Cooling anesthesia a safe, effective alternative to subconjunctival lidocaine


How this method of anesthesia may provide benefits to both the patient and physician

Cooling anesthesia a safe, effective alternative to subconjunctival lidocaine

Cooling anesthesia applied at -15°C for 10 to 15 seconds before intravitreal (IVT) injection is safe and effective over repeated administration and may improve the patient experience as compared with standard-of-care subconjunctival lidocaine, according to a study presented during the 2020 American Society of Retina Specialists virtual annual meeting.

Daniel L. Chao, MD, PhD, Shiley Eye Institute, UC San Diego Health, presented data from the ongoing COOL-2 trial (NCT03956797), a multicenter, open-label study evaluating the safety and efficacy of repeated cooling anesthesia administration before IVT injections.

“As retina specialists, we understand that anesthesia for IVT injection strongly influences the patient experience,” Chao said. “Each of the commonly used forms of anesthesia has various benefits and tradeoffs in terms of patient comfort and speed of onset of anesthesia.”

Currently, anesthesia preference is split among retina specialists in the United States.1 Further, studies have not determined which type of anesthesia is better for pain control, with scores ranging from 0.8 to 4.4 on a zero to 10 pain scale.2

During the discussion, David Chow, University of Toronto and co-founder of the Canadian Retina Society, told attendees the key to the study was its format: “treatment was topical anesthetic followed by betadine, insertion of a lid speculum and then a prototype cooling gun, with a disposable tip applied to the limbus with a 3.5 mm contact zone for 10-15s. The researchers then reintroduced betadine and then injected the intravitreal drug within 30 seconds of the cooling application before the cooling effect wears off.”

Study design

Cooling anesthesia is a rapid, nonpharmacologic form of anesthesia applied between -10°C and -20°C. The concept was introduced as part of a case report using gloved ice as anesthesia in a patient allergic to lidocaine.3 The COOL-1 trial (n=40) demonstrated the proof of concept of a clinical-grade cooling device in humans.

COOL-2 trial enrollment is ongoing. A total of 54 patients (56% women, mean age 72) have enrolled so far, with a combined 289 applications applied. The majority of patients have age-related macular degeneration (51%), followed by diabetic macular edema(28%), retinal vein occlusion (19%), and myopic choroidal neovascularization (2%).

To be included in the trial, patients needed a history of at least three prior IVTs (mean, 18 prior injections), but no prior history of ocular inflammation or retinal surgery. The cooling anesthesia was applied in lieu of their regular anesthesia at -15°C but for different lengths of time (10 seconds versus 15 seconds, 38 patients versus 16 patients, respectively). Patients received cooling anesthesia for their next six IVT injections. Pain was assessed at injection and 5 minutes post-injection. Researchers documented any adverse events and noted patient-reported preference for anesthesia type.


Cooling anesthesia was well tolerated with no serious ocular adverse events described, but two patients did report mild ocular pain. Importantly, pain scores did not change with time with cooling anesthesia and were similar compared to historical controls, with no statistically significant difference between them.

Although the pain scores were largely the same, the overwhelming majority of patients who received -15°C cooling anesthesia for 10 seconds preferred that numbing approach over subconjunctival lidocaine (82%). Patients in the 15-second cooling anesthesia group preferred it as well, but at a lesser rate (52% versus 39%).

“Cooling anesthesia may represent an alternative method of anesthesia, which may provide benefits to both the patient and physician,” Chao concluded. “A multicenter randomized pivotal trial is planned to start later this year.”

Clinical implications

Chow acknowledged the authors “basically showed that the cooling anesthesia was not significantly different from the historical control of anesthesia for intravitreal injections,” but wondered how to know what the true effect of adding cooling anesthesia is.

“We feel that the majority of the effect on a benefit of the cooling device is not related to that single drop of proparacaine, but that will be investigated in future clinical studies,” Chao said. “Now, in terms of what actually might be the benefit of cooling anesthesia, we really think it's part of this more unquantifiable aspect of the patient and physician experience in which there might be the benefit. We don't think necessarily that the cooling anesthesia is providing superior pain control at the time of injection, but because of some unique aspects, in terms of the rapid onset of anesthesia, the ability to perform the injection right after anesthesia, that these may have unique benefits for both the patient and physician alike.”

For instance, he said patients have “really gravitated” toward not having to wait for the physician to return for the injection, and they feel as though they recover quicker from the anesthetics compared with other methods.

Daniel L. Chao, MD, PhD
Chao is a consultant for Recens Medical, a sponsor of the COOL-2 study.
  1. Chaturvedi R, Wannamaker KW, Riviere PJ, Khanani AM, Wykoff CC, Chao DL. Real-World Trends in Intravitreal Injection Practices among American Retina Specialists. Ophthalmol Retina. 2019;3(8):656-662.
  2. Shiroma HF, Takaschima AKK, Farah ME, et al. Patient pain during intravitreal injections under topical anesthesia: a systematic review. Int J Retina Vitreous. 2017;3:23.
  3. Lindsell LB, Miller DM, Brown JL. Use of topical ice for local anesthesia for intravitreal injections. JAMA Ophthalmol. 2014;132(8):1010-1011.
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