EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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50 EW CATARACT October 2012 Talking NSAIDs for phacoemulsification by Maxine Lipner Senior EyeWorld Contributing Writer The dish on drug penetration and prostaglandin inhibition A ccording to two published studies, when it comes to both penetration and prostaglandin inhibition, Acuvail (ketorolac 0.45%, Allergan, Irvine, Calif.) appears to offer a double threat compared to Bromday (bromfenac 0.09%, ISTA Pharmaceuticals, Irvine, Calif.) and Nevanac (nepafenac 0.1%, Alcon, Fort Worth, Texas) for those under- going phacoemulsification, said Frank A. Bucci Jr., M.D., medical director, Bucci Laser Vision Institute, Wilkes-Barre, Pa. Tandem study results published in the December 2011 issue of Current Medical Research and Opinion and the December 2011 issue of Advances in Therapy showed that there is greater penetration of Acuvail as well as heightened prostaglandin inhibition. Dr. Bucci, who led both studies, was spurred to consider this with the market change from Acular LS 0.4% (Allergan) to Acuvail 0.45%. He pointed out that this switch to Acuvail was more than just a change in concentration. The new drug boasted the addition of car- boxymethylcellulose, a component that is also used in a number of arti- ficial tears and gels. "The idea is if it's adherent to the ocular surface, the drug is up against the ocular sur- face and it may increase the amount that's absorbed," Dr. Bucci said. "By taking out preservatives and adding carboxymethylcellulose, [they're doing] two things that help the ocular surface and may also help to deliver more drug to the eye." Cataract continued from page 49 anterior chamber angle configuration before and after cataract surgery. British J Ophthalmol. June 2012. Olson RJ, Jin GJ, Ahmed IK, Crandall AS, Cionni RJ, Jones JJ, [ed]. Chapter 11: Nanophthalmos, Cataract surgery from routine to complex: A practical guide. SLACK Incorporated, Thorofare NJ, 2011. Cao KY, Sit M, Braga-Mele R. Primary piggy- back implantation of 3 intraocular lenses in nanophthalmos. J Cataract Refract Surg. 2007 Apr; 33(4):727-30. Jung KI, Yang JW, Lee YC, Kim SY. Cataract Surgery in Eyes With Nanophthalmos and Relative Anterior Microphthalmos. Am J Ophthalmol. 2012 Jun;153(6):1161-8. doctor-hill.com/iol-main/piggyback.htm Werner L, Mamalis N, Stevens S, Hunter B, Chew JJ, Vargas LG. Interlenticular opacification: dual-optic versus piggyback intraocular lenses. J Cataract Refract Surg. 2006 Apr;32(4):655-61. Editors' note: Drs. Koch and Moss are affiliated with the Cullen Eye Institute, Baylor College of Medicine, Houston. Dr. Koch has financial interests with AMO and Alcon (Fort Worth, Texas). Dr. Moss has no financial interests related to this article. Contact information Koch: dkoch@bcm.edu Moss: Hart.Moss@bcm.edu with 288.7 pg/mL for bromfenac and 320.4 pg/mL for nepafenac. The difference between the ketorolac and the nepafenac prostaglandin levels were statistically significant. These findings suggest that ketorolac may be more effective at keeping prostaglandin levels low than the other agents, Dr. Bucci said. This is important because practition- ers want to know which non- steroidal agent is the best one to use to suppress inflammation as quickly and as much as possible. "The ab- sorption study only tells us we can get more in the eye," Dr. Bucci said. "That's why the complimentary prostaglandin study is so important because we're actually measuring the level of prostaglandin PGE2, which is a direct measure of inflammation control." One limitation of the study was Two-pronged study To see how Acuvail would stack up clinically, investigators performed a randomized, double-masked trial comparing the new agent to brom- fenac and nepafenac. Each of the 121 patients included received a peak dose of the randomized agent. The drugs were used on-label. On the day before surgery, the ketorolac and bromfenac were each given twice a day, and the nepafenac three times. Beginning the next morning the patients were asked to take one drop when they got up and were given another four drops of the medication in the hour prior to surgery. Part of the sample that investigators drew following phacoemulsification was then assayed for absorption and the rest for prostaglandin levels. Results in both arms were prom- ising. Absorption of the Acuvail was higher than for the other agents, including amfenac, which is the me- tabolized product of nepafenac. "We found that the Acuvail absorbed 10 times more than the bromfenac and five times more than the amfenac," Dr. Bucci said. Investigators involved in the study theorized that the higher rates of penetration seen are a result of the increased concentration of the ketorolac in conjunction with a change in PH levels to 6.8, as well as the addition of the carboxymethyl- cellulose. When it came to prostaglandin inhibition, investigators found the concentrations of prostaglandin E2 (PGE2) for ketorolac in the aqueous humor samples were 224.8 pg/mL (picograms per milliliter) compared that in the prostaglandin arm, the levels were taken only at the time of cataract surgery. "Tissue damage causes an inflammatory response. We would love to take the sample 1 day or 1 week after, where we're actually seeing how much prostaglandin is present because we're seeing how the eye responds to the tissue damage," Dr. Bucci said. "By taking it right at the beginning of surgery, we're not doing that." This was not done because it would have been unethical to do so. "The opening wound you're performing anyway—that's when you extract the fluid," he said. "If you did the surgery and then 24-hours later or 1 week later put a needle in the eye and extracted fluid, that wouldn't pass an IRB (internal review board)." Practical perspective Uday Devgan, M.D., chief of ophthalmology, Olive View-UCLA Medical Center, and Devgan Eye Surgery, Los Angeles, noted that from a clinical perspective, he thinks it comes down to practitioners' personal preferences. "I think that all of the branded NSAIDs are quite good and that using one over the other is often based upon surgeons' clinical experiences," he said. "I think that the market has spoken in the U.S. where Acuvail's market share is small compared to Bromday, Nevanac, and the generic NSAIDs," he said. "We know that Acuvail is ketorolac, and that's the continued on page 52