allergy
How to Manage Allergy
Utilize your therapeutic privileges to provide optimum patient care.
DEEPAK GUPTA, O.D., F.A.A.O.

Consumers purchase roughly 40 million bottles of over-the-counter (OTC) anti-allergic eye drops each year and another 4 million prescription drops, according to a 2003 study. These statistics are unfortunate because we have vastly superior prescription medications to help these patients better manage allergic conjunctivitis, one of the most frequently occurring ocular conditions that we see. This also means that allergy is a nice niche for us to fill so we can expand into our therapeutic privileges. In my experience, roughly 85% of patients with systemic allergies suffer from some stage of ocular manifestations, so it's important for us to stay up-to-date in this area. The following discussion should help.

Know the enemy

When most O.D.s think of ocular allergies, they think of seasonal allergic conjunctivitis (SAC). Patients who suffer from SAC are usually symptomatic during the spring and early fall. Tree pollen affects these patients in the spring, grass pollen in the summer and ragweed in the fall. A variant of this condition, called perennial allergic conjunctivitis (PAC), affects patients indoors and all year long. These patients are usually sensitive to things such as dust mites and mold or pet dander.

Two rarer and more severe forms of allergic conjunctivitis (atopic keratoconjunctivitis [AKC] and vernal keratoconjunctivitis [VKC]) also exist. But because the vast majority of cases we see are SAC and PAC, I'll limit my discussion to these two.

Pathogenesis

The immunopathogenesis of SAC is a type-I hypersensitivity IgE-mediated reaction with the mast cell as the most important cellular player. Here's how it works:

The patient experiences sensitization to environmental allergens. This is the sub-clinical form in which the patient develops no symptoms, but the groundwork is laid for subsequent damage. In this stage, the IgE molecule binds to receptors on sensitized mast cells and basophils in a way that prepares them for future allergen exposure.

When future allergen contact happens, the mast cells degranulate within seconds. This leads to the release of a wide assortment of inflammatory mediators. The most important of these is histamine, but prostaglandins, leukotrienes and cytokines are also important. This is the early phase of ocular allergies.

The late phase begins hours after the initial activation and involves additional inflammatory cells. Eosinophils, neutrophils, basophils and T-lymphocytes infiltrate the conjunctival mucosa. These additional inflammatory cells release a variety of mediators that result in the recurrence and prolongation of symptoms.

Differential diagnosis

In most cases, a combination of a patient history and slit lamp examination is enough to confirm a diagnosis. However, there are a few other common anterior segment disorders you should rule out:

►dry eyes
►blepharitis
►bacterial conjunctivitis
►hypersensitivity reactions to medications.

Because the signs of allergy that you observe at the slit lamp can be minimal, it's especially important to take a thorough history. One of the key complaints in allergic conjunctivitis is itching, which may be accompanied by redness, chemosis, tearing and lid swelling. One basic guideline often holds true: If it itches it's allergy, if it burns it's dry eye and if it's sticky it's bacterial.

Patients who just have dry eye don't have itching. Patients who have seasonal allergies rarely demonstrate the discharge associated with bacterial conjunctivitis. Patients who just have blepharitis have some intermittent itching, but it isn't the predominant symptom.

When ruling out hypersensitivity reactions, remember that many eye drops, including some glaucoma medications, contain a benzalkonium chloride preservative that can cause toxicity reactions. In addition, contact lens wearers may have allergic reactions to care solutions or to lenses themselves. Also, in most cases, the onset of symptoms will coincide with the use of a new brand of solution, etc. To eliminate these possible culprits, have the patient temporarily discontinue contact lens use and see if the symptoms resolve.

Managing allergy

You won't be able to treat the vast majority of cases. No medication or remedy that you can offer will cure the patient. Instead, what you're attempting to do is manage the symptoms so the patient is comfortable and no damage occurs to the ocular tissue. With the weapons you have in your arsenal, you should be able to treat individual patients according to their specific ailments and lifestyles.

Over-the-counter drugs

OTC ocular allergy drugs such as Opcon-A (Bausch & Lomb), Visine-A (Pfizer) and Naphcon-A (Alcon Laboratories) contain an H1-receptor antihistamine (either antazoline or pheniramine) and a vasoconstrictor (either naphazoline or tetrahydrozaline). The antihistamine component competitively blocks the H1-receptors on the nociceptive type-C nerves of the mucosal membranes.

The result is a significant decrease in ocular itching. However, it has little effect on ocular redness or swelling. The vasoconstrictor component works on the conjunctival blood vessels to decrease redness. The problems with these OTC drops are manifold. They include:

►Many patients complain that their eyes sting, burn and tear upon instillation.
►Most OTC drops have a duration of action of two hours, but are recommended for use q.i.d. That only covers eight hours of relief. Even q.i.d. dosing is often not enough for patients to obtain sufficient relief.
►Chronic use of these drops often leads to tachyphylaxis, rebound conjunctivitis and a permanent loss of ocular vessel tone.

Prescription is best

These problems are a main reason why we should use the following prescription anti-allergy drugs for our patients. In our practice, we go out of our way to tell patients of the potential consequences of these OTC medications and to write them a prescription instead. The drugs listed in the following categories are more effective and carry fewer adverse effects.

■Topical antihistamines. Antihistamines act against histamine, which degranulation has already released. For symptomatic relief of acute, mild hay fever conjunctivitis, an antihistamine may prove effective. These agents combat redness and swelling as well as itch. They have little impact on other pro-inflammatory mediators, such as prostaglandins and leukotrienes, but provide short-term, rapid symptomatic relief of itch.

However, patients who have chronic ocular surface allergy need to stabilize their mast cells long term. This is one of the chief reasons why these medications have been delegated to second line defense. Topical antihistamines include:

    ►emedastine difumarate (Emadine, Alcon).

    ►levocabastine HCl (Livostin, Novartis).

■Topical mast cell stabilizers. Mast cell degranulation on the conjunctiva causes the clinical symptoms of allergy. A cascade of events results, leading to increased levels of histamine on the ocular surface. Drugs known as mast cell stabilizers reduce the amount of degranulation and histamine that the mast cells release.

Mast cell stabilizers don't relieve existing symptoms of allergy; they prevent them from occurring. This works well in a patient who has a seasonal, predictable history of allergies where you see him or her several weeks before the anticipated onset of symptoms and start him on the drops prophylactically. They don't work well if a patient's allergy isn't limited to discrete, predictable attacks. Once again, these are now second-line agents.

Topical mast cell stabilizers include:

    ►pemirolast potassium (Alamast, Santen)

    ►cromolyn sodium (Crolom, Bausch & Lomb)

    ►lodoxamide tromethamine (Alomide, Alcon)

    ►nedocromil sodium (Alocril, Allergan)

■Topical antihistamines/ mast cell stabilizers. These dual-acting compounds are excellent for treating ocular allergy because they combine the fast response of antihistamines with the prolonged action of mast cell stabilizing activity. They are the first line of defense for most patients with allergies. Topical antihistamines/mast cell stabilizers are:

    ►olopatadine HCl (Patanol, Alcon)

    ►ketotifen fumarate (Zaditor, CIBA Vision)

    ►azelastine HCl (Optivar, MedPointe)

    ►epinastine HCI (Elestat, Inspire).

■Topical corticosteroids. There was a time when doctors only used these agents when severe allergic conjunctivitis didn't respond to other treatment modalities. However, with the emergence of milder steroids that have a much better safety profile, such as loteprednol, that situation has changed.

Steroids block a vital enzyme in the arachidonic acid pathway of prostaglandin and leukotriene synthesis.

Topical corticosteroids include loteprednol etabonate (Alrex and Lotemax, Bausch & Lomb). Practitioners use them to treat allergic conjunctivitis in one of three ways, depending on the individual doctor's level comfort:

    ►For non-responders, use the combination product first; when it doesn't work, prescribe the steroid

    ►For moderate to severe cases, prescribe both and then taper the steroid after one to two weeks

    ►Use the combination product as baseline and use loteprednol etabonate for flare-ups — similar to the way an asthmatic patient uses an inhaler.

Oral medications

The alternative is oral medications. Some of the more popular drugs include diphenhydramine HCl (Benadryl, Pfizer), fexofenadine HCl (Allegra, Sanofi-Aventis), loratadine (Claritin, Scher- ing-Plough) and cetirizine HCl (Zyrtec, Pfizer). However, many of these have poor ocular penetration. I use them more to control systemic conditions when I think eye drops alone won't properly manage a patient's ocular symptoms.

Many patients think that the oral anti-allergy medications are stronger, but beware: These drugs inhibit muscarinic receptors, leading to mucosal dryness. A dry eye with a defective tear film offers less protection against allergens and pollutants.

Thus, oral antihistamines may actually exacerbate ocular allergies by lowering the defense offered by a healthy tear film.

Clinical pearls

Always see patients for follow-up when writing a prescription for allergies. Doing so will confirm that the patient is better and let you pursue additional therapy if the patient is not.

If your patient has allergy complaints regarding only his or her eyes and you've prescribed a systemic medication, consider a change. Topical medications work much better for ocular symptoms.

References available upon request.