New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

Abstract

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice.

Uveal Melanoma

“…HIFU can be used to quickly heat up a local area to temperatures above 56 C, leading to coagulation necrosis without affecting the tissue vascular system. 79 HIFU has been clinically used to treat malignancies such as hepatocellular carcinoma and prostate cancer. 80,81 However, to treat malignancies of the eye, HIFU beams would need to function at a frequency of >10 MHz.…”

“…Iontophoresis is a technique using a low-intensity electric current to increase the biodistribution of ionized drugs, including antimetabolites like bleomycin and carboplatin. 79 One study showed a dose-dependent inhibition of neuroblastoma in mice using iontophoresis of carboplatin, without any corneal toxicity at doses under 10mg/mL. 83 Levels of carboplatin in the retina, choroid, vitreous humor, and optic nerve were higher following iontophoretic administration compared to intravenous.…”

Imaging of Uveal Melanoma—Current Standard and Methods in Development

“…Older age at the time of diagnosis [42] and the male gender are also associated with an unfavorable prognosis [16,43]. Due to poor prognosis and limited treatment options in localized and advanced diseases, accurate diagnosis is critical in this group of patients [44,45].…”

Integration of Bulk RNA Sequencing and Single-Cell RNA Sequencing to Reveal Uveal Melanoma Tumor Heterogeneity and Cells Related to Survival

“…Uveal melanoma (UM) is a rare ocular malignant tumor with a rapidly increasing incidence worldwide ( 4 ). The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy ( 5 ). Even with successful local treatment of primary tumors, more than 50% of UM patients will develop metastatic diseases ( 6 , 7 ).…”