July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Preclinical safety study of ultra-rapid, non-pharmacologic anesthesia for intravitreal injections.
Author Affiliations & Notes
  • Stephen Smith
    Ophthalmology, Stanford University, Mountain View, California, United States
  • Gunho Kim
    Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, United States
  • Kevin P. Pipe
    Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, United States
  • Cagri Besirli
    Ophthalmology, University of Michigan, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Stephen Smith, iRenix (C), iRenix (P), iRenix Inc (I); Gunho Kim, iRenix Inc (P); Kevin Pipe, iRenix Inc (I), iRenix Inc (C), iRenix Inc (P); Cagri Besirli, iRenix Inc (I), iRenix Inc (C), iRenix Inc (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2451. doi:https://doi.org/
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      Stephen Smith, Gunho Kim, Kevin P. Pipe, Cagri Besirli; Preclinical safety study of ultra-rapid, non-pharmacologic anesthesia for intravitreal injections.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2451. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Intravitreal injection treatment (IVT) is one of the most common physician-performed procedures in medicine. Ocular anesthesia is required prior to IVT, both for patient compliance and patient safety. Current forms of ocular anesthesia are lidocaine-based, time consuming, and potentially exacerbate corneal keratopathy. Cooling-based anesthesia represents a novel approach to delivering focal, ultra-rapid ocular anesthesia. Prior to initiation of a human clinical trial with this technology, a preclinical safety study was performed in New Zealand white rabbits to evaluate the safety of this approach.

Methods : A handheld thermoelectric cooling device was developed to rapidly anesthetize a 4 mm x 4 mm area on the surface of the eye. Following UCUCA approval, 20 New Zealand white rabbits (40 eyes) were divided into 2 groups based on treatment times. The first group received a 10 second treatment, and the second group received a 30 second treatment. All rabbits received 4 treatments per eye, with one treatment in each quadrant. Ten temperatures were tested, ranging from +20°C to -40°C. All animals were sacrificed 1 week following treatment and the eyes were removed and sent for processing and histopathologic evaluation. Thirty 5 µm sections at 50 µm intervals were prepared and examined for each eye. Sections were examined histopathologically by a board certified veterinary pathologist and changes were graded as trace, mild, moderate, and severe.

Results : At -35°C and -40°C, mild limbal inflammation was occasionally observed in the vicinity of the treatment sites. No eyes treated at temperatures above -30°C manifested any histopathologic signs of toxicity related to treatment.

Conclusions : Ultra-rapid, focal cooling of rabbit eyes at temperatures as cold as -30°C for up to 30 seconds did not result in any histopathologic signs of toxicity. Temperature-dependent toxicity was mild. These findings suggest that focal ocular cooling at temperatures warmer than -35°C applied for 30 seconds or less is well tolerated in rabbits and may be safe for clinical use.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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