Continuing Education Activity

Allergic conjunctivitis is a prevalent ocular condition encountered frequently by ophthalmologists and cornea specialists, affecting up to 40% of the population. Despite its high prevalence, many affected individuals do not seek medical help, leading to underdiagnosis and undertreatment. Itching remains the hallmark sign, and treatment typically involves topical antihistamines and mast cell inhibitors.

This activity provides clinicians with a comprehensive understanding of allergic conjunctivitis, encompassing its clinical presentation, immunological mechanisms, and therapeutic approaches. Through interactive discussions and the latest pharmacological insights, participants will gain valuable knowledge to optimize patient care and enhance outcomes in allergic conjunctivitis management. The importance of an interprofessional team approach is highlighted as learners explore the collaborative role of primary care providers, optometrists, and ophthalmologists in caring for patients with allergic conjunctivitis. 

Objectives:

• Differentiate between the various subtypes of allergic conjunctivitis, such as seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis.

• Screen patients for allergic conjunctivitis risk factors, including family history, environmental exposures, and atopic history.

• Apply pharmacological and non-pharmacological interventions for managing allergic conjunctivitis, tailoring treatment to individual patient needs.

• Communicate with patients about their condition, treatment options, and potential complications, ensuring patient understanding and adherence.

Introduction

Allergic conjunctivitis is a common, under-appreciated, and largely benign condition.[1] Allergic conjunctivitis prevalence has increased over the past decade, making it one of clinical practice's most frequently encountered conditions. Allergic conjunctivitis results from various factors, including genetics, inflammation, air pollution, atopy, pollen exposure, and contact with pets. Allergic conjunctivitis can convert to keratoconjunctivitis and may result in a visual decline.[2] While rarely posing a threat to vision, it can significantly impair patients' quality of life.

Simple allergic conjunctivitis can be classified into 3 subtypes: acute, seasonal, and perennial. Additionally, allergic conjunctivitis encompasses a broad range of conditions, including seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), and atopic keratoconjunctivitis (AKC).[3]

While VKC and AKC exhibit distinct clinical and pathophysiological features from SAC and PAC, specific markers remain consistent.

Giant papillary conjunctivitis (GPC) is another condition that arises from contact lens use or ocular prostheses-related microtrauma. Treatment and certain aspects of pathophysiology show considerable overlap between atopic conjunctivitis (VKC, AKC) and giant papillary conjunctivitis.[4] Therefore, these conditions are all classified as ocular allergies. Initial treatment strategies may be similar, although outcomes and complication rates vary.[5][6][7]

Etiology

Simple Allergic Conjunctivitis

Most cases of allergic conjunctivitis are secondary to simple allergen exposure on the ocular surface.

Seasonal Allergic Conjunctivitis

This condition, also called "hay fever eyes," tends to worsen during spring and summer. The most common allergens responsible are tree and grass pollens, with the specific allergen varying depending on the geographic location.[8]

Perennial Allergic Conjunctivitis

This conjunctivitis can occur throughout the year and is generally worse in autumn, primarily due to exposure to house mites, animal dander, and fungal spores. Compared to the seasonal subtype, perennial allergic conjunctivitis is less common and generally milder.[9]

Vernal Keratoconjunctivitis

The exact cause of VKC is poorly understood, but it is believed to result from a combination of climate and allergen exposure. Immunoglobulin E (IgE) and cell-mediated immune mechanisms play a vital role in the development of VKC. VKC is classified into 3 forms based on its presentation.[10] These are as follows:

• Palpebral VKC primarily affects the upper tarsal conjunctiva. Palpebral VKC is characterized by significant corneal involvement from the close apposition between the inflamed conjunctiva and the corneal epithelium.

• Limbal VKC is a subtype that predominately affects individuals of black and Asian descent.

• Mixed VKC is a subtype that exhibits a combination of features seen in both palpebral and limbal disease. Mixed VKC presents mixed manifestations involving the upper tarsal conjunctiva and the limbal area.

Atopic Keratoconjunctivitis

The exact etiology of atopic keratoconjunctivitis remains unclear. However, it is believed to arise from various factors, including allergen exposure, atopic dermatitis (present in more than 90% of cases), and genetic predisposition.[11]

Giant Papillary Conjunctivitis

Allergen exposure and the resulting response in giant papillary conjunctivitis can be attributed to ocular foreign bodies. These foreign bodies can either harbor allergens on their surface or cause injury to ocular structures, facilitating allergen infiltration. This condition can be associated with various ocular foreign bodies such as contact lenses, ocular prostheses, cyanoacrylate glue, and sutures.[12]

Epidemiology

Simple Allergic Conjunctivitis

Simple allergic conjunctivitis is a condition that often goes underappreciated. As a result, it is difficult to determine the exact number of affected individuals, as many patients do not seek medical care for their symptoms. However, it is estimated to affect approximately 10% to 30% of the general population. Onset occurs in individuals younger than 20, and the prevalence tends to decrease in older populations. While allergic conjunctivitis can manifest as an isolated finding, it is frequently associated with other allergic conditions such as allergic rhinitis, atopic dermatitis, and asthma.[3]

Vernal Keratoconjunctivitis

VKC is more commonly observed in males, with a male-to-female ratio ranging between 2 to 1 and 3 to 1. Most cases occur in patients between the ages of 5 and 10 years, often with a history of atopy or asthma. Around 95% of patients experience remission by late adolescence, while the remaining individuals may develop atopic keratoconjunctivitis.

VKC is rarely seen in temperate climates and is more prevalent in warm, dry regions such as the Middle East, sub-Saharan Africa, and the Mediterranean region. In temperate regions, 90% of patients present with atopy, asthma, and eczema, and two-thirds have a history of atopy.

The peak onset of VKC occurs in late spring and summer, although mild perennial symptoms may persist.[13]

Atopic Keratoconjunctivitis

AKC is not usually observed before adolescence and reaches its peak prevalence between 30 and 50. It is a rare bilateral disease more commonly seen in individuals with a history of atopic dermatitis and asthma. Most cases of AKC are seen in patients with atopic dermatitis.

Like VKC, there is a male-to-female predominance, with a ratio between 2 to 1 and 3 to 1. Approximately 5% of these patients have a history of childhood VKC. AKC is a chronic condition with a relatively low expectation of resolution and can have low visual morbidity.

AKC tends to be more perennial, often worsening in the winter season, and individuals with AKC are sensitive to a wide range of airborne environmental pathogens.[3]

Giant Papillary Conjunctivitis

GPC is commonly observed in teenagers and young adults, likely due to a temporal association with contact lens use. It is most commonly seen in individuals who use soft contact lenses, with approximately 5% of that population affected. GPC typically develops 1 to 2 years after initiating soft contact lens use, although the onset can vary significantly with other ocular foreign bodies.[14][15][16]

The condition can be triggered by various stimuli affecting the tarsal conjunctiva. GPC is also referred to as contact lens-induced papillary conjunctivitis (CLPC). Protein deposits and cellular debris can accumulate on contact lenses, ocular prostheses, sutures, and scleral buckles. Additionally, deposition on irregular corneal surfaces or filtering blebs can contribute to GPC.

The phenomenon known as mucus fishing syndrome, characterized by a chronic papillary reaction due to repeated mucus removal, can occur in various anterior segment disorders. GPC can also coexist with AKC and VKC.[17]

Pathophysiology

Simple allergic conjunctivitis, including acute, seasonal, and perennial forms, is an immunoglobulin E (IgE) mediated hypersensitivity reaction (Type I) triggered by direct contact between an allergen and the ocular surface. The interaction leads to mast cell degranulation and subsequent release of inflammatory modulators.[1]

The precise mechanism underlying VKC is not fully understood. However, it is believed to involve IgE-mediated hypersensitivity and T-cell involvement in the immune response. Atopic keratoconjunctivitis appears to be a combination of delayed-type (Type IV) and immediate (Type I) hypersensitivity reactions to ocular allergen exposure.

Giant papillary conjunctivitis occurs secondary to direct mechanical irritation or injury, leading to an immune response involving Type I and Type IV hypersensitivity reactions.[18] In GPC, the foreign object may become coated with different allergens or cause epithelial tissue damage, enabling deeper allergen exposure and triggering an immunological response.[19][20]

Histopathology

Vernal Keratoconjunctivitis will show an accumulation of eosinophils, mast cells, and proliferation of fibroblasts. Biochemical stains will reveal the presence of proteases, chymases, and tryptases. The substantia propria is thickened due to collagen deposition. T and B lymphocytes, which release IgE and IgG, are present. The overall picture resembles both type I and type IV hypersensitivity reactions.[13]

A slight increase in eosinophils and mast cells characterizes atopic keratoconjunctivitis. The tears of AKC patients will often contain high levels of IgE. The findings suggest a Type I hypersensitivity reaction.[21]

Giant papillary conjunctivitis is characterized by infiltrating various white blood cells, including plasma cells, mast cells, lymphocytes, basophils, and eosinophils. Additionally, elevated levels of IgE can be detected in the tears of individuals with GPC.[22]

History and Physical

Allergic conjunctivitis frequently accompanies seasonal allergy symptoms, particularly in individuals with known allergy exposures or a history of atopy. As a result, recurrent episodes are commonly observed. When evaluating a patient with suspected allergic conjunctivitis, healthcare practitioners should inquire about personal allergies, atopy, and previous episodes of similar symptoms. Practitioners should ask about symptoms experienced during the current episode and past occurrences. The most commonly reported symptoms in allergic conjunctivitis subtypes are itchiness and diffuse bulbar and tarsal conjunctival injection. Other aspects of the patient's history and physical examination findings may vary depending on the specific subtype of allergic conjunctivitis.[3]

Simple Allergic Conjunctivitis

The most commonly observed discharge in simple allergic conjunctivitis is clear and watery. It is typically bilateral, and minimal crusting may occur in the mornings. Pain and decreased visual acuity are not commonly reported in simple allergic conjunctivitis. If these symptoms are present, it may indicate an alternative diagnosis and should prompt the healthcare practitioner to consider other possibilities. Eyelid edema and chemosis are common and can be quite pronounced (see Image. Allergic Conjunctivitis). 

Patients with simple allergic conjunctivitis often experience transient acute or subacute episodes of redness, watery discharge, and itching. These episodes are commonly associated with sneezing, nasal discharge, and other symptoms of allergic rhinitis. Conjunctival hyperemia with mild papillary reaction is related to variable chemosis and lid edema.[23]

Vernal Keratoconjunctivitis

Symptoms of VKC are usually most severe during the spring season and can include thick mucus discharge, pain, lacrimation, photophobia, and blurred vision. Patients often complain of a foreign body sensation in the eye, and increased blinking may be observed. Upon examination, corneal ulcers and infiltrates on the conjunctival can occasionally be detected. Giant papillae on the tarsal conjunctiva are universally seen during the examination.[24]

Palpebral Vernal Keratoconjunctivitis

In the early stages of palpebral VKC, mild conjunctival hyperemia and diffuse velvety hypertrophy of the superior tarsal plate are present. Macropapillae, smaller than 1 mm in size, appear as flat-topped lesions with a polygonal (cobblestone-like) appearance. These macrophiles may be focal or diffuse in distribution. In more severe cases, whitish inflammatory infiltrates can be observed, indicating intense disease.

Giant papillae, which are more than 1 mm, are small lesions that amalgamate when the dividing septa rupture. Mucus deposits can be seen between giant papillae. Mild conjunctival injection and reduced mucus production are characteristic of decreased disease activity.[10]

Limbal Vernal Keratoconjunctivitis

The limbal form of VKC disease is characterized by gelatinous conjunctival papillae, typically observed at the limbal region of the eye. Another characteristic finding is the presence of transient apically located white cellular collections known as Horner-Trantas dots. These dots represent accumulations of inflammatory cells.

The limbal disease is more severe in tropical regions.[25]

• Keratopathy 
  • is more commonly observed in the palpebral form of VKC. It is characterized by superior punctate epithelial erosions on the cornea, often accompanied by mucus deposition in the superior layers. The macro erosions from the corneal epithelium result from the toxic effects of inflammatory mediators and direct mechanical rubbing from the papillae present in the conjunctiva.
  • In cases of palpebral and mixed VKC, shield ulcers and epithelial plaques can develop. These occur when calcium and phosphate deposits accumulate on the Bowman's membrane, leading to delayed wetting and re-epithelization of the cornea. The management of shield ulcers requires urgent attention to prevent the development of bacterial infections. Subepithelial scarring can occur in VKC and may contribute to reduced visual acuity. The scar typically appears oval-shaped and has a grayish appearance.[26]
  • In cases of limbal disease, a characteristic feature is the development of pseudogerontoxon. This refers to a paralimbal band of superficial scarring that resembles arcus senalis and is located close to the inflamed segment of the limbus. Vascularization in the limbal region is generally less prominent, although some superficial vessel ingrowth can occur, especially superiorly.
• Keratoconus
  • VKC has been associated with an increased risk of developing keratoconus and other corneal ectasias, which are more commonly provoked by eye rubbing. Herpes simplex is another common association, although it is more frequently seen in atopic keratoconjunctivitis.
  • While VKC can sometimes affect both eyes, the eyelid disease in VKC is milder than atopic keratoconjunctivitis.[27]

Atopic Keratoconjunctivitis

The symptoms of AKC are usually perennial and include pain, blurry vision, photophobia, and a foreign body sensation in the eyes. Examination findings are similar to those seen in simple allergic conjunctivitis. However, in AKC, there are additional chronic inflammatory changes to the ocular surface, such as corneal scarring and neovascularization. Changes to the eyelids, particularly the lower lid, and peri-orbital skin can range from mild atopy to lichenification.[28]

In comparison to VKC, the symptoms of AKC are typically less severe but persistent. The skin changes in AKC are more pronounced, including eczema, erythema, dryness, and scaly skin, often associated with thickening. Epidermal integrity is disrupted, leading to fissures,  scratches (excoriation), cracks, and intense itching.[29]

Other associated signs in AKC include chronic staphylococcal blepharitis, madarosis, keratinization of the lid margin, Hertoghe sign (absence of the lateral portion of eyebrows), and Dennie Morgan folds (skin folds on the lower eyelids due to regular itching). Facial skin may have folds, ectropion, and epiphora. Patients can develop ptosis. In AKC, inferior palpebral conjunctival involvement is more common than superior involvement seen in VKC. The discharge in AKC is watery compared to the stringy mucoid discharge typically seen in VKC.

Hyperemia, inflammation, and chemosis may be present during active acute episodes. The papillae are smaller than in VKC, although marcopapillae can also develop. Diffuse conjunctival infiltration and scarring can give a whitish and featherless appearance. In cicatricial disease, symblepharon formation, shortening of the fornix, and caruncular keratinization may occur. Limbal papillae similar to those seen in VKC and Horner-Trantas dots can also arise in AKC.[29] 

• Keratopathy: In AKC, punctate epithelial erosions are commonly observed, particularly in the inferior part of the cornea, and these erosions can be significant. Persistent epithelial defects can occur, leading to cornea thinning, perforation, and descemetocele formation. Corneal plaque formation can also be observed. Another common finding feature in AKC is stromal scarring and peripheral vascularization, which tends to be more prevalent than VKC.

Untreated cases of AKC have a higher risk of developing bacterial and fungal keratitis, and occasionally, herpetic keratitis can also develop.[30]

• Cataract: Patients with AKC may develop cataracts, particularly anterior or posterior subcapsular cataracts, secondary to long-term steroid therapy.[31] These cataracts can be a side effect of using corticosteroid medications to manage the chronic inflammation associated with AKC.
• Retina: AKC has an increased risk of developing endophthalmitis due to a high lid margin and an increased concentration of Staphylococcus aureus in the lid margins. Additionally, AKC patients at high risk for cataract surgery may also face an increased risk of retinal detachment.[32]
• Keratoconus: Keratoconus can be secondary to chronic ocular rubbing and herpes simplex keratitis in patients with AKC.[33] The continuous eye rubbing associated with AKC can weaken and thin the corneal structure, predisposing the cornea to develop keratoconus, characterized by progressive bulging and thinning of the cornea. Additionally, herpes simplex keratitis, an infection caused by the herpes simplex virus, can contribute to corneal thinning and deformation, further increasing the risk of keratoconus development in AKC patients.

Giant Papillary Conjunctivitis

Symptoms consistent with simple allergic conjunctivitis can progress to more severe and persistent symptoms in cases of papillary conjunctivitis. Patients may experience worsening itch and a change in discharge from clear and watery to thick mucus. Additionally, they may report worsening pain, redness, increased mucus production, contact lens intolerance, blurry vision, and a heightened sense of a foreign body, mainly related to contact lenses or sutures. The symptoms usually worsen after contact lens removal.

Findings consistent with simple allergic conjunctivitis and giant papillae covering the tarsal conjunctiva are observed during the examination. When encountering a patient with GPC, it is essential to inquire about contact lens cleaning and maintenance practices.[9]

Various signs and features can be observed during the examination of papillary conjunctivitis. These include variable mucus production, proteinaceous deposits on contact lenses, excessive mobility of contact lenses on the eye, upper tarsal hyperemia, and papillae. Fine and medium-sized papillae are commonly seen in association with GPC. Additionally, focal areas of apical ulceration and white scarring may develop over the more prominent papillae.

Keratopathy can occur in papillary conjunctivitis due to the secretion of inflammatory cytokines. Ptosis can occur due to tissue laxity, irritation, and spasms of tissues resulting from chronic inflammation in the affected area.[34]

Evaluation

Diagnosing allergic conjunctivitis is primarily based on clinical evaluation, which involves a thorough patient history and a classic physical examination.

In cases of concern about corneal abrasion or injury, fluorescein staining of the cornea may be performed to rule out any corneal abrasion. However, in some cases, skin prick or serum allergy testing can help identify the specific allergens responsible for triggering the allergic response. Appropriate avoidance measures can be implemented by identifying the offending allergens to help mitigate the disease process and reduce symptoms.[7][35]

Simple Allergic Conjunctivitis: Conjunctival scraping may be performed to examine eosinophils' presence in allergic conjunctivitis cases. While skin testing for allergens can be valuable in some instances of allergies, it is rarely needed for diagnosing allergic conjunctivitis.[36]

Vernal Keratoconjunctivitis: In cases of VKC, abundant eosinophils are commonly observed on conjunctival scrapings.[13]

Atopic Keratoconjunctivitis: In VKC, conjunctival scraping typically reveals a higher abundance of eosinophils than AKC.[20]

Treatment / Management

Simple Allergic Conjunctivitis

All patients with allergic conjunctivitis should receive education about general allergic eye care practices. They should be discouraged from rubbing their eyes, which causes mast cell degranulation and worsening symptoms. Applying artificial tears and cool compresses frequently can help alleviate discomfort.

Patients should avoid known allergen exposures and remove contact lenses if possible. Mild acute forms, over-the-counter antihistamines, antihistamines, and vasoconstrictor combination drops can be used for short periods.[37] However, patients should be warned about the potential for mild rebound conjunctival injection if they use vasoconstrictor drops for extended periods.

A combination of antihistamine and mast cell stabilizing drops is often recommended for seasonal and perennial allergic conjunctivitis. Topical nonsteroidal anti-inflammatory drops can provide some relief but are ineffective as antihistamines or mast cell stabilizing drops.

In refractory cases, short bursts of corticosteroid drops (less than 2 weeks) can be used but should be done under the supervision of a specialist with appropriate follow-up. Systemic antihistamines and steroids are limited in treating refractory cases, especially when patients have systemic symptoms rather than isolated ocular symptoms.[38][39][40]

The treatment of allergic conjunctivitis generally follows a step ladder approach based on the severity of symptoms. For mild symptoms, artificial eye drops are usually sufficient. Mast cell stabilizers such as sodium cromoglycate, nedocromil sodium, and lodoxamide are prescribed for a few weeks, and their maximal effect is seen after continuous use, making them suitable for long-term management.[41]

Antihistamines such as emedastine, epinastine, bepotastine, and levocabastine are commonly used for acute exacerbations and are as effective as mast cell stabilizers. For severe and recurrent cases, a combination of antihistamines and vasoconstrictors, such as antazoline and xylometazoline, may be prescribed to provide more comprehensive relief.

NSAIDS are effective in reducing inflammation and providing symptomatic relief.

Topical steroids help relieve acute exacerbation, but their use should be limited to a short duration under the guidance of a specialist.

When symptoms are severe, oral antihistamines such as diphenhydramine and loratadine may be needed. Loratadine is preferred over diphenhydramine as it has less sedative action, making it a better option for daily use.[42]

Vernal and Atopic Keratoconjunctivitis

The management of VKC and AKC follows similar principles of treatment. However, AKC generally requires more intensive and prolonged treatment than VKC.

Patients with VKC and AKC should be educated about general allergic eye care, which includes using artificial tears and cool compresses, minimizing allergen exposure, and avoiding rubbing their eyes.

Initial pharmacotherapy for both VKC and AKC typically involves a topical combination of antihistamine and mast cell stabilizing drops, similar to the treatment used for seasonal and perennial allergic conjunctivitis.

In refractory VKC or AKC cases, patients should be referred to a specialist who can prescribe topical corticosteroids. If the patient continues to be refractory to treatment or cannot be weaned from topical steroid therapy, topical or systemic calcineurin inhibitors can be considered an alternative therapeutic option.[10]

General Treatment

The primary goal in managing allergic conjunctivitis, including VKC and AKC, is to avoid exposure to the allergen that triggers the allergic response. In some cases, eye patching may be required, and consulting with a cornea specialist can help determine the appropriate approach. 

Cold compresses can provide relief from inflammation and discomfort. Maintaining good lid hygiene is also essential to prevent and treat staphylococcal blepharitis.

For patients with dry and fissured skin around the eyes, using a moisturizing cream such as E45 can help keep the skin hydrated and improve comfort.

A bandage contact lens may be recommended as part of the treatment plan for persistent epithelial defects. The bandage contact lens can protect the cornea and promote the healing of the defect.[43]

Medical Management

Mast cell stabilizers

Sodium cromoglicate, nedocromil sodium, and lodoxamide are essential medications in managing acute exacerbations of allergic conjunctivitis, including VKC and AKC. They play a role in controlling symptoms and reducing the reliance on steroids, making them essential components of many treatment regimens. However, these medications are often not as effective when used in isolation and are typically combined with other treatments.

In cases of VKC and AKC, treatment may be required for several weeks to achieve significant improvement, and long-term therapy is necessary to maintain symptom control. However, it is essential to note that lodoxamide is not FDA-approved for long-term use.[44]

Topical antihistamines

Emedastine, epinastine, levocabastine, and bepotastine are all equally effective antihistamine drugs that can relieve allergic conjunctivitis symptoms, including VKC and AKC. They act as mast cell stabilizers.

Antihistamines are an excellent choice to alleviate symptoms and relieve acute exacerbations of allergic conjunctivitis quickly. However, medications such as mast cell stabilizers, such as sodium cromoglicate, nedocromil sodium, and lodoxamide, may be required for long-term treatment to control inflammation and reduce dependence on steroids.[10]

A combination of medications, including VKC and AKC, can effectively relieve symptoms when managing allergic conjunctivitis. In some instances, vasoconstrictors like xylometazoline and antazoline can be combined with antihistamines to provide additional comfort.

Combining antihistamines with mast cell stabilizers, such as ketotifen and olopatadine, has proven particularly effective in rapidly relieving symptoms.[42] These medications work together to prevent the release of inflammatory substances from mast cells, further reducing allergic responses.

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac, diclofenac, nepafenac, and bromfenac can relieve and improve comfort by blocking non-histamine mediators involved in the inflammatory response. For some patients, combining an NSAID with a mast cell stabilizer has proven to be an effective drug therapy for managing allergic conjunctivitis.[45]

Topical steroids

Topical steroids are essential in managing severe acute exacerbations, inflammation, and keratopathy. Various commonly used steroids are 0.1% fluorometholone, 0.2% and 0.5% loteprednol, 1% rimexolone, and 1% prednisolone.

To effectively manage the inflammation and associated corneal pathology, a short and intense course of therapy with an hourly regimen may be required, followed by a careful tapering schedule. This approach helps reduce conjunctival inflammation, leading to an improvement in corneal health.

It is crucial to closely monitor patients receiving topical steroids to prevent adverse effects, particularly the elevation of intraocular pressure (IOP) and the development of steroid-induced glaucoma.

Some clinicians prefer to use steroid eye ointments, such as beclomethasone or hydrocortisone 0.5%, to manage AKC. However, strict IOP control and monitoring should be implemented during ointment treatment.[46]

Topical antibiotics

In cases of severe keratopathy associated with allergic conjunctivitis, an antibiotic and steroid combination is often necessary to manage the condition effectively and prevent the development of bacterial keratitis.[47] This combination therapy helps address both the inflammatory component and the risk of secondary bacterial infection.

Mucolytic agents

Acetylcysteine is useful in VKC and AKC for dissolving mucus filaments, deposits, and early plaque development.[48]

Immunomodulators

Ciclosporin (0.05%-2%) may be needed 2 to 6 times daily in cases with a suboptimal response to steroids when steroids are ineffective, poorly tolerated, or when there is an inadequate response. These act as steroid-sparing agents in patients with severe diseases. Immunomodulators take approximately 6 weeks to act, and there can be rebound inflammation if the drug is stopped in between. The side effects are blurred vision and irritation.[49]

Calcineurin inhibitors

Tacrolimus 0.03% eye ointment is an effective alternative to cyclosporin in resolving conjunctival inflammation in cases with refractory allergic conjunctivitis. It is usually instilled at bedtime in the conjunctival fornices.[50]

Supratarsal steroids

Supratarsal steroids are required in patients with the severe palpebral form of the disease who are unresponsive to topical steroids or are non-compliant. The conjunctiva is everted, and injection is given in the supratarsal conjunctiva. An injection of 0.1 ml betamethasone 4 mg/mL, dexamethasone 4 mg/mL, or triamcinolone can be provided.[51]

Systemic Medications

Oral antihistamines

Oral antihistaminics can be given to resolve symptoms, but effectiveness is guaranteed. The oral drugs induce sleep and help reduce itching and eye rubbing. Some medications, such as loratadine, can cause slight drowsiness.[52]

Antibiotics

Doxycycline 50 to 100 mg once daily for 6 weeks and Azithromycin 500 mg once daily for 3 days can be given to reduce blepharitis aggravated inflammation, especially in AKC.[53]

Oral immunosuppressants

Oral steroids, ciclosporin, tacrolimus, and azathioprine are useful in low doses for refractory allergic conjunctivitis. A short trial of high-dose steroids may be required to achieve control of the severe disease. Monoclonal antibodies are helpful in refractory cases. Aspirin has also been tried in patients with VKC but should be used cautiously due to the risk of Reye syndrome in children. Other measures used are allergen desensitization and plasmapheresis in patients with high IgE levels.[54]

Topical drugs

After contact lens removal, instilling mast cell stabilizers can relieve itching. In some instances, long-term use of mast cell stabilizers may be necessary to manage and control allergic conjunctivitis symptoms effectively.

Additionally, NSAIDs and combined antihistamines and mast cell stabilizers can also be beneficial in managing allergic conjunctivitis symptoms.

If acute exacerbations or when the condition is resistant to other treatments, topical steroids may be necessary for their potent anti-inflammatory effects.[8]

Surgical Measures

Glue with bandage contact lenses is required in patients with small corneal perforations. Superficial keratectomy is needed in cases with shield ulcers for debridement and removal of plaques and helps in reepithelization. The topical drugs should be continued to prevent recurrences. Phototherapeutic keratectomy by using an excimer laser is another alternative. Amniotic membrane grafting is required in persistent epithelial defects. The other options are lamellar keratoplasty or patch graft. Botox-induced ptosis is another management option for persistent epithelial defects.[55]

Giant papillary conjunctivitis

The first step in managing giant papillary conjunctivitis is to remove the mechanical irritant, which is most commonly a contact lens. Patients should discontinue lens wear for a few weeks and replace the lens to avoid reexposure to allergens. General allergic eye care should be practiced, such as avoiding eye rubbing, using artificial tears and cool compresses, and allergen avoidance.

Initial pharmacotherapy is similar to other ocular types of allergies, with options like topical antihistamines or a combination of an antihistamine and mast cell stabilizing drops used to alleviate symptoms.[56]

In more severe and refractory cases, topical corticosteroid drops can be prescribed under the supervision of a specialist, similar to the treatment approach for vernal and atopic keratoconjunctivitis. However, calcineurin inhibitors do not play a role in treating GPC. Removing these devices may be necessary for patients with sutures or scleral buckles to reduce mechanical irritation. Regular assessment of prosthetic eye condition and fitting process is crucial.

Filtering blebs requires surgical intervention, such as excision or nonpenetrating glaucoma drainage surgery, followed by a glaucoma drainage device implantation. To prevent contact lens papillary conjunctivitis (CLPC), patients should regularly clean their contact lenses and consider switching to preservative-free solutions. Transitioning to monthly and daily disposable contact lenses is recommended.

Rigid lenses carry a lower risk of CLPC because they are easier to clean. Contact lenses should be stopped and substituted with spectacles, or rare cases may require refractive surgery. Protein removal tablets can be used to clean contact lens protein. For ocular prostheses, washing and cleaning with detergent and a protective coating are essential to maintain hygiene and comfort.[57]

Differential Diagnosis

The differential diagnosis for allergic conjunctivitis can be broad and may include the following conditions:

• Viral conjunctivitis
• Bacterial conjunctivitis
• Molluscum conjunctivitis
• Giant fornix syndrome
• Adult chlamydial conjunctivitis
• Trachoma
• Neonatal conjunctivitis
• Nonallergic eosinophilic conjunctivitis
• Contact allergic blepharoconjunctivitis
• Mucous membrane pemphigoid
• Stevens-Johnson syndrome/toxic epidermal necrolysis (Lyell syndrome)
• Superior limbic keratoconjunctivitis
• Ligneous conjunctivitis
• Parinaud oculoglandular syndrome
• Factitious conjunctivitis

Staging

Table 1. Bonini Clinical Staging of Vernal Keratoconjunctivitis [58]

Table 2. Gokhale Staging of Vernal Keratoconjunctivitis [59]

Prognosis

In most patients, the prognosis for allergic conjunctivitis is good. Complications are rare, but there is a possibility of symptom recurrence. For patients who experience corneal damage, this may lead to visual impairment. Additionally, the medications used to manage allergic conjunctivitis can be associated with the development of cataracts.[24]

Complications

In most cases, allergic conjunctivitis is not a severe health threat, but a common and often benign condition. Complications of allergic conjunctivitis are rare, but when they do occur, they can be severe and may include:

• Scarring of the eye (severe cases).
• Progression to infective conjunctivitis, leading to the spread of infection to other areas of the body and potentially causing serious secondary infections.
• Conjunctival scarring
• Bacterial keratitis
• Corneal neovascularization
• Pannus
• Giant papillae
• Nonresolving epithelial defect
• Shield ulcer
• Steroid-induced glaucoma
• Dry eyes
• Keratoconus
• Herpetic keratitis

Postoperative and Rehabilitation Care

Surgical management is rarely required in cases of allergic conjunctivitis. However, in specific situations where surgical intervention is deemed necessary, such as cases with severe corneal involvement or complications like shield ulcers, amniotic membrane grafting, lamellar keratoplasty, or patch graft may be considered.

Postoperatively, tapering doses of topical steroids should be started. The patient should be educated about the potential short and long-term side effects of steroids. Regular follow-up visits are crucial in the postoperative period to monitor the healing process, evaluate the treatment's effectiveness, and reduce acute exacerbations.[60]

Consultations

Patients with pain, redness, and eye itching should undergo a thorough evaluation for clinical signs of allergic conjunctivitis. Ophthalmologists should be proficient in diagnosing and treating these cases, as allergic conjunctivitis is a common condition encountered in clinical practice.[23]

When the diagnosis is uncertain, or there are complications, the patient should be referred to a cornea and external disease specialist for further evaluation and management. If the patient develops secondary glaucoma, involving a glaucoma specialist is essential to provide the appropriate care and prevent other complications. Similarly, patients with shield ulcers should be managed by a cornea expert.[61]

Deterrence and Patient Education

Prevention plays a crucial role in managing allergic conjunctivitis effectively. Identifying the specific allergen through skin tests performed by allergists can help create a targeted and long-term preventive strategy. By knowing the allergen triggers, patients can take proactive steps to minimize exposure and reduce the frequency and severity of allergic reactions.

Patient education is paramount in managing allergic conjunctivitis. Explaining the nature of the disease, its potential complications, and the importance of adherence to prescribed medications are essential to successful management. Patients should be well-informed about the various treatment options and how to use these drugs effectively.[62]

Pearls and Other Issues

Allergic conjunctivitis encompasses various manifestations, including AKC, VKC, and GPC. Healthcare practitioners should recognize and differentiate between these subtypes based on thorough patient evaluation and history-taking. In some cases of GPC, it is essential to inquire about the history of contact lens use as it is a significant contributing factor.

When managing patients with allergic conjunctivitis, educating them about the chronic nature of the condition and the need for long-term medication use is essential. Patients should be informed about the potential for waxing and waning of symptoms over time. Emphasizing the importance of regular follow-up appointments and medication compliance is vital in ensuring effective disease management and preventing complications.[8]

Enhancing Healthcare Team Outcomes

Most patients with allergic conjunctivitis are initially seen by a pharmacist, nurse practitioner, or primary care provider. Patients may seek over-the-counter treatments at the pharmacy, allowing the pharmacist to provide valuable education. The pharmacist should take the initiative to educate the patient about lifestyle changes to manage allergies effectively and refer patients with severe or recurrent symptoms to an ophthalmologist for further evaluation and specialized care.

Patients with allergic conjunctivitis should prioritize avoiding the offending allergens, necessitating lifestyle changes to manage the condition effectively. Some patients may need to undergo allergy testing to determine the allergen, enabling them to modify their behavior accordingly.

Contact lenses may not be possible for some individuals with allergic conjunctivitis, and they may need to consider alternative eyewear options. All patients with allergic conjunctivitis should be educated on various measures to alleviate symptoms and minimize exposure to allergens. These recommendations include humidifying the home, wearing sunglasses when going outside, avoiding mascara and makeup, using artificial tears liberally, and applying cold compresses to the eye.[63][64][65]

While healthcare practitioners such as primary care providers and nurse practitioners may encounter patients with allergic conjunctivitis in outpatient settings, it is essential to remain vigilant for any visual changes or severe symptoms that could indicate a more serious condition. Empirical prescription of topical steroids by healthcare practitioners is not recommended, as these agents can have potential side effects, including the development of cataracts. 

The potential for misdiagnosis or mistaking allergic conjunctivitis for a more severe condition highlights the importance of vigilance and effective communication among the healthcare team. Nurses, pharmacists, and other healthcare professionals dealing directly with the patient should remain watchful for any signs of poor response to treatment or worsening symptoms. Prompt reporting to the clinical team's interprofessional leader, such as the ophthalmologist or optometrist, is essential.

Patient education is crucial, and healthcare professionals should inform patients about the need for close follow-up if improvement does not occur quickly. Encouraging patients to report any new or worsening symptoms, especially the development of pain, is essential for early intervention and appropriate management.

An interprofessional approach involving open communication and joint education leads to the best possible care for patients with allergic conjunctivitis. By working together, the healthcare team can identify potential treatment failures early on, preventing the development of significant morbidity and avoiding poor outcomes.

Outcomes

The long-term outcomes for PAC and SAC are generally favorable, but many individuals experience eye discomfort and may have suboptimal ocular cosmesis. Some patients may develop recurrences leading to conjunctivochalasis secondary to ongoing limbal conjunctival chemosis.

In more severe cases of allergic conjunctivitis, such as VKC and AKC, there can be additional complications. Corneal opacification and ulcer formation can occur, potentially affecting vision and requiring careful management. Lid involvement may lead to challenges in wearing contact lenses, further impacting the patient's quality of life.

Managing allergic conjunctivitis may also impose other burdens on patients. Frequent visits to eye specialists and the need to purchase prescription eye drops can result in increased healthcare costs and time off from work for appointments. Moreover, using medications to manage allergic symptoms, such as topical steroids, may carry the risk of adverse reactions, including the development of cataracts.[66][67]