electrochemotherapy-3d-ocular-melanoma-spheroids-using-customized

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, ...

Martin-Luther University Halle-Wittenberg

Duisburg Essen University

Congenital nasolacrimal duct obstruction (CNLDO) is the most common cause of epiphora in infancy. Spontaneous resolution occurs in the majority of the cases by 1 year of age. Nevertheless, obstruction has a negative impact on the outcome of conservative or surgical therapy, especially in cases of complex CNLDO. When the condition persists beyond several months, early intervention with dacryoendoscopy (DE) around the age of 1 year could yield good results. The objective of the study is to analyze the success rate and effectiveness of early DE for complex CNLDO in the first year of life.

A Case Series of Dacryoendoscopy in Childhood: A Diagnostic and Therapeutic Alternative for Complex Congenital Nasolacrimal Duct Obstruction Even in the First Year of Life.

Ocular trauma can lead to severe visual impairment and morbidity, depending on the anatomical structures affected. The main causes of ocular trauma include foreign bodies, impact by an object, falls, and chemicals. Most ocular traumas occur in children or young male adults. A meticulous slit lamp examination is crucial for assessing all anatomical structures. Trauma to the crystalline lens can result in dislocation, an intralenticular foreign body, cataract, fragmentation, and capsular breach. An intraocular lens (IOL) can endure subluxation or luxation under the conjunctiva, into the anterior chamber or the vitreous, or can be extruded. The surgical approach depends on the condition and morphology of the lens and the anatomical structures surrounding it. If there is capsular bag support, a secondary IOL can be placed in the sulcus using remnants of the damaged capsule. If there is no capsular bag support, a secondary IOL can be fixated to the anterior chamber angle, to the iris, or to the sclera. A detailed history of injury cannot always be obtained in trauma settings. Proper education, supervision, and certified safety eye protectors could prevent up to 90% of ocular injuries. Lens trauma can be treated with various surgical procedures and fixation techniques, which nevertheless require advanced surgical skills owing to the fine anatomical structure of the anterior segment. A careful surgical strategy should be established for a globe reconstruction after trauma with secondary lens implantation. Clin. Anat. 31:6-15, 2018. © 2017 Wiley Periodicals, Inc.

Methods of fixation of intraocular lenses according to the anatomical structures in trauma eyes.

A traumatic wound dehiscence can occur many years after surgery in 2-6% of all keratoplasties. Intraocular tissue prolapse can lead to severe visual loss. Deep anterior lamellar keratoplasty (DALK) leads to higher wound stability because of the intact Descemet membrane. We report a case of a novel management of wound dehiscence following DALK. A 59-year-old patient underwent uncomplicated DALK for advanced keratoconus. Eighteen months later he experienced a traumatic wound dehiscence (globe rupture) after a fall. Visual acuity decreased to light perception on the affected eye, the iris and prolapsed vitreous were incarcerated, and no retinal details were recognizable. The corneal graft was dehiscent over eight clock hours, the Descemet membrane was ruptured, and the stroma dissolved over 30% of its surface in a bell shape. Primary wound closure was performed with nylon 10-0 single interrupted corneal sutures. One day after emergency treatment, a 23-gauge pars-plana-vitrectomy for vitreous hemorrhage was conducted and a retinal tear was treated with laser photocoagulation. The Descemet membrane was repositioned using a 23 g vitrectomy probe under air and the globe was filled with SF gas. Postoperatively, visual acuity increased to 6/15 and the cornea cleared up. Corneal graft and Descemet membrane repositioning after trauma can avoid a further keratoplasty and the risk of immunological rejection of donor endothelial cells. Clin. Anat. 31:56-59, 2018. © 2017 Wiley Periodicals, Inc.

Traumatic globe rupture after deep anterior lamellar keratoplasty-A novel management technique.

To provide insight into the clinical anatomy of Tenon's capsule and to describe a technique to manage sclerocorneal defects using autologous Tenon's tissue. A thin layer of Tenon's capsule harvested from the patient's own eye is used to seal the defect and act as a scaffold. The Tenon's flap is spread over the defect and held in place by Vicryl sutures. A bandage contact lens is then placed on the eye. Tenon's capsule is composed of thick fibrous tissue with smooth muscle fibers and a thin posterior capsule of orbital fat. It is rich in fibroblasts, which can accelerate wound healing and eventually lead to robust scarring without risk of immunogenicity and without cost. Tenonplasty uses easily-available autologous Tenon's tissue in patients with sclerocorneal defects to preserve globe morphology. The technique is a feasible alternative not limited by the availability of graft tissue. Clin. Anat. 31:72-76, 2018. © 2017 Wiley Periodicals, Inc.

Tenonplasty for closing defects during sclerocorneal surgery-A brief review of its anatomy and clinical applications.

Intraocular pressure lowering surgery in congenital aniridia glaucoma (CAG) can be complicated by dysgenesis of the limbal region, anterior chamber angle, iris, and lens. The anterior segments of 23 eyes (17 patients) with congenital aniridia were investigated under general anesthesia using ultrasound biomicroscopy (UBM). The structures of the anterior segment were examined: distance of ciliary body processes from the anterior chamber angle and positioning of Schlemm's canal. A surgical plan was created on the basis of these data. Schlemm's canal was detected in 21 of the 23 examined eyes. The mean distance from the anterior chamber angle was 1.3 ± 0.4 mm (range: 0.5-to 2.1 mm). The mean distance between the anterior chamber angle and the ciliary body was 561 ± 301 µm (range: 270-1,300 µm). The mean prominence of the ciliary body towards the lens was 799 ± 352 µm (range: 210-1,660 µm). This resulted in a precise UBM-based trabeculotomy. In addition, the ciliary body was detected and coagulated ab externo with a diode laser probe (810 nm) using diaphanoscopy and UBM. An initial UBM examination of the anterior segment is essential in eyes with CAG scheduled for trabeculotomy or cyclophotocoagulation. Clin. Anat. 31:64-67, 2018. © 2017 Wiley Periodicals, Inc.

Clinical anatomy of the anterior chamber angle in congenital aniridia and consequences for trabeculotomy/cyclophotocoagulation.

The aim of this observational study is to evaluate the effectiveness of an adjuvant intracameral corticosteroid injection (ICI) in cases of severe endothelial immune reaction (SEIR) (anterior chamber cells and flare, retrocorneal precipitates, Descemet's folds, and corneal edema) after penetrating keratoplasty and posterior lamellar keratoplasty.

Intracameral Dexamethasone Injection as Adjuvant Therapy in Endothelial Immune Reaction After Penetrating and Posterior Lamellar Keratoplasty: A Retrospective Clinical Observation.

This study aimed to investigate the influence of three muscle relaxants on intraocular pressure (IOP), ocular pulse amplitude (OPA), and vis-à-tergo (VAT) in patients undergoing penetrating keratoplasty (PKP) under general anesthesia.

Muscle Relaxants as a Risk Factor for Vis-à-tergo During Penetrating Keratoplasty: A Prospective Interventional Study.

To investigate the cytotoxic effect of bleomycin, mitomycin C (MMC) and Fluorouracil (5-FU) in combination with electroporation (EP) on human conjunctival melanoma (CM) and normal conjunctival cell lines using 2D and 3D cell culture systems in vitro.

Conjunctival melanoma and electrochemotherapy: preliminary results using 2D and 3D cell culture models in vitro.

Uveal melanoma (UM) is the most common primary intraocular tumor that arises from neoplastic melanocytes in the choroid, iris, and ciliary body. Electrochemotherapy (ECT) has been successfully established for the treatment of skin and soft tissue metastatic lesions, deep-seated tumors of the liver, bone metastases, and unresectable pancreas lesions. The aim of this study was to evaluate the effect of ECT in vitro in 3D spheroid culture systems in primary and metastatic UM cell lines. We also investigated the chick embryo chorioallantoic membrane (CAM) as an in vivo model system for the growth and treatment of UM tumors using ECT. The cytotoxic effect of ECT in 3D spheroids was analyzed seven days following treatment by assessment of the size and MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction] assay. The cytotoxicity of ECT after intratumoral or intraarterial administration was evaluated histologically. In vitro and in vivo ECT caused a significant reduction in tumor size and viability compared to electroporation or chemotherapy in both sections of our study. The current results underline the effectiveness of ECT in the treatment of UM and prepare the way for further investigation of its potential application in UM.

The Potential Use of Electrochemotherapy in the Treatment of Uveal Melanoma: In Vitro Results in 3D Tumor Cultures and In Vivo Results in a Chick Embryo Model.

A serious problem of the treatment of eye diseases is the very short residence time of the drug. The majority of the drug is cleared within few seconds due to the poor capability of the eye to accommodate additional liquids. We developed a new ocular drug delivery system, which is applied in dry form and forms immediately a gel after administration. The system is based on gellan gum/pullulan electrospun nanofibers. The rheological behavior of the spinning solution was investigated followed by further characterization of the in situ formed gel. Three-dimensional X-ray imaging with nanometric resolution (nano-CT) and electron scanning microscopy were used for a detailed characterization of the diameter and alignment of the fibers. A high porosity (87.5 ± 0.5%) and pore interconnectivity (99%) was found. To ensure a good fit to the eye anatomy, the prepared fibers were shaped into curved geometries. Additionally, a new innovative moistening chamber for the in vitro determination of the ocular residence time in porcine eyes was developed which mimics the tear turnover. A clear prolongation of the fluorescein residence time compared to conventional eye drops was achieved with the application of the curved nanofiber in situ gelling mat. In summary, the developed in situ gelling system with adapted geometry is a promising alternative system for ocular drug delivery.

Article	Year
A Case Series of Dacryoendoscopy in Childhood: A Diagnostic and Therapeutic Alternative for Complex Congenital Nasolacrimal Duct Obstruction Even in the First Year of Life. Advances in therapy\| PubMed ID: 28341931	2017
Methods of fixation of intraocular lenses according to the anatomical structures in trauma eyes. Clinical anatomy (New York, N.Y.)\| PubMed ID: 28509425	2018
Traumatic globe rupture after deep anterior lamellar keratoplasty-A novel management technique. Clinical anatomy (New York, N.Y.)\| PubMed ID: 28556252	2018
Tenonplasty for closing defects during sclerocorneal surgery-A brief review of its anatomy and clinical applications. Clinical anatomy (New York, N.Y.)\| PubMed ID: 28612422	2018
Clinical anatomy of the anterior chamber angle in congenital aniridia and consequences for trabeculotomy/cyclophotocoagulation. Clinical anatomy (New York, N.Y.)\| PubMed ID: 28613427	2018
Intracameral Dexamethasone Injection as Adjuvant Therapy in Endothelial Immune Reaction After Penetrating and Posterior Lamellar Keratoplasty: A Retrospective Clinical Observation. Advances in therapy\| PubMed ID: 28667581	2017
Muscle Relaxants as a Risk Factor for Vis-à-tergo During Penetrating Keratoplasty: A Prospective Interventional Study. Advances in therapy\| PubMed ID: 29101713	2017
Conjunctival melanoma and electrochemotherapy: preliminary results using 2D and 3D cell culture models in vitro. Acta ophthalmologica\| PubMed ID: 30548215	2019
The Potential Use of Electrochemotherapy in the Treatment of Uveal Melanoma: In Vitro Results in 3D Tumor Cultures and In Vivo Results in a Chick Embryo Model. Cancers\| PubMed ID: 31514412	2019
Electrospun nanofibers - A promising solid in-situ gelling alternative for ocular drug delivery. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V\| PubMed ID: 31816391	2020

Miltiadis Fiorentzis

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