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

Abstract Purpose To test the safety and preliminary efficacy of rapid, non-pharmacologic anesthesia via cooling for intravitreal injections. Design Single center, randomized, phase 1 dose-ranging safety study (NCT 02872012) Subjects : Adult subjects ≥ 18 years of age with a diagnosis of exudative macular degeneration or diabetic macular edema in both eyes requiring bilateral anti-VEGF therapy were included. Methods A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye immediately prior to intravitreal treatment (IVT). In 22 subjects undergoing bilateral IVT, one eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at one of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS, 1-10) at 2 timepoints: (1) immediately following IVT, and (2) 4 hours post-IVT. Treated eyes were assessed for ocular safety via biomicroscopic examination performed 24-hours post-IVT. Main Outcome Measures We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately post-IVT and 4-hours post-IVT in eyes receiving cooling anesthesia were compared to eyes receiving SOC. Results A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with lidocaine-based anesthesia. There was no dose-related toxicity with the application of cooling anesthesia. Mild, transient adverse events were recorded in 32% of subjects treated with cooling anesthesia versus 44% of subjects receiving SOC. VAS pain scores immediately following intravitreal injection were 2.3 ± 0.4 for subjects receiving SOC and 2.2 ± 0.6 in subjects receiving -10°C cooling anesthesia (P = 0.8, mean ± SEM). Four hour post-injection pain scores were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10°C treatment arms (P = 0.56, mean ± SEM).Total procedure time, including anesthesia and injection, was 124 ± 5 seconds for subjects treated with cooling anesthesia versus 395 ± 40 seconds for the SOC groups (P 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 statistically significant reduction in total procedure time.