With the start of spring almost here, you can expect to see more patients who have ocular allergy in your practice. A significant portion of this population will be children. Consider: Some 12% of children younger than age 18 in the United States suffer from respiratory allergies, 10% from hay fever and 12% from other allergies.¹

Allergic conjunctivitis in children is rarely complicated when treated early and prophylactically. In the past, few drugs were approved for pediatric use, limiting our treatment options for children who had allergic conjunctivitis. Treatment was further complicated by childrens fear of drops and inability to self-administer, and by scheduling of treatment times that often conflicted with school or daycare schedules.

The Causes
Allergies occur in patients who are hypersensitive to a foreign agent (allergen). Allergies have a strong genetic component and many patients usually have a personal or family history of atopy such as allergic rhinitis, asthma or eczema.² The genetic influence appears to be multifactoral, and no single atopy gene has been identified.³

Other factors implicated in influencing this genetic predisposition may include vegetation, cigarette smoke, pollution, prenatal nutrition and early exposure to environmental allergens.³ This influence may be positive or negative in the development of atopic disease. Early exposure to some allergens may be helpful. For example, early high-level exposure to cat allergens (not low level) may protect against the development of asthma.³

Breast feeding, delayed ingestion of solid foods until six months of age, ingestion of fish oil, and avoidance of tobacco smoke appear to play a role in allergy prevention, but further studies are needed before recommendations can be made with confidence.³ Climate also influences the expression of some allergic reactions, especially vernal keratoconjunctivitis.

Differential Diagnosis
The predominant symptom associated with allergic conjunctivitis is itching. If your patient does not complain of itching, consider other etiologies.

Realize that eliciting symptoms may be difficult depending on the childs age and verbal development. You may have to rely on physical indicators of symptoms in nonverbal or preverbal children. For example, excessive rubbing is usually indicative of itching.

Signs associated with allergic conjunctivitis include burning, injection, chemosis, tearing and stringy discharge. Although allergic conjunctivitis may be slightly asymmetrical, it is generally a bilateral condition.

Similar signs may also occur in other types of conjunctivitis. For example, a patient who has viral conjunctivitis may experience burning, injection and tearing but generally will not experience itching. This patient also may have a history of systemic infection or exposure to someone with conjunctivitis.

Similarly, patients who have bacterial conjunctivitis may present with injection, tearing and discharge. However, these patients do not complain of itching and the discharge is not stringy. Also, bacterial and viral conjunctivitis may start in one eye and spread to the other.

Seasonal and Perennial Allergic Conjunctivitis
There are basically three common forms of allergic conjunctivitis in children: seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC) and vernal keratoconjunctivitis (VKC).

Atopic keratoconjunctivitis (AKC) is uncommon in children. Contact lens papillary conjunctivitis (CLPC) may occur in children who wear contact lenses.

SAC and PAC are the most common forms of allergic reactions in the eye. SAC, as the name suggests, occurs seasonally. Tree and grass pollens are the most common triggers during the spring and early summer, while weed pollen may be the offending allergen in the summer and fall.

Children who have PAC may be hypersensitive to indoor and outdoor environmental allergens, so conjunctivitis may occur throughout the year. Indoor offending allergens include dust mites, animal dander and mold. Some 79% of children who have PAC may also be sensitive to outdoor environmental factors, such as pollen, so their symptoms may be exacerbated during the warmer months.⁴

Children who have SAC and PAC classically experience ocular itching and thus rub their eyes. They may note other signs and symptoms, including conjunctival erythema, tearing, burning and chemosis of the bulbar conjunctiva and eyelids. Upon examination, you may observe conjunctival injection, chemosis and fine papillae. The cornea is usually not involved.

SAC and PAC may be seen in association with allergic rhinitis, and the child may complain of excessive sneezing and a runny nose. Children who have SAC and PAC may also have a personal or family history of other atopic disorders, such as asthma and eczema.

Vernal Keratoconjunctivitis
VKC is a chronic allergic reaction of childhood that appears to be mediated by type I and type IV hypersensitivity reactions. Although we do not fully understand its immunopathogenesis, immunoglobulin E (IgE), T lymphocytes, eosinophils, mast cells, and a complex network of interleukins and cell mediators mediate VKC.^5,6

VKC occurs in northern areas but typically affects populations in tropical and subtropical climates and those who live with hot, arid or windy conditions.⁵

VKC may be perennial and occur year round, especially in warmer climates; or it may be seasonal or exacerbated in the warmer months in other areas. When seasonal, the symptoms typically begin in early spring and last until autumn.⁵ Children who have VKC may experience exacerbation of itching and conjunctival redness after exposure to sun, dust, wind, hot weather, salt water and sweating after physical exertion.^4-6

As with SAC and PAC, patients who have VKC commonly have a genetic predisposition, with a personal or family history of atopic disorders.⁵ The age of onset typically occurs in the pre-puberty years with a mean age of 6 years but can range from age 1 to 22.5 The signs and symptoms usually resolve or lessen after puberty. VKC occurs two to four times more frequently in boys than in girls.⁵

Children who have VKC classically present complaining of very itchy eyes or exhibit excessive eye rubbing. This presentation is similar to SAC and PAC, but the clinical hallmark of VKC differs. This hallmark: giant papillae (>1 to 8mm) of the upper tarsal conjunctiva and/or Trantas dots.^5,7 Children who have VKC may also present with varying degrees of conjunctival injection (usually pink, not red), tearing, photophobia, foreign-body sensation, mild to moderate chemosis and a ropy mucous discharge.^5,7

VKC can cause sight-threatening complications ranging from a fine, diffuse punctate epithelial keratitis (PEK) to a severe confluent PEK and in severe cases to shield ulcers.^2,5 Corneal shield ulcers occur in some 3% to 11% of patients and may lead to corneal scarring, vascularization and, rarely, secondary infection.^2,6 So, we must differentiate SAC and PAC from VKC (see SAC/PAC vs. VKC.)

SAC/PAC vs. VKC

Seasonal/perennial allergic conjunctivitis	Vernal keratoconjunctivitis
Papillary reaction but not giant papillae	Possible cobblestone papillae
Limbus normal	Possible limbal papillae with whitish chalky dots (Trantas dots)
Generalized conjunctival chemosis and hyperemia; corneal involvement uncommon	Possible keratitis (may be greater superiorly) or pannus; can develop shield ulcers
SAC: Mostly spring and summer     PAC: Anytime but may be exacerbated in warm months	Intense itching during warm months but may be affected year round

Atopic Keratoconjunctivitis
AKC is a bilateral, chronic keratoconjunctivitis that occurs in patients who have atopic dermatitis (eczema). This is an adult allergic disorder and becomes part of the differential diagnosis as your pediatric allergic patients enter adulthood.⁷ AKC affects males more than females, with a peak incidence between ages 30 and 50, yet symptoms can begin in the late teens or early 20s.⁸ Recognizing this disorder is crucial due to its potential blinding complications and need for appropriate aggressive management. The clinical presentation is similar to VKC and some children with VKC will develop AKC later in life.⁴ AKC differs from VKC in that the conjunctival hyperemia, chemosis and palpebral papillae are usually more prominent inferiorly.⁸

Contact Lens Papillary Conjunctivitis
CLPC, also known as contact lens-associated giant papillary conjunctivitis, is marked by signs and symptoms similar to VKC. It occurs in 5% to 10% of soft contact lens wearers and 4% of gas permeable contact lens wearers.⁷ Although the population of contact lens wearers in children younger than the teen years is minimal, you should consider CLPC if the history includes contact lens wear. Contact lens-like papillary conjunctivitis may also occur in patients who have ocular prostheses, extruded scleral buckles or exposed sutures.⁹

Diagnosis
Diagnosis is usually based on the typical signs and symptoms elicited during a clinical evaluation.

There are two additional tests: the conjunctival provocation test, in which allergens are administered to the eye and the reaction is evaluated, and cytological examination of tear fluid for histamine, tryptase, eosinophils, neutrophils and/or lymphocytes. These tests, however, are not performed in typical cases.¹⁰ In difficult diagnostic cases, conjunctival scrapings may reveal eosinophil infiltration.⁶

Consultation with an allergist may also be helpful in identifying the offending allergens. The allergist will usually perform either a skin test (scratch or prick, intradermal, or patch test) or blood testing to identify the specific allergens.

Treatment
Treatment of ocular allergy in children is generally straightforward, safe and effective.

The first line of defense is to avoid known allergens if possible. An allergen avoidance handout is helpful for parents. A family or personal history of atopic disorders (allergic rhinitis, asthma, or eczema) may reveal allergy-prone children.

Additional treatment options include:

 Cool compresses and preservative-free artificial tears. These may suffice in very mild cases. The cool compresses constrict the blood vessels. This retards the release of mediators from the blood vessels, thus easing itchiness and decreasing inflammation. Artificial tears help dilute and flush out the offending allergens.

In children, it may be difficult to maintain compliance with cool compresses and obtain effective results. In these cases, as well as mild to moderate allergic reactions and VKC, topical pharmaceutical agents are usually required.

Over-the-counter (OTC) eye drops. These are usually weak topical decongestant eye drops that cause vasoconstriction. Some OTC vasoconstrictors are combined with weak antihistamines.

Although less expensive than prescription agents, OTC topical vasoconstrictors exhibit tachyphylaxis with decreased effectiveness over time. They may cause rebound hyperemia, promoting excessive usage. Parents should be warned not to exceed the recommended dosages. One further precaution: If swallowed by infants and children, these may lead to coma and marked reduction in body temperature.¹¹

With the advent of effective, safe, and more potent antihistamines, prescription medications should be recommended for children who have allergic conjunctivitis (see Pharmaceutical Agents Approved for Allergic Reactions in Children). For children, choose a drug with b.i.d. dosing schedule to decrease the need for multiple instillations.

Antihistamines. These histamine₁ (H₁) receptor antagonists compete with H₁ receptor sites to relieve itching. Pure antihistamines are indicated for mild, isolated type I hypersensitivity allergic reactions. In allergic reactions, itching is usually marked. In children, rubbing of the eyes is very difficult to control. The rubbing causes mechanical disruption to the mast cells (degranulation) with additional release of histamine, further increasing the itching and swelling.¹² Cool compresses along with antihistamines will immediately relieve the symptoms.

Mast cell stabilizers. As the name suggests, these stabilize the mast cell membrane and prevent the cells from releasing histamine, thus preventing H₁ and H₂ receptor effects.

Mast cell stabilizers work to completely halt the type I allergic cascade. They are an effective treatment for SAC and PAC and are the mainstay treatment for VKC. In VKC, we usually initiate treatment in early spring and continue treatment throughout the warm season.⁵

Pure mast cell stabilizers take approximately one to two weeks to reduce symptoms. So, during initial treatment with pure mast cell stabilizers, itching with associated rubbing and patient frustration persists, further delaying resolution. Consider starting treatment with an antihistamine/mast cell stabilizer combination such as Patanol (olopatadine, Alcon) b.i.d. for two weeks to reduce the itching and rubbing (antihistamine effect) and to initiate stabilization of the mast cell.

Once youve alleviated the acute symptoms, you can switch a child who exhibits extended seasonal allergies to a pure mast cell stabilizer if cost is an issue. A less expensive combination drug such as Crolom (cromolyn sodium, Bausch & Lomb) is safe for use in children ages 4 and older. For children who have known moderate to severe seasonal allergies and VKC, consider prescribing a mast cell stabilizer before the patient becomes symptomatic.

Steroids. Although rarely needed when treating SAC and PAC, occasional severe swelling may warrant a short dose of topical steroids. Fluorometholone is the only approved steroid for children and is a good first choice due to its low absorption.⁵

Moderate to severe VKC may require occasional doses of more potent steroids, especially when the cornea is threatened. In these cases, consider a consultation with a corneal specialist.⁵ Steroids help to suppress inflammation and allow the mast cell stabilizers to take effect. Topical antibiotics may be needed in conjunction with the steroids when a shield ulcer is present to prevent secondary infection.⁵

Remember children are also susceptible to the cataractogenesis and elevated intraocular pressure side effects of topical steroids and parents should be educated appropriately. Follow-up during treatment is recommended, and refills and chronic use of steroids should be avoided.

Immunosupressants. Investigators are evaluating cyclosporine to treat VKC and whether it may be substituted for and/or alternated with steroids to avoid the side effects associated with long-term steroid usage.^2,5,6 Cyclosporine, an immunosuppressive agent, appears to inhibit T lymphocytes. It also may inhibit histamine release, mediators, and eosinophil recruitment, and may reduce conjunctival fibroblast proliferation rate.

Cyclosporine has not been approved for use in children or for treating VKC. Off-label usage may be a consideration in severe VKC.¹¹ However, steroids are preferred over cyclosporine for patients who have corneal complications, such as shield ulcers, because they are more effective in inhibiting the toxic mediators of inflammation that cause the corneal damage.⁵

Other immunosuppressant agents such as mitomycin C also are being studied for treating VKC.⁵ One study found a statistically significant decrease in ropy mucous discharge, photophobia, conjunctival hyperemia and limbal edema in patients treated with the mitomycin C for two weeks vs. those treated with the placebo.¹³

 Nonsteroidal anti-inflammatory drugs (NSAIDs). Topical NSAIDs are rarely used as an initial treatment for allergic conjunctivitis given the availability of other effective, safe and comfortable options.

Oral antihistamines. Many children with allergic rhinitis and asthma are medicated with oral antihistamines. These drugs may help relieve the signs and symptoms of allergic conjunctivitis as well, but because topical medications are highly effective, we rarely prescribe oral preparations specifically for ocular involvement.

Also, the oral preparations may decrease aqueous tear production. This, in turn, may contribute to a longer contact time of the allergen with the mucous membrane. The natural tears are helpful in flushing unwanted allergens from the eye.

Pharmaceutical Agents Approved for Allergic Reactions in Children

Agent	Age Approval	Dosage	How Supplied
Pure Antihistamine Drops
Emadine (emastadine 0.05% solution, Alcon)	3 and older	1 drop q.i.d.	5ml
Livostin (levocabastine 0.05%, suspension, Novartis Ophthalmics)	12 and older	1 drop q.i.d. for two weeks	5ml, 10ml
Mast Cell Stabilizers
Alamast (pemirolast 0.1%, Vistakon Pharmaceuticals)	3 and older	1 to 2 drops q.i.d.	10ml
Alocril (nedocromil 2%, Allergan)	3 and older	1 to 2 drops b.i.d.	5ml
Alomide (lodoxamide tromethamine 0.1%, Alcon)	2 and older	1 to 2 drops q.i.d. up to 3 months	10ml
Crolom (cromolyn sodium 4%, Bausch & Lomb)	4 and older	1 to 2 drops q.i.d. to six times daily at regular intervals	10ml
Antihistamine/Mast Cell Stabilizer Combinations
Elestat (epinastine 0.05%, Allergan)	3 and older	1 drop b.i.d.	5ml, 10ml
Optivar (azelastine 0.05%, MedPointe Pharmaceuticals)	3 and older	1 drop b.i.d.	3ml, 6ml
Patanol (olopatadine 0.1%, Alcon)	3 and older	1 drop b.i.d.	5ml
Zaditor (ketotifen fumarate 0.025%, Novartis Ophthalmics)	3 and older	1 drop b.i.d	5ml
Corticosteroids
FML (fluorometholone 0.1%, Allergan) suspension or ointment	2 and older	1 drop b.i.d. to q.i.d. or ung apply 1/2 inch q.d. to t.i.d.	suspension: 5ml, 10ml, 15ml ointment: 3.5g
FML Forte (fluorometholone 0.25%, Allergan)	2 and older	1 drop b.i.d. to q.i.d.	2ml, 5ml, 10ml, 15ml

Immunotherapy (allergy shots) in some cases of significant allergic rhinoconjunctivitis and VKC may also be appropriate in children older than 7 or 8 years of age.^3,5 Varying results are reported.² The goal of immunotherapy: to desensitize the child to the offending allergens. Specifically, the body learns from repeated low-dose exposure to the allergen not to react.

Oral treatment is sometimes necessary. Systemic steroids, aspirin and Singulair (montelukast, Merck), an anti-leukotriene drug, have been used to treat VKC.⁶

Rare treatments with severe VKC complications include giant papillae excision for pseudoptosis, oral mucosal grafting, saphenous vein transplantation and amniotic membrane application.⁵

Allergic conjunctivitis in children is rarely complicated when treated early and prophylactically. With the advent of pediatric-approved allergy/anti-inflammatory drugs and drugs with a longer duration of action and therefore a decreased need for multiple instillations, treatment of allergic conjunctivitis in children is simpler and effective. By keeping abreast of allergy treatments for this patient population, you can provide patients with eye care they might not otherwise receive and educate parents about preventing visual complications due to VKC.

Dr. Parisi is a consultant at Pennsylvania College of Optometry in suburban Philadelphia. She has written previously on ocular allergies in children.

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