Long term evaluation of the safety and efficacy of local cooling anesthesia during intravitreal injections: The COOL-2 Trial

Abstract

Background/Objective To evaluate the safety and effectiveness of a medical device providing cooling anesthesia to the eye as local anesthesia for intravitreal (IVT) injections. Subjects/Methods As a multicenter, open label, dose escalation clinical trial, subjects receiving at least 3 IVT injections in the study eye were recruited to participate. All patients received subconjunctival lidocaine as their anesthesia for previous IVT injections. Subjects receiving IVT injections were assigned (non-randomized) to four groups in which the cooling device was applied to the conjunctiva at the location of the intravitreal injection: Group 1: −10˚C for 20 seconds; Group 2: −15˚C for 10 seconds; Group 3: −15˚C for 15 seconds; and Group 4: −15˚C for 20 seconds. The primary outcome was pain during IVT injection assessed by a visual analog scale (0–10). Results Eighty subjects were enrolled at 2 sites. The mean number of prior IVT injections was 20.3 for Group 2 and 15.0 for Group 3. Pain was significantly less for the 10 second vs the 15 second application (2.2 vs 3.6, p = 0.0255). The mean pain score was lower for Group 2 (−15°C for 10 seconds) ranging a score of 1.0 to 2.9 across the study visits, compared with Group 3 (−15°C for 15 seconds) with a mean range of 3.2 to 5.2 across the study visits. Treatment order (visit) significantly decreased by 0.10 pain units per visit (p = 0.0002). Punctate epithelial erosions (PEE) were reported in 20 of 56 eyes (35.7%) in Group 2, none were reported in Group 3. Conclusion Cooling anesthesia device reduced the severity of pain associated with IVT injection during the procedure, although mild and transient PEE may be associated with treatment. Trial registration ClinicalTrials.gov identifier, NCT03956797 .