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

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.