Eyeworld

EW NEWS & OPINION 14 June 2015 Pharmaceutical focus by Maxine Lipner EyeWorld Senior Contributing Writer surgery at Kaiser Permanente from 2007 to 2013. Patients fell into one of 3 groups—cases in which topical prednisolone alone was used, those in which a topical prednisolone plus a generic nonsteroidal was used, and some in which injected triamcinolone was given. The study honed in on visually significant macular edema. When investiga- tors looked at just prophylaxis, the injected triamcinolone group had very similar odds of developing post- operative macular edema to topical prednisolone, Dr. Shorstein reported. However, the group that had topical prednisolone along with the generic nonsteroidal had half the rate of macular edema. The study also showed about a 2.5-fold increased risk of macular edema for epiretinal membrane and PCR patients, as well as for those with a history of iritis or uveitis, he noted, adding that those with diabetic retinopathy had an even higher risk. "One new finding was that Af- rican Americans had a higher risk of postoperative edema," Dr. Shorstein said. They are unsure of why this is, but it might be due to the fact that the retina has been reported to be thicker in these patients. Dr. Shorstein has begun using NSAIDs in these high risk cases. Latest NSAIDs NSAIDs continue to evolve. While there have been no new molecules over the last 5 years, there has been increased formulation and improve- ment of drug delivery. "We've taken nonsteroidals from a 4 times/day drop associated with significant burning and irritation to a once- a-day medication with increased comfort," he said. Bromfenac was the first medication to go to once- a-day dosing with Bromday (ISTA Pharmaceuticals, Irvine, Calif.) and now with Prolensa (Bausch + Lomb, Bridgewater, N.J.). Ilevro (Alcon, Fort Worth, Texas) has taken the nepafenac molecule from 3 times/ day to 1 time/day, he noted. This has been done by making significant changes in the formula- tion, including tripling the concen- tration, changing the PH, and the molecule size, and adding a vehicle that improves contact time on the eye and protects the ocular surface, he explained. Dr. Braga-Mele agreed that the new topical formulations are a step forward. "We're seeing much better penetration with these newer agents and tissue uptake by the appropriate tissues, both in the anterior segment and the posterior chamber," she said. "We're seeing drugs that are ab- sorbed more quickly, penetrate bet- ter, and stay within the tissues for a longer period of time at less dosing." The fact that these new formulations minimize drops means that there is theoretically less corneal toxicity, she said. Dr. Donnenfeld concurred. "By giving the NSAID once a day, the ocular surface has the ability to maintain its integrity," he said. "You don't have the anesthetic effect of the NSAID reducing quality of vision with SPK [superficial punctate keratopathy]." In addition, there is the obvious advantage of patient compliance, Dr. Donnenfeld noted, adding that patients rarely take a drop 4 times/day. Meanwhile, when it comes to intracameral NSAIDs, the big story has been the introduction of Omidria (Omeros, Seattle), he said. "For the first time, we have an in- tracameral nonsteroidal that is FDA approved," Dr. Donnenfeld said. "Omidria is a combination of phen- ylephrine and ketorolac." This com- bination has been found to prevent pupillary miosis during surgery and reduce pain, he explained. He added that it is still unknown whether the intracameral use of ketorolac im- proves postoperative inflammation or reduces the risk of CME. Popular regimens Other types of agents such as ste- roids are also part of the picture. However, even with safe steroids available, Dr. Donnenfeld still finds NSAIDs to be relevant. These work on different pathways and have a synergistic effect, he noted. His own patient regimen includes starting the nonsteroidal drops preop. "We published a paper to show that by giving preoperative nonsteroidals, you increase the pupil size by a mean of 2 mm during sur- gery," he said, adding that this is a significant advantage to the surgeon and to the patient in improving outcomes. He starts the nonsteroidals 3 days prior to surgery, but thinks that 1 day prior is adequate. He continues these for 4 weeks postop in routine cases. In complex cases he continues the nonsteroidals for 3 months postop. In addition to the NSAID, he uses difluprednate, which he begins 1 hour preop. "I use it 4 times a day for the first day and twice a day for 2 weeks and then once a day for the third week," he said. At 3 weeks he stops the steroid but continues the non- steroidal for another week so that he does not stop both anti-inflammato- ries at once. Meanwhile, Dr. Braga-Mele starts the patient on the nonste- roidal the day before surgery. "In a standard patient I continue it for 4 weeks," she said, adding that she puts the patient on this in conjunc- tion with a steroid starting on the day of surgery. She uses a steroid 4 times/day for a week and then lowers it to twice a day for the re- maining time. In high risk patients, she extends this out at least a couple of weeks. "I would continue those patients on a nonsteroidal to at least 6 or 8 weeks postoperatively because their risk of CME is higher," Dr. Braga-Mele said. In patients who have conditions such as keratitis sicca, rheumatoid arthritis, or any risk of epithelial de- fects, Dr. Braga-Mele avoids NSAIDs. However, with most patients, she has no concerns about the possibili- ty of corneal melts. Likewise, Dr. Shorstein stressed that in his recent study there were no corneal melts from using a generic NSAID. Meanwhile, this was effective for reducing the postop risk of macular edema by half. "The next stage of our research is to look at the postoperative visual acuity and try to figure out if adding the NSAIDs in addition to lowering the rate of diagnosis of CME helped visual acuity." EW Editors' note: Dr. Braga-Mele has finan- cial interests with Alcon and Allergan (Irvine, Calif.). Dr. Donnenfeld has financial interests with Alcon, Allergan, Bausch + Lomb, and Omeros. Dr. Shorstein has no related financial interests. Contact information Braga-Mele: rbragamele@rogers.com Donnenfeld: ericdonnenfeld@gmail.com Shorstein: nshorstein@eyeonsight.org Eyeing NSAIDs for cataract surgery W hen it comes to cata- ract surgery, NSAIDs play an integral role, said Eric Donnenfeld, MD, Rockville Centre, N.Y. "NSAIDS are the missing link between good outcomes and great outcomes, and I use them on every patient that I do cataract surgery on," Dr. Donnenfeld said. These serve 3 main functions, Dr. Donnenfeld explained. "Given preoperatively they reduce intraop- erative miosis. They also increase the comfort of the procedure." Finally, they reduce postoperative inflam- mation, including the incidence of cystoid macular edema (CME). Rosa Braga-Mele, MD, profes- sor of ophthalmology, University of Toronto, and director of cataract sur- gery, Kensington Eye Institute, To- ronto, concurred. "I believe nonste- roidals have decreased the amount of postop inflammation," she said. "I use them 1–3 days preoperatively depending on the patient." In addition to helping to quiet the eye on the day before the sur- gery, she finds they also help to keep the pupil dilated during the surgery as well as to decrease postoperative inflammation. "The biggest benefit of a non- steroidal anti-inflammatory is that I believe it reduces the risk of CME— both clinically significant and oth- erwise," she said. "That will thereby improve visual outcomes in the long run, which is especially important with your premium IOL patients." Neal H. Shorstein, MD, Kaiser Permanente, Walnut Creek, Calif., reserves NSAIDs for patients who have a prominent epiretinal mem- brane, those who have concerning diabetic retinopathy, those who have posterior capsular rupture (PCR), and bilateral cataract pa- tients. For routine cases, due to the very low incidence of CME and for assured drug delivery, he tends to use a subconjunctivally injected, long-acting steroid, triamcinolone acetonide, instead. For a time Dr. Shorstein was not using any NSAIDs except for cases involving PCR. But in a study he presented at the 2015 ASCRS•ASOA Symposium & Congress, he did find a benefit to including NSAIDs in the regimen: lowering the risk of CME. The study included 16,000 patients who underwent cataract

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