Controlled trial identifies limited benefits of adjunctive NSAIDs

July 17, 2019

Research does not support routine use to decrease the risk of PCME

A randomized trial found adding a topical NSAID to a topical corticosteroid reduced pain and inflammation compared with corticosteroid treatment alone. A benefit for reducing cystoid macular edema was seen only in at-risk patients.

Reviewed by Sean J. McCafferty, MD

Results of a large prospective, randomly selected trial provide insight on the benefits and role of adjunctive topical nonsteroidal anti-inflammatory drug (NSAID) use in the postoperative medication regimen for patients undergoing cataract surgery. Without industry support, Sean J. McCafferty, MD, and colleagues at Arizona Eye Consultants, Tucson, undertook the ambitious Arizona Surgical Eye Study (ASES).

Outcomes showed that the addition of a topical NSAID to a corticosteroid after cataract surgery significantly reduced the incidence of pain and inflammation at one and six weeks after cataract surgery.

Limited benefit

A benefit for preventing pseudophakic cystoid macular edema (PCME) was seen only in patients with risk factors for that complication. There were no differences between patients who used the combination treatment versus a corticosteroid alone with respect to macular edema, endothelial cell loss, BCVA outcomes, capsular phimosis, or two- and four-year YAG capsulotomy rates, said Dr. McCafferty, founder, Arizona Eye Consultants, and clinical assistant professor, University of Arizona College of Medicine and College of Optical Science, Tucson.

“A survey conducted prior to designing the study showed that the primary reason most cataract surgeons were prescribing a topical NSAID was to reduce the risk of PCME, which is off-label use,” he said. “These medications are indicated for decreasing postoperative inflammation and pain, but they have also been touted for decreasing posterior capsule opacification, capsular phimosis, and endothelial cell loss.”

Dr. McCafferty noted that adding a topical NSAID to corticosteroid treatment after cataract surgery adds cost and can cause discomfort for patients.

“Whether it brings any real benefit for these offlabel uses has been a nagging question,” he said. “Results of our study confirm its efficacy for decreasing inflammation and pain, but do not support its routine use to decrease the risk of PCME or for any other of the described reasons.”

Dr. McCafferty said that, based on the findings of the ASES, he is routinely prescribing a topical NSAID for postoperative use only for patients who have one of the PCME risk factors that was identified in the trial. The ASES included 1000 eyes that were randomized to blinded treatment with placebo or nepafenac 0.3% (Ilevro, Alcon Laboratories) once daily for four weeks.

“A very large sample size was needed to identify differences between treatment groups for the various endpoints,” Dr. McCafferty explained. “The study was designed to evaluate a single NSAID product to avoid having multiple arms and an even larger population.”

Outcomes

Postoperative inflammation was evaluated at one and six weeks after surgery based on cell/flare scores. Mean scores at both visits were low in both study groups, but there was a significant benefit for adjunctive NSAID use.

The analyses of PCME incidence showed a statistically significant benefit of adding topical nepafenac to the corticosteroid in the overall study population. Analyses after stratification of patients based on the absence or presence of purported PCME risk factors showed the rate of PCME was approximately four-fold higher in the subgroup with risk factors versus the subgroup without and that use of topical nepafenac had a significant benefit for reducing risk only in the subgroup with risk factors. The data were also analyzed to determine the association between different clinical variables and risk of PCME.

RELATED: Tonometry can serve as tool in CME preventionThe results showed that a history of PCME in the fellow eye was the most powerful predictor, increasing the risk of PCME 20-fold. Diabetic retinopathy and vein occlusion were each associated with an approximately 13-fold increase in risk of PCME.

Having a macular hole increased the risk almost eight-fold and epiretinal membrane was associated with an approximately six-fold increase in risk. Use of a prostaglandin analogue or macular degeneration did not affect the risk of PCME.

“The lack of an association with prostaglandin analogue use was interesting but also consistent with the findings of a retrospective study that included 40,000 patients,” Dr. McCafferty commented.

Patients enrolled in the study were also asked to complete the Comparison of Ophthalmic Medications for Tolerability (COMTol) questionnaire. Analyses of the collected data showed a statistically significant benefit of the topical NSAID for reducing browache and tearing.

There were no differences between study groups in analyses of any of the other items included in the questionnaire. The results of an ESCRS-sponsored European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics in which adjunctive NSAID treatment had benefit for reducing clinically significant CME in nondiabetic patients [Wielders LHP, et al. ESCRS PREMED Study Group. J Cataract Refract Surg. 2018;44:429-439.].

Offering a possible explanation for the difference, Dr. McCafferty suggested it may be related to the use of different corticosteroids.

“The ESCRS study used dexamethasone 0.1%, and it has lower ocular tissue penetration than prednisolone acetate 1% that was used in the ASES and is more commonly used in the United States,” he said.

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Disclosures:

Sean J. McCafferty, MD
E: sjmccafferty@hotmail.com
Dr. McCafferty has no relevant financial interests to disclose.