tests, and tissue studies.

Some diseases that have symptoms in common with orbital pseudotumor and need to be considered are:

• Infections: Similar symptoms can be caused by a bacterial infection of the eye socket, called orbital cellulitis. However, general symptoms like fever and feeling unwell, sudden onset, and signs of infection on lab tests and imaging are typically associated with orbital cellulitis.
• Systemic diseases: Thyroid eye disease, also known as Graves’ orbitopathy, can present similar symptoms. However, certain antibodies associated with thyroid disease and distinct results from orbital imaging may distinguish thyroid eye disease.
• Malignancies: Conditions such as lymphoma, metastatic carcinoma, and leukemia can show similar clinical and radiological signs. However, early signs of lymphoma can include noticeable orbital masses and progressive, painless swelling of the eyes, whilst imaging findings may reveal distinct features associated with these malignancies.
• Autoimmune disorders: Conditions such as SLE and rheumatoid arthritis can mimic symptoms of orbital pseudotumor but often come with systemic manifestations and specific antibodies, distinguishing them from the condition.
• IgG4-related orbital disease: This disease causes inflammatory disorders affecting the tear gland, leading to swelling. Elevated levels of IgG4 in the blood and specific results from tissue studies can help in its diagnosis.
• Sarcoidosis: A type of sarcoidosis that affects the eye socket can mimic orbital pseudotumor. Patients showing typical imaging features of sarcoidosis, such as tear gland enlargement and bilateral orbital involvement, along with systemic symptoms, may be considered for this diagnosis.

There are also a number of other, more severe conditions that share symptoms with orbital pseudotumor. Some are orbital cellulitis, thyroid eye disease, sarcoidosis, orbital lymphoma, lymphangioma, metastatic carcinoma, leukemia, lymphoproliferative disorder, and rhabdomyosarcoma.

A specific type of orbital pseudotumor, known as bilateral sclerosing orbital pseudotumor, can lead to significant health problems with severe, progressive symptoms. Research suggests this may be a subtype of an IgG4-related disease.

In children, the list of possible diagnoses also includes conditions such as orbital cellulitis, orbital trauma, ruptured dermoid cyst, lymphangioma, neuroblastoma, Langerhans cell histiocytosis, and child-specific cancers such as rhabdomyosarcoma, leukemia, neuroblastoma and metastatic retinoblastoma, as well as inflammatory conditions like IOI and thyroid eye disease.

Laboratory tests, CT scans, MRI, OCT, and biopsies might all be needed to differentiate between conditions that mimic orbital pseudotumor, leading to a precise diagnosis and guiding the treatment strategy.

What to expect with Nonspecific Orbital Inflammation

Orbital pseudotumor is a condition that in some cases may get better on its own without treatment. However, steroids are often used as the primary treatment. Over 75% of patients begin to see improvement within 24 to 48 hours after starting steroid treatment. However, completely curing the disease happens in 37% of cases, and about 52% of patients may experience the condition again, even after steroid treatment.

There are several factors that can make the condition recur more frequently. These factors include patients under 16 years old, having the disease in both eyes, signs of swollen optic disc (which is the end of the nerve that enters the back of the eye), the sclerosing variant (a type of the disease that causes hardening or scarring), responding poorly to steroids, and the disease coming back within 3 months. Additional factors leading to a higher chance of recurrence include not fully getting rid of the inflammation, becoming dependent on corticosteroids, not slowly decreasing the amount of immunosuppressant medication over time, and having underlying autoimmune diseases. Repeated episodes of orbital pseudotumor can worsen vision and function by causing increasing scarring and damage to components of the eye socket.

The outlook for someone with orbital pseudotumor varies widely. It depends on the unique features in each patient, the severity of the disease, and how the patient responds to treatment. With the right care, many patients have good outcomes. But, some may experience complications like double vision, the cornea (the clear layer at the front of the eye) becoming exposed, compression of the optic nerve, and the disease coming back. The importance of close monitoring and care from various healthcare professionals is highlighted in these cases, as this approach can help achieve the best long-term vision and function outcomes possible.

Possible Complications When Diagnosed with Nonspecific Orbital Inflammation

If an orbital pseudotumor isn’t treated or doesn’t respond to treatment, it can cause permanent vision loss and severe eye movement problems. The inflammation can spread to nearby areas such as the area around the eye, the optic nerve, and inside the skull. If swelling or clumps of inflammation press on the optic nerve, this can cause optic nerve disease and permanent vision loss.

Multiple nerves in the skull may be affected, and one-sided weakness or paralysis can occur. Double vision, squinting, and poor eye movement can be caused by problems with the muscles that move the eye or the nerves that control them, which can have a big negative impact on quality of life and vision function.

Severe inflammation may cause a kind of glaucoma because of build up of fluid that cause the front part of the eye to rotate. Advanced bulging eyes can lead to corneal problems and ulcer formation. If patients have bulging eyes and eyelid retraction because of an orbital pseudotumor, they could be at risk for the cornea being exposed, corneal ulcers, and breakdown of the cornea, which could lead to infection and vision problems.

Long-term treatment with systemic corticosteroids can lead to systemic side effects in the treatment of orbital pseudotumor. This includes weakened bones, diabetes, high blood pressure, weight gain, and an increased risk of infections. Regular monitoring of these side effects is important to lessen their effects and adjust treatment if needed.

Potential Complications:

• Permanent vision loss
• Serious eye movement problems
• Optic nerve disease
• One-sided weakness or paralysis
• Double vision
• Squinting
• Poor eye movement
• Glaucoma caused by severe inflammation
• Bulging eyes leading to corneal problems
• Ulcer formation
• Increased risk of infections
• Systemic side effects of long-term corticosteroid therapy

Preventing Nonspecific Orbital Inflammation

If you’re experiencing symptoms like vision loss or eye pain, it’s crucial to see a trained healthcare professional. For those diagnosed with a condition known as orbital pseudotumor, it’s important to continue the prescribed treatment plan.

Understanding your health condition is key to successful treatment of the orbital pseudotumor. By having all the details about it, you can actively participate in decisions about your healthcare, stick to your treatment plan, identify if your condition is getting worse, and know when you need to seek medical help promptly. Having knowledge about orbital pseudotumor; what it does, the treatment options available, and what to expect in the future, allows you to make informed decisions and generally leads to better treatment results.