Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery

Background: Cataract is a leading cause of blindness worldwide. Cataract surgery is commonly performed but can result in postoperative inflammation of the eye. Inadequately controlled inflammation increases the risk of complications. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used to prevent and reduce inflammation following cataract surgery, but these two drug classes work by different mechanisms. Corticosteroids are effective, but NSAIDs may provide an additional benefit to reduce inflammation when given in combination with corticosteroids. A comparison of NSAIDs to corticosteroids alone or combination therapy with these two anti-inflammatory agents will help to determine the role of NSAIDs in controlling inflammation after routine cataract surgery. Objectives: To evaluate the comparative effectiveness of topical NSAIDs (alone or in combination with topical corticosteroids) versus topical corticosteroids alone in controlling intraocular inflammation after uncomplicated phacoemulsification. To assess postoperative best-corrected visual acuity (BCVA), patient-reported discomfort, symptoms, or complications (such as elevation of IOP), and cost-effectiveness with the use of postoperative NSAIDs or corticosteroids. Search methods: To identify studies relevant to this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2016, Issue 12), MEDLINE Ovid (1946 to December 2016), Embase Ovid (1947 to 16 December 2016), PubMed (1948 to December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 16 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 17 June 2013), ClinicalTrials.gov (www.clinicaltrials.gov; searched December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched December 2016). Selection criteria: We included randomized controlled trials (RCTs) in which participants were undergoing phacoemulsification for uncomplicated cataract extraction. We included both trials in which topical NSAIDs were compared with topical corticosteroids and trials in which combination therapy (topical NSAIDs and corticosteroids) was compared with topical corticosteroids alone. The primary outcomes for this review were inflammation and best-corrected visual acuity (BCVA). Data collection and analysis: Two review authors independently screened the full-text articles, extracted data from included trials, and assessed included trials for risk of bias according to Cochrane standards. The two review authors resolved any disagreements by discussion. We graded the certainty of the evidence using GRADE. Main results: This review included 48 RCTs conducted in 17 different countries and two ongoing studies. Ten included studies had a trial registry record. Fifteen studies compared an NSAID with a corticosteroid alone, and 19 studies compared a combination of an NSAID plus a corticosteroid with a corticosteroid alone. Fourteen other studies had more than two study arms. Overall, we judged the studies to be at unclear risk of bias. NSAIDs alone versus corticosteroids alone None of the included studies reported postoperative intraocular inflammation in terms of cells and flare as a dichotomous variable. Inflammation was reported as a continuous variable in seven studies. There was moderate-certainty evidence of no difference in mean cell value in the participants receiving an NSAID compared with the participants receiving a corticosteroid (mean difference (MD) -0.60, 95% confidence interval (CI) -2.19 to 0.99), and there was low-certainty evidence that the mean flare value was lower in the group receiving NSAIDs (MD -13.74, 95% CI -21.45 to -6.04). Only one study reported on corneal edema at one week postoperatively and there was uncertainty as to whether the risk of edema was higher or lower in the group that received NSAIDs (risk ratio (RR) 0.77, 95% CI 0.26 to 2.29). No included studies reported BCVA as a dichotomous outcome and no study reported time to cessation of treatment. None of the included studies reported the proportion of eyes with cystoid macular edema (CME) at one week postoperatively. Based on four RCTs that reported CME at one month, we found low-certainty evidence that participants treated with an NSAID alone had a lower risk of developing CME compared with those treated with a corticosteroid alone (RR 0.26, 95% CI 0.17 to 0.41). No studies reported on other adverse events or economic outcomes. NSAIDs plus corticosteroids versus corticosteroids alone No study described intraocular inflammation in terms of cells and flare as a dichotomous variable and there was not enough continuous data for anterior chamber cell and flare to perform a meta-analysis. One study reported presence of corneal edema at various times. Postoperative treatment with neither a combination treatment with a NSAID plus corticosteroid or with corticosteroid alone was favored (RR 1.07, 95% CI 0.98 to 1.16). We judged this study to have high risk of reporting bias, and the certainty of the evidence was downgraded to moderate. No included study reported the proportion of participants with BCVA better than 20/40 at one week postoperatively or reported time to cessation of treatment. Only one included study reported on the presence of CME at one week after surgery and one study reported on CME at two weeks after surgery. After combining findings from these two studies, we estimated with low-certainty evidence that there was a lower risk of CME in the group that received NSAIDs plus corticosteroids (RR 0.17, 95% CI 0.03 to 0.97). Seven RCTs reported the proportion of participants with CME at one month postoperatively; however there was low-certainty evidence of a lower risk of CME in participants receiving an NSAID plus a corticosteroid compared with those receiving a corticosteroid alone (RR 0.50, 95% CI 0.23 to 1.06). The few adverse events reported were due to phacoemulsification rather than the eye drops. Authors' conclusions: We found insufficient evidence from this review to inform practice for treatment of postoperative inflammation after uncomplicated phacoemulsification. Based on the RCTs included in this review, we could not conclude the equivalence or superiority of NSAIDs with or without corticosteroids versus corticosteroids alone. There may be some risk reduction of CME in the NSAID-alone group and the combination of NSAID plus corticosteroid group. Future RCTs on these interventions should standardize the type of medication used, dosing, and treatment regimen; data should be collected and presented using the Standardization of Uveitis Nomenclature (SUN) outcome measures so that dichotomous outcomes can be analyzed.