AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Immunologic reactions of conjunctiva and cornea

The ocular surface may exhibit a wide variety of immunologic responses that may result in conjunctival and corneal inflammation. In the Gell and Coombs classification system for various immunologic hypersensitivity reactions, 5 classes of reactions are recognized.

Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells, and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell degranulation. This, in turn, causes the release of various preformed and newly formed mediators of the inflammatory cascade, including histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various inflammatory mediators, together with various chemotactic factors, result in increased vascular permeability and migration of eosinophils and neutrophils. The principal ocular type I hypersensitivity reaction is allergic conjunctivitis, which is discussed in further detail in this article.

Type II hypersensitivity reactions are autoimmune reactions and may be complement mediated. These reactions may be the underlying cause of various ocular conditions, such as cicatricial pemphigoid and Mooren ulcer.

Type III hypersensitivity reactions result in antigen-antibody immune complexes, which deposit in tissues and cause inflammation. Classic type III reaction systemically is the Arthus reaction, and ocular type III hypersensitivity reactions include Stevens-Johnson syndrome and marginal infiltrates of the cornea. Corneal immune (Wesley) rings are also an example of type III reactions.

Type IV hypersensitivity reactions, also known as cell-mediated immunity, are mediated by T lymphocytes. While type I reaction is immediate hypersensitivity, this reaction is also known as delayed-type hypersensitivity, since its onset is generally after 48 hours. Type IV hypersensitivity reactions imply immunocompetence on the part of the individual since an intact immune system is required to mount the cell-mediated response. Ocular examples of type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection, contact dermatitis, and drug allergies.

This section focuses primarily on the major type I hypersensitivity reactions involving the conjunctiva, more commonly referred to as allergic conjunctivitis.

Types of allergic conjunctivitis

Allergic conjunctivitis may be divided into 5 major subcategories. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are commonly grouped together. Vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC) constitute the remaining subtypes of allergic conjunctivitis.

Pathophysiology

Seasonal and perennial allergic conjunctivitis

Since conjunctiva is a mucosal surface similar to the nasal mucosa, the same allergens that trigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis. Common airborne antigens, including pollen, grass, and weeds, may provoke the symptoms of acute allergic conjunctivitis, such as ocular itching, redness, burning, and tearing. The main distinction between SAC and PAC, as implied by the name, is the timing of symptoms.

Individuals with SAC typically have symptoms of acute allergic conjunctivitis for a defined period of time, that is, in spring, when the predominant airborne allergen is tree pollen; in summer, when the predominant allergen is grass pollen; or in fall, when the predominant allergen is weed pollen. Typically, persons with SAC are symptom-free during the winter months in cooler climates because of the decreased airborne transmission of these allergens.

In contrast, individuals with PAC may have symptoms that last the whole year; thus, PAC may not be caused exclusively by seasonal allergens, although they may play a role. Other common household allergens, such as dust mite, cockroaches, and pet dander, may be responsible for the symptoms of PAC.

Vernal keratoconjunctivitis

VKC is a chronic bilateral inflammation of the conjunctiva, commonly associated with a personal and/or family history of atopy. More than 90% of patients with VKC exhibit one or more atopic conditions, such as asthma, eczema, or seasonal allergic rhinitis.

Atopic keratoconjunctivitis

AKC is a bilateral inflammation of conjunctiva and eyelids, which has a strong association with atopic dermatitis. It is also a type I hypersensitivity disorder with many similarities to VKC, yet AKC is distinct in a number of ways.

In 1953, Hogan first described the association between atopic dermatitis and conjunctival inflammation.¹ He reported 5 cases of conjunctival inflammation in male patients with atopic dermatitis.¹ Atopic dermatitis is a common hereditary disorder that usually has its onset in childhood; symptoms may regress with advancing age. Approximately 3% of the population is afflicted with atopic dermatitis, and, of these, approximately 25% have ocular involvement.

Giant papillary conjunctivitis

GPC is an immune-mediated inflammatory disorder of superior tarsal conjunctiva. As the name implies, the primary finding is the presence of "giant" papillae, which are typically greater than 0.3 mm in diameter. It is believed that GPC represents an immunologic reaction to a variety of foreign bodies, which may cause prolonged mechanical irritation to the superior tarsal conjunctiva. Although contact lenses (hard and soft) are the most common irritant, ocular prostheses, extruded scleral buckles, and exposed sutures following previous surgical intervention may precipitate GPC.

Frequency

United States

Allergic conjunctivitis occurs very frequently and is seen most commonly in areas with high seasonal allergens.

Mortality/Morbidity

Allergic conjunctivitis rarely causes any visual loss.

Race

• VKC occurs predominantly in areas with tropical and temperate climates, such as the Mediterranean, the Middle East, and Africa.
• The limbal form of VKC commonly occurs in dark-skinned individuals from Africa and India.

Sex

VKC has a significant male preponderance.

Age

VKC typically affects young males with onset generally in the first decade and with duration up to one decade. Its symptoms usually peak prior to the onset of puberty and then subside.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Seasonal and perennial allergic conjunctivitis
• • Diagnosis of allergic conjunctivitis generally is made by taking a thorough history and by careful clinical observation.
  • Important features of history include a personal or family history of atopic disease, such as allergic rhinitis, bronchial asthma, and/or atopic dermatitis. Perhaps the most important feature in the clinical history is the symptom of itching. Without itching, the diagnosis of allergic conjunctivitis is suspect.
• Vernal keratoconjunctivitis
• • As with other allergic or type I hypersensitivity disorders, itching is the most important and most common symptom.
  • Other commonly reported symptoms are photophobia, foreign body sensation, tearing, and blepharospasm.
  • Ocular signs of VKC commonly are seen in the cornea and conjunctiva. In contrast to AKC, the eyelid skin usually is not involved.
• Atopic keratoconjunctivitis
• • In contrast to the symptoms of VKC, the symptoms in AKC are perennial. However, there may be seasonal variation with worsening symptoms during winter months.
  • The single most common symptom is bilateral itching of the eyelids, but watery discharge, redness, photophobia, and pain may be associated.
• Giant papillary conjunctivitis
• • Primary symptoms in GPC are ocular itching with a mucoid or ropy discharge, very similar to that seen in VKC.
  • Another symptom may be a persistent foreign body sensation when using contact lenses, resulting in an inability to wear contact lenses for the desired length of time.

Physical

• Seasonal and perennial allergic conjunctivitis
• • Classic signs of allergic conjunctivitis include injection of conjunctival vessels as well as varying degrees of chemosis (conjunctival edema) and eyelid edema.
  • The conjunctiva often has a milky appearance due to obscuration of superficial blood vessels by edema within the substantia propria of the conjunctiva. Edema is generally believed to be the direct result of increased vascular permeability caused by release of histamine from conjunctival mast cells.
• Vernal keratoconjunctivitis
• • VKC may be subdivided into 2 varieties, as follows: palpebral and limbal. The classic conjunctival sign in palpebral VKC is the presence of giant papillae. They most commonly occur on the superior tarsal conjunctiva; usually, the inferior tarsal conjunctiva is unaffected. Giant papillae assume a flattop appearance, which often is described as "cobblestone papillae." In severe cases, large papillae may cause mechanical ptosis.
  • A ropy mucous discharge may be present, which commonly is associated with tarsal papillae. Large numbers of eosinophils are present in the discharge.
  • The limbal form of VKC commonly occurs in dark-skinned individuals, such as those from Africa or India. As the name implies, papillae tend to occur at the limbus and have a thick gelatinous appearance. They commonly are associated with multiple white spots (Horner-Trantas dots), which are collections of degenerated epithelial cells and eosinophils. Horner-Trantas dots are transient, with each appearance rarely lasting more than 1 week.
  • While corneal vascularization is rare, the cornea may be affected in a variety of ways. Punctate epithelial keratopathy (PEK) may be due to the toxic effect of inflammatory mediators released from the conjunctiva and may be a precursor of the characteristic shield ulcer, which is pathognomonic of VKC. As the areas of PEK coalesce, they may result in frank epithelial erosion resulting in shield ulcer, which is typically shallow with white irregular epithelial borders. Although the pathogenesis of shield ulcer is not well understood, a major factor in promoting development may be chronic mechanical irritation from the giant tarsal papillae. Some evidence suggests that the major basic protein released from eosinophils may promote ulceration.
  • Another type of corneal involvement is vernal pseudogerontoxon, which is a degenerative lesion in the peripheral cornea resembling corneal arcus. Keratoconus may be seen in chronic cases, which may be associated with chronic eye rubbing.
• Atopic keratoconjunctivitis
• • AKC may affect eyelid skin and lid margin, conjunctiva, cornea, and lens. Skin of the eyelids may exhibit eczematoid dermatitis with dry, scaly, and inflamed skin. Lid margins may show meibomian gland dysfunction and keratinization. Staphylococcal colonization of eyelid margins is very common and may result in blepharitis. Conjunctiva may show chemosis and typically a papillary reaction, which is more prominent in the inferior tarsal conjunctiva, in contrast to that seen in vernal keratoconjunctivitis.
  • Hyperplasia of limbal regions may result in a gelatinous thickening, similar to the limbal variant of VKC, and Horner-Trantas dots also may be present, although rarely. Fibrosis or scarring of the conjunctiva may result in a shortened fornix or symblepharon formation with chronic inflammation. Corneal involvement ranges from punctate epithelial keratopathy early in the course of the disease, to neovascularization, stromal scarring, and possibly ulceration. There is a strong association between herpes simplex viral keratitis and AKC.
  • Another corneal finding, which may be associated with AKC, is keratoconus, which may stem from chronic eye rubbing. Characteristic lenticular changes in AKC include anterior or posterior subcapsular cataract formation. Lens opacities are usually bilateral and present in the second decade of life but progress very slowly. There may be an association with the long-term use of topical corticosteroids. Note that there is an increased incidence of retinal detachment following surgical removal of cataracts in patients with atopic dermatitis; the exact mechanism is unknown.
• Major Differentiating Factors Between VKC and AKC

Characteristics	VKC	AKC
Age at onset	Generally presents at a younger age	-
Sex	Males are affected preferentially.	No sex predilection
Seasonal variation	Typically occurs during spring months	Generally perennial
Discharge	Thick mucoid discharge	Watery and clear discharge
Conjunctival scarring	-	Higher incidence of conjunctival scarring
Horner-Trantas dots	Horner-Trantas dots and shield ulcers are commonly seen.	Presence of Horner-Trantas dots is rare.
Corneal neovascularization	Not present	Tends to develop deep corneal neovascularization
Presence of eosinophils in conjunctival scraping	Conjunctival scraping reveals eosinophils to a greater degree in VKC than in AKC.	Presence of eosinophils is less likely.

• Giant papillary conjunctivitis
• • Examination of superior tarsal conjunctiva reveals the presence of large cobblestone papillae, which are generally 0.3 mm or greater in diameter and, in severe cases, may cause mechanical ptosis of the upper lid.
  • In his original description of GPC in 1977, Allansmith described 3 zones of superior tarsal conjunctiva.² Zone 1 is located closest to the fornix and is the most inferior portion of the tarsal conjunctiva seen when the upper eyelid is everted. Zone 3 is located closest to the eyelid margin. Zone 2 is located between zone 1 and zone 3.
  • Papillae typically associated with soft contact lens–related GPC initially appear in zone 1 and progress toward zone 3, while those associated with rigid gas permeable contact lenses exhibit a reverse pattern, with zone 3 affected first. GPC associated with a localized irritant, such as an exposed suture or a filtering bleb, is typically localized to the area overlying these inciting lesions.
  • Another clinical sign of GPC may be chronic bulbar conjunctival injection and inflammation due to prolonged and persistent use of contact lenses.

Causes

See Pathophysiology.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Seasonal and perennial allergic conjunctivitis
• • Superficial conjunctival scrapings may help to establish the diagnosis by revealing eosinophils, but only in the most severe cases, since eosinophils are typically present in the deeper layers of the substantia propria of the conjunctiva. Therefore, the absence of eosinophils on conjunctival scraping does not rule out the diagnosis of allergic conjunctivitis.
  • Many investigators have described measurement of tear levels of various inflammatory mediators, such as IgE, histamine, and tryptase, as indicators of allergic activity.
  • Additionally, skin testing by an allergist may provide definitive diagnosis and pinpoint the offending allergen(s).
• Vernal keratoconjunctivitis: Conjunctival scrapings of the superior tarsal conjunctiva and of Horner-Trantas dots show an abundance of eosinophils.

Histologic Findings

Vernal keratoconjunctivitis

Conjunctival scrapings of the superior tarsal conjunctiva show an abundance of eosinophils. Conjunctival biopsy reveals that there are a large number of mast cells within the substantia propria. Histochemical analysis of mast cells present in VKC reveals neutral proteases tryptase and chymase. There is enhanced fibroblast proliferation, which leads to deposition of collagen within the substantia propria resulting in conjunctival thickening.

B-cell and T-cell lymphocytes are present locally, which combine to produce IgE. Specific IgE and IgG as well as the inflammatory mediators histamine and tryptase have been isolated from tears of patients with VKC. Although VKC is typically recognized as a type I hypersensitivity reaction, evidence has been found that supports some involvement of type IV hypersensitivity reaction.

Atopic keratoconjunctivitis

Conjunctival scrapings of patients with AKC may demonstrate the presence of eosinophils, although the number is not as significant as that seen in VKC. Additionally, free eosinophilic granules, which are seen in VKC, are not seen in AKC. Mast cells also may be found within the substantia propria of the conjunctiva in greater numbers.

There is an increased amount of IgE in the tears of patients with AKC. Although AKC is typically recognized as a type I hypersensitivity reaction, evidence has been found that supports some involvement of type IV hypersensitivity reaction, as is the case in VKC.

Giant papillary conjunctivitis

Histologic findings in GPC consist of cellular infiltration of the conjunctiva by a number of cell types. Plasma cells, lymphocytes, mast cells, eosinophils, and basophils have been identified within the substantia propria. Mast cells also may be found in the epithelium.

Tear levels of immunoglobulin, especially IgE and tryptase also are elevated, as in AKC and VKC, indicating that a combination of type I and type IV hypersensitivity reactions may be responsible for the pathogenesis of GPC. It is believed that the stimulus for development of GPC is an immunologic reaction to a specific antigen in predisposed individuals. Mechanical trauma to the conjunctiva may be a contributing factor.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Seasonal and perennial allergic conjunctivitis
• • Pharmacologic intervention may help alleviate the symptoms of acute allergic conjunctivitis. Various classes of medication may be effective against the symptoms of acute allergic conjunctivitis; each is directed at a specific point in the inflammatory and allergic cascade.
  • Artificial tear substitutes provide a barrier function and help to improve the first-line defense at the level of conjunctival mucosa. These agents help to dilute various allergens and inflammatory mediators that may be present on the ocular surface, and they help flush the ocular surface of these agents.
  • Systemic and/or topical antihistamines may be given to relieve acute symptoms due to interaction of histamine at ocular H1 and H2 receptors. While systemic antihistamines often relieve ocular allergic symptoms, patients may experience systemic adverse affects, such as drowsiness and dry mouth.
  • Topical antihistamines competitively and reversibly block histamine receptors and relieve itching and redness but only for a short time. These medications do not affect other proinflammatory mediators, such as prostaglandins and leukotrienes, which remain uninhibited. A number of topical antihistamines are available, including epinastine (Elestat) and azelastine (Optivar). Both are potent antihistamines that have a rapid onset and are effective in relieving the signs and symptoms of allergic conjunctivitis.
  • Vasoconstrictors are available either alone or in conjunction with antihistamines to provide short-term relief of vascular injection and redness. Common vasoconstrictors include naphazoline, phenylephrine, oxymetazoline, and tetrahydrozoline. Generally, the common problem with vasoconstrictors is that they may cause rebound conjunctival injection and inflammation. These pharmacologic agents are ineffective against severe ocular allergies and against other more severe forms of allergic conjunctivitis, such as atopic and vernal disease.
  • Mast cell stabilizers have a mechanism of action that is unclear. They may aid in the phosphorylation of a 78,000-d protein that terminates secretion of mast cell granules; they may increase calcium influx into the cell preventing membrane changes; and/or they may reduce membrane fluidity prior to mast cell degranulation. End result is a decrease in degranulation of mast cells, which prevents release of histamine and other chemotactic factors that are present in the preformed and newly formed state. Note that mast cell stabilizers do not relieve existing symptoms and are to be used on a prophylactic basis to prevent mast cell degranulation with subsequent exposure to the allergen. Therefore, they need to be used long term in conjunction with various other classes of medications. Common mast cell stabilizers include cromolyn sodium and lodoxamide (Alomide). Olopatadine (Patanol), nedocromil (Alocril), and ketotifen (Zaditor) are mast cell stabilizers and inhibit histamine release.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) act on the cyclooxygenase metabolic pathway and inhibit production of prostaglandins and thromboxanes. They have no role in blocking mediators formed by the lipoxygenase pathway, such as leukotrienes. Common NSAIDs that are approved for allergic indications include ketorolac tromethamine (Acular).
  • Corticosteroids remain one of the most potent pharmacologic agents used in the treatment of ocular allergy. They act at the first step of the arachidonic acid pathway by inhibiting phospholipase, which is responsible for converting membrane phospholipid into arachidonic acid. By preventing the formation of arachidonic acid, corticosteroids effectively block both cyclooxygenase and lipoxygenase pathways, in contrast to NSAIDs, which act only on the cyclooxygenase pathway. Corticosteroids do have limitations, including ocular adverse effects, such as delayed wound healing, secondary infection, elevated intraocular pressure, and formation of cataract. In addition, the anti-inflammatory and immunosuppressive affects are nonspecific.
  • Corticosteroids exist in various forms and potencies. Relatively weak steroids, such as rimexolone, medrysone, and fluorometholone, tend to have less potency with fewer ocular adverse effects. In contrast, agents, such as prednisolone acetate, are more potent and have a higher incidence of adverse effects. Loteprednol etabonate (Lotemax 0.05% and Alrex 0.02%), a steroid, is rapidly metabolized once it enters the anterior chamber of the eye. Therefore, it is extremely useful in treating ocular surface and superficial corneal inflammations. Alrex has a specific indication for ocular allergy and has been shown in clinical studies to have fewer ocular adverse effects. However, a general rule-of-thumb is that topical steroids should be prescribed only for a short period of time and for severe cases that do not respond to conventional therapy.
• Vernal keratoconjunctivitis
• • Various pharmacologic agents may be used to provide varying degrees of relief. Mucolytic agents, such as acetylcysteine, may help minimize the discharge and provide temporary relief. Vasoconstrictors may reduce hyperemia but are not effective in severe cases on a long-term basis. Similarly, topical antihistamines have no significant long-term benefit.
  • Mast cell stabilizers are perhaps the mainstay of treatment of VKC and are safe for long-term use. However, topical corticosteroids generally become necessary for most patients with significant symptoms. Because of their potential adverse effects, topical steroids should be prescribed at the lowest effective concentration and for the shortest duration possible. Pulsed-therapy regimen is generally recommended, such as 1% prednisolone acetate every 2 hours for the first week followed by a rapid taper; this may be repeated if symptoms recur. Systemic steroids may be used but generally are not necessary for moderate cases of VKC.
  • Several reports have shown that topical cyclosporine (Restasis) may be effective in reducing some of the signs and symptoms of VKC without adverse effects. Oral aspirin has been shown to be effective. Treatment of corneal shield ulcer may require antibiotic-steroid ointments.
• Atopic keratoconjunctivitis
• • Treatment of patients with AKC is similar to that of VKC, in that it includes controlling the environment and avoiding allergens and may require topical and systemic medications to provide symptomatic relief. As with VKC, topical vasoconstrictors and antihistamines may provide very limited, short-term relief; they are not the mainstay of treatment.
  • As with VKC, topical mast cell stabilizers and topical corticosteroids provide significant relief of symptoms. Mast cell stabilizers have to be used for several weeks prior to seeing a clinical effect, and, in the interim, topical steroids used in a pulsed fashion may help to control symptoms. Systemic antihistamines that are specific for H1 histamine receptors have been found to be helpful. Systemic steroids rarely are required, except in cases of vision-threatening complications.
  • Systemic cyclosporine, which has been shown to be effective in the treatment of atopic dermatitis, has shown promise in controlling ocular inflammation in AKC. Postulated mechanism of action is inhibition of the ability of T lymphocytes to produce interleukin 2 (IL-2), which is responsible for recruiting and activating new T cells. However, as with any systemic therapy, adverse effects may be significant; therefore, monitoring of serum levels and renal function is essential.
  • Concomitant herpes simplex virus infection should be treated with either topical or oral antiviral agents as needed. A subset of patients with recalcitrant and debilitating AKC may benefit from plasmapheresis, as was described by Aswad in 2 patients, one of whom had hyperimmunoglobulinemia E.³
• Giant papillary conjunctivitis
• • Goal of treatment in GPC is resolution of symptoms and restoration of functional use of contact lenses or ocular prosthetics. Although removal of the responsible foreign body is the definitive treatment, and while that may be appropriate for exposed sutures or scleral buckles, complete discontinuation of contact lenses or ocular prosthetics may be met with some degree of resistance from patients. Fortunately, contact lens wear does not need to be completely discontinued to minimize the symptoms of GPC.
  • Significant reduction in the signs and symptoms may be achieved by changing the contact lens care routine. Disinfecting solutions that contain chemical preservatives should be discontinued. Converting a patient from soft daily-wear contact lenses to disposable or daily-disposable soft contact lenses may prevent the accumulation of proteinaceous deposits, which may be the antigenic stimulus for GPC. Rigid gas permeable contact lenses may provide further relief from symptoms if disposable lenses do not provide adequate response. This relief is because of the decreased proclivity of the rigid gas permeable contact lenses to develop adherent deposits and coatings.
  • Pharmacologic treatment of GPC includes the use of mast cell stabilizers, topical corticosteroids, and antihistamines similar to that in the other immunologic conjunctival disorders discussed previously. As always, care must be taken when using topical corticosteroids; pulsed regimen is recommended to minimize adverse reactions.

Surgical Care

• Vernal keratoconjunctivitis
• • Severe cases of corneal shield ulcer may require superficial keratectomy to promote epithelial regeneration. Generally, shield ulcers are chronic conditions that are often refractory to conventional therapy. There have been reports of excimer laser phototherapeutic keratectomy (PTK) being used to remove fibrin deposits on the Bowman layer and theoretically facilitate epithelial healing.
  • Other surgical procedures, such as cryoablation of giant papillae or surgical removal of papillae with mucosal grafting, generally are not required, but they may be helpful in extremely advanced cases. Remember that since VKC is a self-limited disease, extensive reconstructive surgery may not have an acceptable risk-benefit ratio.
• Atopic keratoconjunctivitis: Penetrating keratoplasty may be undertaken in cases of severe corneal scarring or thinning, but great attention to control ocular surface inflammation is required.

Consultations

Allergists may help in identifying the responsible allergen(s).

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Allergic conjunctivitis can be treated with a variety of drugs, which include topical antihistamines, mast cell stabilizers, NSAIDs, and corticosteroids.

Drug Category: Topical antihistamines

Act by competitive inhibition of histamine at the H1 receptor. Block effects of endogenously released histamine.

Drug Name	Levocabastine (Livostin)
Description	Selective histamine H1 receptor antagonist. Active ingredient is 0.54 mg levocabastine hydrochloride.
Adult Dose	1 gtt in affected eye(s) qid
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; should not be used in people wearing soft contact lenses
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Should be shaken well before use; should not be used if discolored; not for internal (systemic) use

Drug Name	Epinastine (Elestat)
Description	Direct histamine-1 receptor antagonist. Does not penetrate blood-brain barrier and therefore should not induce adverse CNS effects. Indicated for symptoms due to allergic conjunctivitis.
Adult Dose	1 gtt OU bid until exposure to offending allergen is terminated
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Only for topical ophthalmic use; remove contact lenses before instillation; use caution when handling the container to avoid touch contamination; may cause burning sensation, folliculosis, hyperemia, or pruritus

Drug Name	Azelastine (Optivar)
Description	Competes with H1-receptor sites on effector cells and inhibits release of histamine and other mediators involved in allergic response.
Adult Dose	1 gtt into affected eye(s) bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Increases CNS toxicity of CNS depressant medications
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Wait 10 min after instilling solution to insert soft contact lenses (do not use contact lenses if eyes are red)

Drug Category: Mast cell stabilizers

Inhibit sensitized mast cell degeneration when exposed to specific antigens by inhibiting the release of mediators from the mast cells. Block calcium ions from entering the mast cell.

Drug Name	Olopatadine (Patanol, Pataday)
Description	Relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cell. Active ingredient of Patanol is 1.11 mg olopatadine hydrochloride; Pataday is 2.22 mg olopatadine hydrochloride.
Adult Dose	Patanol: 1 gtt in affected eye(s) bid q6-8h Pataday: 1 gtt in affected eye(s) qd
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Should not be used to treat irritation caused by contact lenses; contact lenses to be worn 10 min after instillation

Drug Name	Ketotifen (Zaditor)
Description	Over-the-counter (OTC) antihistamine eye drop. Noncompetitive H1-receptor antagonist and mast cell stabilizer. Inhibits release of mediators from cells involved in hypersensitivity reactions.
Adult Dose	1 gtt into affected eye(s) q8-12h
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	For topical ophthalmic use only; not for treatment of contact lens-related inflammation; wait 10 min before inserting contact lenses after ketotifen use; do not contaminate dropper tip or solution when placing drops into eyes

Drug Name	Nedocromil (Alocril)
Description	Interferes with mast cell degranulation, specifically with release of leukotrienes and platelet activating factor.
Adult Dose	1-2 gtt into affected eye(s) bid
Pediatric Dose	<3 years: Not established >3 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adverse events include ocular irritation/burning, headache, nasal congestion, and unpleasant taste in 10-40% of patients

Drug Category: Corticosteroids

Have both anti-inflammatory (glucocorticoid) and salt retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

Their mechanism of action is believed to be through inhibition of the cyclooxygenase enzyme that is essential in the biosynthesis of prostaglandins, which results in vasoconstriction, decrease in vascular permeability and leukocytosis, and a decrease on intraocular pressure.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Intermittent follow-up care may be necessary as seasonal allergies occur.

Deterrence/Prevention

• Seasonal and perennial allergic conjunctivitis: Avoidance of the offending antigen is the primary behavioral modification; specific testing by an allergist will identify the responsible allergen(s) and help the individual to establish ways to avoid the allergen, whether it is an environmental allergen or a household allergen, such as dust mite or pet dander. In addition, contact reactions caused by medications or cosmetics are treated best by avoidance.
• Vernal keratoconjunctivitis
• • As with most type I hypersensitivity disorders, allergen avoidance should be emphasized as the first-line treatment. Although permanent relocation to a cooler climate is not feasible in many cases, it remains a very effective therapy for VKC.
  • Maintenance of an air-conditioned environment and control of dust particles at home and work also may be helpful. Local measures, such as cold compresses and periodic installation of artificial tears, may provide temporary relief.

Complications

• Complications are very rare, with corneal ulcers or keratoconus occurring rarely.

Prognosis

• Prognosis is favorable. This condition generally clears up readily but may reoccur.

Patient Education

• Patients should be encouraged to identify the allergen that is causing their problem and to avoid it.
• For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education articles Pinkeye, Eye Allergies, and How to Instill Your Eyedrops.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Early diagnosis and treatment will help prevent the rare complications that can occur with this disease.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Hogan MJ. Atopic keratoconjunctivitis. Am J Ophthalmol. 1953;36:937-947.
2. Allansmith MR, Korb DR, Greiner JV, Henriquez AS, Simon MA, Finnemore VM. Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol. May 1977;83(5):697-708. [Medline].
3. Aswad MI, Tauber J, Baum J. Plasmapheresis treatment in patients with severe atopic keratoconjunctivitis. Ophthalmology. Apr 1988;95(4):444-7. [Medline].
4. Abelson MB, Allansmith MR, Friedlaender MH. Effects of topically applied occular decongestant and antihistamine. Am J Ophthalmol. Aug 1980;90(2):254-7. [Medline].
5. Abelson MB, Baird RS, Allansmith MR. Tear histamine levels in vernal conjunctivitis and other ocular inflammations. Ophthalmology. Aug 1980;87(8):812-4. [Medline].
6. Abelson MB, Butrus SI, Weston JH. Aspirin therapy in vernal conjunctivitis. Am J Ophthalmol. Apr 1983;95(4):502-5. [Medline].
7. Abelson MB, Gomes PJ, Vogelson CT, Pasquine TA, Turner FD, Wells DT, et al. Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis. Curr Med Res Opin. May 2005;21(5):683-91. [Medline].
8. Abelson MB, Greiner JV. Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model. Curr Med Res Opin. Dec 2004;20(12):1953-8. [Medline].
9. Abelson MB, Madiwale N, Weston JH. Conjunctival eosinophils in allergic ocular disease. Arch Ophthalmol. Apr 1983;101(4):555-6. [Medline].
10. Abelson MB, Paradis A, George MA, Smith LM, Maguire L, Burns R. Effects of Vasocon-A in the allergen challenge model of acute allergic conjunctivitis. Arch Ophthalmol. Apr 1990;108(4):520-4. [Medline].
11. Abelson MB, Soter NA, Simon MA, Dohlman J, Allansmith MR. Histamine in human tears. Am J Ophthalmol. Mar 1977;83(3):417-8. [Medline].
12. Abiose A, Merz M. Cryosurgery in the management of vernal keratoconjunctivitis. Ann Ophthalmol. Aug 1983;15(8):744-7. [Medline].
13. Allansmith MR, Baird RS, Greiner JV. Vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis compared and contrasted. Am J Ophthalmol. Apr 1979;87(4):544-55. [Medline].
14. Allansmith MR, Ross RN. Ocular allergy and mast cell stabilizers. Surv Ophthalmol. Jan-Feb 1986;30(4):229-44. [Medline].
15. Allansmith MR, Ross RN, Greiner JV. Chapter 43: Giant papillary conjunctivitis: diagnosis and treatment. In: Update 5. Contact Lenses. Little Brown; 1989:1.
16. Azevedo M, Castel-Branco MG, Oliveira JF, Ramos E, Delgado L, Almeida J. Double-blind comparison of levocabastine eye drops with sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy. Nov 1991;21(6):689-94. [Medline].
17. Ballow M, Mendelson L. Specific immunoglobulin E antibodies in tear secretions of patients with vernal conjunctivitis. J Allergy Clin Immunol. Aug 1980;66(2):112-8. [Medline].
18. BenEzra D, Pe'er J, Brodsky M, Cohen E. Cyclosporine eyedrops for the treatment of severe vernal keratoconjunctivitis. Am J Ophthalmol. Mar 15 1986;101(3):278-82. [Medline].
19. Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology. Nov 1991;98(11):1679-84. [Medline].
20. Bonini S. Advances and gaps in ocular allergies. Arch Soc Esp Oftalmol. Apr 2005;80(4):205-7. [Medline].
21. Braude LS, Chandler JW. Atopic corneal disease. Int Ophthalmol Clin. 1984;24(2):145-56. [Medline].
22. Brauninger GE, Centifanto YM. Immunoglobulin E in human tears. Am J Ophthalmol. Sep 1971;72(3):558-61. [Medline].
23. Brunsting LA, Reed WB, Bair HL. Occurrence of cataracts and keratoconus with atopic dermatitis. Arch Dermatol. 1955;72:237.
24. Buckley RJ. Long-term experience with sodium cromoglycate in the management of vernal keratoconjunctivitis. In: Pepys J, Edwards AM, eds. The Mast Cell. London: Pitman Medical; 1980.
25. Buckley RJ. Vernal keratoconjunctivitis. Int Ophthalmol Clin. 1988;28(4):303-8. [Medline].
26. Butrus SI, Leung DY, Gellis S, Baum J, Kenyon KR, Abelson MB. Vernal conjunctivitis in the hyperimmunoglobulinemia E syndrome. Ophthalmology. Oct 1984;91(10):1213-6. [Medline].
27. Butrus SI, Ochsner KI, Abelson MB, Schwartz LB. The level of tryptase in human tears. An indicator of activation of conjunctival mast cells. Ophthalmology. Dec 1990;97(12):1678-83. [Medline].
28. Cameron JA, Antonios SR, Badr IA. Excimer laser phototherapeutic keratectomy for shield ulcers and corneal plaques in vernal keratoconjunctivitis. J Refract Surg. Jan-Feb 1995;11(1):31-5. [Medline].
29. Carr RD, Berke M, Becker SW. Incidence of atopy in the general population. Arch Dermatol. 1964;89:27.
30. Donshik PC, Ballow M. Tear immunoglobulins in giant papillary conjunctivitis induced by contact lenses. Am J Ophthalmol. Oct 1983;96(4):460-6. [Medline].
31. El Hennawi M. Clinical trial with 2% sodium cromoglycate (Opticrom) in vernal keratoconjunctivitis. Br J Ophthalmol. Jul 1980;64(7):483-6. [Medline].
32. Foster CS. Evaluation of topical cromolyn sodium in the treatment of vernal keratoconjunctivitis. Ophthalmology. Feb 1988;95(2):194-201. [Medline].
33. Foster CS, Calonge M. Atopic keratoconjunctivitis. Ophthalmology. Aug 1990;97(8):992-1000. [Medline].
34. Foster CS, Duncan J. Randomized clinical trial of topically administered cromolyn sodium for vernal keratoconjunctivitis. Am J Ophthalmol. Aug 1980;90(2):175-81. [Medline].
35. Foster CS, Rice BA, Dutt JE. Immunopathology of atopic keratoconjunctivitis. Ophthalmology. Aug 1991;98(8):1190-6. [Medline].
36. Friedlaender MH. Allergy and Immunology of the Eye. New York: Harper & Row; 1979.
37. Friedlaender MH. Conjunctival provocation tests: a model of human ocular allergy. Trans Am Ophthalmol Soc. 1990;87:577.
38. Friedlaender MH. Corticosteroid therapy of ocular inflammation. Int Ophthalmol Clin. 1983;23(1):175-82. [Medline].
39. Friedlaender MH, Okumoto M, Kelley J. Diagnosis of allergic conjunctivitis. Arch Ophthalmol. Aug 1984;102(8):1198-9. [Medline].
40. Garrity JA, Liesegang TJ. Ocular complications of atopic dermatitis. Can J Ophthalmol. Feb 1984;19(1):21-4. [Medline].
41. Ghoraishi M, Akova YA, Tugal-Tutkun I, Foster CS. Penetrating keratoplasty in atopic keratoconjunctivitis. Cornea. Nov 1995;14(6):610-3. [Medline].
42. Goen TM, Sieboldt K, Terry JE. Cromolyn sodium in ocular allergic diseases. J Am Optom Assoc. Jul 1986;57(7):526-30. [Medline].
43. Gormaz A, Eggers C. Vernal keratoconjunctivitis and keratoconus. Am J Ophthalmol. Oct 1983;96(4):555-6. [Medline].
44. Greenbaum J, Cockcroft D, Hargreave FE, Dolovich J. Sodium cromoglycate in ragweed-allergic conjunctivitis. J Allergy Clin Immunol. Jun 1977;59(6):437-9. [Medline].
45. Greiner JV, Udell IJ. A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model. Clin Ther. May 2005;27(5):568-77. [Medline].
46. Hoang-Xuan T, Prisant O, Hannouche D, Robin H. Systemic cyclosporine A in severe atopic keratoconjunctivitis. Ophthalmology. Aug 1997;104(8):1300-5. [Medline].
47. Hurlbut WB, Damonkos AN. Cataract and retinal detachment associated with atopic dermatitis. Arch Ophthalmol. 1961;52:852-857.
48. Irani AM, Butrus SI, Tabbara KF, Schwartz LB. Human conjunctival mast cells: distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis. J Allergy Clin Immunol. Jul 1990;86(1):34-40. [Medline].
49. Jolson AS, Jolson SC. Suture barb giant papillary conjunctivitis. Ophthalmic Surg. Feb 1984;15(2):139-40. [Medline].
50. Korb DR, Allansmith MR, Greiner JV, Henriquez AS, Richmond PP, Finnemore VM. Prevalence of conjunctival changes in wearers of hard contact lenses. Am J Ophthalmol. Sep 1980;90(3):336-41. [Medline].
51. Leonardi A. Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. Aug 2005;10(3):505-20. [Medline].
52. Martin NF, Rubinfeld RS, Malley JD, Manzitti V. Giant papillary conjunctivitis and meibomian gland dysfunction blepharitis. CLAO J. Jul 1992;18(3):165-9. [Medline].
53. Meisler DM, Krachmer JH, Goeken JA. An immunopathologic study of giant papillary conjunctivitis associated with an ocular prosthesis. Am J Ophthalmol. Sep 1981;92(3):368-71. [Medline].
54. Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol. Jan 2005;115(1):118-22. [Medline].
55. Rahi AHS. Pathology of corneal plaque in vernal keratoconjunctivitis. In: O'Connor GR, Chandler JW, eds. Advances in Immunology and Immunopathology of the Eye. 1985.
56. Reider N. Sublingual immunotherapy for allergic rhinoconjunctivitis--the seeming and the real. Int Arch Allergy Immunol. Jul 2005;137(3):181-6. [Medline].
57. Robin JB, Regis-Pacheco LF, May WN, Schanzlin DJ, Smith RE. Giant papillary conjunctivitis associated with an extruded scleral buckle. Case report. Arch Ophthalmol. May 1987;105(5):619. [Medline].
58. Roth H, Kierland R. The natural history of atopic dermatitis. Arch Dermatol. 1964;89:209.
59. Schoch C. Effect of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in the guinea pig and ocular immediate hypersensitivity in the albino rat. Ocul Immunol Inflamm. Feb 2005;13(1):39-44. [Medline].
60. Shearer WT, Fleisher TA. The Immune System. In: Middleton E, Reed CE, Ellis EF, eds. Allergy: Principles and Practice. St Louis: Mosby; 1998:1-13.
61. Stegman R, Miller D. A human model of allergic conjunctivitis. Arch Ophthalmol. Dec 1975;93(12):1354-8. [Medline].
62. Tabbara KF, Butrus SI. Vernal keratoconjunctivitis and keratoconus. Am J Ophthalmol. May 1983;95(5):704-5. [Medline].
63. Trocme SD, Kephart GM, Allansmith MR, Bourne WM, Gleich GJ. Conjunctival deposition of eosinophil granule major basic protein in vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. Am J Ophthalmol. Jul 15 1989;108(1):57-63. [Medline].
64. Tse DT, Mandelbaum S, Epstein E, Baerveldt G, Fein W. Mucous membrane grafting for severe palpebral vernal conjunctivitis. Arch Ophthalmol. Dec 1983;101(12):1879-83. [Medline].
65. Tuft SJ et al. Clinical features of atopic keratoconjunctivitis. Ophthalmol. 1991;98:150.
66. Wiens JJ, Jackson WB. New directions in therapy for ocular allergy. Int Ophthalmol Clin. 1988;28(4):332-7. [Medline].

Article Last Updated: Dec 13, 2007