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Ketotifen fumarate (ZaditorĀ®) is an H1-antihistamine available in two forms. In its opthalmic form, it is used to treat allergic conjunctivitis, or the itchy red eyes caused by allergies. In its oral form, it is used to prevent asthma attacks. Side effects include drowsiness, weight gain, dry mouth, irritability, and increased nosebleeds.

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Understanding Allergy Therapy
From Optometric Management, 8/1/05 by Myers, Marc D

Because allergies are so unique in each patient, helping these patients can be tricky.

The human allergic response has various objective signs and physical symptoms. Ocular allergic reactions are among the most common clinical presentations to the optometric practitioner and require your medical intervention. Symptoms can range from subtle and insignificant, such as itchy eyes with mild hyperemia of the conjunctiva, to extensive, involving interactions between the ocular coats and adnexa. In order to treat these sometimesmysterious disorders successfully, you must first understand the allergic response and its various clinical presentations so that you can promptly identify, diagnose and manage the patient.

Almost half of the United States population has some form of allergy symptoms and of those, 50% have ocular manifestations. Exposure to new particulates, pollution and genetic factors all play a role in the changing incidence patterns of allergic reactions.


The allergic response begins when the body's immune system over-reacts to foreign substances known as immunogens or allergens. This response can be innate, or acquired after multiple exposures to a particular antigen.

In the ocular allergic response, the mast cell is key. It's function is not specific, but it is associated with chemotaxis, vasodilation and anticoagulation. Mast cells also aid in controlling vascular permeability and repairing injured connective tissue.

In the conjunctiva, there are 5,000 mast cells/mm. Each cell contains five to 10 picograms of histamine. When mast cells interact with specific allergens, they degranulate, discharging chemical mediators into the tissues.

One of these mediators is histamine, which controls increased vascular permeability, vasodilation, bronchial smooth muscle contraction and increased secretion of mucus, as well as chemotactic factors for eosinophils and neutrophils (ECF-A and NCF). The mediator cells release neutral proteases, which generate other inflammatory mediators that regulate the immune response.

Degranulation also releases arachidonic acid, a crucial compound responsible for the production of leukotrienes, both of which are responsible for the long-term inflammation seen in the average allergic response.

The immunoglobulins

The major components of any allergic reaction also include Immunoglobulin E (IgE). Immunoglobulins (Ig) are composed of five classes of glycoproteins, each of which binds with its own specific antigen.

Unlike other immunoglobulins, IgE is only present in trace amounts under normal circumstances. However, in patients with a high degree of allergic response, IgE levels can be ten times greater than normal. When mast cells interact with IgE receptors, they induce mast cell degranulation and the release of chemical mediators involved in allergic reactions.

In the first phase of the classic allergic reaction, histamine, serotonin, neutral proteases, heparin, and chemotactic agents are released from mast cells and other sources. These agents cause the characteristic reactions of erhythema, edema, and increased vascular permeability, which produce symptoms and signs of irritation in the patient.

The second phase of allergic response is more destructive and results in prolonged inflammation. Polymorphonuclear leukocytes (eosinophils, neutrophils, and basophils) appear within ' eight hours of the first phase. Lymphocytes and macrophages appear within 16 hours. The addition of leukotrienes, prostaglandins and thromboxanes (the mediators of pain) fuel the inflammation further. Therapeutically inhibiting and/or interrupting the pathways that support inflammation and mediator production is the best way to relieve pain and the allergic response.

Hypersensitivity classes

Hypersensitivity reactions are usually classified into one of the following four categories.

* Type I. These are immediate or anaphylactic reactions that are IgE-mediated and result in mast cell degranulation, with the subsequent release of other allergic mediators. Examples include contact dermatitis, hay fever conjunctivitis, vernal keratoconjunctivitis (VKC) and giant papillary conjunctivitis (GPC).

* Type II. Also known as cytotoxic reactions, type II reactions occur when the patient's body directs antibodies towards cell-surface antigens. Diseases associated with this type of hypersensitivity reaction are called autoimmune diseases. The only ocular allergic condition that may be classified in this category is cicatricial ocular pemphigoid.

* Type III. These are immunecomplex reactions. When certain Igs react with soluble, circulating complexes of antigen, the result is a break down of the integrity of blood vessel walls. Examples of this include Steven's-Johnson syndrome, Sjogren's syndrome, Reiter's syndrome, and Systemic Lupus Erythematosus.

* Type IV. Type IV reactions, also referred to as cell-mediated or delayed reactions, occur when antigens and specific T-lymphocytes interact and release destructive mediators. Type IV reactions are associated with contact dermatitis, phylectenulosis and atopic keratoconjunctivitis. Type I and type IV reactions may occur together.

Common ocular allergies

* Hayfever or dust conjunctivitis. Pollen, house dust and animal dander may trigger acute conjunctival chemosis, hyperemia, tearing and itching in sensitive patients. The classic allergic reaction begins a short time after the tissue is exposed.

Symptoms tend to be significant, despite the fact that signs may be minimal. There is usually no significant affect on visual function, as the cornea remains unaffected. The condition is generally seasonal, beginning in the second decade of life. Often, patients who present with this malady have a history of atopic conditions.

* Vernal keratoconjunctivitis (VKC). The clinical picture of vernal keratoconjunctivitis is bilateral inflammation of the superior and limbal palpebral conjunctiva. It is more prevalent in warmer climates, with an onset between the ages of three and mid-20s. Males are typically more affected than females, with reoccurrences for up to ten years or longer.

Unlike hay fever conjunctivitis, VKC can cause significant ocular disease if inadequately managed. Symptoms of VKC vary from itching and tearing to severe burning and photophobia. The hallmark of the disease is large papillae on the superior tarsal plate. Goblet cells of the tarsal plate produce copious amounts of stringy discharge, adding discomfort and visual impairment to the patient's situation. VKC can result in corneal involvement ranging from a simple epithelial keratitis to shield ulcers.

* Atopic keratoconjunctivitis (AKC). The cause of AKC remains unknown. It is thought that mast cells trigger the disease process as in other allergic disorders. This disease is relatively rare, and typically affects young men with atopic dermatitis. AKC causes the eyelids to become thickened, crusted and ulcerated. Patients will complain of decreased visual function, which usually indicates corneal involvement. Punctate staining is very common and can progress to persistent epithelial defects, shield-shaped stromal scars and peripheral corneal neovascularization.


Because there are many strata of ocular allergic reactions, management is primarily aimed at reducing symptoms and preventing ocular tissue damage. Because the etiologies of ocular allergic reactions are similar, the therapeutic managements are similar. The type and frequency of medications will depend upon the diagnosis, severity and your style.

Topical supportive therapies

One of the functions of our biological tears is to wash away debris and environmental allergies. Appropriate cleansing of these particulates plays an obvious role in reducing or even canceling the allergic response. Rule out tear deficiency in chronic, mild allergic conditions prior to initiating treatment.

For patients with dry eye-related burning, gritty, or irritated eyes, artificial tears may suffice. To relieve simple itching, have the patient avoid the offending agent, use soothing cold compresses and topical antihistamine preparations such as emadastine difumarate (Emadine, Alcon) and levocabastine hydrochloride (Livostin, Novartis).

The newest category of anti-allergy medications combines the properties of mast cell stabilizers and antihistamines. Mast cell stabilizers control the receptors before they can degranulate and begin the cycle of the allergic response. Antihistamines provide relief from allergy by blocking the histamine-Hl receptor interaction, thus providing relief from histamine activity.

The first medication developed in this category is olopatadine hydro-chloride (Patanol, Alcon). Its twice daily dosing is convenient, and patients can continue wearing contact lenses while using it. Patanol recently received expanded approval and is now indicated for all signs and symptoms of allergic conjunctivitis.

Ketotifen fumarate (Zaditor, Novartis), Azelastine hydrochloride (Optivar, Bausch & Lomb), and epinastine (Elestat, Allergan,) work through a similar mechanism and are effective as a b.i.d. use medications.

Consider loteprednol etabonate (Alrex, Bausch & Lomb) either two or four times daily for management of cases with more severe ocular inflammation. In those cases that do not respond to Alrex, consider the 0.5% concentration of loteprednol, (Lotemax, Bausch & Lomb). Topical antibiotics are only required in shield ulcer scenarios.

BY MARC D. MYERS, O.D., F.A.A.O., & ANDREW S. GURWOOD, O.D., F.A.A.O. Philadelphia, Pa.

Marc D. Meyers, O.D. is in private practice m southern New Jersey. He also serves as clinical consultant for Pennsylvania College of Optometry and The Eye Institute of Pennsylvania.

Copyright Boucher Communications, Inc. Aug 2005
Provided by ProQuest Information and Learning Company. All rights Reserved

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