Eyeworld

99 EW CORNEA April 2017 cell, blocking the various successive events that propagate the signal and result in degranulation," he said. "That is a novel way of treat- ing allergy because you're stopping the horses from leaving the barn." He views this as a potential game changer from current drugs like an- tihistamines, which simply mask the effect of histamine after the horses have already left the barn. "The Syk inhibitor story, if it pans out, will be a generational shift in our therapy," Mr. Gomes concluded. EW Editors' note: Dr. Abelson and Mr. Gomes have consulted on all products in ocular allergy. Dr. Raizman has financial interests with Alcon, Allergan, and Bausch & Lomb. Dr. Udell has no financial interests related to his com- ments in this article. Contact information Abelson: mabelson@oraclinical.com Gomes: pgomes@oraclinical.com Raizman: mraizman@tuftsmedicalcenter.org Udell: ijudell@aol.com While some people respond better to one combination anti- histamine mast-cell stabilizer than another, these are all essentially spinoffs, Mr. Gomes points out. The initial prototype combination mast-cell stabilizer was Patanol (Alcon, Fort Worth, Texas), a 0.1% product, which was used twice a day, he notes, adding that then there was Pataday (Alcon), which was a once-a-day agent also with olopa- tadine but at a 0.2% concentration, followed by Pazeo (Alcon). Pazeo is the same molecule but at a 3.5 times greater concentration. Dr. Udell finds that these olopa- tadine drugs as well as other combi- nation agents work well. "They're all good drugs," he said. "But the one that I tend to go to is generic Zaditor [ketotifen fumarate ophthalmic solu- tion, Novartis, Basel, Switzerland]." Initially a prescription product, this is now available over-the-counter. "This was the second of the agents that came out on the market that had combined antihistamine mast- cell stabilization," Dr. Udell said. "I find for the vast majority of people it provides adequate relief taken BID." However, there is no agent on the market that gives everyone complete relief, he said. Dr. Abelson said that Lastacaft (alcaftadine, Allergan, Dublin, Ire- land), an antihistamine that also has a strong anti-inflammatory effect is another option. "If Pataday or Pazeo do not work, patients should try Lastacaft because it covers every- thing," Dr. Abelson said, adding that practitioners should opt for this drug as a second tier therapy before steroids as Lastacaft doesn't have the same complications. In addition to having anti-inflammatory proper- ties, it also seems to block the pen- etration of the allergen, Dr. Abelson explained. "It sort of tightens up the spaces between the epithelial cells where the pollens penetrate," he said. In head-to-head studies, Lasta- caft was actually superior to Pataday in itch relief. If other agents aren't sufficient, Dr. Raizman ultimately moves to a steroid. "My preference is lotepred- nol because it is quite effective and safer than alternative steroids," Dr. Raizman said. "Most of the other steroids, including FML [fluoro- metholone ophthalmic suspension, Allergan], actually penetrate the eye a little bit more and have intraocular side effects such as a rise in IOP and cataract formation." While lotepre- dnol can also cause a rise in IOP if patients are using it chronically, for periods of just a month or two, it is extremely safe, he finds. "Generally, it is not a concern and cataract is not a concern either, when it is used that way," he said. The loteprednol comes in two concentrations. While Dr. Raizman finds that they both work, he tends to make his selection based on how symptomatic the patient is. "Alrex [loteprednol etabonate ophthal- mic suspension 0.2%, Bausch + Lomb, Bridgewater, New Jersey] is approved specifically for treating allergy, while Lotemax [loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb] is approved for treating ocular inflammation," he said, adding that he often using the Lotemax formulation, which is a little higher concentration because it is still extremely safe and a little more potent. In the future, new agents will likely come to fore. Mr. Gomes cites a Syk kinase selective inhibitor (Por- tola Pharmaceuticals, San Francisco) as something new in the wings. "What this targets is the signaling pathway," he said, adding that it is the mast cell that is the initiator of allergic disease. Mr. Gomes likens the Syk kinase as part of the com- munication link to the surface of the mast cell. He explains that when an allergen dissolves in the tear film, it penetrates the conjunctiva and bur- rows into IgE receptors on the mast cell surface. "Through the activation of kinase signaling pathways, IgE-an- tibody binding on the cell surface instigates a succession of events within the cell, ultimately causing the mast cell to degranulate," he said. After degranulation, mediators like histamine will within seconds cause the eye to itch, Mr. Gomes explained. "Syk inhibitors cut that tele- phone cord from the surface of the

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