Cooling Anesthesia for Intravitreal Injection: Results of the Prospective Open-Label, Dose-Ranging COOL-1 Trial

Daniel L Chao,1 Nicolas T Rinella,1 Arshad M Khanani,2 Charles C Wykoff,3 Gun-Ho Kim4,5 1Viterbi Family Department of Ophthalmology, University of California, San Diego, CA, USA; 2Sierra Eye Associates and University of Nevada, Reno School of Medicine, Reno, NV, USA; 3Retina Consultants of Texas, Retina Consultants of America; Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Houston, TX, USA; 4RecensMedical, Ulsan, Korea; 5Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, KoreaCorrespondence: Daniel L Chao; Gun-Ho Kim Tel +1- 858-534-6290; +82 31 8043 3036Email Daniel.chao3@gmail.com; gunho.kim@recensmedical.comPurpose: To evaluate the safety and efficacy of a novel medical device to provide cooling anesthesia to the eye as local anesthesia for intravitreal injections.Study Design: First in human, open-label study of 43 subjects assessed at three different doses: − 10°C for 20 seconds (group 1), − 15°C for 15 seconds (group 2), and − 15°C for 20 seconds (group 3). Main outcome measures were safety and pain of injection using a numeric rating scale (NRS).Results: Cooling anesthesia did not result in any serious ocular adverse events. One grade 1 adverse event was a vasovagal response during cooling administration which resolved immediately after cooling. Mean NRS scores at the time of injection for each group ranged from 2.5 to 4.3 There was a statistically significant difference between pain scores of the 3 groups at injection in aggregate but not in pairwise comparisons (P value = 0.047). There was a statistically significant decrease in pain from injection to 5 minutes post injection in all groups (P value = 0.00008, 0.003, 0.0005 for groups 1, 2, 3, respectively) as well as from 5 minutes to 24– 48 hours (P value = 0.00001, 0.018, and 0.0545 for groups 1, 2, 3, respectively).Conclusion: The rapid cooling anesthesia device was well tolerated for achieving local anesthesia among patients receiving intravitreal injections with no serious ocular adverse events.Keywords: intravitreal injection, anesthesia, cooling, pain