Perception of pain during intravitreal injections: a clinical trial on the effect of entry site distance from the limbus on perceived pain

Intravitreal anti-vascular endothelial growth factor injections have become increasingly common over the last decade. Pain perception during these injections varies based on factors such as injection location, type of anesthetic, needle gauge, medication used, etc. However, no previous studies have evaluated pain perception at different injection locations in relation to the limbus. Enhancing patient experience during these procedures may improve long-term compliance to treatment. Thus, this study aimed to evaluate the relationship between pain perception and injection sites at varying distances from the limbus. This prospective, randomized, single-blinded, single-center study examined pain perception in patients receiving intravitreal injections for various ocular conditions. Each patient received two injections at either 3.5 or 4.0 mm from the limbus in the inferotemporal quadrant. The order of injection location was randomized, and patients were blinded to the injection site. Pain was assessed immediately after each injection using a visual analogue scale from 0 to 10. A paired-sample t-test was used to compare pain perception between injection sites, and a repeated measures multivariable linear regression model was applied to predict the effects of other variables on pain perception. A total of 53 patients were enrolled, receiving two injections. The overall mean pain score for all injections was 1.82 ± 1.64, ranging from 0 to 7. Injections administered 3.5 mm away from limbus had a slightly increased mean pain score (1.92 ± 1.64) compared to those at 4.0 mm away (1.72 ± 1.65), but this difference was not statistically significant (p = 0.45). Additional factors, including injection site location, age, gender, ethnicity, diabetic indications, number of prior injections, type of anesthesia, and medication type were not significant predictors of pain score during injections. Pain perception did not significantly differ between injections administered 3.5 mm and 4.0 mm away from the limbus. This study is the first to evaluate pain perception at varying injection distances relative to the limbus. Injection placement should be guided by physician preference and experience. This study was retrospectively registered on ClinicalTrials.gov on November 28, 2022 (ClinicalTrials.gov ID is NCT05640895).