Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.

PURPOSE:To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN:Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS:Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS:A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES:We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS:A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS:Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.