Tool offers ultra-rapid cooling for intravitreal injections

Digital Edition, Ophthalmology Times: February 1, 2021, Volume 46, Issue 2

Precision injection device can improve patient and physician experiences.

This article was reviewed by Cagri G. Besirli, MD, PhD

An innovative approach to anesthesia used in conjunction with intravitreal injections (IVTs) provides rapid anesthesia to cool the ocular surface and is comparable to topical lidocaine treatment.

A novel portable device is under development by iRenix Medical, Inc. to focally cool the ocular tissue and provide rapid anesthesia for IVTs with enhanced pain control and patient comfort.

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In retinas, several million IVTs are administered annually due to the success of anti-vascular endothelial growth factor therapies for a number of retinal diseases. So, making this procedure as anxiety-free as possible for patients and physicians is a clear goal.

According to Cagri G. Besirli, MD, PhD, an associate professor in the Department of Ophthalmology and Visual Sciences at the University of Michigan in Ann Arbor, the patient experience during IVTs was cited by the vast majority of physicians as the primary reason physicians opt for a particular method anesthesia, and about three-quarters of physicians have reported having patients request a different or additional form of anesthesia.

Current anesthesia methods are associated with a number of disadvantages, namely, less-than-optimal pain control, which prompted Besirli and his colleagues to look for a better solution.

“A potential method of providing ocular anesthesia is by cooling, which provides complete nerve conduction block between 0 °C and 8 °C,” Besirli said.

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Besirli and his colleagues performed a preclinical safety study of ultra-rapid nonpharmacologic anesthesia for IVTs in rabbit eyes and found no histologic evidence of damage to the ocular tissues with temperatures as low as –30 °C for as long as 30 seconds.

Investigators then developed a portable, battery-operated, hand-held thermoelectric cooling device that provided ultrarapid cooling ocular anesthesia in 10 to 20 seconds. The device is equipped with a single-use disposable tip.


Phase 1 trial of novel device

According to Besirli, an investigator-initiated, single-center, dose-ranging safety study (NCT02872012) tested the safety, efficacy, and optimal treatment parameters of this novel device compared to standard-of-care lidocaine-based anesthesia.1

Initially, 23 participants were enrolled. After 1 individual declined to participate, 44 eyes of 22 participants (mean age, 71 years; 16 women, 6 men) were randomly given cooling anesthesia in 1 eye and standard-of-care treatment in the fellow eye.

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Within the cooling anesthesia group, different temperatures were tested for different time periods in contact with the ocular surface (ie, –5 °C for 10 seconds and 20 seconds, –7 °C for 20 seconds, and –10 °C for 10 seconds and 20 seconds.) The patients were followed for 1 week.

The primary outcome of the trial was the safety of cooling anesthesia and the secondary outcomes were pain reported by the participants at the time of injection and pain at 4 hours after the injection. The participants had received an average of 29 previous injections before this study.

Besirli reported that this first-in-human trial met the primary outcome of safety with no evidence of cooling dose-related toxicity, no discomfort with the cooling applicator, and rare transient adverse effects associated with the use of povidone-iodine.

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Sixty-seven percent of participants had no ocular adverse effects in the cooling anesthesia eyes compared with 53% in the lidocaine-treated eyes.

The best pain scores measured on a scale of 1 to 10 were 2.2 in the cooling anesthesia group that received –10 °C for 10 or 20 seconds, which was comparable to the standard-of-care group at 2.3.

This result suggested that better pain control was achieved at cooler temperatures and slightly longer exposure times.

The pain scores measured at the 4-hour time point in the group treated with –10° C for 20 seconds was significantly (P = 0.02) lower than the control group, and the time to anesthesia was decreased significantly (P <.0001) by 4.5 minutes per participant in the focal cooling arms.

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Besirli concluded that the first human phase 1 randomly selected controlled trial of cooling anesthesia showed that the procedure was safe, tolerable, and efficacious.

A new, all-in-one anesthesia and automated injection device was developed and currently is in clinical trials.

Read more retina content

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Cagri G. Besirli, MD, PhD
E: cbesirli@med.umich.edu
Besirli holds equity in and receives consulting fees from iRenix Medical, Inc.

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Reference

1. Besirli CG, Smith SJ, Zacks DN, et al. Ophthalmol Retina. 2020;4(10):979–986. doi:10.1016/j.oret.2020.04.001G