Introduction

Sarcoidosis: definition

Sarcoidosis is a chronic inflammatory condition affecting various organs. As an inflammatory condition, sarcoidosis causes the overreaction of the immune system that leads to the clustering of inflammatory immune cells, called granulomas. Primarily, this condition affects the lungs and the lymph nodes but also affects the eyes, skin, heart, and other organs.¹

Overview of ocular sarcoidosis

Ocular sarcoidosis is caused by inflammation or the damage from granulomas. It is the second most common extrapulmonary (outside the lungs) manifestation of sarcoidosis.²

The general symptoms when sarcoidosis involves the eyes are blurring of vision, pain around the eyes, burning or dry eyes, severe redness, and sensitivity to light, which is also known as photophobia.

Different parts of the eyes are affected, including the anterior and posterior chambers, lacrimal gland, sclera, conjunctiva, and orbit. Anterior uveitis is the most common disease of ocular sarcoidosis.

It is necessary to know that all the individuals with sarcoidosis are required to undergo regular eye examinations, as ocular sarcoidosis is a subclinical condition that is mostly asymptomatic.²

Causes of ocular sarcoidosis 

The exact cause of ocular sarcoidosis is not known. However, the presence of bacterial DNA fragments in the sarcoid granulomas has attributed infection as a possible aetiology. Occupational disease and secondary airborne exposure to organic and nonorganic dust are the non-infective causes.

In addition, the HLA-DRB1*1101 allele—which encodes proteins that regulate the immune system— is the genetic factor associated with sarcoidosis.²

Epidemiology and risk factors

Sarcoidosis varies geographically, with higher rates in northern European countries, and uveitis occurring in 12% to 76% of systemic cases. It typically presents between the ages of 20 and 50 years and has a late onset after 60 years. The condition is associated with uveitis and other systemic manifestations.

Children under the age of five years are considered early-onset and usually present with skin manifestations, uveitis, and arthritis, with no lung involvement.²

Clinical presentation

The common manifestations of ocular sarcoidosis include:

• Blurry vision or loss of vision 
• Light sensitivity, also known as photophobia
• Presence of floaters, black spots or lines in field of vision
• Dry or itchy eyes
• Red eyes
• Burning sensation in the eyes
• Pain in the eyes

How does ocular sarcoidosis affect various eye parts?

Lacrimal system

Keratoconjunctivitis is a common manifestation of ocular sarcoidosis. The symptoms include irritation of the eye, corneal manifestations like infiltrates (pass through) and infections, and scar formation.

Lacrimal gland inflammation manifests as proptosis and dry eyes due to decreased aqueous production.²

Eyelid

Eyelid inflammation causes its erythema, or redness,  and can lead to small to large papules.²

Conjunctiva

White deposits are noted in the conjunctiva, which are seen in the bulbar conjunctiva, known as conjunctival nodules.²

Cornea

Superficial punctate keratitis, secondary to dry eye, is the most commonly noted corneal manifestation, along with band-shaped keratopathy and peripheral ulcerative keratitis.²

Uvea

The most common type of eye involvement is uveitis, which is the inflammation of the uvea or middle layer of the eye, including the iris, ciliary body, and choroid.

Types of uveitis include: 

Anterior uveitis

Anterior uveitis is the most common type of uveitis that is seen in ocular sarcoidosis. Primarily, it involves the anterior or the front portion of the eye, which is the iris.

Anterior uveitis is characterised by mutton-fat keratic precipitates; Busacca nodules are also noted in the iris stroma. 

Intermediate uveitis 

The inflammation in the vitreous of the eye presents as floaters, blurred vision, and vision loss. 

Posterior uveitis 

It affects the back of the eye, which includes the retina and the choroid. Choroidal neovascularization, the development of new vasculature (arrangement of blood vessels), may develop from deposited choroidal granulomas, affecting the vision.

Panuveitis

A condition where all parts of the uvea are inflamed is called panuveitis.²

Diagnostic evaluation

Diagnostic criteria 

The following criteria must be met to be diagnosed with ocular sarcoidosis:²

• There must be clinical findings present which are consistent with sarcoidosis as per the international workshop on ocular sarcoidosis (IWOS) criteria³
• Evidence of non-caseating granuloma on tissue biopsy
• Any other causes of granulomatous inflammation should be ruled out

Tissue biopsy

Tissue biopsy is the gold standard for diagnosis of sarcoidosis and, in most cases, can be done for ocular sarcoidosis involving eyelids, lacrimal glands, conjunctival nodules, and orbital tissues. However, in cases where a biopsy cannot be done, the following may be done:

Clinical exam 

During a clinical exam, various characteristic features can be noted, like mutton-fat keratic precipitates (KP) and snowballs noted on the vitreous, which are opaque patches. Nodules (localised elevated areas of inflammation) may also be observed from which a biopsy can be taken if necessary, as they can be helpful in the diagnosis.

Schirmer test

The Schirmer test is a confirmatory test that targets the lacrimal glands. A piece of paper is held at the eye to test for reduced moisture and tear production.

Imaging Techniques

• Chest X-ray and chest CT scan
• Serum Angiotensin-Converting Enzyme (ACE) Levels
• Serum calcium and Serum lysozyme Levels

Management and treatment

The aim of treatment is to bring back the lost vision and to prevent further damage and complications. The medication most commonly used is corticosteroid therapy, which is the mainstay of treatment.⁴

Corticosteroids

These are anti-inflammatory agents used in the management of uveitis, and they can be given as topical, regional, and/or systemic (affects the entire body) treatment, depending on the form of uveitis.

For the anterior uveitis, topical eye drops such as prednisolone acetate 1% or difluprednate 0.05% would suffice. However, these topical eye drops may not be able to reach in cases of posterior uveitis. Regional steroids are used in such cases, like triamcinolone acetonide. In cases of bilateral uveitis (uvea in both eyes) with systemic involvement, systemic corticosteroids are used.⁴

Cycloplegic agents 

Cycloplegic agents are primarily given for the ciliary spasms and eye pain. These include cyclopentolate 1%, homatropine 2%, and atropine 1%.⁴

Systemic immunosuppressive agents

Immunosuppressive agents are used in the cases of corticosteroid resistance and steroid-dependent cases. Some drugs in this category are methotrexate, cyclosporine, and mycophenolate mofetil.⁴

Biologics

In the cases of non-infectious uveitis or resistance, tumour necrosis factor-alpha inhibitors such as infliximab, adalimumab, and golimumab are used.⁴

Ocular complications of uveitis

Glaucoma is a common complication of uveitis, and it is caused by chronic corticosteroid use. It requires monitoring at each visit and may necessitate early medical or surgical intervention. Typically, doctors schedule cataract surgery after the disease has been inactive for three months. 

Uveitic cystoid macular oedema (swelling of the macula in the eyes’ retina), a frequent cause of vision impairment, requires treatment with anti-inflammatory agents. Other complications include central retinal artery occlusion,  epiretinal membrane, intraretinal haemorrhage, and vitreous haemorrhage.²

Prognosis 

The outcomes of ocular sarcoidosis depend on various factors like the severity and chronicity of the disease, along with the presence of complications. The main causes of irreversible vision loss are glaucoma and chronic maculopathy related to posterior segment inflammation (posterior uveitis).⁴

FAQs

What is ocular sarcoidosis?

Ocular sarcoidosis is caused either by the inflammation or the damage caused by granulomas.

What are the symptoms of ocular sarcoidosis?

Symptoms include blurry vision, eye pain, dryness, redness, light sensitivity, and floaters.

How is ocular sarcoidosis diagnosed?

Tissue biopsy is the gold standard for diagnosis of sarcoidosis.

What treatments are available for ocular sarcoidosis?

Treatments include corticosteroids, cycloplegic agents, immunosuppressive drugs, and biologic agents.

What complications can arise from ocular sarcoidosis?

Common complications include glaucoma, cataracts, and uveitic cystoid macular oedema.

How important are regular eye exams for sarcoidosis patients?

It is necessary to know that all individuals with sarcoidosis are required to undergo regular eye examinations, as ocular sarcoidosis is a subclinical condition that is mostly asymptomatic.

Who is at risk for developing ocular sarcoidosis?

Ocular sarcoidosis can affect anyone with sarcoidosis. However, it is more common in people aged 20-50 and has a higher incidence in northern European populations.

What is the role of corticosteroids in treating ocular sarcoidosis?

Corticosteroids are the mainstay treatment for reducing inflammation and managing uveitis associated with ocular sarcoidosis. They can be administered as eye drops, injections, or oral medications.

Are there any side effects of the treatments for ocular sarcoidosis?

Yes, long-term use of corticosteroids can lead to side effects such as glaucoma.

Summary

Ocular sarcoidosis, a chronic inflammatory condition affecting the eyes, often stems from granulomas. It is the second most common extrapulmonary manifestation of sarcoidosis and may present with symptoms like blurry vision, eye pain, dryness, redness, and light sensitivity. Diagnosis typically involves clinical evaluation, tissue biopsy, and imaging techniques. Treatment is primarily done by corticosteroids, cycloplegic agents, immunosuppressive drugs, and biologic agents. Common complications include glaucoma and uveitic cystoid macular oedema. Regular eye examinations are crucial for patients with sarcoidosis to prevent vision loss.