Knowing the different drug classes and their effects is essential to selecting the most appropriate anti- allergy medication for each patient. Also, careful consideration of subtle differences in clinical presentation will help determine the overall goals of the therapy, which is key to successful treatment and management.

Here, we'll review the five major categories of anti-allergy drugs, and then look at four different cases, discussing the pros and cons of various treatment options.

Five Drug Categories

Anti-allergy drugs fall into five broad categories:

• Decongestants. These agents cause blood vessel constriction within minutes, temporarily reducing hyperemia and chemosis. However, decongestants only conceal signs and symptoms; they do not directly affect the allergic reaction cascade. For this reason, these agents are designed for short-term use. Also be aware that long-term use of decongestants may mask symptoms of a greater problem. Most products in this class are available over-the-counter. Decongestant-antihistamine combinations are also available.

• Antihistamines. These agents block histamine from binding to receptor sites. This action relieves allergic symptoms such as rhinitis, itching, tearing, redness and chemosis. All these agents have a rapid onset of action, so they provide symptomatic relief within minutes. Three agents—Zaditor (ketotifen fumarate, Novartis Ophthalmics), Patanol (olopatadine, Alcon Laboratories) and Optivar (azelastin, Muro)--have both antihistamine and mast cell stabilizing properties, and are extremely useful for chronic and acute allergic conditions.

Oral antihistamines may occasionally be used to relieve symptoms of severe allergic conjunctivitis. Three agents—Allegra (fexofenadine, Aventis), Claritin (loratadine, Schering) and Zyrtec (cetirizine, Pfizer)—provide safe and effective relief from allergy symptoms, and are minimally sedating.

1. Giant papillae under high magnification at the inside edge of the tarsal plate on the superior palpebral conjunctiva (zone 1).

• Mast cell stabilizers. These agents inhibit the degranulation of the mast cells, thus preventing the release of histamine from the mast cells. Mast cell stabilizers usually provide relief from allergic symptoms within 1-2 weeks, although they sometimes can take up to 4-6 weeks. This lag in symptomatic relief occurs because they are ineffective against the histamine already released in the patient's system.

Mast cell stabilizers are essential for treating chronic allergies. As with all anti-allergy agents, but particularly with mast cell stabilizers, it is critical to inform the patient that effective therapy depends on administering the drug at the prescribed time intervals.

• Non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are in part responsible for producing symptoms of itch. Acular (ketorolac tromethamine, Allergan), the only FDA-approved NSAID for treating seasonal allergic conjunctivitis, inhibits an enzyme essential to the production of prostaglandins. Studies also have shown that Acular reduces redness, swelling and mucus discharge.^1,2 The onset of relief usually occurs within an hour.

Acular is available in a preservative-free formula (Acular PF). This may be appropriate for patients who complain of burning after instilling the drug. However, Acular PF is not FDA-approved for treatment of allergic conjunctivitis.

2. Giant papillae seen here under low magnification, extending from zone 1 to zone 3.

• Steroids. Corticosteroids have an anti-inflammatory effect by affecting nearly every aspect of the immune system.³ Lotemax (loteprednol etabonate 0.5%, Bausch & Lomb) and Alrex (loteprednol etabonate 0.2%, Bausch & Lomb) are FDA-approved for the treatment of allergic eye disease. Lotemax can decrease the size of papillae in giant papillary conjunctivitis, and alleviate itching and contact lens intolerance.^4,5 Alrex is indicated for seasonal allergic conjunctivitis.

Each of these five drug classes affects a different aspect or mechanism of the ocular immunological response. Some agents combine properties of different drug classes.

Consider the subjective and objective data of the following cases and decide what anti-allergy agents you would prescribe to alleviate each patient's signs and symptoms.

Case 1: Mild Itch, Redness And Lens Intolerance

A 30-year-old white female with a 12-year history of soft contact lens wear presents complaining of mildly itchy red eyes for the last month. She reports lens intolerance, which increases as the day progresses. She has no significant medical or ocular history and no history of recent injury.

Entering acuities through her habitual conventional soft contact lenses are 20/30 O.U.; there is no improvement with pinhole. Slit lamp examination reveals erratic contact lens movement on blink and grade 2+ diffuse deposits covering the lenses. The superior tarsal conjunctiva exhibits large papillae extending from the inside edge of the tarsal plate (zone 1) to the lid margin (zone 3) (figures 1 and 2) and a small amount of white, ropy mucus.

Diagnosis. Giant papillary conjunctivitis (GPC).

Management. The goal is to reduce this patient's symptoms by controlling or removing the causative agents. The GPC has both mechanical and immunological components.^6,7 So, this patient needs to discontinue contact lens wear for about four weeks, then switch to a disposable lens.

Therapeutic options often include mast cell stabilizers and steroids, depending on the severity of symptoms. Considering this patient's symptoms and clinical findings, we have three main options:

• Mast cell stabilizer monotherapy. While a common approach for treating GPC, no mast cell stabilizer is FDA-approved for this purpose. You must inform the patient that this is an "off-label" use.

A mast cell stabilizer would be effective for this patient if she was not experiencing significant discomfort and would be willing to continue status quo for at least one week until the mast cell stabilizer takes effect. There would be a lag of 1-6 weeks until the patient can feel symptomatic relief. So, monotherapy with a mast cell stabilizer is less beneficial for acute clinical presentations or for a clinical entity that requires immediate relief.

Another disadvantage: Mast cell stabilizers generally require qid dosing, which would become difficult when the patient resumes contact lens wear. One mast cell stabilizer—Alocril (nedocromil sodium, Allergan)—requires bid dosing, so the patient can instill it in the morning prior to contact lens insertion and in the evening after lens removal.

You might also consider an antihistamine with mast cell stabilizing properties to provide immediate symptomatic relief and address the long-term aspects of GPC. These agents would provide a more desirable off-label monotherapy than would a mast cell stabilizer alone. Optivar, Patanol and Zaditor also have bid dosing, which makes them more compatible with contact lens wear.

• Steroid monotherapy. This approach is desirable for severe recalcitrant cases, because the steroid's potent mediation can provide immediate symptomatic relief and address chronic allergic eye disease. Lotemax would be a safe and effective choice for this patient. While its qid dosing schedule is not ideal for soft contact lens wearers, patients who wear disposable lenses can use this drug at your discretion.

• Steroid and mast cell stabilizer therapy. This choice in therapy is valuable, especially if there is concern with long-term steroid use. Begin the treatment with both a mast cell stabilizer and a steroid. About 1-2 weeks into therapy, taper the steroid to discontinue use. The patient will appreciate the immediate relief the steroid provides, and the long-term control the mast cell stabilizer brings.

3. Mild allergic chemosis and hyperemia secondary to seasonal allergic conjunctivitis (SAC) (left). 4. Papillae along the superior palpebral conjunctiva in SAC.

Case 2: Itching in Oregon

A 23-year-old white male presents complaining of moderately itchy, red eyes of one week in duration since his move to Oregon. He says he has been using Vasoclear (naphazoline, Novartis Ophthalmics) qid in both eyes with little to no relief. He has no significant medical or ocular history and no history of recent injury.

Entering acuity without correction is 20/20 O.U. Slit lamp examination reveals mild lid swelling, trace conjunctival chemosis and hyperemia (figure 3). The inferior palpebral conjunctiva exhibits grade 3 small papillae, and the superior palpebral conjunctiva exhibits grade 2 small papillae extending from the inside edge of the tarsal plate to the middle area of the tarsal plate (zone 2) (figure 4). Trace white mucus is visible in the lower fornix, with apparent excess tearing.

Diagnosis. Seasonal allergic conjunctivitis (SAC).

Management. The goal is to address this patient's immediate symptoms and keep him comfortable throughout the season. Another consideration is the severity of the case. We can effectively control mild symptoms with cold compresses, decongestants and preservative-free artificial tears. Preservative-free agents are helpful in reducing the risk of further allergic reactions when treating an already inflamed eye.

Considering this patient's history, his lack of success with a decongestant and his moderate discomfort, four main treatment options exist:

• Decongestant-antihistamine combination. This is a conservative choice, but can be an effective one if the patient complies completely with the treatment plan. The decongestant would mask the signs and symptoms, while the antihistamine would mildly suppress the immunological response. An appropriate dosing schedule would be qid. Agents in this category include Vasocon-A (antazoline-naphazoline, Novartis Ophthalmics), Naphcon-A (naphazoline-pheniramine maleate, Alcon Laboratories) and Opcon-A (pheniramine maleate-naphazoline, Bausch & Lomb). Besides the decongestant-antihistamine regimen, this patient should use preservative-free artificial tears and cold compresses, and avoid rubbing his eyes.

The addition of the antihistamine to the decongestant makes this therapy choice slightly more potent than what we might normally suggest for mild symptoms. However, it is not my therapy of choice for this patient. One of my concerns with over-the-counter anti-allergy agents is the risk of medication-induced conjunctivitis with prolonged use.⁸ Another concern: When we encourage patients to use over-the-counter agents, they may try to self-diagnose future cases of red eye, which may not be allergy but infections.

• Mast cell stabilizer monotherapy. This is an effective option for addressing long-term SAC. As in the previous case, however, this patient would experience no immediate symptomatic relief. Palliative therapy, such as cold compresses and preservative-free artificial tears, would be appropriate during this waiting period to improve comfort.

Extensive patient education is necessary. Stress compliance during the initial lag period, when the patient must still endure the uncomfortable symptoms.

• Antihistamine monotherapy. This treatment would address the patient's immediate needs. Also, antihistamines are safe and effective to use throughout the allergy season.

• Antihistamine and mast cell stabilizer. This combination would address both immediate and long-term needs. As the mast cell stabilizer starts to relieve the patient's symptoms (about 1-2 weeks into the treatment), you can discontinue the antihistamine.

An alternative to using two separate agents is to use the combination antihistamine/mast cell stabilizer, such as Optivar, Patanol and Zaditor. These agents would be of exceptional value to the patient. Talk with the patient about his lifestyle, and select a product with a dosing schedule that would aid in compliance. The dosing schedule of these combination products ranges from bid to qid. This increased convenience and decreased cost may improve compliance.

Had this patient presented with severe SAC symptoms, NSAIDs and steroids might have been appropriate. Oral antihistamines might also have been indicated if the symptoms caused sufficient discomfort.

Case 3: Severe Symptoms In 12-Year-Old

5. Limbal papillae and Trantas’ dots in vernal keratoconjunctivitis.

A 12-year-old black male presents complaining of severe itchy eyes for the past three weeks. He says he must constantly rub his eyes, which leads to moderate redness and swelling. He is using drops intended "to take the red out," but to no avail.

His medical history is significant for asthma, which he controls with an albuterol inhaler prn. Ocular history is remarkable for mild seasonal allergies last year, treated with "over-the-counter drops." There is no history of recent injury.

Entering acuity through his habitual Rx is 20/20 O.U. Slit lamp exam reveals mild lid matting and excess tearing. The superior palpebral conjunctiva shows grade 3+ large papillae with mucus caught throughout. Limbal papillae and Trantas' dots appear between the 11 and 1 o'clock positions (figure 5).

Diagnosis. Limbal vernal keratoconjunctivitis (VKC).

Management. The goal here is to reduce symptoms and control this chronic allergic condition. VKC usually afflicts patients in the spring and remains until mid- to late summer. It tends to recur every year, eventually dissipating when the patient is in his or her 20s. So, you not only want to address the immediate condition; you want to prepare for subsequent years. That means you must select an agent that you can institute early in future seasons and that will suppress the immunological response before the patient becomes symptomatic.

Given the patient's complaints, the treatment goals and the available anti-allergy agents, two primary options exist for this case:

• Steroid and mast cell stabilizer. The former delivers potent and immediate relief of the patient's signs and symptoms; the latter, used concurrently, addresses the chronicity of VKC.

Once the patient's symptoms are under control with the mast cell stabilizer, you can taper the steroid. Ideally, you will initiate treatment with a mast cell stabilizer each subsequent season before the patient experiences symptoms. This should obviate future steroid use.

• Antihistamine and mast cell stabilizer. The aim of this option is the same as the previous one. The difference is in the choice of agent to control the symptoms until the mast cell stabilizer takes effect. This option would be valuable in patients for whom steroids are contraindicated.

6. Moderate chemosis and hyperemia associated with allergic conjunctivitis.		7. A mucus strand on the cornea in a patient with allergic conjunctivitis.

Case 4: Discomfort Near Cats

A 27-year-old white female presents complaining of moderate itching and burning O.U. for the past three days. She is visiting her mother for a month and is allergic to her mother's three cats. She reports the use of artificial tears q2h with minimal relief. Medical and ocular history is unremarkable, other than allergies to pet dander.

Entering acuity with her habitual contact lenses is 20/20 O.U. Slit lamp examination reveals mild lid swelling and redness. The conjunctiva is moderately chemotic and hyperemic (figure 6). Trace papillary changes are evident on the superior and inferior palpebral conjunctiva. White mucus spans the cornea, and severe tearing is evident (figure 7).

Diagnosis. Allergic conjunctivitis secondary to cat dander.

Management. Because the patient will be exposed to the offending allergen for a limited time, the treatment goal is to restore her comfort for the remainder of the visit without serious long-term considerations. Two main treatment options exist for this case:

• Decongestant-antihistamine combination. This would address the patient's immediate needs, but a month of continued use may have undesirable ocular side effects. Long-term use of these agents may induce drug-associated toxicity. This option would be more desirable if the visit were only 1-2 weeks rather than a month.

• Antihistamines. An antihistamine would alleviate symptoms rapidly and control the immune response enough to allow for a comfortable visit.

Oral antihistamines could also be valuable in treating this type of allergic presentation if symptoms are severe enough.

Allergic conjunctivitis presents frequently, and a systematic approach is essential for selecting an appropriate anti-allergy agent. This starts with a thorough knowledge of the various classes of agents and careful consideration of your patient's needs and goals.

Dr. Peake is an assistant professor in the ocular disease department at Pacific University College of Optometry in Forest Grove, Ore.

Anti-Allergy Agents Drug Name Manufacturer Dosage FDA-Approved Use Comments Decongestants Relief (0.12% phenylephrine) Allergan qid Temporary relief from minor eye irritations Over the counter. Prefrin (0.12% phenylephrine) Allergan qid Same OTC. Naphcon (0.012% naphazoline) Alcon Laboratories qid Same OTC. Vasoclear (0.02% naphazoline) Novartis Ophthalmics qid Same OTC. Decongestant/Antihistamine Combinations Opcon­A (0.315% pheniramine maleate, 0.02675% naphazoline hydrochloride) Bausch & Lomb up to qid Allergic conjunctivitis OTC. Naphcon­A (0.3% pheniramine maleate, 0.025% naphazoline hydrochloride) Alcon Laboratories up to qid Same OTC. Vasocon­A (0.5% antazoline phosphate, 0.05% naphazoline hydrochloride) Novartis Ophthalmics up to qid Same OTC. Antihistamines (topical) Emadine (0.05% emedastine difumarate) Alcon Laboratories qid Allergic conjunctivitis Livostin (0.05% levocabastine hydrochloride) Novartis Ophthalmics qid Seasonal allergic conjunctivitis Suspension; shake well. Antihistamines (oral) Allegra (fexofenadine hydrochloride) Aventis 60mg bid or 180mg qd Seasonal allergic rhinitis and urticaria Claritin (loratadine) Schering 10mg qd Same Zyrtec (cetirizine hydrochloride) Pfizer 5 or 10mg qd Seasonal and perennial allergic rhinitis and urticaria Mast Cell Stabilizers Alamast (0.1% pemirolast potassium) Santen qid Allergic conjunctivitis Alocril (2% nedocromil sodium) Allergan bid Allergic conjunctivitis Solution is yellow. Alomide (0.1% lodoxamide tromethamine) Alcon Laboratories qid Vernal keratoconjunctivitis Crolom (4% cromolyn sodium) Bausch & Lomb 4-6 times daily Same Opticrom (4% cromolyn sodium) Allergan 4-6 times daily Same Antihistamine/Mast Cell Stabilizer Combinations Optivar (0.05% Azelastine hydrochloride) Muro bid Allergic conjunctivitis Has mild anti-inflammatory properties. Patanol (0.1% olopatadine hydrochloride) Alcon Laboratories bid Same Zaditor (0.025% ketotifen fumarate) Novartis Ophthalmics q8-12h Same Has mild anti-inflammatory properties. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Acular (0.5% ketorolac tromethamine) Allergan qid Seasonal allergic conjunctivitis Acular PF not FDA approved for allergies. Steroids Alrex (0.2% loteprednol etabonate) Bausch & Lomb qid Same Suspension; shake well. Lotemax (0.5% loteprednol etabonate) Bausch & Lomb Up to 1 gt q1h 1st wk, then 1-2 gtt qid thereafter Allergic conjunctivitis and steroid-responsive inflammatory conditions of the conjunctiva, cornea and anterior segment Same.

Top 10 Pearls for Managing Ocular Allergy By the time a patient seeks medical care, the severity of his or her allergic condition most likely is moderate. Understand the patient's immediate needs and long-term goals. This will help you select an appropriate therapy. Try to identify the offending allergen. A cure is better than just treating the patient's symptoms. Distinguish between symptoms of burning and itching. Patients often have difficulty describing their symptoms accurately. Burning symptoms may indicate a dry eye condition. Be aggressive (as appropriate) with your treatment. Try to eliminate, not just reduce, symptoms. Educate the patient. Stress the importance of instilling medication at regular intervals. Don't forget the power of palliative therapies, such as cold compresses and artificial tears. Remind the patient to avoid rubbing his or her eyes. Use non-preserved products when appropriate and available. Schedule a follow-up visit within a week to monitor your patient's progress. Be certain you are dealing with an allergy. Many red eyes can initially present the same. A thorough case history is essential. —E.W.P.