The safety and effectiveness of anesthetic drops for intravitreal drug administration: a meta-analysis

Intravitreal injections (IVI) are increasingly performed for the management of retinal diseases, yet procedural discomfort remains a common concern. Topical anesthetic drops are frequently used to mitigate pain, but evidence regarding their safety and efficacy compared with alternative anesthetic modalities, such as gels or subconjunctival injections, remains heterogeneous and limited.

To systematically evaluate the safety and effectiveness of topical anesthetic drops for intravitreal drug administration, with a focus on patient-reported pain, procedural discomfort, and satisfaction compared with other anesthetic methods.

A systematic literature search was conducted through PubMed, Scopus, EMBASE, ClinicalTrials.gov, and other databases through October 2025. Eligible studies included clinical studies comparing topical anesthetic drops for IVI with other topical anesthetic agents.

Eight studies comprising 637 eyes were included. Topical anesthetic drops demonstrated analgesic efficacy comparable to anesthetic gels and subconjunctival anesthesia, with no statistically significant differences in post-injection pain (SMD -0.11, 95% CI; -0.27 to 0.05, p = 0.18), burning sensation (RR 0.77, 95% CI: 0.56, 1.06, p = 0.11), or overall patient satisfaction (MD -0.09, 95% CI -0.30 to 0.13, p = 0.43). Subgroup analyses confirmed consistent results across different formulations and delivery methods.

Topical anesthetic drops are a safe, effective, and well-tolerated option for IVI, providing analgesia comparable to gels and subconjunctival anesthesia. Their rapid onset and ease of administration support their use as a first-line anesthetic strategy in routine clinical practice, particularly in high-volume injection settings. Further high-quality randomized trials are warranted to confirm these findings across diverse patient populations and clinical contexts.