Understanding Allergy Therapy
Because allergies are so unique
patient, helping these patients can be tricky.
MARC D. MYERS, O.D., F.A.A.O., & ANDREW S. GURWOOD, O.D., F.A.A.O. Philadelphia, Pa.
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 sometimes-mysterious 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.
diagram of the allergic cascade shows the many factors involved in treating eye
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
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.
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.
patient with allergic conjunctivitis.
The major components of any allergic reaction also include Immunoglobulin
E (IgE). Immuno-globulins (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,
and basophils) appear within eight hours of the first phase. Lymphocytes and macrophages
appear within 16 hours. The addition of leukotrienes, prosta-glandins 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 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
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 immune-complex 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
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.
the many, large keratic precipitates in this uveitis patient.
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.
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 involve- ment. Punctate staining is very common and can progress
to persistent epithelial defects, shield-shaped stromal scars and peripheral corneal
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.
A patient with unilateral contact dermatitis.
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
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-H1 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% concentrat- ion of
loteprednol, (Lotemax, Bausch & Lomb). Topical antibiotics are only required
in shield ulcer scenarios.
D. Meyers, O.D. is in private
practice in southern New Jersey. He also serves as clinical consultant for Pennsylvania
College of Optometry and The Eye Institute
Optometric Management, Issue: August 2005