Background

• Atopic keratoconjunctivitis (AKC) is a chronic inflammatory condition that affects the conjunctiva and cornea of the eye. It is commonly associated with atopic dermatitis (eczema) and other systemic allergic conditions. AKC primarily affects adults and is more prevalent with a family history of atopy.
• The condition is characterized by persistent and severe inflammation of conjunctiva and cornea, leading to symptoms such as intense itching, redness, swelling, tearing, and foreign body sensation. The cornea may also be affected, leading to corneal damage, scarring, and visual impairment if left untreated.
• The underlying cause of AKC is an exaggerated immune response to allergens, such as pollen, dust mites, and animal dander. It involves both immunoglobulin E (IgE)-mediated and cell-mediated immune responses. Genetic and environmental factors play an important role in the development of AKC.
• The management of AKC involves a combination of environmental modifications, topical medications, and occasionally systemic therapy. Long-term control of inflammation and prevention of complications are the main goals of treatment. Close monitoring and regular follow-up with an ophthalmologist are necessary to optimize visual outcomes and manage the condition effectively.

Epidemiology

• Prevalence: Atopic keratoconjunctivitis (AKC) is a rare condition compared to other forms of allergic conjunctivitis. The exact prevalence of AKC is not well established.
• Age and Gender: AKC typically affects adults, with most cases presenting in the second to fourth decade of life. It is most common in males than females.
• Atopic Background: AKC is strongly associated with atopic dermatitis (eczema) and other systemic allergic conditions, such as asthma and allergic rhinitis.
• Geographical Variation: The prevalence of AKC may vary among different geographic regions. It is more commonly reported in areas with a higher prevalence of atopic diseases.

Anatomy

Pathophysiology

Immunologic Abnormalities: Atopic keratoconjunctivitis (AKC) is characterized by an underlying immunologic dysfunction, primarily involving type 2 hypersensitivity reactions.

• Mast Cell Activation: Mast cells play a crucial role in the pathogenesis of AKC. Upon exposure to allergens, mast cells release inflammatory mediators such as histamine, leukotrienes, and cytokines, leading to local inflammation and ocular surface damage.
• IgE-Mediated Response: In individuals with a predisposition to atopy, including atopic dermatitis and other allergic conditions, there is an elevated production of allergen-specific immunoglobulin E (IgE) antibodies. These IgE antibodies bind to high-affinity receptors on mast cells, triggering an allergic response upon subsequent exposure to the allergen.
• Inflammatory Cascade: The release of inflammatory mediators by mast cells and other immune cells leads to an inflammatory cascade, including recruitment of eosinophils, lymphocytes, and other inflammatory cells to ocular surface. This chronic inflammation contributes to the characteristic features of AKC, such as conjunctival hyperemia, papillary hypertrophy, and corneal epithelial defects.

Etiology

• Atopic Predisposition: Atopic keratoconjunctivitis (AKC) is commonly seen in individuals with a predisposition to atopic diseases, such as atopic dermatitis (eczema), allergic rhinitis (hay fever), and asthma.
• Allergen Sensitization: AKC is triggered by exposure to specific allergens, such as airborne allergens (pollens, dust mites, animal dander) or food allergens. Sensitization to these allergens leads to an immune response and subsequent inflammation in the conjunctiva and cornea.
• Environmental Factors: Environmental factors like air pollution, exposure to irritants, and dry or dusty environments can exacerbate the symptoms of AKC and contribute to disease severity.
• Immunologic Dysregulation: There is an underlying immunologic dysregulation in AKC, characterized by an imbalance in Th1/Th2 immune responses. There is an overproduction of Th2 cytokines, such as interleukin-4 (IL-4) and interleukin-5 (IL-5), which promote allergic inflammation.

Genetics

Prognostic Factors

• Disease Duration: The duration of atopic keratoconjunctivitis (AKC) can impact the prognosis. Long-standing and chronic cases of AKC may be associated with more severe symptoms and complications.
• Severity of Symptoms: The severity of symptoms like redness, itching, tearing, and discharge, can influence the prognosis. Severe symptoms may lead to significant discomfort and impairment of daily activities.
• Response to Treatment: The response to treatment plays an important role in determining the prognosis of AKC. Prompt and adequate management, including the use of topical medications and avoidance of triggers, can help control symptoms and prevent complications.
• Corneal Involvement: The presence and extent of corneal involvement, such as corneal erosions, ulcers, or scarring, can impact the prognosis. Corneal complications may lead to visual impairment and require specialized interventions.
• Compliance with Treatment: The patient’s adherence to the prescribed treatment regimen, including the consistent use of medications and avoidance of triggers, can influence the long-term prognosis of AKC.

Clinical History

CLINICAL HISTORY

Age group:

• Atopic keratoconjunctivitis (AKC) typically presents in adults, with the onset usually occurring between the ages. However, it can affect children and adolescents.

Physical Examination

PHYSICAL EXAMINATION

External Eye Examination:

• Eyelids: Look for signs of eyelid dermatitis, such as redness, scaling, crusting, or eczematous lesions.
• Eyelashes: Observe for signs of blepharitis, including crusting, debris, or misdirection of eyelashes.
• Conjunctiva: Assess for conjunctival redness (conjunctival injection) and papillary reaction, which may appear as small bumps on the inner surface of the eyelids.
• Tear Film: Evaluate the quantity and quality of tears, which may be decreased or have an altered composition in atopic keratoconjunctivitis.

Slit-Lamp Examination:

• Cornea: Examine the cornea for signs of involvement, such as punctate epithelial erosions, superficial ulcers, or corneal neovascularization.
• Conjunctiva: Look for signs of conjunctival inflammation, including redness, papillary hypertrophy, and thickened conjunctival folds.
• Meibomian Glands: Evaluate the meibomian glands for meibomian gland dysfunction, which can contribute to ocular surface inflammation.

Visual Acuity and Refraction:

• Assess visual acuity to determine if the corneal involvement or other ocular abnormalities affect vision.
• Perform refraction to evaluate for any refractive errors that may contribute to visual impairment.

Allergy Testing:

• Consider performing allergy testing, such as skin prick tests or specific IgE blood tests, to identify specific allergens that may be triggering the allergic response in atopic keratoconjunctivitis.

Additional Investigations:

• In some cases, additional tests such as tear film break-up time (TBUT), Schirmer’s test, or corneal topography may be performed to further assess tear film stability, tear production, or corneal irregularities.

Age group

Associated comorbidity

Associated comorbidity or activity:

Atopic Keratoconjunctivitis is often associated with a history of atopic diseases, such as atopic dermatitis (eczema), allergic rhinitis (hay fever), or asthma. These conditions share a similar underlying immune dysfunction.

Patients with AKC may have a personal or family history of allergies, including food allergies or other allergic eye diseases like vernal keratoconjunctivitis. Environmental factors can exacerbate the symptoms of AKC. Common triggers include pollen, dust mites, pet dander, and certain chemicals.

Associated activity

Acuity of presentation

Acuity of presentation:

• The onset of AKC is usually gradual, with chronic and persistent symptoms. The severity and acuity of presentation can vary among individuals.
• Common symptoms include severe itching, redness (conjunctival injection), tearing, foreign body sensation, and burning or stinging sensation in the eyes.
• Patients with AKC may experience recurrent episodes of exacerbation and remission of symptoms.
• In severe cases, AKC can lead to corneal involvement, including corneal erosions, ulcers, and scarring, which may cause blurred vision and eye discomfort.

Differential Diagnoses

DIFFERENTIAL DIAGNOSIS

• Allergic Conjunctivitis: Allergic conjunctivitis, including seasonal and perennial types, can present with similar symptoms to AKC. However, the severity and chronicity of symptoms are typically more pronounced in AKC.
• Vernal Keratoconjunctivitis: Vernal keratoconjunctivitis is a chronic allergic inflammation of the conjunctiva that primarily affects children and young adults. It shares some clinical features with AKC, but vernal keratoconjunctivitis is typically more prevalent in warmer climates and is associated with giant papillae on the upper tarsal conjunctiva.
• Giant Papillary Conjunctivitis: Giant papillary conjunctivitis is characterized by the formation of large papillae on the upper tarsal conjunctiva, often associated with contact lens use or ocular prostheses.
• Dry Eye Syndrome: It can cause similar symptoms of redness, itching, and irritation in the eyes. A thorough evaluation is needed to differentiate AKC from dry eye syndrome, as both conditions can coexist.
• Infectious Conjunctivitis: Bacterial or viral conjunctivitis can present with redness, discharge, and irritation like AKC. However, the absence of chronicity and specific ocular findings can help differentiate infectious conjunctivitis from AKC.
• Ocular Rosacea: Ocular rosacea can manifest with ocular symptoms, including redness, burning sensation, and gritty feeling in the eyes. Evaluation of additional cutaneous signs of rosacea can aid in distinguishing it from AKC.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Avoidance of Triggers: 

• Identify and avoid allergens or irritants that may exacerbate AKC symptoms, such as dust mites, pet dander, pollen, and certain cosmetics. 

Topical Corticosteroids: 

• Topical corticosteroids are often the mainstay of treatment for AKC to reduce inflammation. 
• They should be used under the guidance of an ophthalmologist and for a limited duration to avoid potential side effects, such as increased intraocular pressure or cataract formation. 

Topical Calcineurin Inhibitors: 

• Tacrolimus and pimecrolimus are topical calcineurin inhibitors that may be used as an alternative or adjunct to corticosteroids. 
• They aid in reducing inflammation and immune response suppression. 

Topical Antihistamines and Mast Cell Stabilizers: 

• In order to stop itching and stop inflammatory mediators from being released, topical antihistamine and mast cells stabilizers might be used. 
• These agents are available in eye drop form. 

Oral Antihistamines: 

• Oral antihistamines may be prescribed to help control systemic allergic symptoms and provide additional relief from itching. 

Artificial Tears and Lubricants: 

• Lubricating eye solutions can ease the irritation and dryness brought on by AKC. 
• They may also help wash away allergens from the ocular surface. 

Systemic Immunomodulators: 

• In severe cases of AKC that do not respond to topical therapy, systemic immunomodulators such as cyclosporine or systemic corticosteroids may be considered. 
• These medications have potential side effects and require close monitoring. 

Ocular Hygiene: 

• Practicing good ocular hygiene, such as regular eyelid cleaning, can help reduce the risk of secondary bacterial infections. 

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-atopic-keratoconjunctivitis

• Environmental Modifications: Identify and minimize exposure to environmental allergens. This may involve using air purifiers, regularly cleaning living spaces, and implementing measures to reduce indoor allergens. 
• Eyelid Hygiene: Practicing good eyelid hygiene is essential in preventing and managing AKC. This includes using warm compresses to reduce inflammation, gently cleansing the eyelids to remove debris, and avoiding eye rubbing. 
• Cold Compresses: Applying the cold compresses to the eyes can help reduce inflammation and soothe symptoms. Cold compresses can be especially useful during acute flare-ups of itching and redness. 
• Protective Eyewear: Wearing sunglasses with wrap-around frames can help protect the eyes from airborne allergens, wind, and other environmental irritants. 
• Avoiding Eye Rubbing: Encourage patients to avoid rubbing their eyes, as this can exacerbate inflammation and potentially lead to corneal damage. 
• Moisture Chamber Goggles: Moisture chamber goggles can be worn to create a barrier that helps retain moisture around the eyes. This may be especially helpful for people who are suffering from the dryness related to AKC. 
• Stress Management: Anxiety can make allergy symptoms worse. Including stress-reduction methods like yoga, prolonged breathing exercises, or meditation can enhance general wellbeing and perhaps lessen symptoms of AKC. 

Role of topical mast cell stabilizers in the treatment of Atopic keratoconjunctivitis

Topical mast cell stabilizers play a crucial role in the treatment of Atopic Keratoconjunctivitis (AKC) by preventing the release of inflammatory mediators, particularly histamine, from mast cells. These medications help control symptoms such as itching, redness, and inflammation associated with AKC. 

Cromolyn Sodium: 

• It acts as a mast cell stabilizer, inhibiting the production of histamine along with other inflammatory chemicals. It is available in eye drop formulations and is used to relieve itching and reduce inflammation in the conjunctiva. 

Nedocromil: 

• Nedocromil is another mast cell stabilizer used in the treatment of allergic conjunctivitis, including AKC. It helps prevent the release of histamine and other allergic mediators, providing relief from symptoms such as itching and redness. 

Lodoxamide: 

• Lodoxamide is a mast cell stabilizer that is available in ophthalmic solutions. It inhibits mast cell degranulation, helping to control the inflammatory response in the eyes and reduce symptoms associated with AKC. 

Role of Topical antihistamines in the treatment of Atopic keratoconjunctivitis

Topical antihistamines play a crucial role in the treatment of Atopic Keratoconjunctivitis (AKC) by targeting the histamine receptors in the eyes. Histamine is a major modulator of the allergic reaction and causes tearing, redness, and itching in allergic corneal disease (AKC). Topical antihistamines help alleviate these symptoms by blocking the effects of histamine.  

• Olopatadine: Olopatadine is a second-generation topical antihistamine that also possesses mast cell-stabilizing properties. It is available in eye drop formulations and is effective in reducing itching and ocular redness associated with AKC. Olopatadine may also have anti-inflammatory effects, contributing to its overall efficacy. 
• Azelastine: Azelastine is another topical antihistamine that is available in both eye drop and nasal spray formulations. It is used to relieve ocular itching and other allergic symptoms. Because it also prevents mast cell histamine release, zelastine functions in two ways. 
• Epinastine: Epinastine is a topical antihistamine with additional mast cell-stabilizing properties. It is available in eye drop formulations and is used to treat itching and other allergic symptoms associated with AKC. 
• Ketotifen: Ketotifen is a drug with two functions: it stabilizes mast cells and reduces allergic reactions. It is available in eye drop formulations and is effective in relieving ocular itching and redness in AKC. 
• Levocabastine: Levocabastine is an older generation topical antihistamine that is less commonly used today. It is available in eye drop formulations and is used to treat allergic conjunctivitis, including AKC. 

Role of Corticosteroids in the treatment of Atopic keratoconjunctivitis

Corticosteroids play an important role in the treatment of Atopic Keratoconjunctivitis (AKC) due to their potent anti-inflammatory properties. They aid in reducing ocular inflammation and immune response suppression, relieving symptoms related to AKC.  

• Prednisolone Acetate: It is a commonly prescribed topical corticosteroid for ocular conditions, including AKC. It works effectively to relieve symptoms like redness and swelling and reduce inflammation. It is accessible as eye drops. 
• Loteprednol Etabonate: Loteprednol etabonate is a newer generation topical corticosteroid with a favorable safety profile. It is available in eye drop formulations and has been used to manage inflammation in various ocular conditions, including AKC. 
• Dexamethasone: Dexamethasone is a potent corticosteroid that may be prescribed for severe cases of AKC. It is available in various formulations, including eye drops, ointments, and intravitreal injections. Dexamethasone provides strong anti-inflammatory effects but is typically reserved for short-term use due to its potential side effects. 

• Fluorometholone: Fluorometholone is a mild to moderate potency corticosteroid available in eye drop and ointment formulations. It is used to reduce inflammation in the eyes and is sometimes prescribed for the management of AKC. 

Role of Immunosuppressants in the treatment of Atopic keratoconjunctivitis 

Immunosuppressants play a role in the treatment of Atopic Keratoconjunctivitis (AKC) by modulating the immune response and reducing inflammation. In cases where AKC is severe or does not respond adequately to other medications, immunosuppressants may be considered. These drugs help suppress the abnormal immune activity responsible for the chronic inflammation seen in AKC. 

• Cyclosporine: It acts as an immunosuppressive drug that prevents activation of T cells and the production of inflammatory cytokines. It is available in ophthalmic emulsion formulations and is used to reduce inflammation and control symptoms in severe cases of AKC. 
• Tacrolimus (FK506): It is another calcineurin inhibitor that has immunosuppressive properties. Like cyclosporine, tacrolimus inhibits T-cell activation and the production of inflammatory cytokines. It may be used in ophthalmic formulations for the treatment of AKC. 

use-of-intervention-with-a-procedure-in-treating-atopic-keratoconjunctivitis

• Cauterization of Papillae: In cases where giant papillae have formed on the conjunctiva due to chronic inflammation, cauterization of papillae may be considered. This procedure involves using a mild cautery agent to shrink or remove the enlarged papillae. 
• Subconjunctival Corticosteroid Injections: Subconjunctival injections of corticosteroids may be considered in severe cases of AKC that do not respond adequately to topical medications. This involves injecting a corticosteroid directly beneath the conjunctiva, providing a more localized and potent anti-inflammatory effect. 
• Amniotic Membrane Transplantation: In cases where there is significant corneal involvement or ulceration, amniotic membrane transplantation may be considered. In order to encourage healing, lessen inflammation, and avoid scarring, a thin coating of amniotic membrane is applied to the surface of the eye during this surgery. 
• Conjunctival Resection or Excision: In some cases of severe AKC with extensive conjunctival involvement, surgical procedures such as conjunctival resection or excision may be considered to remove diseased tissue and improve symptoms. 
• Keratoplasty (Corneal Transplant): In rare cases where AKC has led to significant corneal damage or scarring, a corneal transplant (keratoplasty) may be considered to replace the damaged corneal tissue with healthy donor tissue. 

use-of-phases-in-managing-atopic-keratoconjunctivitis

• Diagnostic Phase: Accurate diagnosis is essential for effective management. This phase involves a comprehensive eye examination, medical history review, and possibly allergy testing to confirm the presence of AKC. Establishing the severity of the condition helps guide the subsequent treatment approach. 
• Acute Symptomatic Phase: In the initial phase, the focus is on alleviating acute symptoms such as itching, redness, and tearing. Topical antihistamines, mast cell stabilizers, and short-term use of topical corticosteroids may be prescribed to provide rapid relief. Lubricating eye drops can also help in soothing the ocular surface. 
• Subacute Phase: As symptoms start to improve, the treatment plan may be adjusted to maintain control and prevent symptom recurrence. Adjustments may include tapering corticosteroid use, continuing mast cell stabilizers, and considering the introduction of other medications like calcineurin inhibitors. 

• Maintenance Phase: Once symptoms are under control, a maintenance phase focuses on long-term management. This often involves the continued use of mast cell stabilizers, topical antihistamines, or other appropriate medications. Ocular hygiene practices, such as eyelid cleaning, may be emphasized to prevent complications. 
• Crisis Management Phase: In some cases, patients may experience exacerbations or flare-ups of AKC. This phase involves addressing acute symptoms promptly, possibly with a short course of topical corticosteroids or other interventions, to prevent progression to more severe complications. 
• Adjunctive and Complementary Therapies: Depending on the individual patient’s response and needs, adjunctive therapies such as artificial tears, cold compresses, or oral antihistamines may be recommended to enhance overall symptom relief and improve the ocular surface. 
• Monitoring and Follow-Up: Regular follow-up appointments are crucial to monitor the patient’s response to treatment, assess any potential side effects of medications, and make necessary adjustments to the management plan. Ophthalmologists may perform periodic eye examinations to evaluate the ocular surface and screen for complications. 
• Preventive Measures: Education on allergen avoidance and lifestyle modifications may be included in the management plan to help prevent or minimize exposure to triggers. This can contribute to long-term symptom control. 

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References

Allergic Conjunctivitis:ncbi.nlm.nih