Written by Cagri Besirli, MD, PhD, Department of Ophthalmology and Visual Sciences (University of Michigan)
Intravitreal treatment has been transformative, saving vision for millions of
patients. The success of anti-VEGF drugs, aging population, diabetes epidemic, and increasing indications have led to a dramatic growth in the number of injections performed, increasing from less than 50,000 a year in the early 2000s to an estimated 6 million injections in 2017.
Current methods of pharmacologic ocular anesthesia used prior to intravitreal injections have several drawbacks, including the need for two patient encounters (the first to administer anesthesia and the second 5-15 minutes later after anesthesia has had time to work), corneal toxicity with blurred vision, and increased rate of hemorrhage seen with subconjunctival lidocaine. In addition, there is concern that certain forms of anesthesia, particularly lidocaine gel and viscous lidocaine drops, may result in suboptimal antiseptic access to the ocular surface, which could theoretically increase the risk of endophthalmitis.
Administering an intravitreal injection safely requires a multi-step process. The anesthesia step is the longest phase and creates a bottleneck in intravitreal injection workflow. Therefore, there is an unmet need for a rapid, non-invasive anesthesia for intraocular injections. With this in mind, we developed focal cooling as a novel method of non-pharmacologic anesthesia to improve the patient experience. To provide focal cooling on the ocular surface, we designed a portable, battery operated device with a single-use, sterile tip that rapidly cools the ocular surface within 10-20 seconds, temporarily halting nerve conduction. There is a wealth of literature showing that nerve conduction is stopped between 0-8 C, and the temperatures chosen for this study were done based on thermal modeling that showed the ability to achieve this temperature range in the sclera prior to an intravitreal injection.
To assess the safety and feasibility of focal cooling for ocular anesthesia, we performed a first-in-human feasibility trial. This was a single center, randomized, unmasked controlled trial that compared non-pharmacologic, ultra-rapid focal cooling to lidocaine-based standard of care anesthesia. The study included patients older than 18 years of age with a diagnosis of exudative age-related macular degeneration or diabetic macular edema requiring bilateral anti-VEGF therapy. One eye of each patient was randomized to the focal cooling treatment arm and the fellow eye was randomized to topical lidocaine (lidocaine gel or lidocaine-soaked cotton tipped applicators). The primary pain outcome was patient reported pain at the time of injection. The secondary pain outcome was post injection pain measured 4 hours post treatment.
The visual analog scale was used to measure injection and post-injection pain. We found effective pain control in the focal cooling groups, with increasing pain control with colder temperatures and longer treatment duration. Similar to injection pain, post-injection pain after non-pharmacologic anesthesia was similar to standard of care. This first-in-human study showed that focal cooling reduced the time patients spent waiting for the injection procedure by approximately 4.5 minutes, which represented a statistically significant improvement, and one that has considerable benefit for patient care.
The first-in-human trial shows that rapid, non-pharmacological anesthesia via focal cooling has the potential to transform the way intravitreal injections are delivered, dramatically improving the patient experience. This technology has now been exclusively licensed to iRenix Medical, with additional development and commercialization planned in the near future.
