EyeWorld Asia-Pacific June 2013 Issue

60 June 2013 EW PHARMACEUTICALS For eyes with compromised surfaces, like this one stained with lissamine green, anecdotal reports show that even one drop of preserved medication may be enough to tip them over the edge. Source: Robert J. Noecker, MD New dimension for glaucoma treatment P rescribing prostaglandins for glaucoma patients has taken on a new dimension. It’s no longer simply a matter of deciding between brand name and generic medications. Practitioners these days have a new type of medication in this prostaglandin class to consider— the preservative-free drug Zioptan (tafluprost ophthalmic solution 0.0015%, Merck, Whitehouse Station, NJ, USA). Since February 2012 when Zioptan won FDA approval, this new option has given practitioners another tool to wield for glaucoma patients. Zioptan has joined the ranks of other classes of glaucoma drugs with non-preserved options, drugs such as preservative-free timolol (Timoptic, Aton Pharma, Madison, NJ, USA) and Cosopt PF (preservative-free dorzolamide/ timolol, Merck), according to Douglas J. Rhee, MD , associate professor of ophthalmology, Harvard Medical School, Boston. While the preservative-free trend may seem very recent, he pointed out that it is a movement that began some time ago. “The preservative- free agents are an extension of a popularized theory to move away from benzalkonium chloride (BAK),” Dr. Rhee said. Initially beginning around 2001, there were alternatively preserved medications such as Alphagan P (brimonidine tartrate ophthalmic solution 0.15%, Allergan, Irvine, Calif., USA), preserved in Purite, followed by the prostaglandin analog Travatan Z (BAK-free travaprost 0.004%, Alcon, Fort Worth, Texas, USA/ Hünenberg, Switzerland), preserved in SofZia, in 2006. “There was the beginning of a realization that we should be using something gentler on the eye,” Dr. Rhee said. “The natural extension to that are these preservative-free agents.” These have all germinated Prostaglandin enters preservative-free zone by Maxine Lipner Senior EyeWorld Contributing Writer from the notion that the glaucoma agents themselves, as well as the preservatives such as BAK, are causing side effects to the surface of the eye. “They can make the eyes more uncomfortable,” Dr. Rhee said. In addition, they can make eyes appear red and feel gritty or sandy. “There is some evidence to show that these changes are long term,” Dr. Rhee said. “It’s not just a sensation, you’re actually changing the conjunctival tissue, specifically the goblet cells.” To combat this, the ophthalmic field has pressed to make therapies gentler so that patients would adhere to the prescribed regimen more frequently, he explained. Prostaglandin first Zioptan is the first prostaglandin medication to offer not just a gentler approach but a totally preservative-free option. The vast majority of glaucoma patients tend to be on prostaglandin medication, noted Adam C. Reynolds, MD , Intermountain Eye and Laser Center, Boise, Idaho, USA. “I would say on average in any given glaucoma situation more than 80% of our patients are on prostaglandin analogs,” said Dr. Reynolds, who views the prostaglandins as a core medical treatment for glaucoma nowadays. This makes it especially important if patients are intolerant of the BAK preservative in Lumigan (topical bimatoprost, Allergan) or Xalatan (latanoprost, Pfizer, New York, NY, USA), generic latanoprost, or even Travatan Z to have an option where there is no additional agent to contend with. Even if patients can’t tolerate these other drops, they may be able to use Zioptan, he said. Weighing the options In some circles, in addition to using this for patients with ocular surface disease, there is the thinking that everyone might do better without preservatives, Dr. Reynolds said. “Maybe you believe that everyone should be on preservative-free therapies because ‘BAK is from Satan,’ as Dr. (John) Samples likes to say, and maybe you don’t believe that Travatan with SofZia is a viable alternative,” Dr. Reynolds said. “Your philosophy may be that if you’re going to treat glaucoma topically, you want to use every preservative-free alternative that’s out there and use them first line.” The rub here, he pointed out, is that most patients seem to “tolerate” generic prostaglandins well. Others stress that when it comes to glaucoma therapy, preservatives such as BAK can pose a particular problem since therapy tends to be ongoing, said Robert J. Noecker, MD , Ophthalmic Consultants of Connecticut, Fairfield, Conn., USA. If patients are temporarily exposed to a little bit of BAK, it’s no problem, but with glaucoma, unfortunately, there may be no reprieve. “The problem with glaucoma therapy is that you’re doing it for so long, day after day, year after year, that there will be a cumulative toxicity to the surface of the eye,” Dr. Noecker said. “That can cause problems with the way that the drugs get into the eye, the way that patients feel in terms of how it can affect their vision; there are also some concerns that it can make the glaucoma worse over time.” The strongest evidence that preservatives can be problematic comes from laboratory models, he pointed out. There, preservatives can be given to one group and withheld from the other. However, with people it can be harder to isolate those exposed to preservatives since patients can have other issues with which to contend, Dr. Noecker said. There is, however, no shortage of anecdotal reports. “We have patients who have such rotten ocular surfaces that one drop of these medications can tip them over the edge,” he said. Unfortunately, rehabilitating the surface doesn’t happen overnight. In some cases, patients with problematic ocular surfaces have been using preserved medications for years. “It will take some time to unravel those,” Dr. Noecker said. “Immediately stopping it you won’t see much change, but over time this will restore their normal ocular surface.” Also, he said the evidence is shaky as to whether removing the preservatives from just one glaucoma medication will help those who are on several other