EyeWorld Asia-Pacific June 2016 Issue

60 EWAP PHARMACEUTICALS June 2016 be careful in how they prescribe nonsteroidals. Such patients may not be the best candidates for nonsteroidals. “If they have severe ocular surface disease, any NSAID may cause ocular irritation,” he said. “But overall, the brand name nonsteroidals are better tolerated.” Dr. Wittpenn likewise finds that the brand name NSAIDs are more likely to spare the ocular surface. “Prolensa and Ilevro are gentler on the ocular surface than the generics,” he said. “With the generic ketorolac, which many people are now getting because that’s all that’s on the formulary, it’s not uncommon to have to stop or reduce the drop after a week because of increasing punctate keratopathy.” If the patient is complaining of increasing stinging or burning from the drops, it’s a sign to look carefully at the cornea for punctate keratopathy and stop the drop if necessary, Dr. Wittpenn said. Cost factor Not everyone is convinced that prophylactic use of NSAIDs is of value. William Myers, MD , health system clinician, Feinberg School of Medicine, Northwestern University, Evanston, Illinois, and in private practice, Skokie, Illinois, said that when he underwent his training, around 1980, no one pretreated with topical agents for CME. If a patient had a problem in the first eye, an oral NSAID might be used, but for the most part this wasn’t treated until there was an actual issue. “Treatment generally solved the problem,” Dr. Myers said. “Within 6 months, a high percentage would usually get better whether they were treated or not, but more would respond when they were treated.” That’s the basis for why all nonsteroidals are used today, Dr. Myers said. “My personal feeling is that all of these topical nonsteroidals are incredibly expensive,” he said, adding that even for generics it’s not uncommon for them to cost close to US$100 a bottle, with most patients ultimately needing two bottles. Meanwhile, he thinks that oral NSAIDs are as effective as the topical ones, if not more so. In Dr. Myers’ view, oral agents are not inferior to topical ones and are safer for the surface of the eye. “They might be riskier in patients who have gastrointestinal disease, but the vast majority of patients don’t have a history of gastritis or ulcers,” he said. “Those people have low rates of trouble taking medicines like naproxen.” Such medicines would cost under US$10 a bottle and would last for awhile, he pointed out. Intraoperative use In addition to using prophylactic drops, the intracameral NSAID Omidria (phenylephrine and ketorolac, Omeros, Seattle) is making inroads. “Omidria is now the only FDA- approved product where you can put the nonsteroidal in the eye,” Dr. Wittpenn said. “It got approved based on its ability to maintain pupillary dilation combined with phenylephrine and decreased pain.” While the studies don’t sort out which element does which, they did show that the combination of the two products enhanced both of these features. He finds that Omidria maintains good pupillary dilation. Dr. Wittpenn thinks this could potentially reduce or eliminate the need for topical NSAIDs because the levels of ketorolac measured in the animal studies are much greater than what could be achieved topically. Many of the newer agents such as Prolensa and Ilevro are currently being dosed once a day, but this schedule has nothing to do with preventing macular thickening. He pointed out that studies done on the prevention of CME or macular thickening utilized ketorolac dosed 4 times a day or nepafenac dosed 3 times a day. These agents block prostaglandin synthesis by binding to the COX enzymes. “When there are insufficient molecules to block all the enzymes, production of prostaglandins resumes. These prostaglandins cannot be eliminated when additional medicine is dosed at a later time. Unlike with an antibiotic where you can hope to kill what you missed with the next, with prostaglandin synthesis, once it is made it remains in the eye tissue to elicit inflammation, pain, and macular changes.” With this in mind, he currently doses topical brand NSAIDs twice a day and is uncertain whether even that is enough. “Now perhaps Omidria will let me get down to once-a-day dosing or even eliminate topical NSAIDs,” Dr. Wittpenn said. Others are looking to perhaps decrease the number of drops patients are taking by eliminating the use of steroids from the postoperative mix. However, it’s currently a fluid question as to whether or not topical NSAIDs can be used alone. Dr. Trattler pointed out that while most nonsteroidals are FDA approved for control of the inflammation after cataract surgery without a steroid, the two together have a synergistic effect because these work on different parts of the inflammatory pathway. “There are surgeons who prefer just using a nonsteroidal and that’s appropriate, but I like the combination,” Dr. Trattler said. Overall, in Dr. Trattler’s view, NSAIDs will continue to be an important part of the cataract regimen. “I think we will continue to work toward lowering the amount of drops used for patients in and around cataract surgery,” Dr. Trattler said. “But we need a nonsteroidal—it’s a very important part of postoperative care for cataract surgery.” EWAP References 1. Shorstein NH, et al. Comparative effectiveness of three prophylactic strategies to prevent clinical macular edema after phacoemulsification surgery. Ophthalmology . 2015;122:2450–2456. 2. Wittpenn JR, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs. steroid alone in low- risk cataract surgery patients. Am J Ophthalmol. 2008;146:554–560. Editors’ note: Dr. Shorstein has no financial interests related to his comments. Dr. Trattler has financial interests with Alcon, Allergan, Bausch + Lomb, and Omeros. Dr. Myers has no financial interests related to his comments. Dr. Wittpenn has financial interests with Bausch + Lomb and Omeros. Contact information Myers: wmyers2020@gmail.com Shorstein: nshorstein@eyeonsight.org Trattler: wtrattler@gmail.com Wittpenn: jrwittpenn@aol.com New focus - from page 59