Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model.

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay.

The Chick Chorioallantoic Membrane as a Xenograft Model for the Quantitative Analysis of Uveal Melanoma Metastasis in Multiple Organs.

Uveal melanoma (UM) is the most common intraocular tumor in adults, and nearly 50% of patients develop metastatic disease with a high mortality rate. Therefore, the development of relevant preclinical in vivo models that accurately recapitulate the metastatic cascade is crucial. We exploited the chick embryo chorioallantoic membrane (CAM) xenograft model to quantify both experimental and spontaneous metastasis by qPCR analysis.

Wolfram-silicone implants as effective radiation shielding for ocular brachytherapy: dosimetric features and in vivo animal study on biocompatibility.

Objective: To evaluate wolfram as a photon and beta absorber in the management of uveal melanoma with radiotherapy, examining its potential ocular adverse effects and physiologic tolerance using an in vivo rabbit ocular model.

Methods: A method of manufacturing implants from mixtures of wolfram and silicone was developed. Their shielding effect on the radiation of sources used in ocular brachytherapy was investigated by dosimetric measurement in an eye phantom as well as numerical simulations.

Prognostic factors for surgical treatment of radiation-induced scleral necrosis after brachytherapy for uveal melanoma.

Purpose: Radiation-induced scleral necrosis (RISN) is a less frequent complication of brachytherapy for uveal melanoma, and may require surgical treatment in selected cases. We aimed to identify the prognostic factors for RISN treatment.

Methods: All patients with brachytherapy for uveal melanoma treated at our institution between 01/1999 and 12/2016 who developed RISN were followed until 02/2021.

Surgical Outcome After Treatment of Radiation-Induced Scleral Necrosis in Patients With Uveal Melanoma.

Purpose: Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery.

Methods: All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.

Leadership in ophthalmology training : Opportunities and risks of medical specialist education.

Medical specialist training requires constant improvement and adaptation of the contents to the current situation. Nowadays, young physicians have the opportunity to select among the most renowned institutions and can choose the one most qualified for their training. Hospitals on the other hand still have the desire to recruit highly qualified physicians for their resident programs, which requires a good, well-rounded and reliable offer by the department under good leadership.

[Leadership in ophthalmology training : Opportunities and risks of medical specialist education].

Medical specialist training requires constant improvement and adaptation of the contents to the current situation. Nowadays, young physicians have the opportunity to select among the most renowned institutions and can choose the best qualified for their training. Hospitals on the other hand still have the desire to recruit highly qualified physicians for continuing education, which requires a good, well-rounded and reliable offer by the department under good leadership.

Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures.

Uveal melanoma (UM) is the most common primary cancer of the eye in adults. A new systemic therapy is needed to reduce the high metastasis and mortality rate. As β-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of β1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM.

Chick Chorioallantoic Membrane as a Patient-Derived Xenograft Model for Uveal Melanoma: Imaging Modalities for Growth and Vascular Evaluation.

Background: Patient-derived tumor xenografts (PDXs) have emerged as valuable preclinical in vivo models in oncology as they largely retain the polygenomic architecture of the human tumors from which they originate. Although animal models are accompanied by cost and time constraints and a low engraftment rate, PDXs have primarily been established in immunodeficient rodent models for the in vivo assessment of tumor characteristics and of novel therapeutic cancer targets. The chick chorioallantoic membrane (CAM) assay represents an attractive alternative in vivo model that has long been used in the research of tumor biology and angiogenesis, and can overcome some of these limitations.

Feasibility, Method and Early Outcome of Image-Guided Volumetric Modulated Arc Radiosurgery Followed by Resection for AJCC Stage IIA-IIIB High-Risk Large Intraocular Melanoma.

The main objective of this prospective observational study was the characterization of the feasibility and early outcome of image-guided (IG) volumetric modulated arc (VMAT) radiosurgery (SRS) followed by resection for patients with large intraocular melanoma. Our study included consecutive patients with unfavorable-risk melanoma, enrolled in an ophthalmic oncology center. IG-VMAT-SRS was applied by high-resolution 4D image guidance and monitoring.

Choroidal Manifestation of Smoldering Myeloma: Case Report.

This case illustrates clinical, histopathological, immunohistochemical, and molecular pathological diagnostic testing of smoldering myeloma with atypical ophthalmic manifestations. In our case, the choroidal lesion presented as a solitary manifestation of a systemic disease. Choroidal lesions of monoclonal plasma cells are extremely rare and should be included in the differential diagnosis of amelanotic choroidal lesions, even if the histopathological examination of the primary lesion is not informative.

The Adrenergic Receptor Antagonist Carvedilol Elicits Anti-Tumor Responses in Uveal Melanoma 3D Tumor Spheroids and May Serve as Co-Adjuvant Therapy with Radiation.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite local tumor control, no effective therapy has been found to prevent metastasis, resulting in a high mortality rate. In the present study, we evaluated the anti-tumor potential of non-selective ß-blockers in 3D tumor spheroids grown from UM cell lines.

Calcium Electroporation Reduces Viability and Proliferation Capacity of Four Uveal Melanoma Cell Lines in 2D and 3D Cultures.

Electrochemotherapy (ECT) is the combination of transient pore formation following electric pulse application with the administration of cytotoxic drugs, which enhances the cytotoxic effect of the applied agent due to membrane changes and permeabilization. Although EP represents an established therapeutic option for solid malignancies, recent advances shift to the investigation of non-cytotoxic agents, such as calcium, which can also induce cell death. The present study aims to evaluate the cytotoxic effect, the morphological changes in tumor spheroids, the effect on the cell viability, and the cell-specific growth rate following calcium electroporation (CaEP) in uveal melanoma (UM) 2D monolayer cell cultures as well as in 3D tumor spheroid models.

Fundus Autofluorescence Imaging in Patients with Choroidal Melanoma.

Choroidal melanocytic lesions require reliable and precise clinical examination and diagnosis to differentiate benign choroidal nevi from choroidal melanoma, as the latter may become life-threatening through metastatic disease. To come to an accurate diagnosis, as well as for monitoring, and to assess the efficacy of therapy, various imaging modalities may be used, one of which is non-invasive fundus autofluorescence (FAF) imaging using novel high-resolution digital imaging technology. FAF imaging is based on the visualization of intrinsic fluorophores in the ocular fundus.

Outcome Measures of New Technologies in Uveal Melanoma: Review from the European Vision Institute Special Interest Focus Group Meeting.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "Outcome Measures of New Technologies in Uveal Melanoma," addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient's well-being.

Optimisation of the Chicken Chorioallantoic Membrane Assay in Uveal Melanoma Research.

The treatment of uveal melanoma and its metastases has not evolved sufficiently over the last decades in comparison to other tumour entities, posing a great challenge in the field of ocular oncology. Despite improvements in the conventional treatment regime and new discoveries about the genetic and molecular background of the primary tumour, effective treatment strategies to either prevent tumours or treat patients with advanced or metastatic disease are still lacking. New therapeutic options are necessary in order to achieve satisfactory local tumour control, reduce the risk of metastasis development, and preserve the eyeball and possibly the visual function of the eye.

Brachytherapy for Peripheral Retinal Capillary Haemangioblastoma in von Hippel-Lindau Disease.

Aim: To report our experience with ruthenium-brachytherapy of peripheral capillary haemangioblastomas in patients with von Hippel-Lindau disease.

Design: Retrospective case series.

Methods: A total of 53 haemangioblastomas, treated with ruthenium-brachytherapy, were included in our study.

Electrochemotherapy with Bleomycin Enhances Radiosensitivity of Uveal Melanomas: First In Vitro Results in 3D Cultures of Primary Uveal Melanoma Cell Lines.

Electrochemotherapy (ECT) is emerging as a complementary treatment modality for local tumor control in various cancer entities. Irradiation is an established therapeutic option for oncologic patients, which is commonly combined with chemotherapy due to its insufficient targeting ability. The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers.

[Echography].

Echography (also ultrasound) is a clinical, non-invasive imaging module that is used for the measurement of the axial length of the eye and for the investigation of pathologic entities of the chamber angle, the iris and the ciliary body. Furthermore, its role in the management of vitreoretinal pathologies and the differentiation of intraocular tumors is indisputable. Echography remains the first-choice imaging tool in case of insufficient visualization of the posterior segment due to opacity or obstruction of the optical media of the eye.

[Traumatic optic pit-Optic nerve evulsion caused by indirect ocular trauma].

This article describes the case of a 28-year-old man who suffered an optic nerve evulsion (ONE) after falling from a height of 5 m. On admission visual acuity in the affected left eye was light perception, direct pupillary reaction was unresponsive, and the eye was hypotonic. Because of deep eyelid laceration, hyphemia and severe vitreous hemorrhage a globe rupture was suspected and a surgical exploration with vitrectomy was performed.

Image Analysis of 3D Conjunctival Melanoma Cell Cultures Following Electrochemotherapy.

Three-dimensional (3D) cell cultures represent small avascular tumors in vitro and simulate some of the biological characteristics of solid tumors, enhancing the evaluation of anticancer drug efficacy. Automated image analysis can be used for the assessment of tumor growth and documentation of changes in the size parameters of 3D tumor spheroids following anticancer treatments such as electrochemotherapy. The objective of this article is to assess the effect of various electroporation (EP) conditions (500-750 Volts/cm, 8-20 pulses, 100 µs pulse duration, 5 Hz repetition rate) combined with different bleomycin concentrations (1-2.

Electrochemotherapy in 3D Ocular Melanoma Spheroids using a Customized Electrode.

Electrochemotherapy (ECT) is the combination of transient pore formation following electric pulse application with the administration of cytotoxic drugs, which enhances the cytotoxic effect of the applied agent due to membrane changes. In vitro 3D culture systems simulate the in vivo tumor growth and preserve the biological characteristics of tumors more accurately than conventional monolayer cell cultures. We describe a protocol for the development of 3D tumor organoids using conjunctival melanoma (CM) and uveal melanoma (UM) cell lines as well as the use of hand-held customized electrodes, suitable for in vitro ECT in the culture well without destruction of the tumor environment.