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

Methodological quality of the review: High confidence

Author: Duan P, Liu Y, Li J.

Region: Not reported

Sector: Cataract surgery

Sub-sector: Anti-inflammatory drugs

Type of cataract: Age-related cataract

Equity focus: None specified

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of anti-inflammatory drugs that are used in ophthalmologic surgery. These drugs do not have a steroid structure, but can inhibit surgery-induced miosis, anterior chamber inflammation, and cystoid macular edema (CME). However, the application of NSAIDs remains controversial.

Research objectives:

To assess the efficacy and safety of NSAIDs for the treatment of anterior chamber inflammation after cataract surgery.

Main findings:

The authors identified a total of 1,127 unique documents, of which 19 studies were included in the review. These were published between 1987 and 2015. The average subject age ranged 65 to 75, and more woman were included in the trials compared to men. All patients had received cataract surgery with posterior chamber intraocular lens implantations, except for one study. Overall most included studies were attributed low risk of bias by the authors.

Authors report that in pair-wise comparisons, bromfenac was significantly inferior to nepafenac (logOR: −0.58; 95% confidence interval (CI): −1.11 to −0.05). Bromfenac was significantly superior to the placebo indirect and network comparisons (logOR: 1.04; 95% CI: 0.62 to 1.46). Diclofenac was superior to flurbiprofen in indirect (logOR: 1.38; 95% CI: 0.21 to 2.55) and network comparisons (logOR: 0.98; 95% CI: 0.06 to 1.90).

Diclofenac was also superior to the placebo in direct (logOR: 2.19; 95% CI: 1.26 to 3.13) and network comparisons (logOR: 1.94; 95% CI: 1.13 to 2.75). Flurbiprofen was significantly better than the placebo for controlling ocular inflammation in all comparisons (network: logOR 0.96; 95% CI: 0.29 to 1.62). Ketorolac showed a significant advantage over the placebo in the network comparison (logOR: 1.31; 95% CI: 0.80 to 1.82), as did nepafenac (logOR: 1.63; 95% CI: 1.30 to 1.95). Authors note that although the quality of the network data for diclofenac is low, the results are robust as the overall quality of the studies is high.

Based on the funnel plot analysis, authors report that no publication bias was detected.

Methodology:

The studies included in this meta-analysis met the following criteria: (1) the study had a blinded, randomized controlled trial (RCT) design, where one group was treated with NSAIDs and another group was treated with a blank, placebo, or alternate NSAID; (2) the study included patients after cataract surgery; (3) the patients received anti-inflammatory treatment after surgery; and (4) one of the following outcomes was included in the study: anterior chamber inflammation, ocular pain relief, or treatment- related/serious ocular adverse events. The exclusion criteria included the following: (1) non-cataract surgery studies; (2) steroid drug-related studies and experimental/control groups combined with steroid drug therapy; (3) anesthesia related studies; (4) surgical method-related studies; and (5) undesired outcome studies. Reviews, case reports, conference reports, basic research, and editorial comments were also excluded.

Two authors independently conducted a search on electronic databases including PubMed, Embase and the Cochrane library. The bibliographies and references of included studies were screened for further relevant studies. Two authors independently extracted data of included studies and assessed the methodological quality of included trials using the Cochrane Collaboration tool. Reviewers also used the GRADE approach to assess the network meta-analysis quality.

Authors performed a meta-analysis using random-effects model for mixed multiple treatment comparisons. Comparison adjusted funnel plots were used to determine whether small-study effects were present in their analysis.

Applicability/external validity:

Authors note that as one of the limitations of this review, authors only included inflammation-related outcomes and the effects on CME remain controversial. In addition, they also note that their analysis had unexplained heterogeneity and global inconsistency, which then resulted in differences in the administered doses, operation processes, concomitant treatments or follow-up durations.

Geographic focus:

Authors did not report the geographic focus of the studies included in the review.

Quality assessment:

Overall, high confidence was attributed in the conclusion about the effects of this study. Authors used appropriate methods to conduct the review in terms of searching for literature, extract data and assess the methodological quality of the included trials.