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Background: Proton beam therapy (PBT) has been gradually introduced for treating choroidal melanoma. This study systematically reviewed clinical reports to evaluate the efficacy and safety of PBT in choroidal melanoma patients. Methods: This systematic review included all the primary studies involving PBT for choroidal melanoma patients through April 2024. Four publicly accessible databases were searched, and the statistical data were analyzed using STATA 15.0. The outcomes of interest included overall survival (OS), metastasis-free survival, local control rate, and adverse reactions. Results: A total of six case series involving 1059 patients with choroidal melanoma were included. The random effect model meta-analysis showed that the 2-, 3-, 5-, and 10-year OS rates of patients with choroidal melanoma treated with PBT were 97%, 92%, 73%, and 39%, respectively. The metastasis-free survival rates at 2, 3, and 5 years were 92%, 89%, and 76%, respectively, and the local control rates at 1, 3, 5, and 10 years were 98%, 92%, 94%, and 88%, respectively. Four studies reported adverse reactions. The most common adverse reactions after PBT were glaucoma, optic neuropathy, and cataracts, with incidence rates ranging from 17.9 to 27%, 12.8–64%, and 29.6–39.8%, respectively. Conclusions: This meta-analysis identified PBT as a vital local treatment strategy against choroidal melanoma. Both OS and local control rates showed excellent results. However, more prospective trials can help compare the efficacy of PBT with typical therapy. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsReport the results of Ruthenium plaque brachytherapy (106Ru) for the management of intraocular tumors in Thailand.We retrospectively reviewed the medical records of 46 eyes of 45 patients who received 106Ru brachytherapy for the treatment of various intraocular tumors in the Department of Ophthalmology of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, between April 2013 and December 2020.Of 46 eyes, 21 (46%) were diagnosed with small to medium choroidal melanoma, 13 (28%) with retinoblastoma, 4 (9%) with choroidal metastases, 2 (4%) with retinal vasoproliferative tumor (VPT), 3 (7%) with choroidal hemangioma (CH), 2 (4%) with RPE adenoma, and 1 (2%) with retinal hemangioblastoma. The mean tumor thickness was 4.8 mm (range, 2.4–6.6). After a mean follow-up of 62.4 months (range, 4.8–122.7), local tumor control was achieved in 39 eyes (85%), which were 100% for choroidal melanoma, 46% for RB, 100% for choroidal metastasis and 100% for benign tumors. Radiation-related complications were found in 28 eyes (61%), including cataracts in 10 (25%), radiation retinopathy in 14 (30%), radiation maculopathy in 14 (30%), radiation papillopathy in 6 (13%), and vitreous hemorrhage in 3 (7%) eyes. All patients with retinoblastoma currently alive without metastasis. Two patients with choroidal melanoma developed systemic metastases and three patients with choroidal metastases died at the end of the study.Patients with intraocular tumors treated with 106Ru brachytherapy showed excellent outcomes in relation to tumor control with few complications. [ABSTRACT FROM AUTHOR]

The prognostic implications of delaying treatment for primary uveal melanoma remain debated. We evaluate the impact of choroidal nevi and melanoma doubling times on metastatic death incidence and compare this impact across different tumor sizes. A literature search in PubMed and Web of Science targeted studies published after 1980 that quantified growth rates for choroidal or ciliochoroidal melanomas or nevi based on serial imaging found 199 melanomas and 87 growing nevi from 5 studies. In a random effects model, the estimated average volume doubling time was 360 days across all patients, with doubling times of 717, 421, and 307 days for small, medium, and large melanomas, respectively, and 6392 days for growing nevi. A mixed-effects model estimated that the 10-year incidence of metastatic death increases by 0.3, 1.8, and 4.0 percentage points every month a small, medium, and large melanoma remains untreated. Similar results were produced using two independent sources for survival data. These findings suggest that choroidal melanoma growth follows a super-exponential curve, with larger tumors exhibiting shorter doubling times. Based on these growth rates, delaying definitive treatment increases the risk of metastatic death by nearly zero to several percentage points per month, depending on tumor size. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence, clinical presentation, treatment, and follow-up of ocular (dermal) melanocytosis (ODM) and its association with choroidal melanoma (CM) in Asian Indian patients. Methods: This was a retrospective case series of patients with ODM conducted in a quaternary eye care center. Results: Of the total 1.48 million patients during the study period, we identified 213 patients with ODM with a prevalence rate of 0.014%. Median age at presentation was 13 years (range 0–76 years). Unilateral presentation of ODM was noted in 87% cases. ODM involved the sclera in 100% cases, the iris in 23%, the choroid in 20%, the eyelid in 29%, and V1 and V2 dermatomes in 53% cases. Nineteen patients (9%) were found to have CM, with 1.3 times increased risk of CM compared to the Caucasian population. The most common tumor location was in the inferior quadrant (n = 8, 44%). The mean tumor thickness was 8.3 ± 2.8 mm with a mean basal diameter of 14.0 ± 4.3 mm. Primary treatment of CM included plaque brachytherapy (n = 6), enucleation (n = 9), and few patients refused for treatment (n = 3). During a mean follow-up period of 21 months, one patient died because of lung metastasis. Conclusion: Although rare, choroidal melanoma does occur in the presence of ODM with an increased risk in Asian Indians compared to the Caucasian population. Patients with ODM should be examined periodically for early detection of CM. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a life-threatening cancer of the eye. There has been ongoing debate about whether treating the main tumor in the eye can actually help patients live longer. In our study, we compared previously published results from patients who received treatment for their eye tumor with those who chose not to receive treatment. By analyzing survival data from both groups, we discovered that patients who did not undergo treatment had a higher risk of death. This finding suggests that treating the primary eye tumor can provide a significant survival benefit for patients with uveal melanoma. Our results also emphasize the importance of timely treatment and may influence future medical guidelines and decisions, ultimately improving patient care for this serious eye cancer. Objective: To evaluate whether primary tumor treatment provides a survival benefit in uveal melanoma by comparing patients who declined treatment (Natural History Study, NHS) with those who received treatment in the Collaborative Ocular Melanoma Study (COMS) for medium-sized choroidal melanomas. Methods: Individual-level survival data were reverse-engineered from cumulative all-cause mortality curves in the original COMS and NHS publications. Censoring patterns were estimated from numbers at risk and descriptive statistics. A Bonferroni-corrected significance level of 0.017 was applied. Additionally, to ensure a conservative approach, NHS cohort data were iteratively adjusted by reducing the 8-year cumulative mortality by one percentage point if the Cox regression hazard ratio for all-cause mortality, the unadjusted risk ratio for death, and the 95% confidence intervals (CIs) of the Kaplan–Meier curves did not show a smaller survival difference than originally reported. Results: Kaplan–Meier analysis revealed significantly higher cumulative mortality in the NHS cohort compared to the COMS cohort (log–rank p = 0.012). When restricting the analysis to the first 8 years to account for unclear censoring patterns beyond this period, the NHS cohort still demonstrated worse survival (p = 0.008). A sensitivity analysis, varying censoring times by ±25% over 1000 iterations, confirmed worse survival in the NHS cohort in 100% of cases. Conclusions: In this re-evaluation, patients who declined treatment for medium-sized choroidal melanomas had significantly worse survival, suggesting a potential survival benefit of primary tumor treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Delays in treating uveal melanoma, a type of eye cancer, may increase the risk of the cancer spreading to other parts of the body. Traditionally, small eye tumors were often observed for growth before deciding on treatment, but new evidence suggests that this approach might allow the cancer to worsen. Our research explores the relationship between treatment delays and the risk of cancer spreading, showing that prompt treatment can reduce this risk. We also review the potential side effects of current treatments, such as radiation therapy, and highlight new strategies, like using medications to protect vision during treatment. The findings of this study may encourage eye specialists to adopt more timely and personalized treatment approaches, ultimately improving survival and quality of life for patients with uveal melanoma. Background: Recent studies suggest that delays in the definitive treatment of uveal melanoma may increase the risk of metastatic disease. This topic has been the subject of considerable debate. Methods: In this study, we combine and contrast medical evidence from several recent publications seeking to clarify the association between treatment delays and prognosis. Results: Emerging evidence indicates that metastatic seeding may continue until the primary tumor is effectively treated. Metastases that arise later in the disease course may carry additional genetic aberrations, enhancing their capacity to establish fatal macrometastases. Importantly, previous reports of shared mutations between primary tumors and metastases should not be interpreted as evidence that all metastases are seeded early. On the contrary, some tumors acquire additional driver mutations in the later stages, which are subsequently shared between the primary tumors and metastases. The increased risk of metastasis in patients with local tumor recurrence further highlights the importance of timely treatment. Additionally, new data on circulating tumor cells and treatment timing challenge the traditional practice of observing small melanomas. Conclusions: Observation is still warranted for indeterminate lesions to confirm malignancy. However, once a melanoma diagnosis has been established, further observation is harmful, and treatment should be administered as soon as reasonably possible. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated whether the anatomical location of metastases from posterior uveal melanoma affects survival. We found that patients with newly diagnosed metastatic posterior uveal melanoma who only have extrahepatic metastases had a significantly longer survival compared to patients with liver metastases. This insight could help clinicians improve the prediction of patient outcomes and enhance the selection of patients in clinical trials. Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 22-year-old male from Mali who presented with a large choroidal tuberculoma in his right eye, initially suspected to be a choroidal melanoma. Despite the absence of systemic signs of tuberculosis, further investigations revealed disseminated tuberculosis involving the central nervous system, lungs, lymph nodes, and bones. The patient underwent treatment with anti-tuberculosis medications for six months, resulting in the resolution of the lesions. The study emphasizes the importance of considering ocular manifestations as potential signs of systemic tuberculosis to prevent vision loss and life-threatening complications. [Extracted from the article]

BackgroundMethodsResultsConclusionsIn 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.A literature review by a broad international panel.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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: The differential diagnosis between small melanocytic lesions and choroidal nevus is challenging. We usually rely on clinical risk factors to establish the need for immediate treatment vs. close monitoring followed by treatment if the lesion grows. We aimed to describe the features of small indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. Our findings show that the vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Choroidal melanomas are treated in the hope of preventing metastatic death; however, such treatment often causes severe visual loss. There is debate as to whether the treatment of small tumors can be deferred until tumor growth is observed. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), this study provides an indication of change in the 15-year absolute risk of metastatic death, according to whether the tumor is treated immediately or after 4 or 12 months, when growth is observed. It considers tumor growth rate, dimensions, laboratory indicators of metastasis risk, prevalence of monosomy 3, patient's age, and sex. Our study suggests that deferring treatment until growth is observed is associated with minimal, if any, increase in the risk of metastatic death with usual tumor growth rates of up to 40% per year. It would seem reasonable to delay treatment until tumor growth is documented, especially if this is likely to cause visual loss. Background: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. Methods: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. Results: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. Conclusions: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year. [ABSTRACT FROM AUTHOR]

Purpose: Choroidal melanoma (CM), a kind of malignant tumor, is the main type of Uveal melanoma and one half of CM patients develop metastases. As a member of Eph/ephrin pathway that plays vital role in tumors, EphrinA3 (EFNA3) has been proved to promote tumorigenesis in many tumors. But the effect of EFNA3 in CM has not been studied yet. Through inhibiting angiogenesis, inducing apoptosis and autophagy and so on, Artesunate (ART) plays a key anti-tumor role in many tumors, including CM. However, the exact mechanisms of anti-tumor in CM remain unclear. Methods: The UALCAN and TIMER v2.0 database analyzed the role of EFNA3 in CM patients. Quantitative real time polymerase chain reaction (qPCR) and Western blot were used to detect the expression of EFNA3 in CM. The growth ability of CM was tested by clonogenic assay and Cell counting kit-8 assay, and the migration ability using Transwell assay. Results: Our results found EFNA3 boosted CM cells’ growth and migration through activating Stat3/Akt signaling pathway, while ART inhibited the tumor promoting effect of CM via downregulating EFNA3. In xenograft tumor model, EFNA3 knockdown and ART significantly inhibited tumor growth. Conclusion: EFNA3 could be a valuable prognostic factor in CM. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to correlate color Doppler with the vascularization of choroidal melanoma (CM) observed in histopathological sections and also to analyze the vascular histopathological prognostic factors of these tumors. Patients, Materials, and Methods: This was an experimental, cross-sectional, and analytical study carried out at Escola Paulista de Medicina - UNIFESP (São Paulo) and at the Ocular Pathology and Translational Research Laboratory of McGill University (Montreal/Canada). Twenty-five enucleated eyes of patients with CM were studied, 10 patients studied at UNIFESP and 15 patients studied at McGill University. The first 10 patients (Brazil), before enucleation, were submitted to color Doppler, all performed at UNIFESP. The resistance index (RI) and maximum systolic velocity of each tumor were calculated. The inclusion criteria of this study were as follows: CMs >8 mm in thickness, enucleation as primary treatment, histopathological blocks sufficient for hematoxylin-eosin staining, periodic acid-Schiff, and CD34 immunohistochemistry. Exclusion criteria included tumors smaller than 8 mm and/or previous treatments such as laser or brachytherapy. Regarding the histopathology of each CM, cell-type classification, vessel diameter measurements, count of the number of mitoses, and vascular clefts were carried out. The latter are considered vessels because they are lined by endothelium (CD34 positive) and surrounded by melanoma cells. Results: There was a statistical correlation between RI and cell type (P < 0.05). Tumors with a better prognosis (spindle cell) showed higher RI compared to epithelioid tumors, with a worse prognosis. The number of mitoses and vascular clefts correlated with the cell type, with a statistically significant difference (P < 0.001). Tumors of worse prognosis (epithelioid) showed an increase in the number of mitoses and in the number of vascular clefts. There was no difference between vessel diameter and cell type. Conclusions: The number of vascular clefts has a positive prognostic correlation with the malignancy of CM. Doppler RI showed a positive prognostic correlation with CM malignancy. For the first time, the usefulness of vascular clefts as prognostic factors was proven, and a new classification of the vascular network in CMs was proposed. [ABSTRACT FROM AUTHOR]

Introduction: Melanoma is a dangerous malignancy primarily involving the choroid, ciliary body, or iris. The most frequent primary intraocular malignant tumor is choroidal melanoma. The tumor most often affects Caucasians of Northern Europe ranging between the ages of 50 and 80. Most choroidal melanomas are pigmented, however, non-pigmented or mixed pigmented and non-pigmented forms can also happen. Compared with other amelanotic choroidal lesions, amelanotic choroidal melanoma showed markedly greater basal diameter, thickness, frequent connection with subretinal fluid, and ultrasonic hollowness. Extrascleral extension is currently detected in 10% to 28% of choroidal melanoma patients, and the mortality rate is much greater than in those without the extension. Case Presentation: We reported a rare case of extraocular extension in a 51-year-old female patient with amelanotic melanoma. The primary complaint was a painful and bleeding mass on her left eye that had developed two months prior to admission. On the conjunctiva of the left eye, there was a solid, palpable mass measuring 4 x 3.5 x 1 cm. It was red, well-defined, and had a hard, solid consistency. It was fixed at the base, had minimal bleeding, and pressed on her eyeball from the inferolateral direction. The cornea appears clear, and there is no light perception in visual acuity. The orbital focus computed tomography scan revealed an Enhancing solid mass containing a fat component. The mass was in the left intraocular, extending from intraconal to extraconal. Conclusions: Amelanotic melanoma with extraocular extension is a rare condition that can be difficult to detect due to its unclear clinical symptoms and wide range of possible causes. Patients and their families must be educated to receive the appropriate first therapy and prevent the illness from worsening. Melanoma management depends on several factors: tumor size, location, related characteristics, opposite eye status, systemic status, and patient preference. Orbital exenteration is one of the management options for choroidal melanoma with significant extraocular extension. By the time ocular treatment begins, the patient's survival may already be predetermined, and this realization could impact how uveal melanoma is treated in the years to come. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurate diagnosis of early-stage choroidal melanoma, the most commonly occurring malignancy of the eye, is extremely important yet highly challenging. Unfortunately, due to challenges in obtaining adequate sampling and the risk of vision loss, intraocular melanoma remains largely a clinical diagnosis, which can be subjective. Most of the existing tools and diagnostic methods lack definitive discriminative features, leading to uncertainties in clinical diagnoses. In this work, we present and evaluate a novel, contrast-free ultrasound-based method for quantitative assessment of microvascular characteristics of choroidal tumors, aiming at distinguishing malignant lesions based on the complex and irregular microvessel formations within them. Using this method, we visualize intratumoral microvascular networks, estimate their morphological features using objective quantitative metrics, and perform statistical analyses demonstrating differences between lesions based on their malignancy status. The results of this preliminary study show promise for further assessment of the method as a complementary diagnostic tool for ocular tumors. Angiogenesis has an essential role in the de novo evolution of choroidal melanoma as well as choroidal nevus transformation into melanoma. Differentiating early-stage melanoma from nevus is of high clinical importance; thus, imaging techniques that provide objective information regarding tumor microvasculature structures could aid accurate early detection. Herein, we investigated the feasibility of quantitative high-definition microvessel imaging (qHDMI) for differentiation of choroidal tumors in humans. This new ultrasound-based technique encompasses a series of morphological filtering and vessel enhancement techniques, enabling the visualization of tumor microvessels as small as 150 microns and extracting vessel morphological features as new tumor biomarkers. Distributional differences between the malignant melanomas and benign nevi were tested on 37 patients with choroidal tumors using a non-parametric Wilcoxon rank-sum test, and statistical significance was declared for biomarkers with p-values < 0.05. The ocular oncology diagnosis was choroidal melanoma (malignant) in 21 and choroidal nevus (benign) in 15 patients. The mean thickness of benign and malignant masses was 1.70 ± 0.40 mm and 3.81 ± 2.63 mm, respectively. Six HDMI biomarkers, including number of vessel segments (p = 0.003), number of branch points (p = 0.003), vessel density (p = 0.03), maximum tortuosity (p = 0.001), microvessel fractal dimension (p = 0.002), and maximum diameter (p = 0.003) exhibited significant distributional differences between the two groups. Contrast-free HDMI provided noninvasive imaging and quantification of microvessels of choroidal tumors. The results of this pilot study indicate the potential use of qHDMI as a complementary tool for characterization of small ocular tumors and early detection of choroidal melanoma. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy is the gold‑standard treatment for choroidal melanoma. This study evaluated iodine‑125 brachytherapy by using Ocuprosta seeds with indigenous non‑collimated plaques in Asian patients. Methods: Retrospective single‑center study in a tertiary care hospital of 12 eyes with choroidal melanoma in 12 Asian patients who underwent brachytherapy with Ocuprosta seeds fixed on non‑collimated plaques and had a follow‑up of at least 32 months (mean: 42.4 ± 9.5 months; median: 40 months). Radiotherapy was planned after developing the digital 3D model of the tumor within the eye by using radiological images and clinical pictures. Ocuprosta iodine‑125 seeds were used on indigenous non‑collimated gold plaques to deliver the radiation for precalculated time. “Successful outcome” was taken as a decrease in the volume of the tumor, and “unsuccessful outcome” was defined as no change in the tumor volume or increase in the tumor volume at 24 months after brachytherapy. Results: The mean decrease in tumor volume was 21% (914.5 ± 912.2 mm³ to 495.7 ± 633.6 mm³ ) after brachytherapy, which correlated with the baseline volume of the tumor. Ten eyes (83.3%) showed a reduction in tumor volume, whereas two eyes showed an increase in the volume of the tumor after brachytherapy. One of the cases with a reduction in tumor size developed neovascular glaucoma. Enucleation was done in three eyes. A globe salvage rate of 75% and tumor regression rate of 83% were seen in the present study using Ocuprosta seeds. Conclusions: Iodine‑125 brachytherapy with uncollimated indigenous gold plaques is an effective treatment modality for choroidal melanomas in Asian patients. [ABSTRACT FROM AUTHOR]

Plaque brachytherapy has been used in the management of small to medium-sized choroidal melanomas for the past few decades. As the inferior oblique muscle lies in close relation to the macula, the placement procedure of plaques often involves sacrificing the inferior oblique muscle, especially in cases of macular or perimacular choroidal melanomas. In this study, we have described a simple maneuver to preserve the inferior oblique muscle. [ABSTRACT FROM AUTHOR]

Introduction: In an effort to replace ultrasonography-based thickness measurements, we investigated whether choroidal melanoma characteristics are related to progression-free survival (PFS) in patients monitored after linear accelerator (LINAC)-based hypofractionated stereotactic photon radiotherapy. Methods: In a retrospective dataset, we used a linear mixed model to assess the associations between PFS and tumor characteristics; in particular, thickness, largest basal diameter (LBD), base area and volume. Results: Thickness and LBD are statistically significantly associated with PFS. In a subgroup of 16 patients undergoing enucleation due to melanoma recurrence or progression, there were statistically significant changes in mean thickness and LBD before surgery. Mean PFS was 42 ± 30 months. Conclusion: Ultrasonography-based thickness measurements may not be necessary for treated choroidal melanoma monitoring; instead, we propose sequential LBD assessments, which should preferably be performed using fundus photography in future. [ABSTRACT FROM AUTHOR]

Purpose: Small choroidal melanocytic lesions have a low rate of metastasis and can be reasonably managed with surveillance until they demonstrate evidence of growth or clinical risk factors for melanoma. However, even choroidal nevi are not stationary, with many exhibiting slow growth over time. We sought to quantify the growth rates of indeterminate choroidal lesions that were initially observed prior to a clinical diagnosis of melanoma. Methods: A single-center retrospective study was performed of patients diagnosed with choroidal melanoma based upon clinical characteristics who were initially followed for indeterminate lesions over at least 6 months. Subjects were included if they had a minimum of two B-scan ultrasound measurements prior to the visit at which melanoma was diagnosed. Demographic and tumor characteristics were collected from the medical record. Growth rates were calculated as the change in lesion thickness in mm per month and were recorded at 6-month intervals; ultrasound measurements less than 1 month apart were excluded. The characteristics of indeterminate lesions with faster versus slower growth rates prior to melanoma diagnosis were compared. Results: Fifty-four patients met inclusion criteria. The mean age at melanoma diagnosis was 67.4 years, and 53.7% were female. Subjects had a median of four B-scan ultrasound measurements prior to melanoma diagnosis (range 2–19) and were followed for a median of 40.6 months (range 9.9–138.0 months). The mean lesion thickness was 1.4 mm (range 0.5–2.2 mm) at presentation, and increased to 2.3 mm (range 1.5–5.7 mm) at melanoma diagnosis. The mean growth rate did not exceed 0.021 mm/month (95% CI: 0.004–0.039; equivalent to 0.25 mm/year) for indeterminate lesions, but increased to 0.057 mm/month (95% CI: 0.043–0.071 mm/month; equivalent to 0.68 mm/year) at the time of melanoma diagnosis. Rapidly growing lesions had a greater tumor thickness and shorter duration of observation at the time of melanoma diagnosis. Conclusion: For most indeterminate choroidal lesions eventually diagnosed as melanoma, the lesion thickness was relatively stable for a period of time, then rose significantly between the penultimate visit and the final visit. These findings confirm the recommendation for continued monitoring of suspicious choroidal lesions, as the growth rate may accelerate just prior to melanoma diagnosis. Lesions with a mean growth rate of up to 0.25 mm/year were observed, whereas lesions clinically determined to have transformed into melanoma demonstrated a mean growth rate of 0.68 mm/year. These values provide a baseline for future studies and potential therapies directed at stabilizing or reducing the growth of indeterminate choroidal lesions or small choroidal melanomas. Limitations of this study include its retrospective nature and reliance on clinical diagnostic criteria. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy is the gold-standard treatment for choroidal melanoma. This study evaluated iodine-125 brachytherapy by using Ocuprosta seeds with indigenous non-collimated plaques in Asian patients. Methods: Retrospective single-center study in a tertiary care hospital of 12 eyes with choroidal melanoma in 12 Asian patients who underwent brachytherapy with Ocuprosta seeds fixed on non-collimated plaques and had a follow-up of at least 32 months (mean: 42.4 ± 9.5 months; median: 40 months). Radiotherapy was planned after developing the digital 3D model of the tumor within the eye by using radiological images and clinical pictures. Ocuprosta iodine-125 seeds were used on indigenous non-collimated gold plaques to deliver the radiation for precalculated time. "Successful outcome" was taken as a decrease in the volume of the tumor, and "unsuccessful outcome" was defined as no change in the tumor volume or increase in the tumor volume at 24 months after brachytherapy. Results: The mean decrease in tumor volume was 21% (914.5 ± 912.2 mm3 to 495.7 ± 633.6 mm3) after brachytherapy, which correlated with the baseline volume of the tumor. Ten eyes (83.3%) showed a reduction in tumor volume, whereas two eyes showed an increase in the volume of the tumor after brachytherapy. One of the cases with a reduction in tumor size developed neovascular glaucoma. Enucleation was done in three eyes. A globe salvage rate of 75% and tumor regression rate of 83% were seen in the present study using Ocuprosta seeds. Conclusions: Iodine-125 brachytherapy with uncollimated indigenous gold plaques is an effective treatment modality for choroidal melanomas in Asian patients. [ABSTRACT FROM AUTHOR]

To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology. Imaging and histologic analysis of a retrospective cohort of patients. Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023. Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA). Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated. Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51–88 years). The median largest basal diameter was 16.10 mm (range, 9.17–21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40–13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative. Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Background: Choroidal melanoma (CM) is an intraocular tumor that arises from melanocytes. While ubiquitin-specific protease 2 (USP2) modulates the progression of numerous diseases, its role in CM is not known. This study aimed to determine the role of USP2 in CM and elucidate its molecular mechanisms. Methods: MTT, Transwell, and wound-scratch assays were used to investigate the function of USP2 in the proliferation and metastasis of CM. Western blotting and qRT-PCR were used to analyze the expression of USP2, Snail, and factors associated with the epithelial-mesenchymal transition (EMT). The relationship between USP2 and Snail was explored by co-immunoprecipitation and in vitro ubiquitination assays. A nude mouse model of CM was established for verifying the role of USP2 in vivo. Results: USP2 overexpression promoted proliferation and metastasis, and induced the EMT in CM cells in vitro, while specific inhibition of USP2 by ML364 produced the opposite effects. ML364 also suppressed CM tumor growth in vivo. Mechanistically, USP2 is known to deubiquitinate Snail, stabilizing the latter through the removal of its K48 poly-ubiquitin chains. However, a catalytically inactive form of USP2 (C276A) had no effect on Snail ubiquitination and failed to increase Snail protein expression. The C276A mutant was also unable to promote CM cell proliferation, migration, and invasion, as well as EMT progression. Furthermore, Snail overexpression partly counteracted the effects of ML364 on proliferation and migration, while rescuing the effects of the inhibitor on the EMT. Conclusions: The findings demonstrated that USP2 modulated CM development through the stabilization of Snail and suggest that USP2 may be a useful target for the development of novel treatments for CM. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma (UM) is a rare cancer highly prone to metastasis. Metastatic risk is currently predicted using clinical and/or tumor biopsy-based information. While tumor biopsy-based molecular information is helpful, there is an unmet need for a liquid biopsy-based approach as a more advantageous alternative to tumor biopsy. Given that UMs primarily arise in the posterior eye segment, vitreous (which fills the posterior eye cavity) represents a fluid source enriched in tumor-derived molecules. Inflammatory microenvironment indicates poor prognosis in UM and cytokines are key mediators of immune response/inflammation. Vitreous cytokine analysis may therefore increase our understanding of UM and inform future clinical strategies. In this study, we analyzed 41 vitreous cytokines in 32 eyes (18 with posterior UM and 14 controls) and identified 26 UM-associated and 6 prognosis-relevant cytokines. Our findings further support the value of vitreous cytokine analysis in UM and the need for additional studies to establish the best candidates for biomarker development and/or therapeutic targeting. Due to the close relationship between the vitreous and posterior eye layers, the microenvironment of these layers can affect the composition of the vitreous. Molecular analysis of the vitreous may therefore provide important insights into the pathogenesis of chorioretinal diseases. In this study, vitreous cytokines (n = 41) were evaluated to gain further insights into the tumor microenvironment in uveal melanoma (UM) arising from the choroid (CM). Cytokine levels were measured using a bead-based multiplex immunoassay panel in vitreous samples obtained from 32 eyes, including 18 with CM and 14 controls. Median fluorescence intensity values were extracted and used as relative quantification of the cytokine abundance. Vitreous cytokine levels were compared between the CM and non-CM groups and between different prognostic categories within the CM group (classified as having low or high metastatic risk using tumor biopsy-based gene expression profiling). Correlations between vitreous cytokine levels and tumor dimensions were also evaluated. Our analysis revealed twenty-six vitreous cytokines significantly upregulated in CM-affected eyes compared to the control eyes. Within the CM group, six vitreous cytokines showed altered levels (five upregulated and one downregulated) in eyes with high- vs. low-risk tumors. Levels of these six plus several other cytokines showed correlations with the tumor dimensions. In conclusion, our study has uncovered several UM-relevant vitreous cytokines, worthy of follow-up in larger studies as potential candidates for liquid biopsy-based biomarker development and/or new therapeutic targeting. [ABSTRACT FROM AUTHOR]

Objective To construct the prognostic prediction model for choroidal melanoma. Methods The clinical data (age, gender, marital status, race, TNM stage, pathological type, bone metastasis, lung metastasis, liver metastasis, surgery information, radiotherapy and chemotherapy, survival time, and survival status, etc.) of 2 235 patients diagnosed with melanoma of choroid from 2010 to 2015 were collected from the National Cancer Institute surveillance, epidemiology, and end results （SEER） database. All data were randomly divided into the model group of 1 584 cases and verification group of 651 cases at a ratio of 7：3. First, the clinical data in the model group were analyzed using the Cox hazard proportional regression model of the "survival" package in the R4. 1. 2 software to conduct univariate and multivariate analysis to obtain independent factors affecting the prognosis of patients with melanoma of choroid. The selected influencing factors were used to construct the prognostic prediction model of melanoma of choroid using the "rms" package in the R4. 1. 2 software. The discrimination and consistency of the prediction model were evaluated by C index, ROC and calibration curve in the model group and the verification group. Results Age, pathological type, T stage, M stage, and local radio‐ therapy were independent factors affecting the prognosis of melanoma of choroid. Based on the above factors, a prognostic prediction model for melanoma of choroid was constructed. The C indices of the prognostic prediction model in the model group and the verification group were 0. 732 (95%CI：0. 710，0. 761) and 0. 713 (95%CI：0. 670，0. 756), respectively. The area under the ROC curve of the model group for 1 year，2 years, and 3 years was 0. 780，0. 766, and 0. 777 respectively； the area under the ROC curve of the verification group for 1，2, and 3 years was 0. 890，0. 755, and 0. 734, respectively. The data of both groups were higher than 0. 7, indicating good discrimination. The calibration curves of the model group and the verification group had a high degree of coincidence with the 45°straight line in the plane cartesian coordinate system, indicating good consistency. Conclusion The prognostic prediction model of melanoma of choroid is successfully established, and it has a good predictive effect on the prognosis of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This is the first study on the tumor microenvironment of uveal melanoma with special regard to the localization within the tumor and the eye. Uveal melanoma is the most common malignant tumor of the eye in adults. Regardless of the treatment of the primary tumor, half of the patients with uveal melanoma die due to metastasis in the long run. The major findings of this study are that blood vessels are mainly located in the middle of the tumor and that immune cells (especially CD68-immunopositive macrophages) are mostly found in the outer section of the tumor. Furthermore, this study found a high representation of lymphocyte activation gene-3 (LAG-3) and Galectin-3 in uveal melanoma. These findings could set a foundation for new therapeutic strategies aimed at improving the survival rate of patients with uveal melanoma. Uveal melanoma (UM) is a highly malignant tumor of the eye. Metastatic spread of UM occurs almost exclusively via blood vessels and is of tremendous interest, as half of the patients with uveal melanoma die of metastasis in the long run. The tumor microenvironment consists of all cellular and non-cellular compounds of a solid tumor, except for the tumor cells. This study aims to provide a more detailed understanding of the tumor microenvironment of UM to build the foundation for new therapeutic targets. Fluorescence immunohistochemistry was performed to examine the localization of various cell types in the tumor microenvironment in UM. Furthermore, the presence of LAG-3 and its ligands Galectine-3 and LSECtin was examined to evaluate the potential efficacy of immune checkpoint inhibitor-based therapies. The main findings are that blood vessels are mainly located in the middle of the tumor, and that immune cells are mostly found in the outer section of the tumor. LAG-3 and Galectine-3 were found to be highly represented, whereas LSECtin barely occurred in UM. Both the predominant location of tumor-associated macrophages in the outer section of the tumor and the high presence of LAG-3 and Galectine-3 in the UM serve as attainable therapeutic targets. [ABSTRACT FROM AUTHOR]

Although melanocytic choroidal tumours of the choroid are a common eye pathology, no standardised protocol exists for their management in the community. Choroidal naevi are found in approximately 6% of the adult White population, whereas choroidal melanomas are rare, with an annual incidence of 5–10/million/year. Multimodal imaging has advanced the understanding of malignancy imaging biomarkers, but distinguishing between a small melanoma and naevus remains difficult and an algorithm for their management by community practitioners has not been uniformly adopted. One of the authors (BD) devised the MOLES scoring system, which indicates malignancy likelihood according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. When applied by ocular oncologists, the system accurately distinguishes choroidal naevi from melanomas. The aim of this study was to evaluate whether community optometrists can appropriately manage patients with melanocytic choroidal tumours using this system. Clinical images of 25 melanocytic choroidal tumours were presented in an online survey, including colour fundus photographs, fundus autofluorescence, optical coherence tomography, and B-scan ultrasound images. Using the MOLES system, 39 optometrists diagnosed tumours as naevus or probable melanoma and decided between community monitoring and ophthalmologist referral. Responses were compared to MOLES grading of the same clinical images by ocular oncologists. Using MOLES, optometrists correctly identified 389/406 probable melanomas (95.8% sensitivity) and 331/516 choroidal naevi (64.1% specificity); correctly referred 773/778 tumours to an ophthalmologist (99.4% sensitivity); and correctly managed 80/144 lesions (55.6% specificity) in the community. Optometrists safely applied the MOLES scoring system in this survey. Further measures are indicated to reduce choroidal naevi over-referral and evaluate MOLES system usage in clinical optometric practice, where some imaging modalities may not be readily available. [ABSTRACT FROM AUTHOR]

Purpose: To develop a prognostic test based on a single blood sample obtained at the time of uveal melanoma diagnosis. Methods: 83 patients diagnosed with posterior uveal melanoma between 1996 and 2000 were included. Peripheral serum samples were obtained at diagnosis and kept at -80 °C until this analysis. Protein profiling of 84 cancer-related proteins was used to screen for potential biomarkers and a prognostic test that stratifies patients into metastatic risk categories was developed (serUM-Px) in a training cohort and then tested in a validation cohort. Results: Low serum leptin levels and high osteopontin levels were found to identify patients with poor prognosis and were therefore selected for inclusion in the final test. In the validation cohort, patient sex and American Joint Committee on Cancer stages were similarly distributed between the low, intermediate, and high metastatic risk categories. With increasing metastatic risk category, patients had shorter metastasis-free- and overall survival, as well as greater cumulative incidence of uveal melanoma-related mortality in competing risk analysis (P = 0.007, 0.018 and 0.029, respectively). In multivariate Cox regression, serUM-Px was an independent predictor of metastasis with tumor size and patient sex as covariates (hazard ratio 3.2, 95% CI 1.5–6.9). Conclusions: A prognostic test based on a single peripheral venous blood sample at the time of uveal melanoma diagnosis stratifies patients into low, intermediate, and high metastatic risk categories. Prospective validation will facilitate its clinical utility. [ABSTRACT FROM AUTHOR]

Background: It is debated if there are sex‐based differences in survival for patients with uveal melanoma. Previous observations of higher mortality for men in studies with <10‐year follow‐up have not been replicated in studies with longer follow‐up. It is therefore hypothesized that women have a worse survival in later periods. Methods: All patients diagnosed with primary uveal melanoma in Sweden between 1980 and 2017 were included (n = 2032). Survival differences between men and women in early (<10 years from diagnosis) and late (≥10 years) periods were analyzed. Results: At baseline, there were no significant differences in mean patient age, tumor thickness, diameter, ciliary body involvement, primary treatment modality, or in American Joint Committee on Cancer (AJCC) T‐category between men and women. In total, 764 patients (425 women and 339 men) survived and were followed ≥10 years. In this group, men were significantly younger, but there were no differences in baseline tumor thickness, diameter, ciliary body involvement, primary treatment, or AJCC T‐category. In competing risk analysis, women had higher incidence of uveal melanoma‐related mortality in the late period (p = 0.036). In univariate Cox regression, male (HR 1.2, p = 0.049) and female sex (HR 1.8, p = 0.034) were significant predictors of uveal melanoma‐related mortality in the early and late periods, respectively. Conclusion: Women with uveal melanoma have better survival in the first decade after diagnosis. Thereafter, female survivors are significantly older than men and have a higher incidence of uveal melanoma‐related mortality. [ABSTRACT FROM AUTHOR]

Background: Various therapies ranging from plaque brachytherapy to enucleation have been applied in uveal melanomas (UM). A gamma knife (GK) is the gold standard modality for head and neck radiation therapy with enhanced precision owing to the paucity of moving parts. The literature on GK usage in UM is rich with the methodology and nuances of GK applications undergoing constant change. Objectives: This article reports on the authors’ experience in using GK for tackling UM followed by a thematic review of the evolution of GK therapy for UM. Materials and Methods: Clinical and radiological data of patients with UM treated with GK at the All India Institute of Medical Sciences, New Delhi, from March 2019 to August 2020 was analyzed. A systematic search for comparative studies and case series evaluating GK usage in UM was performed. Results: Seven UM patients underwent GK, with the median dose being 28 Gy at 50%. All patients underwent clinical follow‑up and 3 patients had a radiological follow‑up. Six (85.7%) eyes were preserved at follow‑up, and 1 (14.28%) patient developed radiation‑induced cataract. There was a reduction in tumor volume in all patients with radiological follow‑up with the minimum being a 33.06% reduction in size compared to the presenting volume and the maximum being the complete disappearance of tumor at follow‑up. A total of 36 articles presenting various facets of GK usage in UM have been thematically reviewed. Conclusion: GK can be a viable and effective eye‑preserving option for UM with catastrophic side effects becoming rare owing to progressive reduction in radiation dose. [ABSTRACT FROM AUTHOR]

Laser treatment has offered a relatively nonsurgical alternative for eye, life, and vision-sparing treatment of malignant melanoma of the choroid. Historically, the most commonly used forms of lasers were xenon-arc, argon laser, krypton laser, and the more recent transpupillary thermotherapy (TTT) and photodynamic therapy (PDT). Melanomas selected for laser treatment tend to be smaller and visibly accessible, which means these tumors are usually located in the posterior choroid. Laser treatments have been associated with both local tumor destruction and side effects. Unlike radiation therapy, laser treatment has been commonly associated with retinal traction, hemorrhage, chorioretinal neovascularization, and extra scleral tumor extension, as well as higher rates of local treatment failure. In addition, however, laser-treatment has been successfully used to treat tumor-related retinal detachments, radiation retinopathy, and neovascular glaucoma. We review the world's experience of ophthalmic laser treatment for choroidal melanoma, offer safety and efficacy guidelines, as well as a comparison of laser treatment to radiation therapy outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient-derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity. Methods: Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient-derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor-embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion. Results: Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross-sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki-67 positivity in Immunohistochemistry (IHC). Conclusion: The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient-specific tumors for preclinical drug screening. [ABSTRACT FROM AUTHOR]

The key to the treatment of choroidal melanoma (CM) is to improve diagnostic efficiency and find a high-performance treatment to replace the traditional treatment of radiotherapy and enucleation. In this paper, for the first time, long afterglow luminescence material was applied to the integrated diagnosis and treatment of eyes, with its unique advantages in photoluminescence and afterglow luminescence to solve the bottleneck problem of real-time irradiation required for photothermal and photodynamic therapy (PTT and PDT). Based on the excellent photoluminescence and afterglow properties of Zn 1.3 Ga 1.4 Ge 0.3 O 4 :Cr 0.004 Yb 0.04 Er 0.004 (ZGGO) nanoparticles, a nanoplatform ZGGO@Au@UiO-66@ZnPc:Dox-FA (GAUZD-FA) for NIR-Ⅱ imaging and triple-synergistic therapy (PTT, PDT and sustained-release drug) was constructed. GAUZD-FA showed excellent imaging and therapeutic ability for CM in vitro and in vivo under a systematic comparison of NIR imaging detection and anti-tumor activity. In addition, the precise active targeting of folic acid (FA) on tumor cells protected normal tissues from damage and stayed intraocularly for a relatively long time. This multi-functional nanoplatform provides a new strategy for an ideal mode of single injection and multiple treatments of CM. [Display omitted] • For the first time, long afterglow nanoplatform was designed for eye treatment. • NIR-Ⅱ imaging and triple-synergistic therapy (PTT, PDT and sustained-release drug). •An ideal mode of single injection and multiple treatments for choroidal melanoma. • A new strategy for integration of diagnosis and treatment of choroidal melanoma. [ABSTRACT FROM AUTHOR]

[Display omitted] The impact of Ang-1 on tumors remains a subject of contention, with its mechanism of action exhibiting complexity in the progression of diverse tumor types. Ang-1 has been shown to promote the progression of glioma, glioma, esophageal and human cervical cancer, whereas it exerts inhibitory effects on the growth of breast and colon cancer. However, the specific function of Ang-1 in CM has not been clarified. This research aims to explore the function of Ang-1 on CM and the underlying mechanism. WB and qPCR were utilized to measure the expression levels of different factors in CM cells. Clonogenic, CCK-8 and Transwell migration assay were used to probe CM cells' proliferation and migration ability. Xenograft tumor model was used to testify the effect of Ang-1 and Artesunate (ART) on the growth of CM in vivo. We found Ang-1 promoted CM proliferation and migration, while it was inhibited by ART in vitro. Moreover, both ART treatment and Ang-1 knockdown had the effect of suppressing tumor growth in CM xenograft model. Mechanically, Ang-1 activated Akt/mTOR pathway and induced epithelial-mesenchymal transition (EMT) in CM cells. Furthermore, ART regulated Akt/mTOR pathway by decreasing the expression of Ang-1 in CM cells. Ang-1 promotes tumorigenesis of CM by regulating Akt/mTOR pathway, which can be inhibited by ART. [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Choroidal melanoma is a highly malignant intraocular neoplasm. It is the most prevalent intraocular tumor in adults and it derives from melanocytes; the liver is the most common site of its metastases. An early and noninvasive diagnosis is essential to enhance patients' chances for early treatment. The OCT and OCTA-A are a noninvasive and noncontact methods used in the diagnostic process and support therapeutic decisions during control visits. These devices allow for detection and the real-time imaging of choroidal melanoma and its differentiation from metastasis and choroidal nevi. In addition to analyzing the currently utilized OCT and OCT-A methods, this review describes also the anatomy and imaging of specific vascular layers of the eye. Choroidal melanoma requires reliable and precise clinical examination and diagnosis to differentiate it from benign choroidal nevi. To achieve accurate diagnosis, as well as monitoring the progression of disease, various imaging modalities are used, including non-invasive optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). This review begins with a historical account of the development of OCT and OCTA and the methods of generation of images. This outlines the understanding of what OCT/OCTA images show, as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are introduced. Then, anatomical aspects of choroidal melanoma, its diagnosis and differentiation from metastasis, and choroidal nevi are presented. The purpose of this review is to critically evaluate application of OCT and OCTA in the diagnosis of choroidal melanoma. [ABSTRACT FROM AUTHOR]

The effects of radiation retinopathy on the retinal vasculature have been well established; however, the literature describing the pathologic changes in the choriocapillaris is relatively lacking. In this report, we describe the histologic findings of a donor eye with a choroidal melanoma with special attention to the choriocapillaris. Clinical and histological findings, including immunohistochemistry and transmission electron microscopy, are described for the retina and choroid of a donor eye affected by radiation retinopathy secondary to treatment of choroidal melanoma. Cells within the tumor exhibited an epithelioid structure and balloon melanosomes. Notable infiltration of macrophages with elongated morphology was also observed. Atrophy of photoreceptors, retinal pigmented epithelium, and choriocapillaris was observed on the inferior edge of the lesion and extending past the tumor. The choriocapillaris endothelium showed more severe dropout at the periphery of the lesion where loss of fenestration, thickened cytosol, and degenerated pericytes were observed. Morphologic analysis revealed choriocapillaris loss with pronounced degeneration of choroidal pericytes. Understanding the differences in sensitivity to radiation injury between different cell types and different patients will provide better insight into radiation retinopathy. [ABSTRACT FROM AUTHOR]

Simple Summary: The ocular fundus contains molecules that emit fluorescence when excited with light of an appropriate wavelength. Fundus autofluorescence imaging is based on the in vivo detection of intrinsic fluorescence and results in topographic autofluorescence mapping of the ocular fundus. In contrast to fluorescence angiography, where the fluorescing agents need to be administered intravenously, autofluorescence imaging is a non-invasive technique. Even though choroidal melanomas do not contain significant autofluorescent molecules themselves, they may lead to secondary alterations in neighbouring tissues with an impact on the autofluorescence signal recording. Fundus autofluorescence imaging in the context of choroidal melanoma is helpful for differential diagnosis and for monitoring variations over time in affected patients before and after treatment. 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. Lipofuscin and melanolipofuscin within the postmitotic retinal pigment epithelium (RPE) cells represent the major fluorophores that contribute to the FAF signal. In addition, the presence or loss of absorbing molecular constituents may have an impact on the FAF signal. A choroidal melanoma can cause secondary retinal and RPE alterations that affect the FAF signal (e.g., occurrence of orange pigment). Therefore, FAF imaging supports multimodal imaging and gives additional information over and above conventional imaging modalities regarding retinal metabolism and RPE health status. This article summarises the features of FAF imaging and the role of FAF imaging in the context of choroidal melanoma, both before and following therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: To assess the long-term prognosis for patients with iris melanomas and compare it with the prognosis for small choroidal melanomas. Design: Retrospective observational case series. Methods: All patients treated for iris melanomas at a single referral institution between January 1st 1986 and January 1st 2016 were included. Patients treated for small choroidal melanomas during the same period were included for comparison. The cumulative incidence of melanoma-related mortality was calculated. Patient and tumor characteristics and size-adjusted hazard ratio (HR) for melanoma-related mortality were compared between iris and small choroidal melanomas. Results: Forty-five iris melanomas and 268 small choroidal melanomas were included. Twenty-four iris melanomas (53%) had been treated with local resection, 12 (27%) with Ruthenium-106 brachytherapy, 7 (16%) with enucleation and 2 (4%) with proton beam irradiation. Twenty-one (68%), 7 (16%) and 2 (4%) of the iris melanomas were of the spindle, mixed and epithelioid cell types, respectively. Twenty-three patients had deceased before the end of follow-up. Median follow-up for the 22 survivors was 13.3 years (SD 9.4). Patients with iris melanomas were more often asymptomatic at presentation and had a trend towards significantly lower age (59 versus 63 years, Student's T-tests p = 0.057). Further, iris melanomas had significantly smaller basal diameter (5.8 versus 8.0 mm, p < 0.0001) and tumor volume (79 mm3 versus 93 mm mm3, p < 0.0001) but greater thickness (3.0 versus 2.5 mm, p < 0.0001). The cumulative incidence of iris melanoma-related mortality was 5% at 5 years after diagnosis, and 8% at 10, 15 and 20 years. The incidence was not significantly different to small choroidal melanomas (Wilcoxon p = 0.46). In multivariate Cox regression with tumor diameter and thickness as covariates, patients with choroidal melanomas did not have increased HR for melanoma-related mortality (HR 2.2, 95% CI 0.5–9.6, p = 0.29). Similarly, there were no significant survival differences in matched subgroups (Wilcoxon p = 0.82). Conclusions: There are no survival differences between iris and choroidal melanomas when adjusting for tumor size. The reason for the relatively favorable prognosis of iris melanomas compared to melanomas of the choroid and ciliary body is likely that they are diagnosed at a smaller size. [ABSTRACT FROM AUTHOR]

Background and purpose: To report the factors predictive of radio‐induced complications (i.e. radiation retinopathy [RR], radiation papillopathy [RP] and neovascular glaucoma [NVG]) in uveal melanoma (UM) patients undergoing gamma knife radiosurgery (GKR). Materials and methods: Longitudinal cohort study on patients with UM treated at the Ocular Oncology Service, San Raffaele Scientific Institute, Milan, between June 1994 and November 2018. Data were retrospectively reviewed. Rates of GKR‐related complications were reported. Variables associated with each complication were investigated using multivariable Cox models and confirmed by logistic regression analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were reported for significant associations. Results: One hundred ninety‐four patients (99 males, 51%) were included, and 184 tumours were primarily located in the choroid (95%). Median follow‐up was 57 months (range 6–286). Local control was achieved in 182 eyes (94%), and 152 eyes (78%) experienced at least one radiation‐induced complication. Radiation retinopathy was documented in 67 eyes (35%) after a median of 23 months. Older age (HR = 0.97, 95% CI = 0.95–0.99, p = 0.02) had a protective effect for RR. Radiation papillopathy was diagnosed in 35 eyes (18%) after a median of 14 months after GKR. Macular or peripapillary location (HR = 3.06, 95% CI = 1.52–6.16, p = 0.002) was associated with increased risk of RP, while older age was protective (HR = 0.95, 95% CI = 0.93–0.98, p = 0.001). New‐onset NVG was found in 53 eyes (27%), and median onset was 28 months. Tumour thickness (HR = 4.41, 95% CI = 2.23–8.72, p < 0.001) and peripapillary location (HR = 2.78, 95% CI = 1.46–5.27, p = 0.002) were the main risk factors associated with NVG. Conclusion: Understanding factors predictive for radiation‐related complications in patients undergoing GKR might help for better counselling and treatment planning. [ABSTRACT FROM AUTHOR]

Objective: To assess the long-term prognosis for patients with iris melanomas and compare it with the prognosis for small choroidal melanomas.Design: Retrospective observational case series.Methods: All patients treated for iris melanomas at a single referral institution between January 1st 1986 and January 1st 2016 were included. Patients treated for small choroidal melanomas during the same period were included for comparison. The cumulative incidence of melanoma-related mortality was calculated. Patient and tumor characteristics and size-adjusted hazard ratio (HR) for melanoma-related mortality were compared between iris and small choroidal melanomas.Results: Forty-five iris melanomas and 268 small choroidal melanomas were included. Twenty-four iris melanomas (53%) had been treated with local resection, 12 (27%) with Ruthenium-106 brachytherapy, 7 (16%) with enucleation and 2 (4%) with proton beam irradiation. Twenty-one (68%), 7 (16%) and 2 (4%) of the iris melanomas were of the spindle, mixed and epithelioid cell types, respectively. Twenty-three patients had deceased before the end of follow-up. Median follow-up for the 22 survivors was 13.3 years (SD 9.4). Patients with iris melanomas were more often asymptomatic at presentation and had a trend towards significantly lower age (59 versus 63 years, Student's T-tests p = 0.057). Further, iris melanomas had significantly smaller basal diameter (5.8 versus 8.0 mm, p < 0.0001) and tumor volume (79 mm3 versus 93 mm mm3, p < 0.0001) but greater thickness (3.0 versus 2.5 mm, p < 0.0001). The cumulative incidence of iris melanoma-related mortality was 5% at 5 years after diagnosis, and 8% at 10, 15 and 20 years. The incidence was not significantly different to small choroidal melanomas (Wilcoxon p = 0.46). In multivariate Cox regression with tumor diameter and thickness as covariates, patients with choroidal melanomas did not have increased HR for melanoma-related mortality (HR 2.2, 95% CI 0.5-9.6, p = 0.29). Similarly, there were no significant survival differences in matched subgroups (Wilcoxon p = 0.82).Conclusions: There are no survival differences between iris and choroidal melanomas when adjusting for tumor size. The reason for the relatively favorable prognosis of iris melanomas compared to melanomas of the choroid and ciliary body is likely that they are diagnosed at a smaller size. [ABSTRACT FROM AUTHOR]

We propose an alternative to LDR brachytherapy for the treatment of ocular melanomas by coupling intensity modulation, through the use of a gold shielded ring applicator, with a middle energy HDR brachytherapy source, Se-75. In this study, we computationally test this proposed design using MCNP6. An array of discrete Se-75 sources is formed into a ring configuration within a gold shielded applicator, which collimates the beam to a conical shape. Varying this angle of collimation allows for the prescription dose to be delivered to the apex of various sized targets. Simulations in MCNP6 were performed to calculate the dosimetric output of the Se-75 ring source for various sized applicators, collimators, and target sizes. The prescription dose was delivered to a range of target apex depths 3.5−8 mm in the eye covering targets 10-15 mm in diameter by using various sized applicators and collimators. For a 16 mm applicator with a collimator opening that delivers the prescription dose to a depth of 5 mm in the eye, the maximum percent dose rate to critical structures was 30.5% to the cornea, 35.7% to the posterior lens, 33.3% to the iris, 20.1% to the optic nerve, 278.0% to the sclera, and 267.3% to the tumor. When using Se-75 in combination with the proposed gold shielded ring applicator, dose distributions are appropriate for ocular brachytherapy. The use of a collimator allows for the dose to more easily conform to the tumor volume. This method also reduces treatment time and cost, and it eliminates hand dose to the surgeon through the use of a remote afterloader device. [ABSTRACT FROM AUTHOR]

To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy. Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years. A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively. Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss. [ABSTRACT FROM AUTHOR]

We describe the case of a 69-year-old woman who presented with a decline in vision in the left eye and was found to have a choroidal lesion with clinical and echographic features concerning for primary uveal melanoma. Systemic imaging identified numerous metastases to the liver, kidneys, paratracheal lymph nodes, lung, and brain. The hepatic lesion was biopsied, and genetic analysis identified a Val600Glu (c.1799T>A) BRAF mutation, consistent with a cutaneous primary malignancy, although no primary tumor was identified. This case highlights that metastasis to the choroid is a rare presentation of nonuveal melanoma that can mimic primary uveal melanoma. Genetic analysis of tumor tissue can identify the origin of the melanoma and guide treatment options. Systemic imaging should be performed prior to intervention for choroidal neoplasms. [ABSTRACT FROM AUTHOR]

Background: Current standard treatment procedures for Ruthenium‐106 (Ru‐106) brachytherapy for choroidal melanomas do not use 3D image‐guided treatment planning. We evaluated the potential impact of introducing 3D treatment planning and quantified the theoretical clinical benefits in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP). Materials and methods: Treatment plans for thirty‐two patients were optimized using 3D image‐guided treatment planning and compared to the original 2D clinical plans. Optimization of plans was done in an image‐based treatment planning system by optimizing the plaque position and treatment time such that the entire tumour received the prescribed dose of 100 Gy. TCP and NTCP for 2D clinical plans and optimized 3D image‐guided plans were estimated from published outcome prediction models and compared within patients using Wilcoxon signed‐rank test. Results: The median minimum tumour dose (D99%) for 2D clinical plans was 93 Gy (range: 23–158 Gy), corresponding to 5‐year TCP of 75% (IQR 61–86%), while median tumour D99% for optimized 3D image‐guided plans was 115 Gy (range 103–141 Gy), corresponding to TCP of 82% (IQR 80–84%). This was a statistically significant increase in estimated TCP (median increase in TCP 8% (IQR: −5–23, p = 0.006). While the dose to normal tissue increased somewhat, there was no significant change in NTCP. Conclusion: 3D treatment planning theoretically allows for improved tumour dose delivery for Ru‐106 brachytherapy of choroidal melanomas, resulting in a significant increase in expected tumour control compared to traditional approaches using 2D calculations. The deliverability of optimized plans, and potential increased risk of late complications, will have to be confirmed in future clinical studies. [ABSTRACT FROM AUTHOR]

To determine the response rate of choroidal melanoma following primary photodynamic therapy, we conducted a meta-analysis of published studies. A total of 7 studies reporting photodynamic therapy as primary treatment of choroidal melanoma in 162 patients with a mean tumor height of 2.8 mm (1.4 to 4.2) were identified. Forty-six percent of tumors were amelanotic, 48% were fully pigmented, and 6% had partial pigmentation. The photodynamic therapy parameters in all studies included 10-minute intravenous infusion of verteporfin (6 mg/m2), but varied in number of sessions (1 to 3), fluence (1× to 19×), and number of spots (single or multiple). The response was defined as tumor regression (partial or total) or lack of growth after initial treatment. The response to photodynamic therapy was predominantly observed as regression (126 [78%]). Overall response rate was 80% (mean) with a wide range among studies (58%–100%) over a period of 50 months (mean) with variable follow-up (range, 1–156 months). None of the studies reported progression- or recurrence-free survival; however, the recurrence rate was not related to the follow-up duration. Favorable prognostic factors were smaller size and lack of pigmentation. The overall response rate of 80% suggests that photodynamic therapy may be an effective primary treatment for small choroidal melanoma, especially in cases without pigmentation. Artifacts in study design (inclusion criteria and outcome measure) may have contributed to the variable observed response rate. Further studies with uniform inclusion criteria, standardized treatment parameters, well-defined outcome measures, and long follow-up are needed. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (106Ru) plaque to treat uveal melanoma. Material and methods: A literature review was performed based on results from searching PubMed, Embase, Web of Science, Scopus, and Cochrane databases, using the following key words: “choroidal melanoma”, “uveal melanoma”, “brachytherapy”, and “ruthenium-106”. We included studies performed on more than 30 patients since 1986, reporting on local control rate, complications rate, mean radiation dose, and mean tumor thickness. The cumulative analysis was performed using Metaprop command of Stata v.16, and meta-regression was conducted based on mean tumor thickness and mean radiation dose to tumor’s apex. Results: Twenty-one retrospective studies were selected, involving 3,913 patients treated primarily with 106Ru plaque brachytherapy. The range of radiation dose to tumor apex was from 70 Gy to 250 Gy. The local control rate following brachytherapy ranged from 59% to 98%, and the overall weighted mean of local control was 84%. However, the heterogeneity between studies’ reports was remarkable (I2 = 95.40%). Meta-regression based on tumor thickness and mean dose of radiation to the apex showed that the studies’ heterogeneity was minimally related to the difference in mean tumor size (I 2 = 92%). The correlation between larger tumor size and lower local control rate was statistically significant (p-value = 0.024). There was no significant correlation between the mean radiation dose and local control rate (p-value = 0.679). The most commonly reported complications were cataract and radiation-related retinopathy. Conclusions: Although the studies’ heterogeneity was high, in a prescription dose ranging from 70 Gy to 250 Gy to the tumor apex, 106Ru brachytherapy seems to be successful in local control of uveal melanoma. The efficacy of 106Ru in controlling uveal melanomas decreased with the increase in tumor thickness. However, these outcomes should be verified in randomized comparative studies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the cytopathological results, surgical complications, and patient outcomes after transretinal biopsy (TRB) for diagnosis of retinal/choroidal tumors Methods: Records of 40 cases who underwent TRB via 23-gauge (23 G) pars plana vitrectomy between March 2011 and March 2020 were reviewed. Study design: Retrospective. Results: Twenty-six (65.0%) cases were women and 14 (35.0%) were men. The mean age at diagnosis was 57.2 (range: 18–83) years. The mean tumor base diameter was 12.0×9.8 mm and the mean tumor thickness was 4.9 mm. According to cytopathological examination, 29 (72.5%) cases had choroidal melanoma, 2 (5.0%) had non-small cell lung cancer metastasis, 1 (2.5%) had adenoma of retinal pigment epithelium, 1 (2.5%) had small cell lung cancer metastasis, 1 (2.5%) had invasive breast cancer metastasis, 1 (2.5%) had retinal astrocytic hamartoma, and 1 (2.5%) had pseudoneoplastic gliosis. Cytopathological examination of 4 (10.0%) cases revealed findings consistent with macular and extramacular degeneration. Postoperative complications were mild vitreous hemorrhage in 16 (40.0%) cases, gradually worsening cataract in 4 (11.8%), retinal detachment in 1 (2.5%), hyphema in 1 (2.5%), glaucoma in 1 (2.5%), and macular hole in 1 (2.5%). During the mean 11.1 (range: 1–55) months follow-up, 1 (3.4%) patient with choroidal melanoma developed liver metastasis. All patients were alive at the end of follow-up. Conclusions: TRB using 23 G pars plana vitrectomy can be used to make the cytopathologic diagnosis of retinal/choroidal tumors whenever the clinical diagnosis is not certain or in cases with known diagnosis to obtain information on cell type/cytogenetics. In our series, the most common diagnosis after cytopathologic examination was choroidal melanoma. [ABSTRACT FROM AUTHOR]