You Can Now Do More for Eye-Allergy Sufferers
A standard research model is yielding a wide array of treatments for your patients' red, itchy eyes.
By Mark B. Abelson, M.D., Andover Eye Associates, Andover, Mass.

In Charles Blackley's book, On Hayfever, published in 1873, he expresses his disappointment in the treatments then available for hay fever, and notes that even those who are "more fortunate" have little success in getting relief from this condition.

Today, the war against allergies that affect the eyes is going quite a bit better. Recently, we've seen an increase in new prescription medications for treating ocular allergies, as these remedies join a number of prescription and over-the-counter (OTC) drugs already in the marketplace. The broad range of options now available offers you a chance to treat the individual patient according to his specific ailments and lifestyle, and also to consider costs -- so that every patient can obtain significant relief from eye allergies.

ILLUSTRATION: SAUL ROSENBAUM

There are now 12 different prescription eye drops available for treating ocular allergy, with the drugs currently categorized into five separate pharmacological classes.

Why are there so many drugs available for eye allergy? Do the newer ones really offer advantages over the older drugs? More importantly, how do you decide when a specific prescription treatment is best for your patient, and when do you simply recommend an OTC medication?

This article will address these questions, offer some insights into the current state of ocular allergy, and discuss possible future directions for new drugs.

Increased focus on eye allergies

There are two major reasons we're seeing more ocular allergy medications coming to market. The first is governed by such factors as epidemiology, demographics and lifestyle. Approximately 50% of the general population is atopic. In other words, they're allergic in some way -- and about 50% of those who are atopic have some form of ocular allergy. Further, it's been widely documented that the incidence of allergy is increasing, which may be due to our increased exposure to allergens, higher levels of environmental pollution and certain genetic factors.

Greater public awareness of allergic conditions and less tolerance of their signs and symptoms are also driving the need for better treatments. People are less likely to put up with red, swollen, tearing eyes when interacting with colleagues and friends at work, or during social situations. Allergic symptoms also interfere greatly with such everyday activities as reading, driving, or working on a computer. Thus, there's a rapidly growing demand for effective treatments for eye allergy.

Advances in the scientific method for rapidly designing and screening multiple compounds are also responsible for driving the development of ocular allergy drugs. (See "New Eye-Allergy Drugs Can Be Quickly Evaluated,".) There's a certain level of reassurance with the pharmacological classes of drugs we see in ocular allergy. Focus within these classes allows for development of more selective and effective drugs with higher safety, efficacy and comfort levels, especially when compared with development-stage drugs for such diseases as glaucoma.

Prescription vs. OTC medications

Looking at trends in allergy drop use, surveys show that 90% of the patients with ocular allergy are now using OTC eye drops. But we also know that OTC drops don't work as well as prescription medications. The OTC drops are indicated for four-times daily dosing -- yet their duration of action is only about 2 hours. Why are we seeing such low penetration of prescription drugs, which have obvious advantages in terms of efficacy and duration?

It's because most ophthalmologists aren't asking their patients enough questions about eye allergy, except in severe cases, and certainly not when patients are seen during off-season when they display no signs and symptoms.

By asking your patients if they have eye allergy at other times of the year, and if they need relief from certain signs and symptoms at those times, you should more readily be able to identify those who may require a prescription. Integrating questions about eye allergies into patient questionnaires or screening forms can also help. Otherwise, patients will continue using less-effective OTC eye drops.

So how do we go about choosing the right medication for the patient and differentiating between the various drugs?

The first step lies in obtaining relevant information from the patient regarding:

• when the symptoms occur
• how long they last
• how frequent are the episodes.

In mild cases, emphasize avoidance of the known allergen. The patient may also use artificial tears. They provide a barrier function to protect the eye from allergens, dilute any antigens present in the tears, and act as a tear substitute. In fact, artificial tears produce a significant short-term therapeutic effect in the vehicle-control groups in controlled clinical trials.

When you determine that a patient requires pharmacological intervention for his allergies, proper diagnosis of the specific signs and symptoms that the patient is experiencing will lead you to select the appropriate treatment.

Note that most of the patients referred to you for eye allergy actually suffer from a specific external ocular disease. Proper differential diagnosis of such problems as dry eye, bacterial conjunctivitis, or a drug-induced allergy is crucial to proper treatment, and will determine if the patient will do better on a tear substitute or antibiotic rather than an allergy drop. The golden rule that "if it itches it's allergy; if it burns it's dry eye, and if it's sticky it's bacterial" holds true most of the time and can help in distinguishing between these diseases. Allergic conjunctivitis has a hallmark symptom -- itching -- which can be accompanied by any of the following: redness, chemosis, tearing and lid swelling.

Examining your options

Treatment options include drugs from one of the following five categories: (1) antihistamine/vasoconstrictor combinations (2) antihistamines (3) mast cell stabilizers (4) dual-acting antihistamine/mast cell stabilizers and (5) steroids.

Antihistamine/vasoconstrictor combinations. Over-the-counter allergy drops contain both an antihistamine (antazoline, pheniramine) and vasoconstrictor (tetrahydrozaline, naphazoline). The antihistamines in these drops help to decrease itch, but aren't effective on redness. The vasoconstrictor thus complements them by working on reducing redness and swelling. However, while these agents are relatively fast acting, the duration of action (2 hours) does not provide daylong relief. In addition, ocular irritation may be caused by use beyond the indicated four-times daily dosing.

Antihistamines. Levocabastine (Livostin) and emadastine (Emadine) are prescription antihistamines that have longer duration of actions (3-4 hours) compared with the OTC antihistamines. These agents work on redness and swelling as well as itch. Emadine is the newest and most potent antihistamine of this class.

Mast cell stabilizers. These medications, all of which are effective only against itch, include: cromolyn (Crolom, Opticrom) indicated for q.i.d.; lodoxamide (Alomide) indicated for q.i.d., nedocromil (Alocril) indicated b.i.d.; and pemirolast (Alamast) indicated for q.i.d. However, a recent study showed that Alamast is as effective when used b.i.d. These agents all require a loading period. While nedocromil is newer than cromolyn and lodoxamide, pemirolast was evaluated in a 16-week clinical trial and not only reduced -- but completely eliminated -- itch in some subjects.

Dual-action drugs. The newest class consists of agents that have dual activity. These are antihistamines that also act as mast cell stabilizers. Olopatadine (Patanol), ketotifen (Zaditor), and azelastine (Optivor) are in this class. Azelastine is actually an older compound that was recently introduced as an eye drop. It must be remembered that mast cells are tissue- and species-specific, and that data showing mast cell stabilizing activity in animal studies doesn't have as much relevance as the data from human clinical trials.

The advantage of these dual-acting compounds is that they have the quick-acting qualities of antihistamines, plus a long duration of action due to the mast cell stabilizing activity. Thus, they are indicated for twice-daily dosing. Olopatadine has a broad range of indications, and has been proven effective in reducing all five aspects of allergy, including itch, redness, chemosis, tearing, and lid swelling. Ketotifen is a cost-effective medication for treating itch.

Steroids. Selective use of steroids is indicated in treating allergic conjunctivitis when relief can't be obtained with other treatment modalities. Steroids may also be used for more severe forms of allergy, including vernal keratoconjunctiviits (VKC), atopic keratoconjunctivitis (AKC), allergic giant papillary conjunctivitis (GPC), and drug-induced allergic conjunctivitis. When a significant allergic condition requires the use of steroids, the safety and efficacy profile of loteprednol (Alrex) has made it a popular choice. Alrex is also effective for GPC.

A study done by our research group, and presented at the Association for Research in Vision and Ophthalmology 2000 meeting (Slugg A, Ousler G, Abelson M) demonstrated that the systemic antihistamine loratadine (Claritin) has no place in treating eye allergy. While the newer systemic antihistamines are effective in relieving nasal symptoms and are non-sedating, they are not non-drying. Through action on the muscarinic-3 receptors, they reduce both the production of tears from the lacrimal glands and the secretion of mucin from the goblet cells. As mentioned above, tears serve a barrier function as a diluent. The drying effects of systemic antihistamines cannot compete with treating the disease with a topical medication.

More advances on the horizon

The future will bring us new and potent anti-allergic medications with multiple therapeutic characteristics. Agents such as binding proteins, which are naturally secreted by certain insects to counteract the host's immune system, and immuno globulin E (IgE) blockers, show promise as effective, longer-acting agents. Newer treatments will act on all the signs and symptoms of eye allergy, and will show greater efficacy on chemosis and lid swelling. As the market expands for ocular allergy medications, the indication will increasingly attract larger pharmaceutical companies that have potent new drugs in the pipeline. Their researchers will become more interested in developing these therapies as eye drops.

In sum, the proper diagnosis of the signs and symptoms of individual patients will aid you in selecting appropriate treatments. A patient's comfort with a specific treatment shouldn't be overlooked, as itching shouldn't be replaced by burning. And of course, a specific treatment's adverse effect on a patient's comfort can raise a compliance issue.

While you may find all the new options a bit confusing at first, by systematically evaluating your individual patients' complaints and lifestyles, you'll find that the current therapies can be very useful in your practice.

Mark B. Abelson, M.D., is a senior clinical scientist at Schepens Eye Research Institute and associate clinical professor at Harvard Medical School. He is an active clinician at his practice, Andover Eye Associates, in Andover, Mass, and also consults on ophthalmic pharmaceuticals.