allergy update
Targeting  Allergies
BY ROBERT E. PROUTY, O.D., F.A.A.O., Denver, Colo.

Sixty million to 80 million people in the United States live with allergy, yet ocular allergy is underreported, underestimated and generally under treated. Ocular allergy is a multifaceted disorder that could prove difficult to diagnose if you're concentrating on a patient's ocular health or contact lens care. So what can we do to improve these numbers? It helps to know the treatments available including newly introduced treatments and those on the way.

Self treating

Much too frequently patients live with their allergies for so long that they consider their symptoms normal. Patients routinely use over-the-counter (OTC) medications that can inadvertently mask their allergy symptoms. But the OTC medications don't work for all patients. The newer prescription medications have so significantly improved patient management that they have prompted many practitioners to take a deeper look into the allergic processes that were taking place to decide if the "new" medications were truly superior to OTC medications.

OTC vasoconstrictors, artificial tears and changing the contact lens solution system were the typical first answer for most optometrists, but now we're learning that this may not always be the best first approach. That's why it's important to know your options, which I'll now discuss.

Gauging allergic reaction

The typical type-I hypersensitivity reaction involved in seasonal allergy occurs when the eye is exposed to an allergen (an antigen) for the first time. Typically, the initial exposure doesn't have any overt symptoms or signs. The sensitization process begins when the attacking allergen diffuses through the conjunctival mucosa and is taken up and processed to be identified by the T-cell lymphocytes. The T-cells are the major cellular regulators of the immune response. They induce the B-cell lymphocytes (from the bone marrow) to produce allergen-specific antibodies (immunoglobulins such as Ig-E) that coat the antigenic protein. The Ig-E antibodies then bind to the surface of the mast cells, completing the process of sensitization.

When a previously sensitized eye is exposed to the same allergen on a subsequent occasion, an allergic response will be elicited as the allergen binds to the Ig-E molecules on the surface of the mast cells. As a result, the mast cell's outer membrane ruptures and degranulates, immediately releasing pre-formed early phase mediators (histamine, tryptase, chymase, platelet activation factor, etc.) and eventually, outside of the mast cell, newly formed late phase mediators (prostaglan-dins, leukotrienes, thromboxanes, etc.) are formed. These late-phase mediators are more typically involved in reactions such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, but not the typical seasonal allergic conjunctivitis or even perennial allergy without chronicity.

It's important to understand that late-phase responses aren't a common ocular presentation for most O.D.s. A clinician will see many cases of acute allergy presentation. True late-phase allergy is a different disease and isn't generally viewed as a cascade of events starting with the early phase moving through the acute phase and into the late phase. Late-phase reactions, seen in both atopic and vernal keratoconjunctivitis, don't occur in allergic conjunctivitis. We treat these types of atopic diseases differently.

IMAGERY BY ERIC LINDLEY

Understanding mast cells

The predominant "player" in acute seasonal allergy is the mast cell. Historically, mast cells were considered "one size fits all" in that any mast cell stabilizer could effectively block mast cell degranulation and the subsequent release of histamine. Other early phase, preformed enzymes (tryptase and chymase) are destructive proteolytic enzymes that are secreted as soon as the cell breaks open.

These enzymes allow the differentiation between mast cell populations. Tryptase mast cells are located predominantly within the respiratory airway and tryptase/chymase mast cells are predominantly in the conjunctiva and skin. John Yanni, Ph.D., has also shown that these various mast cell populations react differently to various medications, which helps the doctor select the most appropriate medication based on anatomical location and individual patient response.

The first time a person experiences an itch and rubs his eyes, he's breaking open mast cells and releasing large packets of histamine that trigger a significant ocular tissue response. In addition to the preformed mediators eosino-phils, cytokines and other pro-inflammatory constituents are also variably distributed within the human body. There is an apparent intraspecies differences because not every patient responds the same way to every medication.

Diagnosing ocular allergy

Chronic allergy patients are recognizable by their physical appearance and by systemic symptoms such as nasal sinus congestion, itchy eyes and post-nasal drip. Diagnosing ocular allergy is a clinical challenge because ocular surface disease, dry eye and allergy can all superimpose themselves on top of one another. Sometimes when patients self-medicate with an OTC oral antihistamine, they actually dry their eyes further, and increase their ocular manifestations. Allergic eyes will have the classic red appearance with serous discharge, papillary response, conjunctival chemosis, general irritation and allergic rhinitis.

But not every patient has all of these signs and symptoms because contact lenses, dry eyes, blepharitis and lid disease can complicate the differential diagnosis. If this occurs, then treatment is also complicated because the choice of medication that solely suppresses histamine is the appropriate treatment for the immediate allergic response but doesn't address prevention of symptomology or late-phase changes.

Taking the step to treat

With some of the newest topical and oral medications on the market, you can manage ocular allergy easily in a way that's convenient for patients. You can also work with family physicians to assist with the commonly associated rhinitis. Other than when it's combined with extensive atopy, seasonal allergy isn't a terribly destructive process for the majority of patients.

Patients want immediate relief from their itching. An antihistamine will bind with the receptor and relieve the itch, but it doesn't negate the ongoing process or the release and development of other late-phase and chemotactic mediators. Nonsteroidal anti-inflammatory drugs sting on instillation and rely on their mild anesthetic action to relieve pain and itch, yet they also fail to prevent the ongoing process or the late-phase effects. A dual mechanism medication achieves both actions by relieving itch and stabilizing mast cells. The value of combination mast call inhibitors with antihistaminic action is that they meet these two patient needs.

However, when that method fails, the problem may be a different subset of mast cells or a different allergen process or someplace else in the inflammatory cascade such as prostaglandins or leukotrienes. Switching to another medication is prudent. If your diagnosis of allergy is correct, then the medication may be wrong for that patient. If he's not responding with the first drug of choice, then select another combination mast cell stabilizer that has antihistamine activity.

For many systemic allergy symptoms, a nasal corticosteroid can prove as effective as an oral antihistamine. It's important to differentiate between oral antihistamine and inhaled steroids because different risk factors exist between the two. Nasal Neosynephrine compounds or cromolyn sodium solution (NasalCrom) used in conjunction with a topical ocular medication offers a significant success rate without having to use systemic antihistamines or inhaled steroids.

Immunomodulators

An ongoing debate in optometry is the use of corticosteroids, which are actually immunomodulators that act to reduce inflammation without regard for the cause. Their activity spans virtually every aspect of the cellular inflammatory response by (1) modulating gene expression, (2) stabilizing both intracellular and extracellular membranes, and (3) interrupting the activation of phospholipase A2, thereby preventing the formation of archidonic acid (needed for prosta-glandin formation).

This results in a decrease in the production of the inflammatory precursor proteins, up regulation of inhibitory proteins, suppression of lymphocyte and mast cell proliferation, reduction of eosinophils and monocytes and interference with macrophagic activity and antigen processing.

So steroids potentially block the production of all of the inflammatory chemical mediators as well as reduce capillary permeability and cellular exudation. They suppress lymphocyte and mast cell proliferation and inhibit cell-mediated immune responses as well as relieve most ocular signs and symptoms.

However, their risks are just as broad. Glaucoma (or IOP increase) and infection are the two most prevalent ocular side effects, yet reduction of immunological activity is also significant.

The risk-benefit ratio just isn't in the favor of the use of topical steroids for seasonal ocular allergy, particularly for low-dose steroids. Severe atopic allergy or inflammatory reactions may require aggressive oral antihistamines and topical high-dose steroids to squelch the immediate inflammation, but management would usually not include their sustained use.

With the recent release of cyclosporine (Restasis), a new generation of immunomodulators is now commercially available. The use of cyclosporine is currently limited by the FDA to dry eye treatment but it's just a matter of time before expanded use in allergic disease is sought. The primary use will probably be in allergy inhibition when used in conjunction with mast cell stabilizers and/or topical antihistamines.

Choose wisely

We currently have a plethora of topical options to choose from when treating seasonal allergic conjunctivitis, from single-action antihistamines and mast cell stabilizers to the combination agents and with the addition of the new immunomodulators. Judicious selection of a combination mast cell stabilizer-antihis- tamine that has high specificity for ocular mast cells should offer effective treatment of the symptoms of ocular allergy and greatly improve a patient's quality of life.

Appropriate treatment regimens are more likely to reduce the use of other healthcare resources for patients who self-medicate with inappropriate OTC preparations or for those who ignore their symptoms because they're unaware of better treatments. The new immunomodulators hold promise for further improvements in the management of ocular allergy as the landscape of treatment continues to change.

References available on request.

Dr. Prouty is director of Centers of Omni Eye Specialists, P.C. He's also a member of the American Optometric Association and is a fellow in the American Academy of Optometry.