Therapeutic Levels of Hypothermia Achieved in Isolated Porcine Eyes Using a Scleral Contact Interface.

Abstract

The neuroprotective effect of hypothermia for mitigation of ischemic and hypoxic damage to the retina is well documented, yet technology to achieve targeted, controlled ocular hypothermia in vivo is lacking. This study evaluated controlled cooling of ocular tissues using a novel scleral contact eye cooler designed to be practical in a clinical setting. Excised fresh adult porcine eyes (n = 5) were imaged (at 9.4 T MRI) to document gross anatomy, instrumented with temperature sensors at five key locations, and partially lowered into a warm oil bath (37 °C) to represent surrounding extraocular tissues. A scleral contact ring (SCR) interfaced with an active heat pump was lowered to contact the eye. The SCR was brought to 4 °C and maintained at that temperature using feedback control while monitoring sensor temperatures. After the eye tissues reached thermal equilibrium in the cooled state, the experiment was terminated, and a micro-CT image was obtained to verify the location of each temperature sensor. Average equilibrium temperatures of the anterior sclera and optic nerve sensors were 10.7 and 30.2 °C, achieved within 3.2 and 11.7 min, respectively. These temperatures have been shown to be neuroprotective against hypoxic damage. In the non-perfused eye model, therapeutically relevant temperatures could be induced throughout the eye and maintained indefinitely. Demonstration of targeted and controlled cooling of eye tissues using a minimally invasive scleral contact ring will enable in vivo therapeutic hypothermia research using a design amenable to clinical translation.