EyeWorld Asia-Pacific June 2017 Issue

67 EWAP PHARMACEUTICALS June 2017 drop in, the cold actually feels good and ends up lowering the surface temperature of the eye,” Dr. Raizman said. “The tears wash away any environmental irritants and allergens that have gotten onto the ocular surface and also flushes away some mediators that are in the tear film—histamine, in particular.” Dr. Udell agrees that tears can help dilute the allergen but finds that these rarely suffice alone. “I can reduce the load in a sense by using the teardrops, but as long as some of that allergen gets through the tissue through the conjunctiva into the substantia propria of the conjunctiva where the mast cells reside, there will be some degranulation of those cells in the inflammatory cascade, leading to some inflammatory reaction, which the patient will become symptomatic from,” he said. “If a patient can use artificial tears and get complete relief, that’s great, but my experience is that that’s not the typical patient.” One option patients may turn to are over-the-counter (OTC) agents. “The prototype OTC is the vasoconstrictor antihistamine,” Dr. Udell said. “They work for itch and redness, but they have short activity.” What’s more, they cause tachyphyaxis, so if you use them frequently, you’re not going to get much of an effect and will, in fact, ultimately see more redness in the eye, he stressed. Of these, Dr. Udell tends to recommend Vasocon-A (antazoline phosphate 0.5% and naphazoline, Novartis, Basel, Switzerland), with the active ingredient naphazoline, which in his experience tends to have the least amount of patient complaints. Such agents can work for those who have an occasional episode of an allergic response if used sparingly, he finds. Prescription products On the prescription end, Dr. Raizman finds that while mast- cell stabilizers, which keep the mast cell from degranulating, are a possibility, he rarely uses these anymore. “Some of my patients have used cromolyn (various manufacturers) and like it,” Dr. Raizman said. “But most patients get more relief from a dual-action product.” He tends to recommend the dual-action antihistamine mast-cell stabilizers such as olopatadine and alcaftadine. If insurance does not cover these products, there are inexpensive over-the-counter dual-action agents that are safe and effective, especially ketotifen. While some people respond better to one combination antihistamine mast-cell stabilizer than another, these are all essentially spinoffs, Mr. Gomes points out. The initial prototype combination mast-cell stabilizer was Patanol (Alcon, Ft. 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 olopatadine 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 olopatadine drugs as well as other combination 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 solution, Novartis].” 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, Ireland), 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 everything,” 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 properties, it also seems to block the penetration 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, Lastacaft was actually superior to Pataday in itch relief. If other agents aren’t sufficient, Dr. Raizman ultimately moves to a steroid. “My preference is loteprednol because it is quite effective and safer than alternative steroids,” Dr. Raizman said. “Most of the other steroids, including FML [fluorometholone 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 loteprednol 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 ophthalmic 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 (Portola 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 communication link to the surface of the mast cell. He explains that when an allergen dissolves in the tear film, it penetrates the conjunctiva and burrows into IgE receptors on the mast cell surface. “Through the activation of kinase signaling pathways, IgE-antibody 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 telephone cord from the surface of the cell, blocking the various successive events that propagate the signal and result in degranulation,” he said. “That is a novel way of treating allergy because you’re stopping the horses from leaving the barn.” He views this as a potential game changer from current drugs like antihistamines, 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. EWAP 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 comments in this article. Contact information Abelson : mabelson@oraclinical.com Gomes : pgomes@oraclinical.com Raizman : mraizman@tuftsmedicalcenter.org Udell : ijudell@aol.com