Cystoid macular edema 4 weeks after cataract surgery with 20/50 vision
Source: Stephen J. Kim, MD
Surgeons share differing views on NSAID effectiveness
Surgeons fall divisively on different sides of the debate when they discuss the use of non-steroidal anti-inflammatory drugs (NSAIDs) for routine cataract surgery.
Topical corticosteroid use in cataract surgery patients is the norm, although many surgeons feel that the addition of an NSAID can help reduce the chance of cystoid macular edema (CME).
Even though NSAIDs can have some benefits, there are also many surgeons who feel there’s not enough of an advantage to prescribe them in all routine patients.
“There is strong evidence that the benefit of routine NSAID use is small and the number of patients you’d have to treat to see any benefit is large,” said Stephen J. Kim, MD, Department of Ophthalmology and Visual Sciences, Vanderbilt University of Medicine, Nashville. “You have to treat nearly 300 people for one person to show a reduction in CME that may translate in a short-term but not long-term improvement in vision in routine patients. The cost/benefit analysis of NSAID use does not support their routine use,” said Dr. Kim, who was the lead author of a 2015 review article on the topic of NSAIDs and cataract surgery.1 His report found a lack of level 1 evidence that supports the long-term benefit of NSAID use to prevent vision loss from CME at 3 months postoperatively.
“Published studies have been limited by many factors, including small size, inadequate power; inconsistent protocols, such as topical NSAIDs plus corticosteroids compared to corticosteroids alone or NSAIDs compared to corticosteroids; variable duration of follow-up, lack of blinding, lack of a good internal control group, and potential bias from funding sources,” said James P. Dunn, MD, director, Uveitis Unit, Wills Eye Hospital, Philadelphia. Dr. Dunn mentioned a recent Cochrane review that analyzed 34 studies with more than 5,000 patients that only found low-certainty evidence of a reduction in central retinal thickness or vision improvement.2
“There is good evidence that NSAIDs should be used prophylactically after routine cataract surgery. I would recommend to use them in every patient,” said Line Kessel, MD, PhD, Glostrup Hospital, Department of Ophthalmology, Glostrup, Denmark. In Dr. Kessel’s 2014 meta-analysis that focused on pseudophakic edema after cataract surgery, she and fellow researchers found that 25% of those who received steroids alone had edema as seen on fluorescein angiogram or OCT versus 4% in the NSAID-only group.3
“There’s a vast peer-review literature in Europe regarding the protection of the macula with nonsteroidals,” said John Sheppard, MD, professor of ophthalmology, microbiology and molecular biology, and clinical director, Thomas R. Lee Center for Ocular Pharmacology, Eastern Virginia Medical School, Norfolk, Virginia. “I think there’s no doubt that most American surgeons view them to be effective.”
Surgeons who do not routinely use NSAIDs in cataract patients say they can be effective—they are just not effective enough or cost-effective enough to replace or add to topical corticosteroid therapy. William G. Myers, MD, Chicago, said it is likely more cost-effective to increase the dosing of topical corticosteroids as needed rather than have patients use topical NSAIDs.
High-risk and special patient populations
In certain patient groups, the benefits of NSAID use associated with cataract surgery may not have an abundance of evidence, but surgeons feel strongly that it could help cut the risk for CME. This includes patients with diabetes; in fact, the European Society for Cataract and Refractive Surgeons is leading a multicenter trial called PREMED (PREvention of Macular EDema after cataract surgery) to assess the better prophylactic regime for this group, Dr. Kessel said.
Other patients considered high risk who may benefit from NSAIDs include those with previous retinal vein occlusions, those with epiretinal membranes, and those with uveitis, Dr. Kessel said.
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 uveitis patients, there is no compelling evidence that they have a role since they have a much weaker anti-inflammatory 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 cataract 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 effective when started before surgery, although just how long before surgery is not clear,” Dr. Dunn said. “If one follows the same principles that apply for corticosteroids, it probably 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., potentially making compliance and administration easier. There is no evidence to date that intracameral ketorolac provides a synergistic effect 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 clinical trials for this area. One recent meta-analysis focusing on topical NSAID safety found that topical piroxicam had fewer adverse effects than bromfenac, diclofenac, flurbiprofen, 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 reports of corneal melting and allergic reactions, Dr. Kim said. However, corneal melting was far more common 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 ocular 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 prescribes 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 surgery, in addition to topical NSAIDs?
“There potentially could be, but we don’t have evidence to demonstrate this,” Dr. Kim said. “We do know oral NSAIDs are much less effective in getting into the anterior chamber of the eye. Topical application achieves much higher levels of drug in the aqueous.”
“There are no good data comparing 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 corticosteroids, 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 immunosuppressants and oral nonsteroidals. 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 surgery explicitly exclude concomitant oral NSAID use.
1. Kim SJ, et al. Topical nonsteroidal anti-inflammatory drugs and cataract surgery: A report by the American Academy of Ophthalmology. Ophthalmology. 2015;122:2159–68.
2. Lim BX, et al. Prophylactic non-steroidal anti-inflammatory drugs for the prevention 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-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2017 Jan 27 [epub ahead of print].
Editors’ note: Dr. Sheppard has financial interests with Alcon (Fort Worth, Texas), Allergan (Irvine, California), Bausch + Lomb (Bridgewater, New Jersey), and other ophthalmic companies. The other physicians interviewed have no financial interests related to their comments.