Eyeworld

119 EW FEATURE April 2017 • Controversies in cataract surgery steroids, as is frequently the case in patients with uveitic cataracts." "Oral NSAIDs don't have a big role, but there's a cadre of patients who respond well to them for a variety of conditions, including existing rheumatoid arthritis as well as scleritis or episcleritis. These patients do well on a mix of immu- nosuppressants and oral nonsteroid- als. I'll maintain the patient on the oral nonsteroidals if there are no other risk factors for bleeding during cataract surgery," Dr. Sheppard said. He also noted that virtually all FDA trials for NSAID use for cataract sur- gery explicitly exclude concomitant oral NSAID use. EW References 1. Kim SJ, et al. Topical nonsteroidal anti-in- flammatory drugs and cataract surgery: A report by the American Academy of Ophthal- mology. Ophthalmology. 2015;122:2159–68. 2. Lim BX, et al. Prophylactic non-steroi- dal anti-inflammatory drugs for the preven- tion of macular oedema after cataract surgery. Cochrane Database Syst Rev. 2016 Nov 1;11:CD006683. 3. Kessel L, et al. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review. Ophthalmology. 2014;121:1915–24. 4. Duan P, et al. The comparative efficacy and safety of topical non-steroidal anti-inflam- matory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-anal- ysis. Graefes Arch Clin Exp Ophthalmol. 2017 Jan 27 [epub ahead of print]. Editors' note: Dr. Sheppard has finan- cial interests with Alcon (Fort Worth, Texas), Allergan (Irvine, California), Bausch + Lomb (Bridgewater, New Jer- sey), and other ophthalmic companies. The other physicians interviewed have no financial interests related to their comments. Contact information Dunn: jpdunn@willseye.org Kessel: line.kessel.01@regionh.dk Kim: skim30@gmail.com Myers: wmyers2020@gmail.com Sheppard: jsheppard@vec2020.com Based on his research, Dr. Kim is still a little skeptical about the need for NSAIDs. "In diabetic patients, there may be some small benefit because of their higher risk and prevalence, but the evidence is inconsistent and not robust. In uve- itis patients, there is no compelling evidence that they have a role since they have a much weaker anti-in- flammatory effect when compared to corticosteroids that have adequate intraocular penetration," he said. Dr. Myers also favors the possible use of NSAIDs in patients with diabetic macular edema that is already present and vitreous macular traction. One emerging patient group that may push surgeons to prescribe NSAIDs is those receiving premium IOLs, Dr. Sheppard said. "These patients have skyrocketing demands and expectations. The last thing you want is a patient paying cash who then develops postop visual degradation due to macular edema. Most doctors believe that once you add edema, metrics like contrast sensitivity are compromised, even if the Snellen visual acuity is 20/20," he said. Although Dr. Myers is not a big fan of multifocal premium IOLs, he also sees this as a group that may be more likely to receive NSAIDs. "The patient is paying a lot of money, so they probably don't mind buying another bottle. But for routine cata- ract surgery, I don't think this makes a major difference," he said. Analyzing dosing and agents There also are different approaches regarding dosing for NSAIDs, with the basic conclusion that ideal dosing for NSAIDs is not clear. "The Food and Drug Administration [FDA] labeling usually reads 1 day preop and 2 weeks postop, but that doesn't mean some doctors don't adapt for personal preference or for specific patient circumstances," Dr. Sheppard said. "In the context of routine cataract surgery, many doctors feel that 2 weeks postop is adequate for pain and inflammation. On the other hand, off-label use is somewhat up in the air because of the lack of longer term FDA studies, particularly for high risk groups. In fact, high risk patients, including diabetic or glaucomatous eyes, are generally excluded from the FDA trials." "Topical NSAIDs are more ef- fective when started before surgery, although just how long before sur- gery is not clear," Dr. Dunn said. "If one follows the same principles that apply for corticosteroids, it proba- bly makes the most sense to start topical NSAIDs at least several days before surgery, rather than just prior to surgery or after surgery has been completed." "At my institution, treatment begins 3 days prior to surgery, and the patients use one bottle of eye drops per eye, for approximately 3 to 4 weeks of treatment postop," Dr. Kessel said. Surgeons also generally lean toward less frequent dosing—such as the once-daily formulations—for better compliance and to cut down on any NSAID risk factors. "Reduced dosing decreases the total exposure of the cornea to drug and vehicle, so the risks decrease," Dr. Kim said. To add to the decision-making mix, there is now an FDA-approved intracameral NSAID (0.3% ketorolac with 1% phenylephrine, Omidria, Omeros, Seattle) in the U.S., po- tentially making compliance and administration easier. There is no evidence to date that intracameral ketorolac provides a synergistic ef- fect or precludes subsequent topical NSAIDs. It's not yet clear if some NSAID agents work better than others because there is a lack of good clin- ical trials for this area. One recent meta-analysis focusing on topical NSAID safety found that topical piroxicam had fewer adverse effects than bromfenac, diclofenac, flurbi- profen, ketorolac, and nepafenac, but the quality of evidence was low, according to researchers. 4 Topical NSAID risks Another reason surgeons remain vigilant against NSAID use is because of uncommon but still very real risk factors. These can include rare re- ports of corneal melting and allergic reactions, Dr. Kim said. However, corneal melting was far more com- mon with older and generic NSAIDs, Dr. Sheppard added. Dr. Kessel's meta-analysis of 446 patients randomized to receive NSAIDs found no reports of corneal melting. 3 There are also possible effects on the ocular surface. "Both the drug itself and the preservatives in the bottle may precipitate or worsen oc- ular surface disease," Dr. Dunn said. One concern Dr. Sheppard has is the switch from a brand name prescription to a generic, which may be associated with greater risks for patients. "The frightening aspect is that when a doctor pre- scribes a branded topical NSAID, and the pharmacist replaces it with a generic, the surgeon often doesn't know about this substitution until the postop healing phase," he said. For this reason, Dr. Sheppard is very cautious about the use of NSAIDs in patients with autoimmune diseases, systemic neoplasms, severe ocular surface disease, or limbal stem cell deficiency, who may be more prone to corneal melts. A role for oral NSAIDs? Patients are accustomed to popping oral NSAIDs when they have pain or inflammation—so does this type of medicine have a role in cataract sur- gery, in addition to topical NSAIDs? "There potentially could be, but we don't have evidence to demon- strate this," Dr. Kim said. "We do know oral NSAIDs are much less effective in getting into the anterior chamber of the eye. Topical applica- tion achieves much higher levels of drug in the aqueous." "There are no good data com- paring oral to topical NSAIDs for the treatment or prophylaxis of CME," Dr. Dunn said. "Until such data prove that oral NSAIDs are more effective, it seems prudent to avoid their systemic risks, especially if the patient is also taking oral cortico-

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