Sympathetic Ophthalmia: Comprehensive Overview and Care Options

Sympathetic ophthalmia (SO) is a rare but serious bilateral granulomatous uveitis that develops following eye trauma or surgery. Following a penetrating injury to one eye, known as the “exciting eye,” the unaffected eye, known as the “sympathizing eye,” develops inflammation, leading to vision-threatening complications if not promptly identified and treated.

The pathophysiology of sympathetic ophthalmia

The exact mechanism that causes sympathetic ophthalmia is unknown, but it is thought to be an autoimmune response. When the eye is subjected to penetrating trauma, ocular antigens that are normally sequestered and unaffected by the immune system are released into the bloodstream. These antigens are thought to cause an autoimmune response, in which the body’s immune system misidentifies its own ocular tissues as foreign. This response can then spread to the uninjured, or sympathetic, eye, resulting in bilateral inflammation.

The inflammation in sympathetic ophthalmia primarily affects the uveal tract, which includes the iris, ciliary body, and choroid. This is a case of panuveitis, which means it affects all layers of the uvea. The immune response in sympathetic ophthalmia involves the infiltration of inflammatory cells into the uvea, resulting in granuloma formation, which can cause tissue damage and, if left untreated, severe visual impairment or blindness.

Historical Background

Sympathetic ophthalmia has been known for centuries, with one of the earliest documented cases dating from the early nineteenth century. A series of cases reported following eye injuries sustained during the Napoleonic Wars drew significant attention to the condition in the medical community. Over time, our understanding of sympathetic ophthalmia evolved, particularly with the advent of modern immunology, which helped to clarify the disease’s autoimmune origin.

Despite its long history, sympathetic ophthalmia is still a rare condition, with an estimated incidence of 0.01% to 0.5% of cases after penetrating eye injury or surgery. However, due to the risk of severe vision loss, it is a serious concern in ophthalmology.

Causes and Risk Factors

Sympathetic ophthalmia is typically associated with penetrating ocular trauma, but it can also occur following intraocular surgery, particularly procedures involving the posterior segment of the eye, such as cataract extraction, vitrectomy, or retinal detachment repair. The condition has been linked to both accidental injuries from sharp objects or shrapnel and surgical procedures, including the removal of intraocular foreign bodies.

Several factors may increase the risk of developing sympathetic ophthalmia:

1. Injury Nature: The risk of sympathetic ophthalmia is higher in severe or complex penetrating injuries to the uvea or posterior segment of the eye. Injuries that disrupt the ocular capsule, exposing uveal tissue to the immune system, are more likely to cause SO.
2. Injury Timing and Surgery: If the injured eye is not surgically repaired as soon as possible, the risk of sympathetic ophthalmia increases. Delays in wound closure increase the likelihood of antigen exposure and subsequent immune activation. Furthermore, patients who have multiple surgeries or suffer from complications such as infection or persistent inflammation are at a higher risk.
3. Presence of Intraocular Foreign Bodies: Retained intraocular foreign bodies, particularly those made of organic material, can increase the risk of sympathetic ophthalmia. These foreign bodies may carry bacteria or other pathogens, resulting in chronic inflammation and immune activation.
4. Genetic Predisposition: While the exact genetic factors involved in sympathetic ophthalmia are unknown, it is thought that people with specific HLA (human leukocyte antigen) types may be more prone to developing autoimmune responses after ocular injury. HLA-DR4, in particular, has been associated with an increased risk of autoimmune uveitis, including SO.
5. Age and Gender: Sympathetic ophthalmia can occur at any age, but it is more commonly seen in young people and men. This could be due to a higher incidence of ocular injuries in these populations, particularly in the context of sports, accidents, or military service.

Symptoms Of Sympathetic Ophthalmia

Sympathetic ophthalmia symptoms vary in severity and onset. The condition usually appears within a few weeks to several months of the initial ocular injury or surgery, though it has been known to develop years later. The symptoms typically begin in the sympathizing eye, but the exciting eye may also exhibit inflammation if it has not already been enucleated (surgically removed). Common symptoms include:

1. Blurry Vision: One of the first and most common signs of sympathetic ophthalmia is a gradual loss of visual acuity. Patients may notice their vision becoming increasingly blurry, which can affect both near and distant vision.
2. Photophobia: One of the most common symptoms of SO is light sensitivity, or photophobia. Patients may feel discomfort or pain when exposed to bright lights, which can interfere with daily activities like driving or reading.
3. Eye Pain: Sympathetic ophthalmia patients frequently report mild to moderate eye pain or discomfort. This pain could be caused by uveal tract inflammation, which can be exacerbated by eye movement or pressure.
4. Redness and Inflammation: The underlying uveitis can cause the affected eye to appear red and inflamed. The redness is typically diffuse, affecting the entire conjunctiva and sclera.
5. Floaters: Patients with SO may experience an increase in floaters, which are small dark spots or lines that move across their field of vision. Inflammatory cells and debris in the vitreous humor, which fills the eye, cause these floaters.
6. Visual Field Defects: As the inflammation progresses, patients may develop visual field defects, which are loss or obscured areas of their vision. These defects can vary in size and location, depending on the severity and location of the uveitis.
7. Loss of Accommodation: Patients with sympathetic ophthalmia may have difficulty focusing on close objects, a process known as accommodation. The ciliary body, which controls the shape and focusing ability of the lens, plays a role in this.
8. Sympathetic Symptoms in the Exciting Eye: In some cases, the eye that suffered the initial injury (the exciting eye) may show signs of inflammation, especially if it was not removed or if the initial trauma caused significant damage. Pain, redness, and decreased vision are symptoms that may be similar to those of the sympathizing eye.

Complications of Sympathetic Ophthalmia

If left untreated, sympathetic ophthalmia can cause serious complications that impair vision in both eyes. Some of the possible complications are:

1. Chronic Uveitis: Persistent uveal inflammation can progress to chronic uveitis, which is difficult to treat and may necessitate long-term immunosuppressive therapy. Chronic uveitis can result in ongoing discomfort, pain, and progressive vision loss.
2. Cataract Formation: SO-induced inflammation can hasten the development of cataracts, which are cloudy lenses that impair vision. Cataracts may require surgical removal, but active inflammation can complicate the procedure and increase the risk of postoperative complications.
3. Glaucoma: Increased intraocular pressure (IOP) is a common side effect of sympathetic ophthalmia, especially if the inflammation affects the trabecular meshwork, the eye’s drainage system. If not treated properly, glaucoma can cause optic nerve damage and irreversible vision loss.
4. Retinal Detachment: In severe cases, inflammation can cause the retina to separate from the surrounding tissue, resulting in retinal detachment. Retinal detachment is a medical emergency requiring immediate surgical intervention to preserve vision.
5. Optic Nerve Damage: Chronic inflammation can damage the optic nerve, resulting in optic neuropathy and permanent vision loss. Optic nerve damage is a serious, potentially irreversible side effect of SO.
6. Panuveitis: Sympathetic ophthalmia is a type of panuveitis, which affects all layers of the uvea. This extensive inflammation can cause widespread tissue damage, scarring, and a significant decrease in visual acuity.
7. Blindness: If not treated quickly and effectively, sympathetic ophthalmia can cause blindness in both sympathizing and exciting eyes. Blindness is the most serious complication of SO, emphasizing the importance of early diagnosis and treatment.

Prognosis

The prognosis for sympathetic ophthalmia depends on the severity of the condition, the timing of treatment, and the patient’s response to therapy. Many patients can achieve good inflammation control and maintain their vision with early diagnosis and appropriate management. However, some patients may develop recurring or chronic inflammation, necessitating long-term treatment and monitoring. The risk of complications, such as cataracts, glaucoma, or optic nerve damage, emphasizes the importance of close monitoring and aggressive treatment to avoid vision loss.

Diagnostic methods

Diagnosing sympathetic ophthalmia requires a high level of suspicion, especially in patients with a history of ocular trauma or surgery. The condition is frequently difficult to diagnose due to its rarity and variability in presentation. A thorough clinical evaluation, along with imaging studies and laboratory tests, is required to confirm the diagnosis and distinguish sympathetic ophthalmia from other causes of uveitis.

Clinical Examination

The clinical examination is the foundation for diagnosing sympathetic ophthalmia. A thorough ophthalmologic examination includes a slit-lamp examination, which allows the ophthalmologist to closely examine the anterior segment of the eye, including the cornea, iris, and lens. During the slit-lamp examination, the clinician looks for signs of anterior uveitis, such as:

1. Anterior Chamber Cells: The presence of inflammatory cells in the anterior chamber of the eye is indicative of uveitis. These cells appear as tiny white dots floating in the aqueous humor, a clear fluid that fills the space between the cornea and the lens.
2. Keratic Precipitates are small, whitish deposits of inflammatory cells found on the cornea’s inner surface. Keratic precipitates are a common finding in granulomatous uveitis, which is associated with sympathetic ophthalmia.
3. Iris Nodules: In some cases, small yellowish nodules may develop on the iris. These nodules, known as Koeppe or Busacca nodules, indicate granulomatous inflammation and are frequently associated with SO.
4. Posterior synechiae: These are adhesions between the iris and the lens caused by chronic inflammation. Posterior synechiae can cause irregular pupil shape and impaired pupil movement, resulting in visual disturbances.

Fundoscopy Examination

A fundoscopic (or ophthalmoscopic) examination allows the ophthalmologist to inspect the retina, optic disc, and posterior segment of the eye. The following symptoms may be present in sympathetic ophthalmia:

1. Choroidal Infiltrates: These are inflammations in the choroid, the vascular layer of the eye that lies between the retina and the sclera. Choroidal infiltrates, which can appear as yellowish or white patches, are a common feature of SO.
2. Dalen-Fuchs Nodules: These small, whitish lesions at the retina-choroid interface are pathognomonic (specifically indicative) of sympathetic ophthalmia. Dalen-Fuchs nodules are focal collections of inflammatory cells that are indicative of granulomatous inflammation.
3. Optic Disc Edema: Swelling of the optic disc, where the optic nerve enters the eye, can occur in SO due to inflammation. Optic disc edema can cause visual field defects and, in severe cases, permanent optic nerve damage.
4. Vitreous Cells and Haze: Inflammatory cells can accumulate in the vitreous humor, resulting in the cloudy appearance known as vitreous haze. Vitreous cells are another sign of posterior uveitis in sympathetic ophthalmia.

Imaging Studies

Imaging studies are frequently used to confirm the clinical diagnosis of sympathetic ophthalmia and determine the extent of inflammation. Common imaging techniques include the following:

1. Fluorescein Angiography (FA): This imaging technique involves injecting a fluorescent dye into the bloodstream and then taking images of the dye as it circulates through the retinal and choroidal blood vessels. In SO, FA may reveal areas of choroidal hypoperfusion (low blood flow), leakage from inflamed vessels, and Dalen-Fuchs nodules.
2. Indocyanine Green Angiography (ICGA): Similar to fluorescein angiography, ICGA uses a different dye to provide a better view of the choroidal circulation. ICGA can detect choroidal abnormalities that are not visible on FA, making it a useful tool for diagnosing and tracking SO.
3. Optical Coherence Tomography (OCT) is a non-invasive imaging technique that generates cross-sectional images of the retina and choroid. OCT can detect structural changes in the retina in patients with sympathetic ophthalmia, including retinal edema, subretinal fluid accumulation, and the presence of Dalen-Fuchs nodules. OCT is also useful for tracking treatment outcomes.
4. Ultrasound B-Scan: B-scan ultrasonography is an imaging technique that employs high-frequency sound waves to produce images of the eye’s internal structures. It is especially useful for assessing the posterior segment of the eye when media opacities, such as dense cataracts or vitreous haze, prevent direct visualization with ophthalmoscopy. A B-scan may reveal choroidal thickening, retinal detachment, or the presence of intraocular foreign bodies in SO patients.

Lab Tests

While laboratory tests are not specific to sympathetic ophthalmia, they can help rule out other causes of uveitis and identify systemic conditions linked to the disease. Common laboratory tests are:

1. Complete Blood Count (CBC): A CBC can detect signs of systemic infection or inflammation, such as high white blood cell counts. However, it is not specific to SO.
2. Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) are indicators of systemic inflammation. Elevated levels of ESR and CRP may indicate an ongoing inflammatory process, but they are not specific to sympathetic ophthalmia.
3. HLA Typing: In some cases, HLA typing can be used to determine genetic susceptibility to autoimmune uveitis. As previously stated, some HLA types, such as HLA-DR4, may be associated with an increased risk of developing SO.
4. Angiotensin-Converting Enzyme (ACE) and Lysozyme Levels: These tests are sometimes used to rule out sarcoidosis, a granulomatous uveitis that can look similar to SO. Elevated ACE and lysozyme levels are common in sarcoidosis, but not in sympathetic ophthalmia.

Differential Diagnosis

Given the rarity of sympathetic ophthalmia, it is critical to distinguish it from other conditions that may produce similar symptoms. The differential diagnosis for SO includes the following:

1. Vogt-Koyanagi-Harada (VKH) Syndrome: VKH syndrome is a granulomatous uveitis that affects the uveal tract and can present with symptoms similar to SO, such as choroidal inflammation and Dalen-Fuchs nodules. However, VKH is frequently associated with systemic symptoms such as vitiligo, alopecia, and neurologic signs, which can aid in distinguishing it from SO.
2. As previously stated, sarcoidosis is a systemic granulomatous disease that can cause uveitis. Systemic symptoms, such as lung involvement, as well as elevated ACE levels, can help distinguish sarcoidosis from sympathetic ophthalmia.
3. Infectious Uveitis: Infections such as tuberculosis, syphilis, and toxoplasmosis can cause uveitis similar to SO. Serologic testing and imaging studies are critical in ruling out these infectious causes.
4. Idiopathic Panuveitis: When no specific cause of uveitis can be determined, the condition is classified as idiopathic panuveitis. A thorough examination is required to rule out other possible diagnoses, including sympathetic ophthalmia.

Sympathetic Ophthalmia Management

The treatment of sympathetic ophthalmia (SO) focuses on reducing inflammation, preserving vision, and avoiding further complications. Because the condition is autoimmune, immunosuppressive therapy is the primary treatment option to reduce the immune system’s attack on ocular tissues. Early and aggressive treatment is critical for improving prognosis and avoiding vision loss in both eyes. Medical and surgical treatments are two broad categories of management strategies.

Medical Treatment

1. Corticosteroids: Corticosteroids are the primary treatment for sympathetic ophthalmia. These potent anti-inflammatory medications help to suppress the immune system and reduce inflammation in the uveal tract. Corticosteroids can be administered in a variety of ways, depending on the severity of the condition:

• Topical Corticosteroids: For mild anterior uveitis, corticosteroid eye drops may be enough to control inflammation. Prednisolone acetate and dexamethasone are two commonly used topical steroids.
• Systemic Corticosteroids: For severe or widespread inflammation, oral or intravenous corticosteroids are frequently required. Oral prednisone is frequently prescribed, beginning with a high dose and gradually tapering as the inflammation resolves. Intravenous methylprednisolone can be used to treat severe cases quickly.
• Periocular or Intraocular Steroid Injections: In some cases, steroid injections around or within the eye may be used to deliver high levels of the drug directly to the site of inflammation. This approach is especially useful for patients who cannot tolerate systemic steroids or who have localized inflammation that is resistant to topical therapy.

1. Immunosuppressive Agents: In patients with chronic or recurring sympathetic ophthalmia, long-term immunosuppressive therapy may be required to control inflammation and prevent relapses. Immunosuppressive drugs work by inhibiting various immune system components, reducing the autoimmune response that causes SO. Commonly used immunosuppressive agents are:

• Methotrexate: Methotrexate inhibits immune cell proliferation by acting as a folate antagonist. It is frequently used as a first-line immunosuppressive in SO patients who require steroid-free therapy.
• Azathioprine: Azathioprine is an immunosuppressive drug that inhibits DNA synthesis, reducing the activity of immune cells. It is commonly used in conjunction with corticosteroids to treat uveitis in SO.
• Cyclosporine: Cyclosporine is a calcineurin inhibitor that inhibits the activation of T cells, which are essential components of the immune response. It is used in patients who do not respond to or cannot tolerate other immunosuppressive drugs.
• Mycophenolate Mofetil: Mycophenolate mofetil is an immunosuppressive medication that prevents the proliferation of T and B cells. It is frequently used in conjunction with other immunosuppressive drugs to improve inflammation control.

1. Biologic Agents: In recent years, biologic agents have emerged as a viable treatment option for refractory sympathetic ophthalmia. These drugs target specific molecules involved in the immune response, providing a more precise approach to immunosuppression. Examples of biological agents used in SO are:

• Infliximab and Adalimumab are anti-TNF-α antibodies that inhibit the activity of TNF-α, a major inflammatory cytokine. They are used for SO patients who do not respond to standard immunosuppressive therapy.
• Rituximab: Rituximab is an anti-CD20 monoclonal antibody that eliminates B cells, which are involved in the autoimmune response. It is used for refractory uveitis, including SO.

1. Adjunctive Therapies: In addition to immunosuppressive therapy, patients with SO may benefit from other treatments that help manage symptoms and prevent complications. This may include:

• Cycloplegic Agents: Eye drops containing cyclopentolate or atropine are used to relax the ciliary muscle and relieve pain caused by ciliary spasms. They also help to prevent the formation of posterior synechiae, which are adhesions between the iris and lenses.
• Glaucoma Medications: If inflammation or steroid treatment causes elevated intraocular pressure, glaucoma medications may be required to protect the optic nerve and maintain vision. These could include beta-blockers, prostaglandin analogs, or carbonic anhydrase inhibitors.

Surgical Treatment

1. Enucleation of the Exciting Eye: In cases where the injured eye (the exciting eye) is severely damaged and no longer functional, enucleation (surgical removal of the eye) may be considered as a preventive measure to reduce the risk of sympathetic ophthalmia in the sympathizing eye. Enucleation is most effective when performed within two weeks of injury. However, as immunosuppressive therapy has advanced, this option is becoming less popular.
2. Cataract Surgery: Patients with sympathetic ophthalmia who develop cataracts as a result of chronic inflammation or long-term corticosteroid use may need cataract surgery to restore vision. The timing of surgery is critical, as performing it during active inflammation can worsen the condition. Perioperative immunosuppression can reduce the risk of postoperative complications.
3. Surgical Management of Glaucoma: If medical therapy fails to control intraocular pressure, surgical intervention may be required to avoid glaucoma-related vision loss. Surgical options include trabeculectomy, glaucoma drainage devices, and cyclodestructive procedures.

Long-Term Management and Follow-up

Long-term management of sympathetic ophthalmia entails regular follow-up visits with an ophthalmologist to assess treatment efficacy, identify complications, and adjust therapy as necessary. Patients with SO may require lifelong immunosuppressive therapy to keep the inflammation under control and avoid relapses. Long-term management aims to preserve vision, reduce treatment-related side effects, and enhance the patient’s overall quality of life.

Trusted Resources and Support

Books

• “Uveitis: Fundamentals and Clinical Practice” by Robert B. Nussenblatt and Scott M. Whitcup: This comprehensive textbook covers the diagnosis and management of uveitis, including sympathetic ophthalmia. It is a valuable resource for ophthalmologists, residents, and medical students.
• “Ocular Immunology in Health and Disease” by Stephen Foster and Albert T. Vitale: This book provides an in-depth exploration of the immune mechanisms underlying various ocular conditions, including SO. It offers insights into both basic science and clinical management.

Organizations

• American Uveitis Society (AUS): The AUS is a professional organization dedicated to the study and treatment of uveitis. It offers resources for both healthcare professionals and patients, including information on the latest research and treatment guidelines for conditions like sympathetic ophthalmia.
• National Eye Institute (NEI): Part of the U.S. National Institutes of Health, the NEI provides a wealth of information on eye conditions, including uveitis and sympathetic ophthalmia. The NEI supports research and provides educational materials to help patients and their families understand and manage their eye health.