Evaluating the effectiveness of different topical anesthetic methods in reducing pain during intravitreal injections: a systematic review and meta-analysis

BACKGROUND: The rapid rise in intravitreal injections (IVIs) for vitreoretinal disorders underscores the need to optimize the procedure and support long-term patient compliance. Patient-reported pain and discomfort remain significant barriers to adherence. This systematic review evaluates the efficacy and safety of various local anesthetic methods for mitigating pain during IVIs. METHODS: Conducted in accordance with PRISMA guidelines, a comprehensive search of PubMed and Google Scholar was performed to identify English-language randomized controlled trials (RCTs). Eligible studies included patients aged 18 years and older receiving local anesthesia for IVIs, where pain was quantified using standard visual or oral analog scales (0-10 or 0-100). RESULTS: Our systematic review and meta-analysis included 14 RCTs comprising 1,300 patients. Analysis of topical lidocaine, tetracaine, and proparacaine formulations showed comparable analgesic efficacy, with all agents consistently achieving mild mean Visual Analog Scale (VAS) pain scores. No clinically meaningful superiority was identified among these primary agents (p = 0.62). Adjunctive therapies, particularly physical cooling (e.g., ice patches), demonstrated significant pain-reducing potential. While oxybuprocaine alone was less effective, its combination with physical cooling achieved the lowest mean pain scores. Meanwhile, topical NSAIDs showed limited additional benefit. Regarding safety, subconjunctival anesthetic injections were associated with a significantly higher incidence of subconjunctival hemorrhage and chemosis compared to topical applications, suggesting that topical strategies provide a favorable safety and efficacy profile for routine intravitreal injections. CONCLUSION: In conclusion, this systematic review and meta-analysis confirms that no single topical anesthetic is superior for intravitreal injections; all primary agents provide comparable, effective pain control. Topical application is safer than subconjunctival injection, which is associated with higher rates of hemorrhage and chemosis. Consequently, clinical protocols should standardize low-risk topical methods and incorporate simple non-pharmacological adjuncts, such as physical cooling, to optimize patient comfort.