Topical Nonsteroidal Anti-inflammatory Drugs for Pain Resulting from Intravitreal Injections: A Meta-Analysis

The role of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of ocular pain after intravitreal injections (IVIs) has been explored. To provide clarity on the evidence for these agents, the present meta-analysis of randomized controlled trials (RCTs) was undertaken.

No standard of care regimen exists for the management of pain resulting from IVIs.

A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central from inception through July 2019. The RCTs that treated patients with a topical NSAID and assessed postprocedural pain were included. Risk of bias was assessed using the Cochrane guidelines. For all analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were reported. Random effects models were used for all analyses. The primary analysis analyzed pain on a 0- to 10-point visual analog scale. Literature estimates were categorized into the following postprocedure time point groups: 1 hour or less, 1 to 24 hours (although data were available only at 6 hours), and 24 hours or more. A subgroup analysis stratified studies based on agent and preprocedure versus postprocedure administration.

From 241 results, 9 RCTs and 598 eyes were included. A low to medium risk of bias was found across the included studies. The mean pain score on a 0-to-10 visual analog scale was significantly lower after topical NSAID administration relative to control at 1 hour or less after IVI (WMD, -1.01 units; 95% CI, -1.38 to -0.65; P < 0.001), 6 hours after IVI (WMD, -2.17 units; 95% CI, -2.67 to -1.68; P < 0.001; threshold met for clinical significance, defined as WMD >1.2 units), and more than 24 hours after IVI (WMD, -0.75 units; 95% CI, -1.11 to -0.38; P < 0.001). A greater effect size was seen with administration of NSAIDs before versus after IVI, as well as topical nepafenac relative to ketorolac or diclofenac.

At 6 hours after the procedure, NSAIDs provide a clinically meaningful reduction in pain relative to a control group. The administration of NSAIDs before the procedure, specifically topical nepafenac, was associated with the greatest improvement in pain relative to the control group.