Ocular Manifestations of Stevens-Johnson Syndrome

Stevens-Johnson Syndrome (SJS) is a serious, potentially fatal condition that primarily affects the skin and mucous membranes, including the eyes. It is distinguished by a hypersensitive reaction that can be induced by a variety of medications, infections, or other factors, resulting in widespread cell death in the epidermis and mucosal tissues. The condition frequently manifests as flu-like symptoms, followed by the rapid onset of painful skin rashes, blisters, and epidermal detachment resembling a burn. The syndrome is considered a medical emergency, necessitating immediate hospitalization and intensive care.

The Relationship Between Stevens-Johnson Syndrome and Eyes

The ocular manifestations of Stevens-Johnson Syndrome are among the most serious and potentially fatal complications of the illness. The involvement of the eyes can range from mild conjunctivitis to severe corneal damage, which can lead to permanent vision loss. The eyes are especially vulnerable because, like the skin and other mucous membranes, the widespread inflammatory process that characterizes SJS directly affects them.

Ocular involvement in SJS can occur during both the acute and chronic phases of the disease. The acute phase of SJS occurs at the time of the initial episode, whereas the chronic phase can last for months or even years, often resulting in long-term visual impairment or blindness if not managed properly.

Pathophysiology Of Ocular Involvement in SJS

Stevens-Johnson Syndrome pathophysiology consists of a complex immune-mediated reaction that is usually triggered by certain medications or infections. These triggers cause the immune system to mistakenly target the body’s own cells, resulting in widespread cell death and epidermal and mucosal detachment. The exact mechanisms underlying this immune response are unknown, but it is thought to be a combination of genetic susceptibility and environmental factors.

When it comes to the eyes, the immune response causes inflammation of the conjunctiva, a thin, transparent membrane that covers the white part of the eye and the inside surface of the eyelids. This inflammation can progress to affect the cornea, eyelids, and other ocular structures, resulting in a variety of symptoms and complications.

Acute Stage of Ocular Involvement

SJS’s acute phase frequently causes severe damage to the eyes. Common ocular manifestations at this stage include:

1. Conjunctivitis: One of the first symptoms of SJS is conjunctival inflammation. Patients may notice redness, swelling, tearing, and a burning sensation in their eyes. Conjunctivitis in SJS can be mild or severe, and in severe cases, pseudomembranes can form on the surface of the conjunctiva and adhere to the underlying tissue.
2. Eyelid Edema: Another common sign of SJS is swelling of the eyelids (eyelid edema). This swelling can be severe and may make opening the eyes difficult, exacerbating the discomfort and irritation caused by conjunctivitis.
3. Corneal Erosions: The inflammatory process can cause erosions in the cornea, the transparent front part of the eye. The breakdown of the corneal epithelium causes these erosions, which cause pain, photophobia (light sensitivity), and blurred vision. Corneal erosions are especially concerning because they can lead to corneal ulcers, raising the risk of scarring and permanent vision loss.
4. Symblepharon Formation: Symblepharon is the adhesion of the conjunctiva to the eyelids, a complication that can develop during the acute phase of SJS. This condition can limit eye movement, cause discomfort, and lead to additional complications like entropion (inward turning of the eyelids) and trichiasis (misdirected eyelashes that rub against the cornea).
5. Ocular Discharge: Patients with SJS frequently have significant ocular discharge, which can be either serous (clear) or purulent (pus-like), depending on the presence of a secondary bacterial infection. The discharge can cause crusting around the eyes, exacerbating the already inflamed ocular tissues.
6. Membrane Formation: In some cases, inflammation in SJS causes membranes to form on the conjunctiva or cornea. These membranes can be tough and difficult to remove, and they can lead to additional scarring and vision loss.

Chronic Stage of Ocular Involvement

Even after the acute phase of SJS has passed, many patients continue to experience chronic ocular complications, which can have serious consequences for their vision and quality of life. The chronic phase of ocular involvement in SJS is defined as the following:

1. Chronic Dry Eye (Keratoconjunctivitis Sicca) is a common and debilitating long-term complication of SJS. SJS-induced inflammation and scarring can damage the lacrimal glands, resulting in reduced tear production and severe dry eye. This condition can cause chronic discomfort, a gritty sensation in the eyes, and difficulty with activities like reading or using a computer. In severe cases, chronic dry eye can cause additional corneal damage, such as corneal ulcers and scarring.
2. Corneal Scarring and Opacification: During the acute phase of SJS, corneal erosions and ulcers may heal with scarring, resulting in corneal opacification. Corneal scarring reduces transparency and can cause significant visual impairment or blindness, depending on its location and extent.
3. Ocular Surface Disease: Chronic inflammation and damage to the ocular surface in SJS can lead to a condition known as ocular surface disease. This category includes a variety of conjunctival and corneal disorders, such as chronic inflammation, epithelial defects, and persistent corneal ulcers. Ocular surface disease is difficult to manage and frequently necessitates ongoing treatment to avoid further damage and preserve vision.
4. Limbal Stem Cell Deficiency: The limbus, located at the junction of the cornea and sclera (the white of the eye), contains stem cells required for corneal epithelial regeneration. In SJS, these stem cells can become damaged or destroyed, resulting in limbal stem cell deficiency. This condition impairs the cornea’s ability to heal and regenerate, causing chronic epithelial defects, neovascularization (the formation of new blood vessels), and additional corneal scarring.
5. Glaucoma: In some cases, patients with chronic ocular involvement from SJS may develop glaucoma, a condition characterized by elevated intraocular pressure that can harm the optic nerve. Chronic inflammation, corticosteroid use, or scarring that obstructs aqueous humor drainage (the fluid within the eye) can all cause glaucoma in SJS. If left untreated, glaucoma can cause irreversible vision loss.
6. Entropion and Trichiasis: SJS-related scarring and fibrosis in the eyelids can cause entropion (inward turning of the eyelid) and trichiasis (misdirected eyelashes). These conditions cause eyelashes to rub against the cornea, resulting in chronic irritation, epithelial damage, and an increased risk of corneal ulcers.
7. Symblepharon and Fornix Shortening: Symblepharon formation can continue into the chronic phase, resulting in shortening of the conjunctival fornices. This can limit eye movement, cause discomfort, and make wearing contact lenses or other dry eye treatments more difficult.

Prognosis and Effects on Quality of Life

The ocular symptoms of Stevens-Johnson Syndrome can have a significant impact on a patient’s quality of life. Chronic dry eye, corneal scarring, and other complications can cause ongoing discomfort, vision impairment, and, in some cases, blindness. Dealing with these long-term complications can have a significant psychological and emotional impact, leading to depression, anxiety, and a lower quality of life.

Early detection and aggressive management of ocular involvement in SJS are critical for reducing long-term damage and maintaining vision. The severity of the initial ocular involvement, the effectiveness of the treatment, and the patient’s overall health all influence the prognosis. Some patients may notice a significant improvement in their symptoms after receiving appropriate care, while others may continue to struggle with chronic complications that require ongoing management.

Diagnostic methods

The ocular manifestations of Stevens-Johnson Syndrome are diagnosed using a combination of clinical evaluation, specialized tests, and imaging studies to determine the extent of ocular involvement and inform treatment decisions. Early detection is critical for initiating prompt and appropriate treatment to avoid long-term complications and maintain vision.

Clinical Examination

A thorough clinical examination by an ophthalmologist is the foundation for diagnosing ocular involvement in SJS. The exam typically includes:

1. Visual Acuity Testing: Visual acuity testing is used to determine the effects of SJS on the patient’s vision. This test helps to quantify vision loss and establishes a baseline for tracking changes over time.
2. Slit-Lamp Biomicroscopy: Slit-lamp biomicroscopy is a valuable diagnostic tool for examining the anterior segment of the eye, which includes the conjunctiva, cornea, and eyelids. The slit lamp provides detailed visualization of the ocular surface, allowing the ophthalmologist to detect inflammation, corneal erosions, conjunctival scarring, symblepharon formation, and other complications associated with SJS.
3. Tear Film Evaluation: Evaluating the tear film is critical in diagnosing dry eye disease associated with SJS. The tear film break-up time (TBUT) and Schirmer’s test are commonly used tests to assess tear production and tear film stability.

• Tear Film Break-Up Time (TBUT): TBUT is the time it takes for the tear film to break up after blinking. A shorter TBUT indicates an unstable tear film, which is characteristic of dry eye disease. This test is especially useful in determining the severity of dry eye in SJS patients.
• Schirmer’s Test: This test measures the amount of tears produced. A small strip of filter paper is placed beneath the lower eyelid, and the amount of wetting on the paper is measured after a few minutes. Low tear production, defined as less than 5 mm of wetting, indicates significant lacrimal gland dysfunction, which is common in chronic SJS.

1. Conjunctival Examination: The conjunctiva is thoroughly examined for signs of inflammation, pseudomembrane formation, and symblepharon. The presence of these findings may indicate the severity of ocular surface involvement, necessitating more aggressive treatment.
2. Corneal Staining: The cornea and conjunctiva are stained with fluorescein or rose bengal dyes to reveal epithelial damage or ulceration. Corneal staining aids in the identification of erosions, ulcers, and areas of poor epithelial healing, which are critical for determining the extent of corneal involvement and planning appropriate interventions.
3. Eyelid Examination: Look for edema, entropion, trichiasis, and scarring on the eyelids. The presence of these features may indicate a more severe disease and necessitate specialized treatment to prevent further ocular damage.

Imaging Studies

In some cases, imaging studies may be required to evaluate the extent of ocular involvement in SJS, particularly when complications such as limbal stem cell deficiency or deep corneal involvement are suspected.

1. Anterior Segment Optical Coherence Tomography (AS-OCT): AS-OCT is a non-invasive imaging technique that generates high-resolution cross-sectional images of the eye’s anterior segment, which includes the cornea, conjunctiva, and limbus. This imaging technique is especially useful for determining corneal thickness, detecting epithelial defects, and assessing limbal stem cell deficiency.
2. Confocal Microscopy: Confocal microscopy enables detailed imaging of corneal layers at the cellular level. It can be used to evaluate the health of the corneal epithelium, detect early signs of keratopathy, and determine the presence of limbal stem cell deficiency. Confocal microscopy is useful for monitoring the progression of ocular surface disease in chronic SJS.
3. Ocular Surface Photography: High-resolution photographs of the ocular surface can be used to document the extent of conjunctival and corneal involvement, track disease progression, and evaluate treatment response. Serial photographs are especially useful in chronic cases where long-term monitoring is required.

Lab Tests

While laboratory tests are typically not used to diagnose the ocular manifestations of SJS directly, they can be helpful in confirming the diagnosis of SJS and identifying potential triggers:

1. Complete Blood Count (CBC): A CBC can detect signs of systemic inflammation or infection that may be associated with SJS.
2. Serological Tests: Serological tests for specific infections or autoantibodies may be used to identify potential SJS triggers, especially when an infectious or autoimmune etiology is suspected.
3. HLA Typing: Certain HLA (human leukocyte antigen) types, particularly in certain populations, are associated with an increased risk of drug-induced SJS. If a patient has a history of drug exposure, HLA typing may help to identify them as being at risk for SJS.
4. Drug Hypersensitivity Testing: If SJS is suspected to be drug-induced, drug hypersensitivity testing may be used to determine the causative agent. An allergist or immunologist will usually perform this test under controlled conditions.

Differential Diagnosis

The differential diagnosis of ocular involvement in SJS includes several conditions that can cause similar symptoms, such as:

• Toxic Epidermal Necrolysis (TEN): TEN is a more severe form of SJS that affects the skin, mucous membranes, and even the eyes. The primary distinction between SJS and TEN is the extent of skin detachment, with TEN affecting more than 30% of the body’s surface area.
• Ocular Cicatricial Pemphigoid: This autoimmune condition, like SJS, can cause chronic conjunctivitis, scarring, and the formation of symblepharons. However, ocular cicatricial pemphigoid is usually a long-term, progressive disease rather than an acute reaction.
• Erythema Multiforme: Erythema multiforme is a hypersensitivity reaction that can result in mucocutaneous lesions, including in the eyes. However, it is less severe than SJS and does not usually result in the same level of ocular involvement.

Stevens-Johnson Syndrome Ocular Manifestations Management

Ophthalmologists, dermatologists, and other specialists must collaborate to manage the complex ocular manifestations of Stevens-Johnson Syndrome (SJS). Treatment goals include managing acute symptoms, preventing complications, and addressing chronic issues that may persist after the acute phase. Early and aggressive intervention is critical for maintaining vision and improving quality of life.

Acute Phase Management

During the acute phase of Stevens-Johnson Syndrome, immediate and intensive care is required. The goal is to control inflammation, prevent infection, and protect the ocular surface.

1. Intensive Ocular Lubrication: One of the most important concerns during the acute phase is keeping the ocular surface adequately lubricated. Preservative-free artificial tears or lubricating ointments are frequently used to keep the eyes moist and prevent the cornea from drying out. In severe cases, moisture chamber goggles can help retain humidity and provide a safe environment for the eyes.
2. Topical Steroids: Topical corticosteroids are frequently used to reduce inflammation and prevent scar tissue formation during the acute phase. These are usually prescribed in small doses and under close supervision to reduce the risk of complications like increased intraocular pressure or secondary infections. The goal is to reduce conjunctival inflammation while preventing symblepharon and other scarring complications.
3. Antibiotic Eye Drops: Prophylactic antibiotic eye drops may be used to prevent secondary bacterial infections, which can be serious due to the compromised ocular surface in SJS. These drops help to avoid infection-related complications like corneal ulcers.
4. Debridement of Pseudomembranes: If pseudomembranes form on the conjunctiva, thorough debridement may be required. This procedure involves gently removing these false membranes to keep them from adhering to the conjunctiva and causing additional scarring. To avoid further trauma to the ocular surface, an experienced ophthalmologist should perform the debridement.
5. Amniotic Membrane Transplantation: In severe cases with extensive corneal involvement or epithelial defects, amniotic membrane transplantation may be an option. The amniotic membrane functions as a biological bandage, promoting healing, reducing inflammation, and minimizing scarring. It can be used as a graft or as part of a specialized contact lens (Prokera), which delivers the membrane’s therapeutic properties directly to the ocular surface.
6. Symblepharon Lysis: If symblepharon (conjunctival adhesion to the eyelid) develops, early surgical intervention may be required to release the adhesions and prevent permanent damage to the ocular surface. To keep the fornices open and prevent adhesions from forming, use symblepharon rings or glass rods.

Chronic Phase Management

The chronic phase of ocular involvement in Stevens-Johnson Syndrome can be particularly difficult because patients may develop long-term complications that necessitate ongoing management.

1. Management of Chronic Dry Eye: Chronic dry eye (keratoconjunctivitis sicca) is a common and debilitating side effect of SJS. Management strategies include:

• Artificial Tears and Lubricants: Using preservative-free artificial tears on a regular basis is still an important part of management. For nighttime relief, thicker lubricating ointments or gels can be used.
• Punctal Plugs: To preserve natural tears, punctal plugs can be inserted into the tear ducts to prevent drainage, increasing tear film stability and alleviating dry eye symptoms.
• Autologous Serum Eye Drops: Autologous serum eye drops, made from the patient’s own blood, can be used to treat severe dry eye that does not respond to other treatments. These drops contain growth factors and nutrients that promote healing and preserve the health of the ocular surface.

1. Management of Corneal Scarring: Corneal scarring and opacification are serious complications that can cause significant vision loss. Management may include:

• Scleral Lenses: These are large, gas-permeable contact lenses that vault over the cornea and rest on the sclera. They act as a fluid reservoir over the cornea, protecting it from further damage while also improving vision by smoothing out scarring.
• Corneal Transplantation: In cases of severe corneal scarring that significantly impairs vision, corneal transplantation may be considered. This procedure replaces damaged corneal tissue with a donor cornea. However, chronic inflammation and dry eye disease can reduce the success rate of corneal transplants in SJS patients.
• Limbal Stem Cell Transplantation: For patients with limbal stem cell deficiency, limbal stem cell transplantation may be required to restore the corneal epithelium’s regenerative capacity. This complex procedure entails transplanting healthy stem cells from a donor or another area of the patient’s eye.

1. Management of Entropion and Trichiasis: Entropion (inward turning of the eyelids) and trichiasis (misdirected eyelashes) necessitate surgical intervention to prevent further corneal damage.

• Eyelid Surgery: Procedures such as eyelid repositioning or tarsorrhaphy (partial or complete closure of the eyelids) may be used to correct entropion and protect the cornea.
• Eyelash Epilation: Trichiasis can be treated by plucking the misdirected eyelashes or using more permanent methods like electrolysis or cryotherapy.

1. Glaucoma Treatment: Glaucoma management in SJS patients is frequently complex, necessitating a combination of medical and surgical interventions. Topical intraocular pressure-lowering medications, laser therapy, or surgical procedures may be required to control glaucoma and protect the optic nerve.
2. Psychosocial Support and Counseling: The long-term nature of ocular complications in SJS can have a significant impact on a patient’s psychological health. Access to psychosocial support, counseling, and support groups is an essential component of comprehensive care for these patients.

Ongoing Monitoring and Follow-up

Patients with SJS should see their ophthalmologist on a regular basis to monitor disease progression, assess treatment effectiveness, and address any new complications that may arise. Lifelong monitoring is often required, especially in patients with severe ocular involvement.

Trusted Resources and Support

Books

1. “Ocular Surface Disease: Cornea, Conjunctiva, and Tear Film” by Edward J. Holland: This book provides an in-depth exploration of ocular surface diseases, including the management of complex conditions like Stevens-Johnson Syndrome. It is a valuable resource for ophthalmologists and other eye care professionals.
2. “Stevens-Johnson Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide” by Icon Health Publications: This comprehensive guide offers a wealth of information on Stevens-Johnson Syndrome, including its ocular manifestations. It is an essential resource for patients and healthcare providers seeking to understand the condition.

Organizations

1. American Academy of Ophthalmology (AAO): The AAO is a leading organization that provides extensive resources on eye health, including the management of complex conditions like Stevens-Johnson Syndrome. Their website offers educational materials, clinical guidelines, and updates on the latest research.
2. Stevens-Johnson Syndrome Foundation (Julie Foundation): The Stevens-Johnson Syndrome Foundation offers support, advocacy, and resources for patients and families affected by SJS. Their mission is to increase awareness, provide educational materials, and support research into the prevention and treatment of SJS.
3. National Eye Institute (NEI): The NEI is a part of the U.S. National Institutes of Health and provides valuable information on eye diseases, including the ocular manifestations of Stevens-Johnson Syndrome. They offer research updates, clinical trial information, and patient education resources.