Which quadrant is less painful for intravitreal injection? A prospective study

Purpose: To evaluate the relationship between injection site and pain severity following intravitreal injection of bevacizumab (IVB). Design: Prospective, randomized, four-armed, clinical trial. Methods: The present study was a prospective, randomized, four-armed clinical trial, which included 1004 eyes from 1004 patients. Patients receiving IVB were randomly assigned into four groups: superotemporal (ST); superonasal (SN); inferotemporal (IT); and inferonasal (IN) injections. The visual analog scale (VAS) was used to assess pain. Primary study variables were the relationship between pain severity and injection site, number of previous injections, age, sex, and indication for injection. Secondary variables included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes 1 month post IVB. Results: Overall mean pain score was 2.86 +/- 2.2. Indications for injection were diabetic macular edema (84.1%), neovascular age-related macular degeneration (7.7%), and macular edema secondary to retinal vein occlusion (8.2%). The mean VAS scores in the SN, IN, ST, and IT groups were 1.5 +/- 1.7, 3 +/- 2.3, 4 +/- 2, and 3 +/- 2.1, respectively. Pain severity was significantly correlated with injection site (p < 0.001) and sex (p < 0.001); females showed higher pain scores. A negative correlation existed between pain score and number of previous injections (p = 0.03). Pain severity was not associated with age (p = 0.659), lens status (p = 0.478), vitreous reflux (p = 0.648), or indication for injection (p = 0.390). No significant complications were observed. Conclusions: ST quadrant was the most painful and SN quadrant was the least painful sites for IVB. Pain severity score was significantly associated with injection site, number of injections, and sex.