How to Treat and Manage Uveitis: Corticosteroids, Biologics, and More

Everything You Need to Know About Uveitis

Uveitis refers to a group of inflammatory conditions affecting the uvea, the middle layer of the eye. It is a sight-threatening disorder that accounts for about 10% of blindness worldwide and is commonly encountered in ophthalmology practices. The condition can affect individuals of all ages, but it predominantly affects people between 20 and 60 years old. Uveitis can be caused by infections, autoimmune diseases, or trauma, but in many cases, the cause remains idiopathic.

This article aims to provide a comprehensive overview of uveitis, covering its types, causes, clinical presentation, diagnostic methods, treatment options, and complications. The target audience includes medical students and doctors, particularly those in ophthalmology and rheumatology.

Anatomy of the Uvea: Understanding the Affected Area

To fully grasp the pathophysiology of uveitis, it is important to understand the anatomy of the uvea, which consists of three major parts:

• Iris: The colored part of the eye that regulates the amount of light entering the eye by controlling the size of the pupil.
• Ciliary Body: Produces the aqueous humor (the fluid in the eye) and controls lens accommodation for focusing.
• Choroid: A layer of blood vessels that nourishes the retina, the light-sensitive layer at the back of the eye.

The uvea plays a crucial role in maintaining the eye’s blood supply and regulating intraocular pressure. Inflammation in any part of the uvea can disrupt these functions and lead to various ocular complications, including vision loss.

What is Uveitis?

Uveitis is an umbrella term that refers to inflammation of the uvea. However, it can also extend to other parts of the eye, including the retina, vitreous, and optic nerve. Uveitis can be acute or chronic, unilateral or bilateral, and its severity can range from mild to severe. Based on the location of the inflammation, uveitis is classified into several types:

1. Anterior Uveitis

Anterior uveitis, also known as iritis, is the most common form and involves inflammation of the iris and anterior chamber. It accounts for approximately 60-90% of all uveitis cases and often presents acutely.

• Symptoms: Eye pain, photophobia, redness, and blurred vision.
• Causes: Autoimmune disorders such as ankylosing spondylitis, sarcoidosis, and juvenile idiopathic arthritis (JIA) are common triggers. Infections, trauma, and idiopathic causes are also possible.

2. Intermediate Uveitis

Intermediate uveitis affects the vitreous and peripheral retina. It is sometimes referred to as pars planitis when there is no identifiable systemic cause. This form is less common and often affects younger individuals.

• Symptoms: Floaters, blurred vision, and sometimes mild eye discomfort.
• Causes: Idiopathic in most cases, but can be associated with multiple sclerosis, sarcoidosis, or infections like Lyme disease.

3. Posterior Uveitis

Posterior uveitis involves inflammation of the choroid and retina. It is less common than anterior uveitis but more serious, as it directly affects the retina and can lead to permanent vision loss.

• Symptoms: Blurred vision, floaters, and visual field defects.
• Causes: Autoimmune diseases, infections (toxoplasmosis, cytomegalovirus, tuberculosis), and neoplasms.

4. Panuveitis

Panuveitis is the most severe form of uveitis and involves inflammation of all parts of the uvea (anterior, intermediate, and posterior). It has a more diffuse presentation and can be sight-threatening if not treated aggressively.

• Symptoms: Severe eye pain, vision loss, photophobia, redness, and floaters.
• Causes: Can be caused by systemic autoimmune diseases, infections, or idiopathic factors. Behçet’s disease and sarcoidosis are common autoimmune causes.

Causes of Uveitis

The causes of uveitis can be classified into several categories: infectious, non-infectious (autoimmune), traumatic, and idiopathic. Identifying the underlying cause is crucial for effective treatment and long-term management.

1. Infectious Causes

Various bacterial, viral, fungal, and parasitic infections can trigger uveitis. Infectious causes are more commonly associated with posterior uveitis. Some of the more common infectious agents include:

• Toxoplasmosis: The most common cause of posterior uveitis, often associated with congenital or acquired toxoplasmosis infection.
• Herpes Simplex Virus (HSV) and Herpes Zoster Virus (HZV): These viruses can cause recurrent anterior or posterior uveitis.
• Tuberculosis (TB): Can cause chronic granulomatous uveitis, often affecting both the anterior and posterior segments.
• Syphilis: Known as the “great imitator,” syphilis can cause any form of uveitis and requires systemic treatment with antibiotics.
• Cytomegalovirus (CMV): Particularly in immunocompromised individuals, CMV can lead to severe posterior uveitis or retinitis.

2. Autoimmune and Inflammatory Causes

Non-infectious causes are usually autoimmune or inflammatory in nature and are often associated with systemic diseases. Common autoimmune diseases that cause uveitis include:

• Ankylosing Spondylitis: A form of arthritis primarily affecting the spine, commonly associated with acute anterior uveitis.
• Sarcoidosis: A multi-system granulomatous disorder that can cause chronic anterior or posterior uveitis.
• Behçet’s Disease: A systemic inflammatory disease characterized by recurrent oral ulcers, genital ulcers, and panuveitis. It is known for causing sight-threatening retinal vasculitis.
• Juvenile Idiopathic Arthritis (JIA): Commonly associated with chronic anterior uveitis in children, often asymptomatic in the early stages but can lead to complications like cataracts and glaucoma if untreated.

3. Trauma-Related Uveitis

Ocular trauma, including surgical trauma (postoperative uveitis), can trigger inflammation in the uvea. Postoperative uveitis is typically seen after procedures such as cataract surgery and intraocular lens implantation.

4. Idiopathic Uveitis

In many cases, despite extensive investigation, the underlying cause of uveitis remains unknown, and these cases are classified as idiopathic. Idiopathic uveitis is typically treated symptomatically and monitored for any signs of systemic disease that may develop later.

Clinical Presentation of Uveitis

The symptoms of uveitis vary depending on the type and severity of inflammation, as well as the part of the eye affected. Early recognition of the signs and symptoms is critical for prompt diagnosis and treatment to prevent complications.

Common Symptoms of Uveitis:

• Eye Pain: Especially in anterior uveitis, patients often report a deep, aching pain.
• Redness: Redness of the eye is a hallmark symptom, particularly in anterior uveitis.
• Photophobia: Sensitivity to light is common, especially when the iris is inflamed.
• Blurred Vision: Vision may be mildly or severely blurred, depending on the severity and location of the inflammation.
• Floaters: Patients with posterior or intermediate uveitis often report seeing floaters.
• Reduced Visual Acuity: Chronic or untreated uveitis can lead to significant vision loss.

Diagnosis of Uveitis

Diagnosing uveitis involves a thorough patient history, comprehensive eye examination, and a variety of laboratory and imaging tests to identify the underlying cause and determine the extent of inflammation.

1. Slit-Lamp Examination

A slit-lamp biomicroscopy exam allows the ophthalmologist to inspect the anterior chamber for signs of inflammation, such as the presence of cells and flare (protein leakage). In intermediate and posterior uveitis, signs such as vitreous cells, snowballs, or retinal vasculitis may be observed.

2. Dilated Fundoscopy

In cases of posterior uveitis, a dilated fundoscopy is essential for visualizing the retina, choroid, and optic nerve. The doctor will look for signs of retinitis, choroiditis, vasculitis, or optic disc swelling.

3. Optical Coherence Tomography (OCT)

OCT provides high-resolution cross-sectional images of the retina and is particularly useful for detecting macular edema, a common complication of uveitis. It can also monitor disease progression and treatment response.

4. Fluorescein Angiography (FA)

FA is used to assess retinal and choroidal blood vessel leakage, a hallmark of retinal vasculitis and posterior uveitis. It is also helpful in diagnosing specific conditions like Behçet’s disease and birdshot retinochoroidopathy.

5. Laboratory Tests

The choice of laboratory tests depends on the clinical presentation and suspected underlying cause. These tests may include:

• Complete Blood Count (CBC): To check for signs of infection or systemic inflammation.
• ESR and CRP: Inflammatory markers that may be elevated in autoimmune conditions.
• Rheumatoid Factor (RF) and ANA: Useful in diagnosing autoimmune diseases like rheumatoid arthritis and juvenile idiopathic arthritis.
• HLA-B27 Testing: Associated with ankylosing spondylitis and other seronegative spondyloarthropathies that commonly cause anterior uveitis.
• Serologic Tests: For infectious causes such as syphilis, toxoplasmosis, TB, and viral infections like CMV or HSV.

Complications of Uveitis

If not treated promptly and effectively, uveitis can lead to a number of sight-threatening complications. Some of the most common complications include:

1. Cataracts

Chronic inflammation or prolonged use of corticosteroids can lead to cataract formation, particularly posterior subcapsular cataracts, which significantly impair vision.

2. Glaucoma

Increased intraocular pressure due to inflammation or steroid treatment can cause secondary glaucoma, leading to optic nerve damage and permanent vision loss.

3. Macular Edema

One of the most frequent causes of vision loss in uveitis, macular edema occurs when fluid accumulates in the macula, the central part of the retina responsible for sharp vision.

4. Retinal Detachment

Chronic inflammation, especially in posterior uveitis, can lead to retinal detachment, a medical emergency that requires prompt surgical intervention.

5. Optic Nerve Damage

Optic neuritis or swelling of the optic nerve can occur in severe cases of uveitis, particularly in panuveitis or posterior uveitis. This can result in permanent vision loss if left untreated.

Treatment and Management of Uveitis

The treatment of uveitis is aimed at reducing inflammation, relieving symptoms, and preventing complications. The specific treatment plan depends on the type, severity, and underlying cause of uveitis.

1. Corticosteroids

Corticosteroids are the cornerstone of uveitis treatment due to their potent anti-inflammatory effects. They can be administered in various forms:

• Topical Steroids: Used for anterior uveitis (e.g., prednisolone eye drops).
• Oral Steroids: Used for more severe or posterior uveitis (e.g., prednisone).
• Intravitreal Steroids: Injections or implants (e.g., dexamethasone implant) are used for chronic or refractory cases, particularly in posterior uveitis.

2. Immunosuppressive Drugs

In cases where corticosteroids are insufficient or cannot be used long-term due to side effects, immunosuppressive agents like methotrexate, azathioprine, or cyclosporine may be prescribed. These drugs are especially useful in autoimmune-related uveitis.

3. Biologic Therapies

For refractory uveitis, biologics targeting specific inflammatory pathways have emerged as effective treatments. Adalimumab and infliximab, both TNF-alpha inhibitors, are examples of biologic therapies that have shown success in treating autoimmune uveitis.

4. Antibiotics and Antivirals

For infectious causes of uveitis, treatment is directed at the underlying pathogen:

• Antibiotics: For bacterial causes such as TB or syphilis.
• Antivirals: For viral infections such as HSV, HZV, or CMV.
• Antifungals: For fungal infections like histoplasmosis or candidiasis.

5. Surgery

In cases of severe complications such as cataracts, glaucoma, or retinal detachment, surgical intervention may be necessary. Vitrectomy is often performed to remove the vitreous in cases of persistent posterior uveitis or to address complications like retinal detachment.

Prognosis of Uveitis

The prognosis for patients with uveitis depends on several factors, including the underlying cause, the severity of inflammation, and the timeliness of treatment. Early detection and aggressive treatment are crucial for preventing permanent vision loss. While some cases of acute uveitis resolve without long-term complications, chronic uveitis requires ongoing management and regular follow-up to monitor for recurrences or complications.

Conclusion

Uveitis is a complex and potentially sight-threatening condition that requires prompt and effective treatment to prevent complications. A thorough understanding of the types, causes, and clinical manifestations of uveitis is essential for healthcare professionals, particularly those in ophthalmology and rheumatology. Early diagnosis, aggressive treatment, and close monitoring can significantly improve patient outcomes, preventing vision loss and improving quality of life.

With advancements in biologic therapies and immunosuppressive treatments, the outlook for patients with uveitis continues to improve. Research into the underlying mechanisms of uveitis and potential new treatments holds promise for future developments in the management of this challenging condition.