Background

The rare, persistent inflammatory disease known as superior limbic keratoconjunctivitis (SLK) affects the superior conjunctiva and cornea. It is characterized by inflammation, redness, discomfort, and burning or foreign body sensation in the affected eye. 

SLK typically occurs in both eyes but may be asymmetric. It primarily affects the superior portion of the eyes, hence the name. Though its precise etiology is unknown, SLK is thought to be caused by mechanical friction, persistent irritation, or a confluence of disorders such thyroid eye illness, eyelids, dry eye, or eyelid abnormalities. 

Epidemiology

• Age and Gender: SLK is often diagnosed in adults, and there appears to be a slight female predominance. Women, particularly those in their 30s and 40s, are reported to be more commonly affected than men. 
• Association with Thyroid Dysfunction: There is a recognized association between SLK and thyroid dysfunction, particularly Graves’ disease. Patients with thyroid disorders, especially hyperthyroidism, may have an increased risk of developing SLK. 
• Underlying Conditions: SLK has been linked to various underlying conditions, including dry eye syndrome, contact lens use, and abnormalities of the eyelids. Chronic mechanical irritation and inflammation may contribute to the development of SLK. 
• Recurrent Nature: SLK often exhibits a chronic and recurrent course. Fluctuations in symptoms and periods of exacerbation are common. 
• Incidence and Prevalence: Specific incidence and prevalence rates for SLK are not well-established, possibly due to its rarity. Because it is not a widely studied condition, epidemiological data may vary, and prevalence rates in different populations remain unclear. 

Anatomy

Pathophysiology

• Mechanical Friction: One of the primary factors associated with SLK is mechanical friction between the superior tarsal conjunctiva (the thin membrane covering the upper eyelid) and the superior bulbar conjunctiva (covering the white part of the eye). Chronic discomfort and inflammation may result from this friction. 
• Dry Eye Syndrome: It is characterized by inadequate tear production or low-quality tears, is frequently linked to SLK. Dry eyes can contribute to increased friction between the conjunctiva and the eyelid, exacerbating the inflammatory response. 
• Abnormalities in Tear Film Composition: Changes in the composition of the tear film, including alterations in mucin, lipid, and aqueous components, may contribute to the development of SLK. An unstable tear film can lead to inadequate lubrication and increased susceptibility to irritation. 
• Eyelid Abnormalities: Structural abnormalities of the eyelids, such as superior limbic hypertrophy or prominent conjunctival blood vessels, may contribute to the mechanical irritation observed in SLK.  
• Thyroid Dysfunction: There is a recognized association between SLK and thyroid disorders, particularly hyperthyroidism, such as in Graves’ disease. Autoimmune mechanisms and systemic inflammation associated with thyroid dysfunction may play a role in the pathophysiology of SLK. 
• Chronic Inflammation: The chronic nature of SLK suggests an ongoing inflammatory process. It is possible for inflammatory mediators like chemokines and cytokines to prolong tissue damage and inflammation. 

Etiology

• Eyelid Abnormalities: Structural abnormalities of the eyelids, such as meibomian gland dysfunction, can contribute to mechanical irritation and inflammation of the ocular surface in SLK. 

• Thyroid Dysfunction: There is a recognized association between SLK and thyroid disorders, particularly hyperthyroidism, such as in Graves’ disease. Autoimmune mechanisms associated with thyroid dysfunction may play a role in the pathogenesis of SLK. 
• Contact Lens Use: The development of SLK has been linked to long-term usage of contact lenses, particularly rigid gas permeable lenses. Contact lens wear can cause mechanical irritation and disrupt the tear film, predisposing the eyes to inflammation. 
• Allergic Reactions: Some cases of SLK may be associated with allergic reactions to environmental allergens or contact allergens, leading to chronic inflammation of the ocular surface. 
• Microbial Infections: While less common, microbial infections, such as viral or bacterial conjunctivitis, can contribute to the development of SLK, particularly if left untreated or if there is a compromised immune response. 
• Genetic Predisposition: Although particular genetic variables have not been found, there may be a hereditary propensity to developing SLK. 

Genetics

Prognostic Factors

• Underlying Causes and Conditions: Identifying and addressing underlying causes or conditions contributing to SLK is crucial for prognosis. For example, treating thyroid dysfunction (if present) or managing dry eye syndrome can have a positive impact on the course of SLK. 
• Patient Compliance: Adherence to the prescribed treatment plan and follow-up appointments is essential. Patients who consistently use prescribed eye drops, follow eyelid hygiene measures, and attend regular check-ups are more likely to manage their symptoms effectively and prevent complications. 
• Severity of Inflammation: The extent and severity of inflammation in SLK can influence prognosis. Cases with mild to moderate inflammation may respond well to conservative treatments, while severe and chronic inflammation may require more aggressive interventions. 
• Corneal Involvement: Corneal complications, such as epithelial defects, erosions, or ulcers, can occur in advanced cases of SLK. The presence of corneal involvement may impact prognosis and require closer monitoring and specialized interventions to prevent long-term damage. 
• Response to Treatment: The responsiveness of SLK to treatment is a significant prognostic factor. Individuals who experience relief of symptoms and improvement in ocular surface health with prescribed therapies, such as lubricating eye drops, anti-inflammatory medications, or surgical interventions, generally have a better prognosis. 

Clinical History

Age Group: 

Adults (30s to 40s): 

Clinical Presentation: 

• Commonly presents with symptoms such as burning, itching, or foreign body sensation in the superior aspect of the eye. 
• Redness and irritation, particularly in the upper conjunctiva.
• Dry eye symptoms, including intermittent blurred vision and fluctuating discomfort. 

Children and Adolescents:

Clinical Presentation: 

• Less common in this age group compared to adults. 
• Symptoms may include redness, irritation, or discomfort in the superior part of the eye. 
• Presence of SLK may suggest underlying ocular or systemic conditions. 

Physical Examination

Visual Acuity Assessment: 

• Measure visual acuity using an eye chart to determine if there is any impact on vision. 

External Examination: 

• Evaluate the external structures of the eyes, including eyelids and lashes, for signs of inflammation, redness, or anatomical abnormalities. 

Slit-Lamp Examination: 

• Use a slit lamp, a specialized microscope with a bright light, to examine the anterior segment of the eye in detail. 
• Assess the superior tarsal and bulbar conjunctiva for signs of inflammation, hyperemia (redness), and papillary hypertrophy. 
• Examine the cornea for any epithelial defects, erosions, or other abnormalities. 

Conjunctival Staining: 

• Perform fluorescein staining of the cornea to identify any surface irregularities, defects, or abrasions. 

Tear Film Assessment: 

• Analyze the tear film’s amount and quality. 
• Assess for signs of dry eye, such as reduced tear breakup time or decreased tear production. 

Assessment of Superior Limbus: 

• Pay special attention to the superior limbus, as SLK primarily affects this region. 
• Look for signs of superior limbic inflammation, hypertrophy, and the characteristic gelatinous appearance. 

Age group

Associated comorbidity

• Often associated with thyroid dysfunction, particularly hyperthyroidism (Graves’ disease), in this age group.
• Prolonged reading or computer use may exacerbate symptoms due to increased ocular surface irritation. 

Children and Adolescents: 

• SLK in children and adolescents may be associated with conditions such as atopic dermatitis or allergic conjunctivitis. 
• Outdoor activities or exposure to allergens may exacerbate symptoms. 

Associated activity

Acuity of presentation

• Symptoms may present gradually and become chronic over time, with intermittent exacerbations. 

Children and Adolescents: 

• Symptoms may develop gradually and may not be as pronounced as in adults. 

Differential Diagnoses

• Dry Eye Syndrome: Dry eye can cause ocular discomfort, redness, and a foreign body sensation, which are also common symptoms in SLK. Tear film evaluation and other dry eye tests can help differentiate between the two conditions. 
• Allergic Conjunctivitis: Allergic conjunctivitis can present with redness, itching, and tearing, similar to SLK. A careful history, including seasonal patterns and exposure to allergens, can aid in distinguishing between the two. 
• Conjunctivochalasis: Conjunctivochalasis involves redundant and loose conjunctival tissue, often causing irritation and discomfort. It may share symptoms with SLK, but the clinical features and location of the inflammation differ. 
• Giant Papillary Conjunctivitis (GPC): GPC is an inflammatory condition often associated with contact lens use. It can cause itching, tearing, and a foreign body sensation. Differentiating between GPC and SLK may require consideration of the patient’s history of contact lens wear and specific clinical features. 
• Corneal Dystrophies: Certain corneal dystrophies can present with discomfort and redness. Corneal examination and specialized tests may be necessary to rule out dystrophic changes. 
• Pingueculitis/Pterygium: Pingueculitis and pterygium involve growths on the conjunctiva that can cause redness and irritation. However, their location and appearance distinguish them from SLK. 
• Corneal Erosions or Abrasions: Corneal injuries, erosions, or abrasions can cause symptoms similar to SLK. Fluorescein staining and detailed corneal examination are crucial to identify corneal involvement. 
• Episcleritis/Scleritis: Inflammatory conditions affecting the episclera or sclera can present with redness and discomfort. A careful examination can help differentiate between these conditions and SLK. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• Artificial Tears and Lubricants: Preservative-free artificial tears and lubricating eye drops can provide symptomatic relief by improving tear film stability and reducing dryness. Frequent use throughout the day, even in the absence of symptoms, can be beneficial. 
• Topical Anti-Inflammatory Medications: Short-term use of topical corticosteroids may be considered during acute exacerbations to control inflammation. However, because to the possibility of complications such as elevated pressure in the eyes and cataract development, extended usage should be avoided. 
• Topical Cyclosporine A: Immunosuppressive agents like topical cyclosporine A may be prescribed to modulate the immune response and reduce inflammation. When other therapies fail to reduce inflammation, this can be very helpful. 
• Eyelid Hygiene: Proper eyelid hygiene measures, including warm compresses and lid scrubs, can help manage conditions such as meibomian gland dysfunction and reduce mechanical irritation. 
• Moisture-Chamber Goggles or Shields: Protective goggles or shields can help reduce exposure to environmental factors, such as wind and dust, which may exacerbate symptoms. 
• Treatment of Underlying Conditions: If SLK is associated with systemic conditions, such as thyroid dysfunction, appropriate management of the underlying condition is crucial. Collaboration with other healthcare professionals may be necessary. 
• Contact Lens Management: For individuals who wear contact lenses, reassessment of lens type, fit, and wearing schedule may be necessary. In some cases, discontinuation of contact lens wear may be recommended. 
• Amniotic Membrane Transplantation: In severe and refractory cases, amniotic membrane transplantation may be considered to promote healing and reduce inflammation. This surgical intervention aims to provide a protective environment for the ocular surface. 
• Anti-Allergic Medications: In cases with an allergic component, oral antihistamines or other anti-allergic medications may be prescribed to manage symptoms. 
• Regular Follow-Up: Regular monitoring and follow-up with an eye care professional are essential to assess treatment efficacy, adjust management strategies, and address any complications that may arise. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-a-non-pharmacological-approach-for-treating-superior-limbic-keratoconjunctivitis

• Artificial Tears and Lubricating Eye Drops: Frequent use of preservative-free artificial tears can provide relief by lubricating the ocular surface and improving tear film stability. These drops help alleviate dryness and reduce friction between the superior tarsal and bulbar conjunctiva. 
• Eyelid Hygiene: Proper eyelid hygiene is essential to manage conditions like meibomian gland dysfunction, which may contribute to SLK. Warm compresses and lid scrubs can help maintain a healthy tear film and reduce mechanical irritation. 
• Moisture-Chamber Goggles or Shields: Wearing moisture-chamber goggles or shields helps create a microenvironment that minimizes exposure to environmental factors, such as wind and dust. For those with SLK who might be sensitive to certain irritants, this can be very helpful. 
• Protective Eyewear: Encouraging the use of sunglasses with side shields can protect the eyes from environmental elements, reducing exposure to wind, dust, and other potential irritants. 

• Punctal Plugs: Punctal plugs may be considered to reduce tear drainage, thereby increasing the retention time of natural tears on the ocular surface. This can help alleviate dryness and enhance lubrication. 
• Contact Lens Management: Reassessing contact lens type, fit, and wearing schedule is crucial for individuals who wear contact lenses. In some cases, discontinuation of contact lens wear may be recommended to reduce mechanical irritation. 
• Humidification: Using humidifiers in indoor environments can help maintain a more comfortable humidity level, reducing the likelihood of dry eyes and irritation. 
• Environmental Modifications: Advising patients to avoid exposure to smoke, airborne allergens, and other environmental irritants can contribute to symptom relief. 
• Behavioral Modifications: Educating patients about minimizing eye rubbing or touching can prevent exacerbation of symptoms and reduce mechanical friction on the ocular surface. 

Role of Mast Cell Stabilizers of the treatment of Superior limbic keratoconjunctivitis

Mast cell stabilizers are a class of medications that can be used in the treatment of inflammatory conditions of the eye, including Superior Limbic Keratoconjunctivitis (SLK). These drugs reduce inflammation and the symptoms of disorders like SLK by blocking mast cell production of histamine along with other inflammatory mediators. Mast cell stabilizers stop pro-inflammatory substances like histamine from being released by mast cells. This helps reduce the inflammatory response on the ocular surface, which is beneficial in conditions characterized by chronic inflammation, such as SLK. 

• Cromolyn Sodium: It is a commonly used mast cell stabilizer. It is available in various forms, including eye drops. Cromolyn sodium eye drops may be prescribed for their anti-inflammatory effects on the ocular surface. 
• Lodoxamide Tromethamine: It is another mast cell stabilizer available in the form of eye drops. It helps prevent the release of inflammatory substances from mast cells, contributing to the management of ocular surface inflammation. 
• Nedocromil Sodium: It is a mast cell stabilizer that may be used in the form of eye drops to manage allergic and inflammatory conditions on the ocular surface. 

Role of Cauterizing Agents in the treatment of Superior limbic keratoconjunctivitis

Keratinized conjunctivae are treated by topical use of cauterizing chemicals. 

Silver nitrate: Superior limbic keratoconjunctivitis symptoms often go away after 4–6 weeks when silver nitrate is applied to the anesthetized conjunctiva. The course of therapy can then be safely continued. 

Role of Immunomodulators in the treatment of Superior limbic keratoconjunctivitis

Immunomodulators significantly treat Superior Limbic Keratoconjunctivitis (SLK) by modulating the immune response and reducing inflammation. SLK is characterized by chronic superior conjunctiva and cornea inflammation, and immunomodulators can help manage this immune-mediated process.  

Topical Cyclosporine A: Cyclosporine A is an immunomodulatory agent that suppresses the immune response by inhibiting T-cell activation. It effectively manages ocular surface inflammation and improves symptoms associated with SLK. It helps stabilize the tear film and reduce the chronic inflammatory response on the ocular surface. 

use-of-intervention-with-a-procedure-in-treating-superior-limbic-keratoconjunctivitis

• Amniotic Membrane Transplantation: Amniotic membrane transplantation involves placing a thin layer of amniotic membrane onto the ocular surface. This procedure provides a natural scaffold for healing, reduces inflammation, and promotes epithelialization. It can benefit cases with persistent epithelial defects, corneal involvement, or severe inflammation in SLK. 
• Superior Limbic Tarsal Conjunctival Flap (Noble’s Procedure): This surgical procedure involves creating a conjunctival flap from the superior tarsal conjunctiva and transposing it onto the superior limbus. The flap is a protective barrier, reducing mechanical friction and improving ocular surface health. 
• Conjunctival Resection or Excision: Surgical removal or excision of hypertrophic or inflamed conjunctival tissue, especially in the superior tarsal conjunctiva, can be considered in cases where conservative measures have failed. This procedure aims to reduce mechanical irritation and inflammation. 
• Limbal Stem Cell Transplantation: In cases where SLK has resulted in limbal stem cell deficiency, transplantation may be considered. This procedure involves grafting healthy limbal tissue onto the affected area to restore normal epithelial function. 
• Electrocautery: In some cases, localized cauterization using electrocautery may be performed to remove hypertrophic tissue or address specific inflammation areas. This procedure is generally used with caution due to the potential for scarring. 

use-of-phases-in-managing-superior-limbic-keratoconjunctivitis

Phase 1: Diagnosis and Assessment 

Clinical Evaluation: 

• Conduct a thorough clinical examination to assess symptoms like redness, discomfort, and foreign body sensation. 
• Use a slit lamp to examine the superior tarsal and bulbar conjunctiva, cornea, and eyelids for signs of inflammation and mechanical irritation. 

Patient History: 

• Gather information about the patient’s medical history, including any underlying systemic conditions, previous ocular surgeries, and environmental factors. 

Phase 2: Non-Pharmacological Interventions 

Eyelid Hygiene: 

• Implement proper eyelid hygiene measures, including warm compresses and lid scrubs, to manage meibomian gland dysfunction and reduce mechanical irritation. 

Artificial Tears: 

• Prescribe preservative-free artificial tears to improve tear film stability and alleviate dryness. 

Moisture-Chamber Goggles or Shields: 

• Use moisture-chamber goggles or shields to protect the eyes from environmental irritants. 

Protective Eyewear: 

• Encourage using sunglasses with side shields to shield the eyes from wind, dust, and other irritants. 

Punctal Plugs: 

• Consider the placement of punctal plugs to increase tear retention and enhance lubrication. 

Phase 3: Pharmacological Interventions 

Topical Corticosteroids: 

• Prescribe short-term use of topical corticosteroids during acute exacerbations to control inflammation. Because of the possible adverse consequences, prolonged usage should be avoided. 

Topical Mast Cell Stabilizers: 

• Consider using mast cell stabilizers, such as sodium cromoglicate or lodoxamide tromethamine, to reduce inflammation associated with allergic components. 

Topical Immunomodulators: 

• Employ topical immunomodulators, such as cyclosporine A or tacrolimus, to modulate the immune response and manage chronic inflammation. 

Phase 4: Surgical or Invasive Interventions 

Amniotic Membrane Transplantation: 

• Consider amniotic membrane transplantation in severe or refractory SLK cases to promote healing and reduce inflammation. 

Phase 5: Long-Term Management and Follow-Up 

Patient Education: 

• Educate the patient about the chronic nature of SLK and the importance of long-term management. 

Adjustment of Treatment Plan: 

• Adjust the treatment plan in light of the patient’s development, any new problems, or changes in symptoms. 

Systemic Evaluation: 

• If SLK is associated with systemic conditions, collaborate with other healthcare professionals for a more comprehensive systemic evaluation and management. 

Medication

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References

Superior Limbic Keratoconjunctivitis:ncbi.nlm.nih