Irreversible Electroporation of Human Primary Uveal Melanoma in Enucleated Eyes

Yossi Mandel,Michael Belkin,Shahar Frenkel,Shlomi Laufer,Jacob Pe'Er,Boris Rubinsky,Vladimir N Uversky

doi:10.1371/journal.pone.0071789

Abstract

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50–100 µs, 1000–2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment.

Highlights

Uveal melanoma (UM) is the most common primary intraocular tumor in adults [1]
The effect required time to become apparent and was not noticed when the tumor was immediately fixed after treatment (Fig. 1C)
Of interest is the complete destruction of the epitheloid tumor cells upon irreversible electroporation (IRE) treatment in the treated tumor (Fig. 2B) as compared to the untreated specimen (Fig. 2A)

Summary

Introduction

Uveal melanoma (UM) is the most common primary intraocular tumor in adults [1]. It is a highly malignant neoplasm, which threatens the patient with metastatic death, loss of the eye, and irreversible visual deficit. Complications of brachytherapy include neovascular glaucoma (with prevalence up to 45% in large tumors, 12% needed enucleation due to glaucoma), cataract (up to 68%, [4,5,6]) irradiation retinopathy with visual loss (up to 62%), retinal detachment and tears, optic nerve neuropathy The effect of this complication is a decrease of 2 lines of Snellen acuity in 26–62% of treated eyes [7]. The COMS identified 5- and 10year cumulative metastasis rates of 25% and 34%, respectively, with 80% of the metastatic patients dying in the first year, and 92% in the first two years after the diagnosis of metastases [12]

Methods

Results

Conclusion