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

Topic: 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. Clinical Relevance: No standard of care regimen exists for the management of pain resulting from IVIs. Methods: 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 post-procedural 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. Results: 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. Discussion: 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. (C) 2020 by the American Academy of Ophthalmology