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August 2012 Dr. Brown agreed that beta blockers can be problematic. "The beta blocker has the contraindica- tions of asthma or any sort of breathing issues like emphysema or chronic obstructive pulmonary disease," he said. Also, any allergic intolerance to brimonidine or dorzolamide can factor in to the decision of which combination agent to choose. In addition, Dr. Shaarawy finds that the combinations differ in terms of how individual patients react. It becomes a question of trial and error. "What is important for the general ophthalmologist to re- member is that if this combination doesn't work with this patient, it might work with another," Dr. Shaarawy said. "So individual re- sponses to a fixed combination are very important not to discard." However, for the most part he finds that there are no dramatic differ- ences from one fixed glaucoma com- bination to another that would push a physician toward a particular prod- uct. The preservative-free Cosopt, however, enjoys a bit of a special niche. "For a person who has an ocular surface disease, you would probably go for a combination that is preservative free like Cosopt-S, which is available in Europe," Dr. Shaarawy said. This was recently ap- proved in the U.S. under the Cosopt PF label. Dr. Brown also pegs those with allergies as more amenable to a pre- servative-free approach. "Patients who have had more problems with allergy would certainly be more ap- propriate for the preservative-free medication," Dr. Brown said. "It's probably more expensive, which is the only drawback." He has just started using the preservative-free product. "I think that it's always good to have as few extraneous chemicals as possible," he said. "But it's a balance between cost and bene- fit." Dr. Shaarawy has found that the preservative-free product appeals to the sensibilities of many of his pa- tients. In his experience, however, there are two caveats. "The mono- doses need a certain degree of manipulation by the hands of the patients," he said. "So an elderly patient with rheumatic arthritis, for example, will not be able to use it well." Also, the tip of the single dose bottle is not as forgiving as that of the multi-dose. "The tip of the mono-doses are relatively trau- matic," he said. "The patient has to be very well educated so he doesn't traumatize his cornea while he is applying it." Glaucoma therapy as a whole is continuing to evolve. Still, even with emerging new approaches such as the use of micro-invasive glau- coma surgery (MIGS) devices, many of which are already CE marked, Dr. Shaarawy doesn't see this as sup- planting combination agents. "At this point, we don't have a proce- dure that would leave the majority of our patients medically free of medications for the rest of their lives." Dr. Brown thinks that if any- thing, the use of MIGS may signal an increasing role for combination drugs, which are likely to be used in conjunction with medical therapy. "It will be what medication can get the best pressure lowering with the fewest side effects and the least has- sle," Dr. Brown said. "The combina- tion medications are often more effective than the single medication so they will definitely have a role with MIGS." Dr. Shaarawy is looking forward to having fixed complications in dif- ferent classes. "We are still at the mercy of having to ask the patients to put in the drops once or twice a day, which is ridiculous in this day and age." In the near future he envi- sions having a slow release combina- tion agent at the ready that could be used perhaps once a month or even once a year. "We should not be far from that," Dr. Shaarawy said. EW Editors' note: Dr. Brown has financial interests with Merck and Allergan. Dr. Novack has financial interests with numerous firms in the ophthalmic development area. Dr. Shaarawy has no financial interests related to this article. Contact information Brown: 404-252-1194, reaymary@comcast.net Novack: 415-472-2181, gary_novack@pharmalogic.com Shaarawy: +41 22 3828 400, tarek.shaarawy@hcuge.ch