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Uveal melanoma (UM) is the most common primary intraocular tumor in adults, with no standardized treatment for advanced disease. Based on preliminary bioinformatical analyses DTYMK and PARP1 were selected as potential therapeutic targets. High levels of both proteins were detected in uveal melanoma cells and correlated with increased tumor growth and poor prognosis. In vitro tests on MP41 (BAP1 positive) and MP46 (BAP1 negative) cancer cell lines using inhibitors pamiparib (PARP1) and Ymu1 (DTYMK) demonstrated significant cytotoxic effects. Combined treatment had synergistic effects in MP41 and additive in MP46 cell lines, reducing cell proliferation and inhibiting the mTOR signaling pathway. Furthermore, the applied inhibitors in combination decreased cell motility and migration speed, especially for BAP1-negative cell lines. Our hypothesis of the double hit into tumoral DNA metabolism as a possible therapeutic option in uveal melanoma was confirmed since combined targeting of DTYMK and PARP1 affected all tested cytophysiological parameters with the highest efficiency. Our in vitro findings provide insights into novel therapeutic avenues for managing uveal melanoma, warranting further exploration in preclinical and clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of iridociliary and choroidal melanoma relies on the patient's systemic health, tumor size, location, related features, state of the opposing eye, and personal preferences. The two categories are radiation and surgical techniques. Transpupillary thermotherapy, plaque radiotherapy, charged particle irradiation, local resection, enucleation, orbital exenteration, and experimental nanoparticle therapy are all options for treating choroidal melanoma. Case Presentation: The method that entails creating a partial thickness circular, rectangular, or polyhedral scleral flap in the region covering the tumor after removing a portion of the extraocular muscles is the most popular method for local excision in choroidal or choroidal-ciliary body cancers. We discuss our experience treating iridociliary melanoma using block excision and stereotactic irradiation on a linear accelerator with TD 20.0 Gy. Conclusion: One of the treatment modalities is the combined treatment approach using stereotactic irradiation and tumor resection, and our results 1 year after therapy are comparable to the rates of local control and anatomic eye preservation to those achieved in studies of comparable uveal melanoma treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: To examine the role of the strain ratio in elastosonography for the differential diagnosis of common intraocular tumors such as choroidal melanoma, choroidal hemangioma, choroidal metastatic carcinoma, and retinoblastoma. Methods: This study included patients suffering from intraocular space-occupying lesions and who visited Beijing Tongren Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from June 2016 to March 2020. All patients underwent a physical examination, fundus examination with mydriasis, color Doppler ultrasonography, elastosonography, magnetic resonance imaging (MRI), and fundus angiography within 1 week. All patients were grouped as choroidal melanoma, choroidal metastatic carcinoma, retinoblastoma, choroidal hemangioma, and optic disk melanocytoma. A receiver operating characteristic (ROC) curve analysis was performed to assess the strain ratio for diagnosing malignant intraocular tumors. Results: A total of 155 patients (161 eyes) were recruited. The strain ratios measured were 39.59 ± 15.92 for choroidal melanoma, 36.85 ± 13.64 for choroidal metastatic carcinoma, 38.93 ± 17.27 for retinoblastoma, 13.42 ± 10.93 for choroidal hemangioma, and 3.84 ± 1.32 for optic disk melanocytoma. The strain ratios of the three malignant lesions were significantly higher than those of the two benign lesions (all P < 0.001). The area under the ROC curve was 0.95 ± 0.028. The optimal cutoff point was 22.67, with 85.7% sensitivity and 96.4% specificity. Conclusion: There were significant differences in elasticity between the malignant and benign intraocular tumors. The strain ratio using elastosonography could serve as an important auxiliary examination to distinguish between benign and malignant intraocular tumors. [ABSTRACT FROM AUTHOR]

Massive retinal gliosis (MRG) is a rare condition of non-neoplastic glial proliferation, which forms massive lesions that fill the eye. MRG is commonly associated with phthisis bulbi (a non-functional eye), congenital anomalies, or malformations. Herein, we report a case of massive retinal gliosis associated with a traumatic phthisis bulbi, which was initially mistaken as a malignant intraocular tumor and confirmed only after an eye enucleation. A 70-year-old woman presented with a protruding ocular mass in her left eye which had slowly grown for a year. She had phthisis bulbi in her left eye due to trauma during her childhood. An orbital CT revealed an intraocular mass lesion with calcifications, raising the possibility of retinoblastoma or other malignant intraocular tumors. Enucleation of the left eye globe was performed. Histopathologic examination revealed exuberant proliferation of the glial cells, metaplastic bone formation, hyalinized vessels, and hyperplasia of the retinal pigment epithelium, confirming the diagnosis of MRG. Although rare, the possibility of MRG should be considered as a differential diagnosis when encountering an intraocular mass lesion, as it can be misdiagnosed as a malignant tumor. [ABSTRACT FROM AUTHOR]

Purpose: Plaque therapy is a well-recognized treatment for intraocular tumors. In current study, we aimed to prospectively investigate the short-term effects of ruthenium 106 (Ru-106) plaque therapy on the cornea and ocular surface parameters.Methods: Twenty-five patients diagnosed with choroidal melanoma which undergone Ru-106 plaque therapy from 2016 to 2018 were included. Tear osmolarity, tear film break-up time, Schirmer test I, fluorescein dye staining based on Oxford staining method; Ocular Surface Disease Index (OSDI) questionnaire and corneal specular microscopy were performed. These tests were assessed preoperatively and then 3 months postoperatively.Results: The mean (±SD) age of subjects was 48.52 ± 15.18 years. The patients were followed for a mean(±SD) period of 3.64 ± 2.40 months. Total mean (+SD) delivered radiation dose to the tumor apex and total received radiation by the sclera was 83.20 ± 26.31 and 640.65 ± 472.69 Gray (Gy), respectively. In longitudinal analysis, OSDI score and Oxford staining score increased significantly (P = 0.002 for both variables) and the prevalence of dry eye disease (DED) increased from 20% preoperatively to 72% at 3 months postoperatively (P = 0.001).The changes in the all specular microscopy parameters were statistically nonsignificant (all P values > 0.05).Conclusion: There is a considerable increase in the rate of DED following plaque therapy for the treatment of choroidal melanoma in short-term follow-up. The OSDI questionnaire and fluorescein staining test are valuable tools for early detection of DED postoperatively. [ABSTRACT FROM AUTHOR]

A customized Collaborative Ocular Melanoma Study (COMS)-style eye plaque may provide superior dosimetric coverage compared with standard models for certain intraocular tumor locations and shapes. This work provides a recipe for developing and validating such customized plaques. The concept-into-clinical treatment process for a customized COMS-style eye plaque begins with a CAD model design that meets the specifications of the radiation oncologist and surgeon based on magnetic resonance, ultrasound, and clinical measurements, as well as a TG-43 hybrid heterogeneity-corrected dose prediction to model the dose distribution. Next, a 3D printed plastic prototype is created and reviewed. After design approval, a Modulay plaque is commercially fabricated. Quality assurance (QA) is subsequently performed to verify the physical measurements of the Modulay and Silastic and also includes dosimetric measurement of the calibration, depth dose, and dose profiles. Sterilization instructions are provided by the commercial fabricator. This customization procedure and QA methodology is demonstrated with a narrow-slotted plaque that was recently constructed for the treatment of a circumpapillary (e.g., surrounding the optic disk) ocular tumor. The production of a customized COMS-style eye plaque is a multistep process. Dosimetric modeling is recommended to ensure that the design will meet the patient's needs, and QA is essential to confirm that the plaque has the proper dimensions and dose distribution. The customized narrow-slotted plaque presented herein was successfully implemented in the clinic, and provided superior dose coverage of juxtapapillary and circumpapillary tumors compared with standard or notched COMS-style plaques. Plaque development required approximately 30 h of physicist time and a fabrication cost of $1500. Customized eye plaques may be used to treat intraocular tumors that cannot be adequately managed with standard models. The procedure by which a customized COMS-style plaque may be designed, fabricated, and validated was presented along with a clinical example. [ABSTRACT FROM AUTHOR]

The incidence of lung cancer with intraocular metastasis is low, of which choroidal metastasis is the most painful metastatic lesion. The clinical symptoms resulting from choroidal metastasis from lung cancer easily detected although they are rarely identified prior to the diagnosis of the primary malignancy. The quality of life of patients is inevitably impaired. Some lung cancer patients complain of ocular symptoms as the first manifestation of lung cancer. Early diagnosis and treatment can significantly overcome or delay the visual impairment and improve prognosis. The main therapeutic modalities include systemic and local treatments, while observation is also a treatment option. Currently, the feasibility and effectiveness of various treatment options are controversial worldwide. Herein, we summarize the underlying mechanisms, epidemiology, clinical features, auxiliary examinations, diagnosis, and recent treatment options for intraocular metastases. [ABSTRACT FROM AUTHOR]

To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of intraocular tumors. Observational case series. Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas. Hematoxylin–eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed. Distribution of PAX8 expression in normal and neoplastic tissue. Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic tumors (iris melanoma, ciliary–choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma. PAX8 has proven to be a very useful diagnostic marker in a select group of adult intraocular tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging intraocular neoplasms. [ABSTRACT FROM AUTHOR]

Objective: To report the surgical excision of an iridociliary adenoma and iridal melanocytoma using a postero-anterior cyclo-iridectomy in two dogs. Procedure: A 7 year old neutered male English springer spaniel (case 1) and a 7 year old neutered male Labrador mix (case 2) were presented for evaluation of an intrairidal mass OS. Results: Complete ophthalmic examination revealed a large, dorsonasal, well-demarcated, intrairidal mass OS. A tan to pink intrairidal mass extending into the iridocorneal angle (case 1) and a pigmented intrairidal mass (case 2) were present. B-mode ultrasonography showed a focal, soft tissue, homogenous mass within the uvea adjacent to and contacting the lens. Neither pars plana involvement nor vitreal extension was present. A postero-anterior cyclo-iridectomy was performed through a polyhedral scleral flap. Thermocautery was used to complete the cyclo-iridectomy (case 1) and partial iridectomy (case 2) to excise the mass en bloc. Histopathology revealed a completely excised iridociliary adenoma (case 1) and iris melanocytoma (case 2). The surgery sites healed without complication. Mild uveitis (cases 1 and 2), scant vitreal hemorrhage (case 1), and mild hyphema (case 2) were present three days postoperatively but had resolved ten days postoperatively. The patients remain visual twenty-two months (case 1) and seven months (case 2) postoperatively with a normal intraocular examination other than an iridal defect and mild dorsonasal lens capsular opacities. Conclusions: The surgical approach described in these cases is utilized in physicianbased medicine. This approach and the use of thermocautery provide a viable surgical option for excision of large iridociliary tumors in dogs. [ABSTRACT FROM AUTHOR]

The objective of this paper is to describe clinical behavior, histopathologic features, and immunohistochemical staining of two-related horses with intraocular teratoid medulloepithelioma. Two-related Quarter Horses with similar intraocular masses presented to the UF- CVM Comparative Ophthalmology Service for evaluation and treatment. The first horse, a 3-year-old gelding, had glaucoma and a cyst-like mass in the anterior chamber. Enucleation was performed. Histopathology revealed a teratoid medulloepithelioma. The tumor was considered to be completely excised. Fifteen months later, the gelding presented with swelling of the enucleated orbit and local lymph nodes with deformation of the skull. Cytology revealed neuroectodermal neoplastic cells. Necropsy confirmed tumor metastasis. Six weeks later, a 9-year-old mare, a full sibling to the gelding, presented for examination. An infiltrative mass of the iris and ciliary body was found that extended into the anterior, posterior, and vitreal chambers. Uveitis was present, but secondary glaucoma was not noted. Enucleation was performed and the histopathologic diagnosis was also teratoid medulloepithelioma. The mare has had no recurrence to date, 2 years following enucleation. Metastasis of intraocular teratoid medulloepithelioma is possible. Staging is recommended in cases where the diagnosis of teratoid medulloepithelioma is confirmed. Surveillance of full siblings is recommended until more information regarding etiology is known. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-proliferative effect of puerarin on retinoblastoma cells. Methods: The effect of puerarin was examined on human retinoblastoma Y79 cells using cell proliferation assays and reverse transcription-polymerase chain reaction (RT-PCR). The effect of puerarin on the cell cycle was also investigated. Western blot and RT-PCR analyses were also performed to identify the putative mechanism of action. Results: The results showed that cell viability was suppressed by puerarin in a concentrationdependent manner with a half-maximal inhibitory concentration (IC50) of 0.184 ± 0.034 µmol/L. Moreover, puerarin increased the proportion of cells in G1 phase from 42.6 ± 3.1 to 62.83 ± 4.1, 75.76 ± 3.4 and 91.33 ± 5.1 % in a concentration-dependent manner at concentrations of 0.1, 0.2, and 0.4 µmol/L, respectively. The results also indicate that Bmi-1 mRNA and protein levels decreased after puerarin treatment. Additionally, flow cytometry data showed that Bmi-1 knock-down through siRNA resulted in G1-cell cycle arrest. The proportion of cells in G1 were 51.2 ± 2.5 and 71.4 ± 4.5 % for control and Bmi-1 siRNA-treated groups, respectively. Conclusions: The results show that puerarin exert suppressive effects on human retinoblastoma Y79 cells and therefore may find application in the treatment of intraocular tumor. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery. Methods: The software for segmentation (3D Slicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D®) and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid. Results: In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient's eye with intraocular tumor. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma) were treated. The median tumor volume was 0.5 cm3 (0.2-1.6 cm3). The radiation dose was 35.0 Gy by 99% of dose volume histogram. Conclusion: The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. [ABSTRACT FROM AUTHOR]

Aims: To report the management of vision-threatening complications of vasoproliferative tumors of the retina. Methods: Clinical records of 31 eyes of 30 patients treated at our centers from 1998 through 2013 were reviewed. The main outcome measures included: type of treatment, tumor regression, tumor relapse and final visual acuity. Results: Seventeen patients (57%) underwent vitrectomy for epimacular membranes (n = 10), rhegmatogenous retinal detachment (n = 2), vitreous hemorrhage (n = 2), tractional retinal detachment (n = 1), serous retinal detachment (n = 1) and subhyaloid hemorrhage (n = 1). After the initial treatment, 10 additional surgeries were performed for vitreoretinal complications. Tumor activity was treated in all eyes either with photocoagulation or cryotherapy. Control of tumor activity was achieved in all cases, after treatment of recurrences. There were no statistically significant differences between initial and final visual acuity (p = 0.437). Recurrence showed a statistically significant association with the presence of proliferative vitreoretinopathy (p = 0.024), tumor thickness (p = 0.026), basal diameter (p = 0.031), and use of photocoagulation alone as initial treatment (p = 0.006, logistic regression). Conclusion: In our series, more than half of vasoproliferative tumors of the retina required surgery as the initial treatment. Recurrence was associated with tumor size, presence of proliferative vitreoretinopathy, and use of photocoagulation alone as the initial treatment. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Adenoma of the non-pigmented ciliary epithelium (ANPCE) is extremely rare. The aim of this study is to present our experience in treating this rare entity and to determine the long-term surgical outcomes of local tumor resection (partial iridocyclectomy with lamellar sclerouvectomy) in five cases of ANPCE in China. Patients and methods: The medical data of four women and one man ranging in age from 28 to 46 years (median, 38 years) with ANPCE were reviewed retrospectively at the Zhongshan Ophthalmic Center of Sun Yat-sen University, China. All patients had received local tumor resection and the diagnosis was confirmed by histopathological examination. Results: All five cases experienced blurred vision. The right eye was affected in four cases and the left in one. Slit-lamp biomicroscopy revealed a nodular, non-pigmented, gray-white mass with a slightly irregular surface. Tumor invasion through the peripheral iris was observed in two patients, two patients had multiple iris or ciliary cysts, and one patient had a partially bloodstained cornea. All tumors transmitted light readily. Ultrasound biomicroscopy showed a middle- or hyper-echoic solid mass in the ciliary body. MRI examination showed the tumor hyperintense to vitreous on T1WI and hypointense to vitreous on T2WI. Local resection was performed in all cases. After a median of 5.0 years of follow-up, no tumor recurrence was present in any of the cases and all involved eyes were saved. The visual acuity improved seven lines in three cases, decreased one line in one case, and vision was lost in one case. Conclusions: ANPCE often presents in adults as gray-white in color, with an irregular and sometimes multilobulated surface. The tumor transmits light well. Local resection of the mass generally provides the patient with useful vision. Recurrence after surgical removal is unlikely. [ABSTRACT FROM AUTHOR]

A 66-year-old woman presented with a blind, painful, hypertensive, and proptotic left eye. Computed tomographic imaging revealed a well-circumscribed mass involving the left orbit and globe. Metastatic work-up failed to reveal extraorbital lesions and the tumor was removed in toto via an evisceration approach orbitotomy. Histopathology and immunohistochemistry were most consistent with mammary-type myofibroblastoma with fascicles of bland, uniform spindle cells that stained positive for desmin and CD34. We are not aware of previous reports of orbital or ocular myofibroblastoma. This neoplasm has not been shown to recur, undergo malignant transformation, or metastasize. Familiarity with its clinical, histopathologic, and immunohistochemical features may improve diagnostic accuracy and treatment decisions for patients presenting with similar findings. [ABSTRACT FROM AUTHOR]

Choroidal metastasis represents the most common type of intraocular malignancy and preferably involves the posterior uveal tract. Breast and lung cancer - known or so far undiagnosed - are most frequently identified as the underlying tumor disease. The majority of patients diagnosed with uveal metastasis have additional metastatic manifestations elsewhere, so re-staging before treatment is recommended. The importance of a multidisciplinary approach is obvious. Early diagnosis and timely initiation of treatment are mandatory in case of vision-threatening situations. External beam radiation remains the therapy of choice. Overall survival of patients with uveal metastasis is limited, averaging six to twelve months. The other eye is frequently enough affected as well, justifying regular ophthalmologic follow-up during the further course of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the patients with intraocular tumors who underwent diagnostic fine-needle aspiration biopsy. Material and Method: Between May 2003 and June 2009, fine-needle aspiration biopsy was performed in 14 patients with an intraocular tumor. For 6 cases with iris, iridocorneal angle or iridociliary pathology, aspiration was done with a 26-gauge needle under the surgical microscope. For 6 of the 8 cases with vitreous, retinal, optic disc or choroid pathology, aspiration was done with 20 D lens, indirect ophthalmoscope and 22-gauge needle. For the remaining 2 cases, aspiration biopsy was done by using 20-gauge pars plana vitrectomy and 22-gauge needle. A histopathologist examined the aspiration material in the operating room during the procedure. Results: Fine-needle aspiration biopsy of 14 patients showed that 3 had optic nerve melanocytoma, 2 had chorodial melanoma, 1 had iridociliary medulloepithelioma, 1 had iris melanoma, 1 had trabecular meshwork melanoma, 1 had iris nevus, 1 had leukemic infiltration, 1 had lymphoma, 1 had neuroendocrine carcinoma,1 had xanthogranuloma, and 1 patient had normal fine-needle aspiration biopsy findings. Discussion: Fine-needle aspiration biopsy and cytopathology have an important role in the diagnosis of intraocular tumors that can not be reliably diagnosed by clinical examination. [ABSTRACT FROM AUTHOR]

A tumor of the left eye with involvement of the brain and kidney was diagnosed in a 4-year-old Neapolitan mastiff.The dog presented with acute glaucoma of the left eye. Peripheral corneal vascularization and severe corneal edema obscured examination of deeper structures. Because of concurrent progressive neurologic signs the dog was euthanized and a postmortem examination was performed. The eyes, brain and samples from the lung, heart, liver and kidneys were fixed in 4% neutral buffered formalin and embedded in paraffin wax. Sections were examined by light microscopy including histochemical and immunohistochemical staining.The ocular tumor originated from the ciliary body and was composed of small islets and cords of poorly differentiated, oval to polyhedral cells surrounded by abundant ground substance. Areas with chondroid differentiation were observed. Rosettes were not found. Metastases with the same morphology were present in the brain and in one kidney.An intraocular malignant teratoid medulloepithelioma with metastases to the brain and kidney is presented. [ABSTRACT FROM AUTHOR]

Background: Choroidal nevi are benign melanocytic lesions of the posterior uvea, which rarely exceed 5mm diameter and 1mm width, with a prevalence between 4.6% and 7.9% in Caucasians. In comparison, choroidal melanoma is rare (6/1mil. Caucasian), but it is the most common primary intraocular malignancy and the second most common intraocular tumor, according to the American Academy of Ophthalmology. Objective: We present the case of a 75 years old woman, having a right eye choroidal tumor, accidentally discovered at the ophthalmologic examination. It can be hardly decided whether it's benign or malign tumor. Materials and methods: The fundoscopic exam revealed a melanocytic tumor formation in inferior-temporal equatorial region of the right eye, with dimensions 8,3/6,6mm diameter and area of 39mm2, located at choroidal level. The lesion had a gray color, with hyperpigmented black areas on the tumor surface, respectively yellow deposits of lipofuscin at the periphery. The OCT exam reveals the presence of intra-retinal serous collections, without the presence of Drusen and the ocular echography identifies a width of 2mm of the tumor. Results: The tumor cannot have a certain clinical diagnostic of a benign or malign lesion, because it has some characteristics from both types, according to the American Academy of Ophthalmology guideline, and there is no possibility for a biopsy. As follows up after one respectively two months, the evolution of the tumor is stationary. The patient will be given no medication and she will be re-evaluated periodically. Conclusions: The diagnosis of an intraocular tumor can sometimes be very problematic. In the presented case, only a careful monitoring of the tumor and an objective comparison with the guides values can reveal the real type of lesion: malign or benign. [ABSTRACT FROM AUTHOR]