Ocular allergies and dry eye syndromes are chronic ocular surface diseases that can share similar features such as ocular surface inflammation and mediator release. Ophthalmologists have learned that both ocular allergies and dry eyes are inflammatory conditions that may, in fact, interact with each other; the presence of one may affect the severity of the other. Dry eye syndromes can worsen the symptoms of ocular allergies because the altered tear film in these patients allows more antigens to enter the conjunctiva, thereby intensifying the allergic response. Conversely, chronic ocular surface irritation from ocular allergies may potentially trigger the inflammatory process, which is now thought to cause many dry eye syndromes. Therefore, treating ocular allergies can potentially improve dry eye symptoms, and addressing the inflammatory component of dry eye syndromes may alleviate ocular allergic symptoms.
UNDERSTANDING OCULAR ALLERGIES
Patients experience ocular allergies when their eyes become exposed to an antigen that dissolves in the tear film and encounters mast cells in the conjunctiva. The antigen binds to receptors on the mast cells, causing them to degranulate, which initiates a cascade of biochemical reactions that produce the clinical syndrome known as seasonal or perennial allergic conjunctivitis (or, in the nose, rhinitis). If the tear film is robust enough, the patient may be able to clear the antigen simply by blinking; it may be flushed into the tear drainage system before encountering enough of the ocular surface to elicit an allergic response.
On days when the pollen count is low, ocular allergy patients with a robust tear film may be asymptomatic. A patient with dry eye syndrome, however, has reduced tear production, which allows more of the antigen to concentrate on the surface of the eye rather than be cleared by the tear film. These patients are therefore more susceptible to developing ocular surface allergies and will experience more intense symptoms than patients with normal tear production. Incidentally, one important subgroup of patients may suffer from a higher incidence of both dry eyes and ocular allergies: menopausal women. A study by Joseph Tauber, MD, evaluated approximately 1,100 patients diagnosed with allergic conjunctivitis and found that nearly half of the subjects were postmenopausal women.1 This finding supports the contention that there may be a higher incidence of ocular allergies in this subgroup of dry eye patients.
DRY EYES AND OCULAR ALLERGIES
Ophthalmologists now know that dry eye syndromes may involve an inflammatory feedback mechanism. The mechanism may be triggered by a variety of causes, including chronic ocular surface irritation, which can produce ocular surface damage and alter neural feedback from the surface to the lacrimal glands. Interrupting signals to the lacrimal glands can make them susceptible to inflammation and T-cell accumulation and activation within the glands. Furthermore, cytokines produced by activated T-cells in the lacrimal glands can damage their tissue and enter the tears, which are secreted onto the ocular surface. Cytokines on the ocular surface, in turn, can induce ocular surface inflammation, specifically T-cell recruitment and activation and tissue damage, which can further alter the neural feedback to the lacrimal glands and perpetuate this inflammatory cycle.
Because chronic ocular surface allergies can produce chronic ocular surface irritation and tissue damage, they may also trigger this inflammatory feedback cycle. In turn, chronic ocular surface dryness can exacerbate the symptoms of ocular allergies by intensifying the allergic response. Thus, a strong potential interaction exists between dry eyes and ocular allergies.
DRY EYE AND REFRACTIVE SURGERY
Dry eye syndromes are more prevalent in patients during the first few months after they undergo LASIK, because cutting the LASIK flap severs the nerves that carry neural feedback from the ocular surface to the lacrimal glands. As a result, patients with ocular allergies may suffer from more intense symptoms immediately postoperatively, increasing their risk of postrefractive complications. For example, ocular allergies can stimulate itching, which can predispose patients to conscious or unconscious eye rubbing. Should this occur in the immediate postoperative period, there is a significant risk of striae formation or frank flap dislocation.
Moreover, several studies have reported that chronic ocular allergies can predispose refractive surgery patients to postoperative complications. One study indicated an increased risk of haze and regression after PRK in patients who had pre-existing ocular allergies, whereas controlling the allergic process in these patients reduced the risk.2 Another study found an increased risk of DLK in patients who had pre-existing ocular allergies; again, the risk decreased when the treating surgeons controlled the allergies preoperatively.3 These researchers hypothesized that the mast cell mediators released onto the ocular surface by the allergic process contributed to these complications and that they may play an important role in the wound-healing processes in the cornea. Therefore, controlling these factors preoperatively may yield more predictable refractive surgical results, whether performing surface ablation or a LASIK procedure.
THERAPEUTICS
For refractive surgery patients with ocular allergies, ophthalmologists must try to manage the postoperative dry eye and allergic processes with medication that (1) comprehensively controls the entire allergic inflammatory process but (2) will not simultaneously worsen the dry eye syndrome by drying the ocular surface. Medications with a long duration of action and requiring the least frequent topical dosing are preferable, because they minimize the amount of toxic medication administered to the ocular surface and stave off breakthrough symptoms that may cause the patient to rub his eye and induce flap slippage in the immediate postoperative period. Medications such as Alocril (nedocromil sodium ophthalmic solution 2%; Allergan, Inc., Irvine, CA) have a long duration of action and a true b.i.d. dosing regimen that will effectively control the symptoms throughout the entire day when administered in the morning.
In addition, some research has shown that topical antihistamines, especially when used in conjunction with systemic antihistamines, may worsen dry eye symptoms in these patients.4 Because Alocril does not contain an antihistamine (although it does inhibit histamine release), it will not aggravate the dry eye symptoms of these patients, a fact that makes it an excellent choice for postrefractive surgical patients with ocular allergies.
Topical allergy medications used after refractive surgery should also provide comprehensive control against the entire allergic inflammatory cascade, as Alocril does, in order to minimize breakthrough symptoms and eliminate the need to administer additional topical medications to the ocular surface. One study performed by Michael Alexander, MD, showed that Alocril was even effective when dosed q.d. for maintenance, after the acute symptoms were brought under control with a short course of b.i.d. dosing.5 Although both ketotifen and olopatadine call for b.i.d. dosing, their product inserts state that these drugs require dosing anywhere from q6h to q8h; therefore, they may require additional dosing during the middle of the day.
ABOUT THE DRUG
Alocril is a second-generation mast cell stabilizer. Compared with other available eye drops, it relieves itching very quickly.6,7 In Dr. Alexander's study, Alocril relieved itching in 37% of the patients within 2 minutes and 77% of the patients within 15 minutes of instillation. This rapid onset of itch relief is comparable to that of topical antihistamines.
Although some patients may be sensitive to Alocril, there are no specific contraindications for the drug. It is one of the safest topical antiallergy medications. It is pregnancy categoryB, which may give surgeons an extra measure of confidence when prescribing it for women of child-bearing age.
Jodi Luchs, MD, FACS, is in private practice at South Shore Eye Care in Wantagh, New York, and is Assistant Professor of Ophthalmology and Visual Sciences at the Albert Einstein College of Medicine in New York City. He is also on the Cornea Service at Long Island Jewish Medical Center in New Hyde Park, New York. He holds no financial interest in any company or product discussed herein. Dr. Luchs may be reached at (516) 785-3900; jluchs@aol.com.1. King BJ, Tauber J. Efficacy of nedocromil sodium 2% ophthalmic solution in menopausal women with allergic conjunctivitis: Results from a community-based trial. Paper presented at: The Association for Research in Vision and Ophthalmology; May 2003; Fort Lauderdale, FL.
2. Yang HY, Fujishima H, Toda I, et al. Allergic conjunctivitis as a risk factor for regression and haze after photorefractive keratectomy. Am J Ophthalmol. 1998;125:1:54-58.
3. Boorstein SM, Henk HJ, Elner VM. Atopy: A patient-specific risk factor for diffuse lamellar keratitis. Ophthalmology. 2003;110:1:131-137.
4. Blaho K. AOA's current trends in pharmacology and therapeutics histamine and antihistamine agents. J Am Optom Assoc. 1999;64:85:586-588.
5. Alexander M, Allergo S, Hicks A. Twice-daily and once-daily nedrocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Adv Ther. 2002;19:1:9-16.
6. Alexander M, Rosen L, Yang W. Comparison of topical nedocromil sodium and oral terfenadine for the treatment of seasonal allergic conjunctivitis. Clin Ther. 1999;21:11:1900-1907.
7. Rothman J, Raizman M. Comparison of 2% nedocromil sodium eye drops with Patanol for the treatment of cat dander allergic conjunctivitis. Invest Ophthalmol Vis Sci. 2000;41:4:S367.
