EyeWorld India March 2012 Issue

56 EW PHARMA FOCUS March 2012 Designer steroids and novel anti-inflammatory agents E ven with modern phaco technique, there’s no getting around it: Practitioners still need steroids and NSAIDs, according to Terrence P. O’Brien, MD, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Fla., USA. There is still inflammation triggered that makes use of steroids a necessary part of the equation. Likewise, while NSAIDs can reduce the inflammation at the time of surgery, by themselves they are not enough. “Physicians tried to go it alone with nonsteroidals, and many times the patients would have some rebound inflammation or come in with more discomfort or more inflammation,” Dr. O’Brien said. Steroid power Steroids such as prednisolone acetate (Pred Forte, Allergan, Irvine, Calif., USA), Lotemax (loteprednol, Bausch + Lomb, Rochester, NY, USA), and Durezol (difluprednate, Alcon, Fort Worth, Texas, USA/ Hünenberg, Switzerland) continue to be a key part of the cataract surgery routine. All of these, however, are not the same. William Trattler, MD, director of cornea, Center for Excellence in Eye Care, Miami, Fla., USA, sees prednisolone acetate as the “go to” drop. “It’s probably the most commonly used steroid in and around cataract surgery,” he said. He typically uses this for routine cataract cases. Dr. O’Brien agrees that prednisolone acetate has been the “prototypical corticosteroid” for years. He pointed out, however, that one drawback is that this is a suspension rather than a solution and needs to be agitated prior to instillation to provide effect. By contrast, difluprednate, a newer ophthalmic corticosteroid, is an emulsion, with each drop delivering a uniform amount of active drug. “Difluprednate has been shown to be more potent in controlling inflammation than prednisolone acetate in patients with uveitis,” Not just a drop in the phaco bucket by Maxine Lipner Senior EyeWorld Contributing Editor Dr. O’Brien said. It has also been shown to be a more potent steroid with fewer drops required relative to prednisolone acetate, he said. Dr. Trattler sees difluprednate as the one that provides the strongest anti-inflammatory impact. “It’s going to be the one that is going to help if there is a patient who has a larger cataract.” It can also help with others who are more at risk for inflammation after cataract surgery such as those with diabetes or Fuchs’ dystrophy. Likewise, Dr. O’Brien tends to reserve this for more challenging cataract cases. “When the surgery is going to require more manipulation, that’s when the difluprednate is particularly attractive because of its greater potency,” Dr. O’Brien said. Meanwhile, loteprednol is a designer steroid created by looking at prednisolone’s side effects and working backward to design a molecule to avoid these. “It truly has had fewer side effects,” Dr. O’Brien said. It works on a corticosteroid mechanism, but it has a different chemical structure so it doesn’t lead to a cataract. However, there has been some question whether it is as potent as prednisolone. “I know that there is some published data that suggest equivalency, but I think for most of us in practice it is slightly less potent than pred but without the propensity to raise pressure as much,” Dr. O’Brien said. He sees loteprednol as attractive for routine cataract surgery without any premorbid conditions. “It’s potent enough to provide the additional anti-inflammatory effect but with a safety profile that is desirable,” Dr. O’Brien said. This may be especially helpful for a younger phakic patient who may be on a steroid longer since it is less likely to cause a cataract or pressure spike. In fact, Dr. Trattler reserves this for patients with pressure issues or who are on a glaucoma medication. “The big advantage is that it works well for people who are more pressure sensitive,” he said. NSAID protection Use of NSAIDs is also a vital part of the equation. “NSAIDs are important for protecting the retina, so they help us to prevent CME [cystoid macular edema],” Dr. Trattler said. In addition, they also help to alleviate pain. Dr. Trattler, who was part of the FDA clinical trial for Acuvail (ketorolac 0.45%, Allergan), sees this drug as offering good lubrication and packing a lot of punch. “It has got a carboxymethylcellulose, so it has a lubricating drop in it,” he said. “It’s indicated twice a day, and it gives about twice the levels of nonsteroidals into the eye compared to standard Acular [Allergan], but it’s safer because it has a lubrication part in it.” Nevanac (nepafenac, Alcon), another ophthalmic NSAID, is less toxic to the ocular surface. “That has a pro-drug formulation that is uniquely designed to try and decrease the toxicity of some nonsteroidals that lead to the breakdown of the cornea,” Dr. O’Brien said. The medication is broken down into its active form by the enzymes that are present in the tear film and in the cornea. “As the drop is applied these hydrolases convert the nepafenac to amfenac, which is the active component of nepafenac,” he said. Dr. O’Brien views this as a way to dose topically and have less ocular surface irritation yet have a very potent drug inside the eye. The company still provides some samples of Nevanac, just as it used to of prednisolone acetate before the advent of Durezol, but Dr. O’Brien sees such samples as likely becoming obsolete. Ultimately given the expense of branded medicines, when potent antibiotics are needed, he thinks that it becomes a “Sophie’s choice” for practitioners having to decide which branded medicine is most necessary. Bromday (bromfenac ophthalmic solution, ISTA Pharmaceuticals, Irvine, Calif., USA) offers an attractive dosing schedule. Dr. Trattler tends to use this more than Acular since it can be administered just once a day rather than twice for the latter. A new related NSAID dubbed Prolensa (bromfenac ophthalmic solution, ISTA Pharmaceuticals) is now under U.S. FDA consideration, according to Steven M. Silverstein, MD, associate clinical professor, University of Missouri School of Medicine, Columbia, Mo., USA, and Kansas City University of Medicine and Biosciences, Mo., USA. “It’s a new optimized formula that permits at least equal efficacy to once-daily bromfenac while lowering the concentration,” Dr. Silverstein said. The idea is the less frequently patients need to take the drug, the better the patient compliance and the better it is for the ocular surface. Dr. Silverstein is optimistic about the drug. “The results of the phase III study were highly correlative to everything that we saw as a result of leading to the FDA approval of Bromday,” he said. “It worked at least as well if not better at a lower concentration.” The hope is that Prolensa will soon be available. “ISTA’s plan is to apply for an NDA as early as possible in the first quarter of 2012,” Dr. Silverstein said. “[The company] hopes to have products on the market either by the end of the year or the beginning of the following year.” Also coming down the pike is the introduction of selective glucocorticoid agonists (SEGRA) agents. “These drugs are designed to share many of the favorable anti-inflammatory and immunomodulatory properties of classical glucocorticoid drugs but with fewer side effects,” Dr. O’Brien said. “These appear very promising for providing that potency, but because they have nonsteroidal structures, they don’t have the negative effects of the steroids.” EW Editors’ note: Dr. O’Brien is an ad hoc non-salaried consultant for Alcon, Allergan, and Bausch + Lomb. Dr. Silverstein has financial interests with Alcon, Allergan, and ISTA. Dr. Trattler has financial interests with Alcon, Allergan, Bausch + Lomb, and ISTA. Contact information O’Brien: 561-515-1544, tobrien@med.miami.edu Silverstein: 816-358-3600, ssilverstein@silversteineyecenters.com Trattler: 305-598-2020, wtrattler@gmail.com