What is Ocular Sarcoidosis?

Sarcoidosis is a long-term illness that affects multiple body systems. This illness is signaled by the accumulation of particular types of inflammation clusters, known as non-caseating granulomas, in various tissues in the body. There’s a specific type of this disease, known as ocular sarcoidosis, that causes inflammation in different parts of the eye. This can lead to issues like inflammations on the white part of the eye, inside the eye, damage to the optic nerve, and inflammation in the tissues surrounding the eye, resulting in swollen tear glands and inflammation in the eye area.

The course of this condition can vary from person to person. Some patients may experience a sudden onset of the disease that resolves on its own, while others may have a long-lasting, gradually worsening condition. The primary treatment for this condition has typically been medications called corticosteroids, which reduce inflammation. More recently, doctors have begun to include other treatments such as immunosuppressants, which weaken the body’s immune response, and biologics, which are drugs made from living cells, among the treatment options.

What Causes Ocular Sarcoidosis?

The exact cause of sarcoidosis, a disease that results in clumps of cells or nodules, is still not completely understood. It’s thought to happen because of infectious, non-infectious, and genetic reasons.

Some believe that sarcoidosis can be caused by an infection. Evidence for this includes finding pieces of bacterial DNA in the nodules caused by sarcoidosis and observing similar responses in animals that have been exposed to the disease. Some patients have also developed sarcoidosis after receiving organ transplants, indicating that perhaps there’s a transmittable agent involved. There’s even a theory that sarcoidosis and tuberculosis may be different manifestations of the same disease, due to their similar symptoms, geographic spread, immune responses, and molecular connections. Some studies have pointed to certain types of bacteria, Mycobacterium or Propionibacterium, as possible culprits.

Sarcoidosis can also happen because of non-infectious causes. In cases where sarcoidosis affects the lungs, it’s sometimes considered as an occupational disease, which means it’s associated with certain jobs that expose workers to airborne organic and nonorganic dust.

Genetically, there has been noticed a link between sarcoidosis and certain genes present in our immune system known as human leukocyte antigen (HLA) types. For instance, people with the HLA-DRB1*1101 allele, a specific string of DNA, have a higher risk of developing sarcoidosis. Sarcoidosis appears to be more common in some families, including siblings and parent-offspring pairs. This suggests that genetic factors, along with environmental factors, play a significant role in developing the disease. For example, siblings have five times the normal risk of developing sarcoidosis.

Risk Factors and Frequency for Ocular Sarcoidosis

Sarcoidosis is a condition that can affect different parts of your body and its prevalence can greatly vary across different regions. This is due to multiple factors such as how the disease is defined, its symptomless nature, limited screening, and bias in diagnoses. In the United States, the incidence rate for sarcoidosis is three times higher in Black individuals than in White individuals.

In recent research, it was discovered that while the general occurrence rate is about 8.1 per 100,000 for White Americans, it goes up to 17.8 in African Americans. With a rate of 40 in 100,000, Northern European countries have the highest prevalence for sarcoidosis. Sarcoidosis may also cause eye-related issues in patients, with the most common being uveitis. Women are more likely to experience ocular symptoms than men, with prevalence rates being 56% and 23% respectively.

The usual age for sarcoidosis to present itself is between 20 to 50 years.
However, it also serves as a major cause for uveitis in individuals over the age of 60.
In fact, about 10% of all uveitis cases are attributed to sarcoidosis.
Those diagnosed with sarcoidosis after the age of 65 are more likely to display symptoms of uveitis, asthenia, and skin lesions.
Children under the age of five usually present with skin rashes, uveitis, and arthritis but rarely have lung diseases.
Older children may experience multi-system involvement similar to adults, including enlarged lymph nodes in the lungs and lung involvement.

Signs and Symptoms of Ocular Sarcoidosis

Sarcoidosis is a disease that can affect many parts of the body, but most commonly impacts the lungs and chest lymph nodes. This often leads to symptoms like cough, shortness of breath, and chest pain. Other parts of the body can also be affected, leading to a variety of symptoms such as:

Upper respiratory tract issues, causing symptoms like a runny nose, frequent sinus infections, and damage to the nasal septum and turbinates
Skin symptoms, like bumps, nodules, patches, ulcers, and a red rash on the shins (erythema nodosum)
Heart complications leading to irregular heartbeats and heart blockages
Brain and nerve complications (neurosarcoidosis) which occur in about 5 to 10% of sarcoidosis patients, primarily affecting the leptomeninges and cranial nerves
Eye inflammation (ocular sarcoidosis) in about 30 to 40% of cases, commonly causing inflammation inside the eye (uveitis in 30 to 70% of cases) and conjunctival nodules (in 40% of cases)

This disease can also cause various diseases affecting the eyes and their surrounding tissues. For instance, it can lead to conditions like:

Orbital disease, where orbital structures like orbital fat, extraocular muscles, and the optic nerve sheath get affected, causing symptoms like bulging eyes, globe displacement, eye pain, vision loss, and double vision
Lacrimal system disease, such as dry eye syndrome (keratoconjunctivitis sicca), which causes symptoms like eye irritation, excessive tearing, corneal infiltration and scar, and inflammation of the tear sac and lacrimal drainage system
Eyelid and ocular surface disease, where an inflammatory response can cause eyelid swelling, drooping eyelid, inward turned eyelid, abnormal lash growth, and loss of eyelashes. Inflammation can also lead to conjunctival nodules, scleritis (inflammation of the white part of the eye), and various corneal diseases
Uveitis causing symptoms like eye pain, red eyes, blurry vision, and sensitivity to light

Sarcoidosis can also result in other systemic syndromes such as Löfgren syndrome, which includes a combination of joint inflammation, erythema nodosum, and hilar lymphadenopathy, and Heerfordt-Waldenström syndrome which presents as swelling of the salivary glands, fever, uveitis, and facial nerve paralysis.

Testing for Ocular Sarcoidosis

If your doctor suspects that you have ocular sarcoidosis, which is an inflammatory disease that can affect your eyes, there are certain criteria they need to meet to confirm this diagnosis. These criteria include:

You’re showing signs and symptoms which match up with ocular sarcoidosis, according to internationally agreed-upon guidelines.
A tissue biopsy from your body shows non-caseating granuloma, which is a specific type of inflammation, and is often seen in individuals with sarcoidosis.
Other potential causes of similar inflammation, such as tuberculosis or syphilis, have been ruled out.

The most trusted way to diagnose sarcoidosis is through a tissue biopsy, in which a small part of your body tissue is taken for further testing. In ocular sarcoidosis, a biopsy can be done on different parts of your eye and surrounding tissues. However, in some instances where biopsy isn’t possible, other tests like a chest x-ray, chest CT scan, blood tests for certain markers such as ACE, calcium, and lysozyme levels can help to arrive at a probable diagnosis.

Further, several eye imaging techniques can help to improve the diagnosis and monitor your condition. They include:

Fundus photography, which helps to document and compare the changes in the back of your eye over time.
Fundus fluorescein angiography, which helps to document inflammation of the blood vessels in your retina (vasculitis) and the growth of new blood vessels.
Fundus autofluorescence imaging, which helps to detect changes in the layer beneath your retina and monitor your treatment response.
Optical coherence tomography, which helps to assess fluid buildup (edema) in the macula, a part of your retina, as well as changes in your eye layers.
Ultrasound and ultrasound biomicroscopy that allow detailed evaluation of various structures in your eyes.
Visual field testing that checks for vision loss at the sides or peripheral vision.

In more complex cases, a procedure called diagnostic vitrectomy may be used, where a sample of vitreous gel from your eye is taken for further analyses.

If ocular sarcoidosis is suspected, your doctor may also order several investigations to check if other parts of your body are affected. These include a chest X-ray or a specialized CT scan of your chest called HRCT, which can identify any changes in your lungs and lymph nodes that are commonly seen in sarcoidosis. Other tests like Pulmonary Function Tests, blood tests for ACE, bronchoalveolar lavage (a method to look at cells in the lungs), radionuclide scans, lung biopsy may also be done. In certain cases, an MRI scan of the brain may be required to identify any changes due to sarcoidosis.

These tests together will help to form a clearer picture of your condition, allowing your doctor to diagnose accurately and start the best treatment plan for you.

Treatment Options for Ocular Sarcoidosis

Corticosteroids are a type of powerful medication used to reduce inflammation often found useful in treating uveitis, an inflammation of the uvea in the eye. They can be applied directly to the eye as drops for a type of uveitis that affects the front of the eye (anterior uveitis). However, this method isn’t always effective enough to treat uveitis that occurs at the back of the eye (posterior uveitis).

In cases of posterior uveitis or when eye drops prove ineffective or impractical, corticosteroids can be applied directly to the affected area behind the eye through a technique similar to an injection. Some corticosteroids come as an implant that releases the medicine slowly over time, providing a long-lasting anti-inflammatory effect. However, it should be known that this method can lead to glaucoma or cataracts, hence requiring careful monitoring and timely treatment.

Systemic corticosteroids, which are administered orally or injected, are preferred if uveitis is affecting both eyes or if local treatment isn’t effective. These corticosteroids are typically given in a high dose, which is then gradually reduced.

Along with corticosteroids, cycloplegic agents, medications that relax the eye muscles and reduce pain, can also be administered.

In some cases, the inflammation from uveitis may not respond to, or may depend heavily on, corticosteroids. If the side effects of the corticosteroids start to outweigh their benefits, doctors may resort to systemic immunosuppressive agents. These medications work by suppressing the immune system, which can in turn reduce the inflammation.

Biologic agents are another type of medication that can help people with refractory non-infectious uveitis, a type of uveitis that doesn’t improve with standard treatments. These medications work by directly targeting the part of the immune system that causes inflammation. Doctors would typically test for conditions like latent tuberculosis and hepatitis B before initiating this treatment as they could potentially reactivcate these infections.

Treating inflammation in the orbit (the cavity that contains the eyeball) may require systemic steroids or immunosuppressive agents. In cases of chronic swelling in the eyelid or lacrimal gland (which produces tears), a biopsy may be needed to rule out tumors.

For inflammation on the surface of the eye, the initial treatment is typically with non-steroidal anti-inflammatory drugs (NSAIDs), with steroids and immunosuppressants reserved for resistant cases.

Several complications can arise from uveitis like glaucoma, the eye disease that can damage the optic nerve, and cataracts, the clouding of the eye’s lens. Therefore, regular monitoring is important, as early intervention for these complications can prevent further damage. The complication causing fluid build-up in the retina (the light-sensitive layer at the back of the eye), known as cystoid macular edema, requires the use of anti-inflammatory agents. In some cases, an injectable drug or surgery may be required.

Sarcoidosis is a condition that can affect various parts of the eye in different ways, with a range of symptoms. When doctors see these symptoms, they need to consider a number of other conditions that could potentially cause them. These conditions include:

Iris nodules: these might also be found with illnesses such as tuberculosis, leprosy, and syphilis, as well as tumors in the iris, and cases of retinoblastoma, which is a cancer that forms in the light-detecting cells in the back of the eye.
Intermediate uveitis: this might also be found with no known cause, or related to Lyme disease, TB, and multiple sclerosis, a condition that affects the central nervous system.
Chorioretinitis: this might also be associated with tuberculosis, histoplasmosis (an infection caused by a fungus found in bird and bat droppings), toxoplasmosis (an infection due to a parasite), and syphilis.
Choroidal infiltrates: this might also be seen in ‘white dot syndromes’ such as acute posterior multifocal placoid pigment epitheliopathy, birdshot choroidopathy, Vogt-Koyanagi-Harada disease, as well as amelanotic melanoma (a type of eye cancer) and metastatic infiltrates (cancer that spreads to the eye from another part of the body).
Dacryoadenopathy: this could also be evidence of tuberculosis, brucellosis (an infection caused by a type of bacteria), Hodgkin’s lymphoma (a type of cancer), and tumors in the parotid gland (the gland that produces saliva).
Peripheral retinal neovascularization: this might also occur in diabetic retinopathy (a diabetes complication that affects eyes), vein occlusions (blockages of the blood vessels that carry blood away from the retina), sickle cell retinopathy (complications due to sickle cell disease), and Eales disease (a rare eye disease that can cause loss of vision).

So in diagnosing sarcoidosis, doctors have to examine these many possibilities carefully.

What to expect with Ocular Sarcoidosis

The outcome of a disease called ocular sarcoidosis, a condition that causes inflammation in the eyes, is influenced by various factors. These include how severe the disease is, how long the person has had the disease, when they first sought medical help, and any complications caused by long-term eye inflammation. Overall, the outlook for people with ocular sarcoidosis is usually positive—most people recover without any significant damage to how their eyes function.

Permanent vision loss is typically caused by conditions like glaucoma (a disease that damages the optic nerve) and chronic maculopathy (a condition that affects the central part of the retina). There’s a study suggesting that the presence of a genetic factor known as the HLA DQB1*0201 allele can protect against severe forms of sarcoidosis.

Certain factors can lead to poor vision outcomes in people with ocular sarcoidosis, including being of African descent, not seeking specialist care promptly, having glaucoma or inflammation in the middle or back of the eye, swelling in the macula (the part of the retina responsible for sharp, central vision), and using systemic steroids (medications used to reduce inflammation). It’s worth noting that the overall death rate from sarcoidosis can be as high as 5% or even 10% in cases with nervous system involvement (known as neurosarcoidosis).

Poor prognosis in sarcoidosis can also be influenced by being female (compared to male), developing the disease early in life, being African-American, having chronic sarcoidosis, carrying specific genetic factors (Annexin A11 gene, HLA-DQB1*1501, HLA-DQB1*0602), suffering from pulmonary fibrosis (a lung disease that occurs when lung tissue becomes damaged and scarred), poor lung function test results, involvement of the optic nerve, inflammation throughout the entire eye (panuveitis), skin conditions like lupus pernio, chronic arthritis, and being at stages 3 or 4 of the disease as shown in imagery tests.

Possible Complications When Diagnosed with Ocular Sarcoidosis

Possible eye issues can include:

Glaucoma
Cataract
Blockage of the main blood supply in the eye
Fluid-filled area in the main part of the eye
Scar tissue forming on the retina
Bleeding inside the retina
Bleeding inside the jelly-like substance that fills your eye
Shrinkage or atrophy of the eye

Possible general health issues can include:

Neurological complications from sarcoidosis, a disease that affects various body organs
High blood pressure in the arteries to your lungs
Severe damage to the lungs

Preventing Ocular Sarcoidosis

Ocular sarcoidosis, a condition affecting the eye, can sometimes begin suddenly and last for only a limited period of time. However, in some cases, patients may experience a long-lasting version of this disease. Patients with this chronic form of ocular sarcoidosis should be aware of the possible complications due to long term inflammation, including glaucoma (a condition causing damage to the optic nerve), cataracts (clouding in the lens of the eye), cystoid macular edema (swelling in the eye), and the formation of epiretinal membranes (scar tissue in the eye).

Patients should also understand the significance of following the prescribed treatment plan and be aware of any possible side effects of the medication. Furthermore, patients with a form of ocular sarcoidosis known as sarcoid uveitis should know they’re at risk of experiencing neurological issues, which can affect the nervous system and brain, for at least the next 15 years.