Evaluating ex-vivo ocular treatment depth from a low-cost, reusable, CO2-based cryotherapy system

Abstract

Purpose : Cryoablation as an adjunct to surgical excision of ocular surface tumors is the standard of care in most developed countries. Barriers to access to this technology in lower-income countries include the expense of liquid nitrogen or argon gas and the cost of disposable cryo probes. A carbon dioxide (CO2)-based cryotherapy system with an autoclavable tip has been developed for use in breast cancer; this study explored the effects of this device on ocular tissue.

Methods : This was an ex vivo study of the effects of a CO₂ based cryoablation device on ocular tissue. Whole human eyes at room temperature received application of the device at the limbus, mimicking treatment of an ocular surface tumor. A thermocouple placed within the sclera at approximately 90% depth was used to measure the tissue temperature. In 4 separate locations, the time required to obtain a tissue temperature of -20°C was measured. Then, using 4 quadrants of the limbus of 3 separate whole globes, applications of therapy for 50%, 100%, and a double freeze-thaw cycle of 100% time were performed. The globes were then fixed and sectioned. H&E stains were used to evaluate qualitative histological evidence of depth of treatment.

Results : The average time to -20°C was 67 seconds (95% CI 55.0-78.1). The probe was not able to consistently achieve tissue temperatures of -40°C. Table 1 details the apparent depth of treatment effect with varying treatment times. Representative photos 1-3 demonstrate 0% scleral effect depth after 50% treatment time (33 seconds), and 30% and 60% treatment depth after two freeze-thaw cycles of 67s (100% treatment time) each.

Conclusions : This ex vivo model demonstrated that a reusable, CO₂-based cryoablation device was able to consistently obtain tissue temperatures of -20°C within a clinically-relevant treatment time. In keeping with current surgical techniques, a double freeze-thaw cycle demonstrated an increase in tissue distortion. With additional refinement of tip design to accomodate ocular applications, further studies in animal models are necessary to develop clinical treatment protocols.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Figure 2. Estimated 30% treatment depth (after treatment time of 66s; black arrowheads demonstrate demarcation line in sclera

 

Table 1. Observed depth of treatment effect as a function of time of treatment. Each treatment duration was repeated in 4 separate locations.