UNASSIGNED: In the past few decades, the primary management for uveal melanoma has evolved from enucleation to eye-preserving treatments. However, despite achieving a high rate of local tumour control, complications following eye-preserving treatments still occur and are partly responsible for functional loss and secondary enucleation.
UNASSIGNED: A literature review by a broad international panel.
UNASSIGNED: We summarised the current literature on utilizing vitreoretinal (VR) surgery for managing the complications of uveal melanoma. We also provided insights from the authors\' personal experience and practical recommendations for clinical care.
UNASSIGNED: With the advancement of VR instruments and surgical techniques and the combination of VR and ocular oncology knowledge (\"Onco-VR\"), it is now possible to manage or even prevent complications such as vitreous haemorrhage, retinal detachment, and toxic tumour syndrome.

UNASSIGNED: Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation.
UNASSIGNED: Potential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice.
UNASSIGNED: Research has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM.
UNASSIGNED: This study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

Background: This study aimed to evaluate the potential of human-machine interaction (HMI) in a deep learning software for discerning the malignancy of choroidal melanocytic lesions based on fundus photographs. Methods: The study enrolled individuals diagnosed with a choroidal melanocytic lesion at a tertiary clinic between 2011 and 2023, resulting in a cohort of 762 eligible cases. A deep learning-based assistant integrated into the software underwent training using a dataset comprising 762 color fundus photographs (CFPs) of choroidal lesions captured by various fundus cameras. The dataset was categorized into benign nevi, untreated choroidal melanomas, and irradiated choroidal melanomas. The reference standard for evaluation was established by retinal specialists using multimodal imaging. Trinary and binary models were trained, and their classification performance was evaluated on a test set consisting of 100 independent images. The discriminative performance of deep learning models was evaluated based on accuracy, recall, and specificity. Results: The final accuracy rates on the independent test set for multi-class and binary (benign vs. malignant) classification were 84.8% and 90.9%, respectively. Recall and specificity ranged from 0.85 to 0.90 and 0.91 to 0.92, respectively. The mean area under the curve (AUC) values were 0.96 and 0.99, respectively. Optimal discriminative performance was observed in binary classification with the incorporation of a single imaging modality, achieving an accuracy of 95.8%. Conclusions: The deep learning models demonstrated commendable performance in distinguishing the malignancy of choroidal lesions. The software exhibits promise for resource-efficient and cost-effective pre-stratification.

OBJECTIVE: To report a case of atypical nodular posterior scleritis mimicking as a melanotic choroidal melanoma.
METHODS: Descriptive case report.
RESULTS: A 38-year-old female presented with sudden onset diminution of vision, severe pain and redness in her right eye. She was diagnosed to have choroidal melanoma in her left eye one year ago and underwent enucleation. On examination, conjunctiva was injected in right eye with cells in anterior vitreous face (AVF). Fundus examination revealed a large pigmented choroidal mass temporal to macula with exudative retinal detachment. Systemic evaluation and multimodal imaging ruled out the possibility of a choroidal melanoma or metastasis, with a presumptive diagnosis of nodular posterior scleritis. Three cycles of intravenous methyl prednisolone (IVMP) with a tapering dose of oral corticosteroids showed drastic improvement in symptoms with resolution of choroidal mass - further confirming the diagnosis.
CONCLUSIONS: In cases of choroidal mass with an inflammatory component, a trial of steroids is worthwhile to prevent clinical misjudgement and devastating treatment outcomes including enucleation.

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

MicroRNAs (miRNAs) are short non-coding RNAs (18-25 nucleotides in length) that are important participants in the regulation of gene expression. In 2003, their active role in oncogenesis was demonstrated. In 2008, the first report on the isolation of miRNAs from uveal melanoma (UM) tissue was published. Four years later (2012), the presence of miRNAs in the plasma of patients with this category was shown. To date, changes in the expression level of 100 miRNAs in the plasma of cancer patients (with cancer of various localizations) out of the 2654 miRNAs described in mirbase.org have been proven. In the plasma of patients with UM, changes in the expression of only 13 miRNAs have been confirmed. As a rule, studies were conducted in patients at the stage of hematogenous metastasis of UM.
OBJECTIVE: This study analyzed the expression pattern of miRNA-223 and miRNA-126 in patients with localized choroidal melanoma (CM) taking into account biometric parameters in the absence of metastases.
METHODS: Blood plasma of 84 patients with M0N0 CM aged 35-86 years (mean age 63.4±1.2 years) was investigated. The basis for the diagnosis of CM was the results of ophthalmological examination, optical coherence tomography, and ultrasound scanning. In all cases, the absence of metastases was proven (using computed tomography or magnetic resonance imaging). Control - plasma of 28 volunteers (mean age 62.9±1.42 years, age range 45-78 years), who did not have tumoral, autoimmune, or chronic inflammatory processes. The expression levels of miRNAs circulating in blood plasma were determined by real-time polymerase chain reaction.
RESULTS: An increase in the expression levels of miRNA-223 and miRNA-126 in the plasma of all 84 patients with CM was confirmed compared to the control group. Features of the miRNA expression pattern that emerged with changes in the tumor\'s quantitative parameters were identified.
CONCLUSIONS: Evaluation of the levels of miRNA-223 and miRNA-126 in the blood plasma of patients with CM can be used in clinical practice to clarify the diagnosis of CM, as well as to predict the development of hematogenous metastases.
МикроРНК — малые РНК (размером 18—25 нуклеотидов) — важные участники процесса регуляции экспрессии генов. В 2003 г. показано их активное участие в онкогенезе. В 2008 г. опубликовано первое сообщение о выделении микроРНК из ткани увеальной меланомы (УМ). Спустя 4 года (2012) было показано присутствие микроРНК в плазме крови больных этой категории. Из 2654 микроРНК, аннотированных в mirbase.org в плазме крови онкологических больных (рак различных локализаций), к настоящему времени доказаны изменения уровня экспрессии 100 микроРНК. В плазме крови больных УМ подтверждено изменение экспрессии только 13 микроРНК. Как правило, исследования проводили у больных на стадии гематогенного метастазирования УМ.
UNASSIGNED: Проанализировать характер экспрессии микроРНК-223 и микроРНК-126 у пациентов с локальной меланомой хориоидеи (МХ) с учетом биометрических показателей при условии отсутствия метастазов.
UNASSIGNED: Исследована плазма крови 84 больных МХ M0N0 в возрасте 35—86 лет (в среднем 63,4±1,2 года). Основание для постановки диагноза МХ — результаты офтальмологического обследования, оптической когерентной томографии и ультразвукового сканирования. Во всех случаях доказано отсутствие метастазов (с помощью компьютерной или магнитно-резонансной томографии). Контроль — плазма крови 28 волонтеров (средний возраст — 62,9±1,42 года, диапазон возраста — 45—78 лет), не имевших опухолевых, аутоиммунных, хронических воспалительных процессов. Уровни экспрессии микроРНК, циркулирующих в плазме крови, определяли методом полимеразной цепной реакции в режиме реального времени.
UNASSIGNED: Подтверждено увеличение уровня экспрессии микроРНК-223 и микроРНК-126 в плазме крови у всех 84 пациентов с МХ по сравнению с контрольной группой. Выделены особенности характера экспрессии микроРНК по мере увеличения метрических показателей опухоли.
UNASSIGNED: Исследование уровня микроРНК-223 и микроРНК-126 в плазме крови больных МХ может быть использовано в клинической практике с целью не только уточнения диагноза МХ, но и прогнозирования развития гематогенных метастазов.

In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness (p = 0.00), greatest basal diameter (p = 0.00), number of risk factors (p = 0.00), symptoms (p = 0.001; relative risk [RR]: 4.3), orange pigment (p = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); p = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm (p = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter (p = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors.

UNASSIGNED: Stereotactic radiotherapy (SRT) in the treatment of choroidal melanoma (CM) may be indicated if the tumour is located close to the optic nerve or is unsuitable for a radiotherapeutic plaque. It is thought that the rate of visual decline and ocular sequelae with SRT is influenced by dose and location of radiation in relation to important visual structures. This study therefore aimed to look at these prognoses with respect to localisation and dose of radiation when treatment of CM with SRT occurs.
UNASSIGNED: A retrospective data analysis was conducted on all patients at Dunedin Hospital (DH) from August 2001 to May 2017 who were followed up for 4 years. SRT consisted of 50 Gy divided into five fractions over 5 days to tumours, with 2-mm treatment margins. The primary outcome measure was retention of functional vision - better than hand movements (HMs) within the treated eye. Secondary outcome measures included time to non-functional vision (HM or less) in relation to location, dose and tumour thickness, the presence of radiation retinopathy, local and metastatic tumour progression, enucleation, and disease-specific mortality.
UNASSIGNED: Seventy-five patients were identified in this study. Follow-up was incomplete in 10 patients, and 4 patients became deceased within the 4-year study period. Twenty-nine patients (48%) retained visual acuity (VA) better than HMs in the treated eye at 4 years, and thirty-two (52%) of patients did not. Calculated dose to the optic nerve and macula and proximity of the tumour to the optic nerve and macula were not statistically determinative of vision outcomes, although presenting VA was. Fifty-six per cent of patients developed radiation retinopathy involving the macula. The local progression, metastatic progression and enucleation rates were 4.6%, 6%, and 12.3%, representing 3, 4, and 8 patients, respectively.
UNASSIGNED: This study demonstrates that approximately half of patients treated with SRT can expect to maintain functional vision better than HM at 4 years. The rate of visual decline and final vision outcome are independent of location of the tumour in relation to the optic nerve and macula. While it affirms that SRT achieves high rates of local tumour control and eye retention, preservation of functional VA remains an unpredictable endpoint for individual cases and highlights the therapeutic challenge of this treatment modality.

UNASSIGNED: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions.
UNASSIGNED: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied.
UNASSIGNED: CEUS analysis showed that the time-averaged estimated contrast was significantly higher (p = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM (p = 0.001 for CH cases and p < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher (p = 0.032) for CH (m = 0.61) than for CM (m = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher (p = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM.
UNASSIGNED: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions.

UNASSIGNED: This study was conducted to develop a comprehensive nomogram for individuals with choroidal melanoma (CM) to determine their cancer-specific survival (CSS).
UNASSIGNED: Data of individuals with CM, diagnosed between 2004 and 2015, were accessed at the Surveillance, Epidemiology, and End Results (SEER) database. The selected individuals were randomly categorized into a training and validation cohort. Multivariate Cox regression analysis was applied to screen the relevant variables. Followed by the development of a nomogram based on independent variables. Ultimately, the net reclassification index (NRI), concordance index (C-index), calibration charts, integrated discrimination improvement (IDI), receiver operating characteristic curves (ROC), area under the curve (AUC), and decision-curve analysis (DCA), were utilized to evaluate the discrimination, accuracy, and effectiveness of the model.
UNASSIGNED: This study enrolled 3,782 patients. Seven independent factors linked to prognosis were screened via multivariate Cox regression analysis, encompassing age at diagnosis; race; AJCC (American Joint Committee on Cancer) stage; histologic type; and therapy method of radiotherapy, surgery, and chemotherapy. The respective C-indexes of the training and validation cohorts were 0.709 and 0.726, indicative of the excellent accuracy of the nomogram. Furthermore, the AUCs of the training and validation cohorts across 3, 5, and 8 years were 0.767, 0.744, and 0.722 as well as 0.772, 0.770, and 0.753, respectively. Evident of the superiority of the established nomogram over the AJCC staging, both the NRI and IDI values exhibited improvement. The favorable clinical impact and good performance of the nomogram were evident via decision curve analyses (DCAs) and calibration plots, respectively.
UNASSIGNED: This research dealt with establishing and validating a nomogram as a prognostic tool for assessing the prognosis of adult patients with CM utilizing the SEER database. A comprehensive assessment of the nomogram via diverse variables demonstrated its accuracy in predicting the CSS probabilities of CM patients across 3, 5, and 8 years in clinical settings. Notably, its performance surpassed that of the AJCC staging system.