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PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ PRAME classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS).RESULTS15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/ PRAME (-), 80.6% (95% CI, 73.9 to 87.9) for class 1/ PRAME (+), 58.3% (95% CI, 51.1 to 66.4) for class 2/ PRAME (-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/ PRAME (+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter.CONCLUSIONIn the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/ PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

Purpose: To determine the incidence and type of strabismus in patients with uveal melanoma treated with plaque brachytherapy., Design: Multicenter, retrospective incidence estimation study., Methods: A total of 438 eyes of 438 patients with uveal melanoma treated with plaque brachytherapy between October 2011 and May 2021. Intervention was Iodine 125, and Palladium 103 plaque brachytherapy. The variables reviewed included incidence of nonresolving strabismus post-plaque brachytherapy, type of strabismus developed, extraocular muscles operated, and modality of treatment received., Results: A total of 438 patients underwent plaque brachytherapy treatment for uveal melanoma. Eleven patients developed strabismus post-plaque brachytherapy (2.5%, n = 11/438). Of these patients, 5 (1.1%, n = 5/438) developed strabismus immediately postoperation. Specifically, 2 patients (0.5%, n = 2/438) developed strabismus immediately postoperation due to slipped muscles, 2 patients (0.5%, n = 2/438) due to decompensated phorias, and 1 patient (0.5%, n = 1/438) due to a fibrotic muscle. Six patients (1.4%, n = 6/438) developed late-onset sensory strabismus. A total of 355 patients (81.1%, n = 355/438) had their extraocular muscles disinserted during surgery, with the lateral rectus being the most common, accounting for 45.4% (n = 161/355), followed by the superior rectus at 26.8% (n = 95/355). Strabismus surgery was the most common treatment modality, comprising 72.7% (n = 8/11) of patients., Conclusions: The incidence of strabismus after plaque brachytherapy treatment for uveal melanoma was low and primarily classified as late-onset sensory strabismus. Previous studies may underestimate the long-term incidence of strabismus after plaque brachytherapy by focusing primarily on strabismus present immediately postoperatively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Advancements in the treatment of uveal melanoma have not improved survival; therefore, identifying modifiable risk factors is critical to improving outcomes. This study aims to investigate the association between sunlamp use and the development of uveal melanoma., Design: This study is designed as a meta-analysis., Methods: Literature was searched and reviewed through the MEDLINE (with both OVID and PubMed), EMBASE, MD Consult, and Web of Science databases. These databases were searched from 1966 to 2019 using the following keywords to identify articles examining risk factors for uveal melanoma: ultraviolet, sun, sunlight, uveal melanoma, eye cancer, eye melanoma, nevus, and risk factor. All articles were evaluated for inclusion based on methodology and data reporting association between sunlamp use and uveal melanoma. The Meta-analysis of Observational Studies in Epidemiology guidelines and the Newcastle-Ottawa Scale were used to assess data quality and validity. A random effects model was employed., Results: A total of 5 studies, enrolling a total of 1753 uveal melanoma cases and 3399 controls were included in this meta-analysis. The results of this study showed a positive association between sunlamp use and uveal melanoma (odds ratio = 2.15; 95% confidence interval 1.27-3.64). Meta-regression of between study heterogeneity did not reveal a statistically significant association when publication year, site latitude, melanoma tissue location (specifically, inclusion of iris tumors), or control type (population versus clinic) were evaluated., Conclusion: This meta-analysis identified a statistically significant association between sunlamp use and uveal melanoma, supporting sunlamp use as a modifiable risk factor for uveal melanoma., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents., (Copyright ©2020. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of the Digital Journal of Ophthalmology is prohibited.)

Purpose: The purpose of the study was to determine dosimetric effects of performing concurrent I-125 Collaborative Ocular Melanoma Study plaque brachytherapy and vitrectomy with replacement using silicone oil, previously shown to be a means of shielding uninvolved parts of the eye., Methods and Materials: Monte Carlo simulations using MCNP6 were performed to compare the dosimetry with all eye materials assigned as water, and for the vitreous (excluding the tumor), composed of polydimethylsiloxane oil for three generic, one large tumor, and two patient geometry scenarios. Dose was scored at the tumor apex, along the sclera, and within a 3D grid encompassing the eye. The assessed patient cases included vitrectomies to treat intraocular pathologies; not to enhance attenuation/shielding., Results: The doses along the sclera and for the entire eye were decreased when the silicone oil replaced the vitreal fluid, with a maximum decrease at the opposite sclera of 63%. Yet, absolute changes in dose to critical structures were often small and likely not clinically significant. The dose at the tumor apex was decreased by 3.1-9.4%. Dose was also decreased at the edges of the tumor because of decreased backscatter at the tumor-oil interface., Conclusions: Concurrent silicone vitrectomy was found to reduce total radiation dose to the eye. Based on current radiation retinopathy predictive models, the evaluation of the absolute doses revealed only a subset of patients in which a clinically significant difference in outcomes is expected. Furthermore, the presence of the silicone oil decreased dose to the tumor edges, indicating that the tumor could be underdosed if the oil is unaccounted for., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the dose calculation accuracy in water medium of the Advanced Collapsed cone Engine (ACE) for three sizes of COMS eye plaques loaded with low-energy I-125 seeds., Methods: A model of the Oncura 6711 I-125 seed was created for use with ACE in Oncentra ® Brachy (OcB) using primary-scatter separated (PSS) point dose kernel and Task Group (TG) 43 datasets. COMS eye plaque models of diameters 12, 16, and 20 mm were introduced into the OcB applicator library based on 3D CAD drawings of the plaques and Silastic inserts. To perform TG-186 level 1 commissioning, treatment plans were created in OcB for a single source in water and for each COMS plaque in water for two scenarios: with only one centrally loaded seed, or with all seed positions loaded. ACE dose calculations were performed in high accuracy mode with a 0.5 × 0.5 × 0.5 mm 3 calculation grid. The resulting dose data were evaluated against Monte Carlo (MC) calculated doses obtained with MCNP6, using both local and global percent differences., Results: ACE doses around the source for the single seed in water agreed with MC doses on average within < 5% inside a 6 × 6 × 6 cm 3 region, and within < 1.5% inside a 2 × 2 × 2 cm 3 region. The PSS data were generated at a higher resolution within 2 cm from the source, resulting in this improved agreement closer to the source due to fewer approximations in the ACE dose calculation. Average differences in both investigated plaque loading patterns in front of the plaques and on the plaque central axes were ≤ 2.5%, though larger differences (up to 12%) were found near the plaque lip., Conclusions: Overall, good agreement was found between ACE and MC dose calculations for a single I-125 seed and in front of the COMS plaques in water. More complex scenarios need to be investigated to determine how well ACE handles heterogeneous patient materials., (© 2018 American Association of Physicists in Medicine.)

Objective: There are limited studies on uveal melanoma and patient quality of life. However, the burden of implementing a patient-reported outcome measure to collect this information in a clinical setting is unknown. The objectives of this study were (i) to understand the issues of quality of life that are most important to patients undergoing treatment for uveal melanoma, (ii) to explore patient views on the European Organization for Research and Treatment of Cancer's (EORTC) ophthalmic oncology quality of life questionnaire (QLQ-OPT30), and (iii) to assess patient willingness to complete questionnaires measuring quality of life on an ongoing basis., Design: This was a qualitative study., Participants: The study included 10 patients treated for uveal melanoma with brachytherapy at the Alberta Ocular Brachytherapy Program, with a mean follow-up period of 16.3 months (range 5-33 months) after diagnosis., Methods: The participants completed a qualitative interview over the phone with a trained interviewer between November 2014 and January 2015. Participants completed the QLQ-OPT30 according to their current symptoms and then elaborated on their responses. The participants then completed a semistructured interview to provide more information about the symptoms or issues that had the most impact on quality of life., Results: The participants expressed positive feelings about the QLQ-OPT30; however, the participants' responses revealed that several themes, including mental health, impact of diagnosis and treatment on family, travel and financial burdens of treatment, and impact on work and home life, were missing in the questionnaire., Conclusions: The QLQ-OPT30 performed well, but some missing constructs were identified. Furthermore, participants took 23 minutes to complete the QLQ-OPT30 with a trained interviewer, and this could present logistical challenges when using it at the point of care., (Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate the total dosimetric uncertainty at the tumor apex for ocular brachytherapy treatments delivered using 16 mm Collaborative Ocular Melanoma Study (COMS) and Super9 plaques loaded with (125)I seeds in order to determine the size of the apex margin that would be required to ensure adequate dosimetric coverage of the tumor., Methods: The total dosimetric uncertainty was assessed for three reference tumor heights: 3, 5, and 10 mm, using the Guide to the expression of Uncertainty in Measurement/National Institute of Standards and Technology approach. Uncertainties pertaining to seed construction, source strength, plaque assembly, treatment planning calculations, tumor height measurement, plaque placement, and plaque tilt for a simple dome-shaped tumor were investigated and quantified to estimate the total dosimetric uncertainty at the tumor apex. Uncertainties in seed construction were determined using EBT3 Gafchromic film measurements around single seeds, plaque assembly uncertainties were determined using high resolution microCT scanning of loaded plaques to measure seed positions in the plaques, and all other uncertainties were determined from the previously published studies and recommended values. All dose calculations were performed using plaque simulator v5.7.6 ophthalmic treatment planning system with the inclusion of plaque heterogeneity corrections., Results: The total dosimetric uncertainties at 3, 5, and 10 mm tumor heights for the 16 mm COMS plaque were 17.3%, 16.1%, and 14.2%, respectively, and for the Super9 plaque were 18.2%, 14.4%, and 13.1%, respectively (all values with coverage factor k = 2). The apex margins at 3, 5, and 10 mm tumor heights required to adequately account for these uncertainties were 1.3, 1.3, and 1.4 mm, respectively, for the 16 mm COMS plaque, and 1.8, 1.4, and 1.2 mm, respectively, for the Super9 plaque. These uncertainties and associated margins are dependent on the dose gradient at the given prescription depth, thus resulting in the changing uncertainties and margins with depth., Conclusions: The margins determined in this work can be used as a guide for determining an appropriate apex margin for a given treatment, which can be chosen based on the tumor height. The required margin may need to be increased for more complex scenarios (mushroom shaped tumors, tumors close to the optic nerve, oblique muscle related tilt, etc.) than the simple dome-shaped tumor examined and should be chosen on a case-by-case basis. The sources of uncertainty contributing most significantly to the total dosimetric uncertainty are seed placement within the plaques, treatment planning calculations, tumor height measurement, and plaque tilt. This work presents an uncertainty-based, rational approach to estimating an appropriate apex margin.

Purpose: To study the relationship between cutaneous and iris nevi with uveal melanoma., Design: Meta-analysis., Methods: Three researchers independently searched the literature using Medline from 1966 to August 2007 (with both Ovid and PubMed), EMBASE, MD Consult, and the Web of Science. All bibliographies were searched, and an attempt to contact all primary authors was made to find further unpublished studies., Main Outcome Measures: Risk factor data were extracted into 4 a priori groups: (1) atypical cutaneous nevi, (2) common cutaneous nevi, (3) cutaneous freckles, and (4) iris nevi., Results: Meta-analysis of 4 studies (850 cases) examining atypical cutaneous nevi yielded a summary odds ratio (OR) of 2.82 (95% confidence interval [CI], 1.10-7.26; P=0.032). Common cutaneous nevi were reported in 4 studies (825 cases), yielding a summary OR of 1.74 (CI, 1.27-2.39; P=0.001). Cutaneous freckles using 7 studies (2122 cases) found an OR of 1.22 (CI, 1.03-1.45; P=0.022). Iris nevi using 4 studies (825 cases) found an OR of 1.53 (CI, 1.03-2.27; P=0.036). There was no evidence of publication bias for the aforementioned risk factors, with the exception of atypical cutaneous nevi (P=0.03)., Conclusions: This meta-analysis supports an association between uveal melanoma and atypical cutaneous nevi, common cutaneous nevi, cutaneous freckles, and iris nevi.

Objective: To conduct a meta-analysis, using observational studies, to examine the association between host susceptibility factors and uveal melanoma., Methods: A review of 132 published reports on risk factors for uveal melanoma revealed 10 case-control studies that provided enough information to calculate odds ratios (ORs) and standard errors for host susceptibility factors. Data from these studies were extracted and categorized. Summary statistics were calculated for all risk factors reported by at least 4 independent studies., Results: Summary statistics using meta-analysis are presented as ORs and their 95% confidence intervals (CIs). Statistically significant risk factors include light eye color (OR, 1.75 [95% CI, 1.31-2.34]), using 10 studies (1732 cases); fair skin color (OR, 1.80 [95% CI, 1.31-2.47]), using 5 studies (586 cases); and ability to tan (OR, 1.64 [95% CI, 1.29-2.09]), using 6 studies (1021 cases). Blond or red hair color, using 7 studies (1012 cases), was not a statistically significant independent risk factor (OR, 1.02 [95% CI, 0.82-1.26])., Conclusion: This meta-analysis yielded strong evidence associating the host susceptibility factors of iris color, skin color, and ability to tan with uveal melanoma.

Objective: To examine the association between ultraviolet light exposure and uveal melanoma., Design: Meta-analysis., Methods: A review of 133 published reports on risk factors for uveal melanoma revealed 12 studies that provided sufficient information to calculate odds ratios (ORs) and standard errors for ultraviolet light exposure factors. Data from these studies were extracted and categorized into intermittent ultraviolet exposure factors (welding, outdoor leisure, photokeratitis) and chronic ultraviolet exposure factors (occupational sunlight exposure, birth latitude, lifetime ultraviolet exposure index). Summary statistics were calculated for all risk factors reported by > or =4 independent studies., Main Exposure Measures: Welding, outdoor leisure, photokeratitis, occupational sunlight exposure, birth latitude, and lifetime ultraviolet exposure index., Results: For intermittent ultraviolet exposure, welding was found to be a significant risk factor (5 studies, 1137 cases; OR, 2.05 [95% confidence interval [CI], 1.20-3.51]). Outdoor leisure was found to be nonsignificant (4 studies, 1332 cases; OR, 0.86 [95% CI, 0.71-1.04]). Photokeratitis conferred susceptibility in 3 reports studying this variable, but there were too few studies to validate meta-analyses. For chronic ultraviolet exposure, meta-analysis found occupational sunlight exposure to be a borderline nonsignificant risk factor for development of uveal melanoma (4 studies, 572 cases; OR, 1.37 [95% CI, 0.96-1.96]). Latitude of birth was found to be nonsignificant (5 studies, 1765 cases; OR, 1.08 [95% CI, 0.67-1.74])., Conclusion: This meta-analysis yielded inconsistent results associating ultraviolet light with development of uveal melanoma. There was evidence implicating welding as a possible risk factor for uveal melanoma.

Introduction Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are highly related to the size of the tumour, timely and accurate diagnosis can increase the chance for cure. Methods A consensus-based guideline was developed to inform practitioners. PubMed was searched for publications related to this topic. Reference lists of key publications were hand-searched. The National Guidelines Clearinghouse and individual guideline organizations were searched for relevant guidelines. Consensus discussions by a group of content experts from medical, radiation, and surgical oncology were used to formulate the recommendations. Results Eighty-four publications, including fve existing guidelines, formed the evidence base. Summary Key recommendations highlight that, for uveal melanoma and its indeterminate melanocytic lesions in the uveal tract, management is complex and requires experienced specialists with training in ophthalmologic oncology. Staging examinations include serum and radiologic investigations. Large lesions are still most often treated with enucleation, and yet radiotherapy is the most common treatment for tumours that qualify. Adjuvant therapy has yet to demonstrate effcacy in reducing the risk of metastasis, and no systemic therapy clearly improves outcomes in metastatic disease. Where available, enrolment in clinical trials is encouraged for patients with metastatic disease. Highly selected patients might beneft from surgical resection of liver metastases. [ABSTRACT FROM AUTHOR]