Better understanding of allergic cascade leads to innovative new treatments

The general principles of ocular allergy treatment remain the same: antihistamine and mast cell stabilization. However, developments have been made in recent years in understanding the allergic cascade.

“The mast-cell stabilizers used in early days were appropriate for mast cells present on internal mucosa, but the mast cells on external surface are different,” Arthur B. Epstein, OD, FAAO, told Primary Care Optometry News in an interview. These external cells respond differently to mast-cell modulating drugs.

Today’s treatment modalities offer better palliative and long-term relief, and patients are well aware of the potential improvement in quality of life.

“Allergy is a phenomenal opportunity for optometrists, because few things deliver the bang for the buck in terms of patient awareness of successful therapy,” Dr. Epstein said.

Allergy and dry eye

Systemic medications intended to treat general allergies are inappropriate for ocular surface disease, according to Dr. Epstein, because they diminish tear volume, which increases allergen concentration and causes further irritation.

“Whatever gain you get from the antihistaminic activity is often countered by a depleted tear film with a higher concentration of allergens and inflammatory mediators,” Dr. Epstein said.

He prefers olopatadine-based products (Alcon’s Patanol, olopatadine HCl, 0.1%; and Pataday, olopatadine HCl, 0.2%) as first-line therapy because of the combined mast cell stabilizing and antihistaminic properties. Patanol is approved by the U.S. Food and Drug Administration for twice-daily instillation and Pataday is approved for once-a-day use.

The low frequency instillation is another attractive advantage of these products, according to Dr. Epstein.

“[Compliance is] critically important,” he said. “Anything you can do to minimize the disruption caused by ocular allergy is important, and simpler is always better.”

Timing the once-daily dose may be important in improving its efficacy, according to Dr. Epstein. Patients with severe allergies may wish to dose in the morning so they can achieve high tissue concentration when they might be most exposed, and patients who wear contacts may wish to dose at night so drop instillation does not inhibit lens wear.

Another treatment option for ocular allergy is Elestat (epinastine HCl, 0.05%, Inspire and Allergan). According to Jill C. Autry, OD, RPh, “Elestat is touted to stop itching on contact, and it really does,” she told PCON in an interview.

Dr. Autry said she also likes the agent because epinastine effectively treats allergy without harming the ocular surface. The prevalence of dry eye in ocular allergy sufferers is underestimated, she said, and dry eye is not listed as a side effect of Elestat.

Dr. Autry added that this topical antihistamine may be important in treating women with ocular allergy because they tend to have a higher incidence of dry eye.

“The dry eye aspect really needs to be explained, because when you start adding oral medications like Claritin [loratadine, Schering] or Benadryl [diphenhydramine, McNeil], which patients will do on their own, the incidence of dry eye along with allergy becomes a dual problem,” she said.

A new option for treatment may be available in the next year. Ista Pharmaceuticals completed a new drug application in November 2008 for Bepreve (bepotastine ophthalmic solution). In a release announcing the FDA filing, Ista said that bepotastine is a combined histamine agonist and mast-cell stabilizer that also “suppresses the migration into and activation of eosinophils in inflamed tissue.”

Ista is seeking approval for bepotastine as an eye drop treatment for ocular itching associated with allergic conjunctivitis. According to the release, Ista is expecting a standard 10-month review of its product.

Adjunctive, alternative therapy

According to Dr. Epstein, artificial tears have a limited role in primary therapy, because, even though they may provide palliative relief, they do not treat the underlying problem. “You need to shut down the cascade and, preferably, the more specific the therapy, the more effective it will be for the patient,” Dr. Epstein said.

According to Dr. Autry, the palliative relief offered by artificial tears is additive. In her view, anything that can be done for the patient has a beneficial effect. “Artificial tears are useful to keep the allergen out of the eye, to keep it washed and flushed, and to make sure the allergen is not sitting on the ocular surface,” Dr. Autry said. “I think artificial tears have a role in helping the antihistamine or mast-cell inhibitor work better.”

PCON Editorial Board member Paul M. Karpecki, OD, FAAO, said in an interview that he often prescribes combination agents such as Elestat and Pataday, but over-the-counter eye drops, such as Zaditor (ketotifen fumarate, Novartis), Alaway (ketotifen fumarate, Bausch & Lomb) or Refresh Eye Itch Relief (ketotifen fumarate, Allergan), may become more popular in coming months due to the current economic climate. He said he has found himself discussing such options more frequently with patients expressing financial concerns.

Dr. Karpecki said he also advocates palliative approaches to managing ocular allergy, including cold compresses to relieve symptoms and artificial tears to keep allergens off the ocular surface, in addition to treating the patient with topical agents

“Because these patients tend to be atopic and prone to reacting to other compounds such as preservatives, I recommend preservative-free artificial tears,” he said.

Another aspect of palliative management, Dr. Karpecki said, is control of the environment: replacing bed pillows, turning down ceiling fans that will kick up allergens, avoiding rubbing the eyes, showering frequently and chilling eye drops in the refrigerator.

Systemic agents should also be considered, he said, but with care. Oral agents such as Claritin, Allegra (fexofenadine, Sanofi Aventis) or Benadryl are beneficial, Dr. Karpecki said, but they will dry the eye.

“You need to be careful about exacerbating the primary complaint by treating the secondary systemic complaints,” he said, “so I tend to not recommend oral antihistamines at the initial visit. If they need something systemic, I will recommend an inhaler. Astelin [azelastine, Meda] works in some patients; steroid inhalers such as Beconase [beclomethasone, GlaxoSmithKline] and Flonase [fluticasone, GlaxoSmithKline] work well but have side effects.”

Steroids, advanced disease

Caution is also needed with steroids. According to Dr. Autry, severe symptomatology, as in vernal keratoconjunctivitis, warrants steroid therapy, but it should be limited in acute cases and it is not appropriate for regular seasonal allergy, she said.

Dr. Epstein echoes the need for a cautious approach to steroid therapy. “Steroids are among the most dangerous drugs we deal with on a regular basis,” he said. “Steroids have a place, but they tend to be overused.”

Dr. Karpecki agreed that steroids should be used with caution and has developed guidelines for when they are useful. He uses steroids in patients on an OTC medication who are still having symptoms. “If an OTC such as ketotifen fumarate doesn’t help, other prescription mast cell/antihistamine combination agents may not either,” he said, “and a steroid, such as loteprednol, is often the most effective.

He also uses steroids in patients with later-stage disease (symptoms lasting more than 7 to 10 days), increased inflammatory markers and patients with symptoms limiting daily activities.

Dr. Karpecki said corticosteroids should not be used indiscriminately, but they are underutilized and are effective, especially ester-based corticosteroids, for many forms of allergic eye disease.

For more information:

• Arthur B. Epstein, OD, FAAO, is a founding partner of North Shore Contact Lens & Vision Consultants, Long Island, N.Y., and attending staff North Shore University Hospital, NYU School of Medicine. He can be reached at NSCL&VC, One Expressway Plaza, Ste. 100, Roslyn Heights, NY 11577; (516) 299-4540; e-mail: artepstein@artepstein.com. Dr. Epstein is a paid consultant for Alcon.

• Jill C. Autry, OD, RPh, is a PCON Editorial Board member and can be reached at the Eye Center of Texas, 6565 West Loop South, Ste. 650, Bellaire, TX 77401; (713) 797-1010; e-mail: jillautry@eyecenteroftexas.com. Dr. Autry has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

• Paul M. Karpecki, OD, FAAO, is director of research in Cornea and External Disease Service for Koffler Vision Group and a PCON News Editorial Board member. He can be reached at Eagle Creek Medical Plaza, 120 N. Eagle Creek Drive, Ste. 431, Lexington, KY 40509; (859) 263-4631; e-mail: paul@karpecki.com. Dr. Karpecki is a paid consultant for Allergan, Inspire and Bausch & Lomb.