New Ways to Ease Allergy Symptoms

New pharmacologic and immunotherapeutic agents may offer options for allergy sufferers.

Michelle Stephenson, Contributing Editor
3/8/2012

Allergy season is quickly approaching, and more people than ever before will be looking for ways to relieve their ocular allergy symptoms. According to current estimates, approximately 3 percent of Americans have ocular allergy, and it is increasing in frequency.


Prevention

Although ocular allergy can be broken down into five categories, seasonal and perennial allergic conjunctivitis are the most common forms. Seasonal allergic conjunctivitis is the most common and accounts for 90 percent of cases, while perennial allergic conjunctivitis accounts for 5 percent of cases.
Ocular allergy is usually bilateral, and symptoms include ocular itch, hyperemia, lid edema, photophobia, chemosis, burning/stinging and tearing.
(Image courtesy Stephen Pflugfelder, MD.)
The signs and symptoms of both are similar (bilateral ocular itch, hyperemia, lid edema, photophobia, chemosis, burning/stinging and tearing), and primary management involves avoidance strategies.

One strategy is to keep allergens off of the eye by wearing daily disposable contact lenses. A recent study has found that daily disposable contact lenses offer a barrier to airborne allergen that is enhanced by new lens technologies with enhanced lubricating agents.1 In this study, 10 patients with confirmed allergic sensitivity to grass pollen had their ocular symptoms and appearance graded before and five minutes after exposure to 400 grains of grass pollen for two minutes in a purpose-designed exposure chamber that simulated the conditions found on a very high pollen-count day. This was repeated three times. On one occasion, patients wore etafilcon A contact lenses. On another occasion, they wore netfilcon A lenses with enhanced lubricating agents; and on a third, they wore no contact lenses.

While only the symptoms of burning and stinging were reduced in severity by the lenses with enhanced lubricating agents, overall symptoms were significantly reduced in duration. Additionally, bulbar hyperemia, corneal and conjunctival staining, and palpebral conjunctival roughness were significantly reduced by daily disposable lens wear, and limbal and palpebral conjunctival redness was further reduced by the lenses with enhanced lubricating agents.


Intervention

Because complete avoidance is not possible, pharmacological agents may be necessary to control symptoms. Additionally, refrigerated artificial tears and cold compresses may help to relieve symptoms. A wide range of anti-allergy medications are currently available, such as mast-cell stabilizers, antihistamines and dual-action medications. Severe cases that do not respond to conventional therapy may require anti-inflammatories, immunomodulators or immunotherapy.

Allergic conjunctivitis is usually accompanied by allergic rhinitis.
Topical vasoconstrictors can reduce redness but use should be limited to 10 days. (Image courtesy Stephen Pflugfelder, MD.)
If symptoms are mild, an oral antihistamine may relieve symptoms. “If patients have nasal symptoms, intranasal steroids are also very helpful, because they assist in decongestion while antihistamines do not,” says Leonard Bielory, MD, of the Center for Environmental Prediction at Rutgers University, and the Section of Allergy and Immunology at Robert Johnson University Hospital, New Brunswick, N.J.

If oral medications do not improve symptoms, topical medications are frequently used. When using any type of topical medication, Dr. Bielory recommends refrigerating the drop before instillation. “Just the cooling of the eye will provide incredible and immediate relief,” he explains.

Topical vasoconstrictors can be used to get the red out. However, Dr. Bielory cautions against using them for more than 10 days because chronic use of an ocular decongestant can cause side effects.

First-line therapy has traditionally been antihistamines and mast-cell stabilizers, which block histamine from the histamine receptor and primarily relieve itching. However, new areas of interest have been aimed upstream at the ocular surface, where pollen first enters the eye. The eye’s first line of defense is the tears and then the ocular surface. Normally, conjunctival epithelial cells are very tight and not much can get in between these cells. However, a recent study showed that, during allergy season or right after allergy season, biopsies from patients with allergies showed marked degradation in the tight gap junctional proteins that are holding that first line of defense—the epithelial cells.2

As an allergen penetrates the ocular surface, it starts tearing away at the tight fabric, allowing more allergen to go through. New agents have been found to stabilize the tight junctions and prevent some of the allergen from penetrating the ocular surface.


Antihistamines

Alcaftadine (Lastacaft) is a new antihistamine, and a recent study has shown that it has therapeutic properties beyond its antihistamine action. The study compared two antihistamines, olopatadine and alcaftadine, regarding their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.3 In this study, sensitized mice were challenged with topical allergen with or without drug treatments. Groups were assayed for acute-phase and delayed-phase responses, and assessed for allergy symptoms and conjunctival mast cell numbers.

The study found that mice treated with both drugs had similar efficacy profiles and mast cell numbers, suggesting that both were able to relieve symptoms in the acute phase. However, mice treated with alcaftadine had significantly lower conjunctival eosinophil infiltration than either controls or the mice treated with olopatadine.

Additionally, another study found that alcaftadine was significantly better than placebo for reducing ocular itching and conjunctival redness.4 The study was conducted to assess the effectiveness of alcaftadine 0.05%, 0.1% and 0.25% ophthalmic solutions in treating the signs and symptoms of allergic conjunctivitis when compared with olopatadine hydrochloride 0.1 percent and placebo. The study included 170 patients (164 patients completed all visits). The conjunctival allergen challenge was performed to confirm patients’ eligibility and then again on day 0 ±3 (16 hours after medication instillation) and on day 14 ±3 (15 minutes after instillation). Ocular itching and conjunctival redness were evaluated. Eyes treated with alcaftadine 0.25% and olopatadine 0.1% had significantly lower mean scores compared with eyes treated with placebo for ocular itching and conjunctival redness at both post-treatment visits. No serious treatment-related adverse events occurred.

Another promising new antihistamine is oral bilastine. A study conducted in Spain has shown that bilastine, an H1 antihistamine, effectively controls the ocular symptoms of allergic rhinoconjunctivitis.5 Bilastine has an excellent safety profile and was developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. It is currently not approved for use in the United States.


Mast-Cell Stabilizers

Topical mast-cell stabilizers, such as cromolyn, are commonly used for the treatment of ocular allergy. According to Dr. Bielory, cromolyn effectively relieves mild to moderate symptoms, and it improves healing of any patients who have vernal keratoconjunctivitis. “The mast-cell stabilizers have been shown to have more of a healing effect. In most of the studies with cromolyn, it has been indicated not for allergic conjunctivitis, but for vernal conjunctivitis and healing of pannus formation,” he explains.

A recent study comparing the efficacy and safety of topical cromolyn with and without preservative found that it was safe and effective for treating allergic conjunctivitis.6 In this double-masked study, 37 patients received cromolyn sodium 2% ophthalmic solution with or without 0.01% benzalkonium chloride in either eye. The study found no significant difference between cromolyn with and without BAK in subjective or objective scores. The study concluded that the short-term use of cromolyn 2% with 0.01% BAK would not cause significant toxicity in patients with allergic conjunctivitis.


Topical NSAIDs and Steroids

According to Dr. Bielory, topical nonsteroidal anti-inflammatory drugs can also be used to relieve ocular allergy symptoms. If NSAIDs are unable to relieve symptoms, ophthalmologists may want to consider a short burst of topical steroids. “Steroids in the loteprednol family are approved for ocular allergy and are very interesting,” Dr. Bielory adds. They are quickly metabolized at the ocular surface, so they have limited intraocular complications, such as increased intraocular pressure or cataract formation.


Immunotherapy

If daily medication is not relieving patients’ symptoms and steroids are frequently required to control symptoms, then immunotherapy should be considered, according to Dr. Bielory. “When you do proper immunotherapy, the patient can be exposed to 100- to 1,000-fold more allergen than before immunotherapy, and he will develop the same severity of symptoms,” he says. “Immunotherapy educates the immune system to decrease the reaction pattern, and it is quite impressive when you actually do a study with a conjunctival provocation test. You may need 100 times more or 1,000 times more allergen to induce symptoms.”

Thomas John, MD, notes that sublingual immunotherapy (SLIT) is a promising new type of immunotherapy. “Normal immunotherapy consists of allergy shots, and the patient has to visit the doctor’s office every couple of weeks. With SLIT, you actually put drops of allergy extract under the tongue. It has been used in Europe for many years, but it is not currently FDA-approved in the United States,” says Dr. John, a clinical associate professor at Loyola University at Chicago.

One example of SLIT is Oralair, which is a sublingual grass pollen immunotherapy tablet that was approved in Europe in 2009 and is currently in Phase III clinical trials in the United States.7 It is indicated for the management of allergic rhinitis with or without conjunctivitis caused by grass pollen in adults and children older than five years. Treatment should be initiated approximately four months before pollen season and should continue until pollen season is over.

Additionally, a Cochrane systematic review has found that SLIT is effective in reducing ocular symptom scores in patients with allergic rhinoconjunctivitis or allergic conjunctivitis.8 In this review, 109 full-text studies were reviewed, and 42 studies with 3,958 patients had data suitable for inclusion. Of these 3,958 patients, 2,011 received SLIT, and 1,947 received placebo. SLIT induced a significant reduction in both total ocular symptom scores and individual ocular symptom scores compared with placebo.


Perennial Conjunctivitis

Perennial conjunctivitis is more difficult to treat than seasonal conjunctivitis, and a new generation of drugs is needed. Companies are currently assessing a new type of steroid that looks promising for treating patients with perennial conjunctivitis as well as breakthroughs and non-responders in seasonal conjunctivitis.

A selective glucocorticoid receptor agonist (SEGRA), sometimes called a dissociated glucocorticoid receptor agonist (DIGRA), is an experimental drug that is designed to share many of the desirable anti-inflammatory and immunosuppressive properties of classical glucocorticoid drugs but with fewer side effects, such as skin atrophy.

Mapracorat is one of the most developed SEGRAs. A study conducted in Italy found mapracorat to be promising for the topical treatment of allergic eye disorders. “In cultured human eosinophils, mapracorat showed the same potency as dexamethasone but displayed higher efficacy in increasing spontaneous apoptosis and in counteracting cytokine-sustained eosinophil survival,” the authors reported.9 “It maintains an anti-allergic profile similar to that of dexamethasone but seems to have fewer transactivation effects in comparison to this classical glucocorticoid. Some of its cellular targets may contribute to eosinophil apoptosis and/or preventing their recruitment and activation and to inhibiting the release of cytokines and chemokines.”  REVIEW



1. Wolffsohn JS, Emberlin JC. Role of contact lenses in relieving ocular allergy. Cont Lens Anterior Eye 2011;34(4):169-172.
2. Hughes JL, Lackie PM, Wilson SJ, Church MK, McGill JI. Reduced structural proteins in the conjunctival epithelium in allergic eye disease. Allergy 2006;61:1268-1274.
3. Ono SJ, Lane K. Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis. Drug Des Devel Ther 2011;5:77-84.
4. Greiner JV, Edwards-Swanson K, Ingerman A. Evaluation of alcaftadine 0.25% ophthalmic solution in acute allergic conjunctivitis at 15 minutes and 16 hours after instillation versus placebo and olopatadine 0.1%. Clin Ophthalmol. 2011;5:87-93.
5. Bartra J, Mullol J, Montoro J, et al. Effect of bilastine upon the ocular symptoms of allergic rhinoconjunctivitis. J Investig Allergol Clin Immunol 2011;21 Suppl 3:24-33.
6. Liu YL, Hu FR, Wang IJ, Chen WL, Hou YC. A double-masked study to compare the efficacy and safety of topical cromolyn for the treatment of allergic conjunctivitis. J Formos Med Assoc 2011;110(11):690-694.
7. Hong J, Bielory L. Oralair: sublingual immunotherapy for the treatment of grass pollen allergic rhinoconjunctivitis. Expert Rev Clin Immunol 2011;7(4):437-444.
8. Calderon MA, Penagos M, Sheikh A, Canonica GW, Durham SR. Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis. Clin Exp Allergy 2011;41(9):1263-1272.
9. Baiula M, Sparta A, Bedini A, et al. Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. Mol Vis 2011;17:3208-3223.