Arun D. Singh

Importance: There is lack of evidence assessing surveillance protocols to detect metastasis in patients with uveal melanoma (UM). Objective: To explore hypothetical surveillance schedules anchored in the real-world data of our patient cohort with known prognostication status wherein, surveillance intervals ranging from every 1-month to every 12-months were statistically analysed. Design: Retrospective, cohort study. Setting: Single center. Participants: Patients clinically diagnosed with UM and managed with standard of care local therapy who underwent prognostication by commercially available Gene Expression Profile (GEP) (Castle Biosciences, Friendswood, Texas, USA). Those classified as having low risk (Class 1) were offered a standard protocol (SP; hepatic ultrasonography (US) at 6-month intervals) while those with high risk (Class 2) were recommended to undergo enhanced protocol (EP) that incorporated either higher frequency (US every 3 months) or enhanced modality (EM, hepatic computed tomography/magnetic resonance imaging). Main outcome Measures: Optimal scan interval. Results: 349 patients with median age of 62 years and 54% were male. Most patients were Class 1 (65%) and had choroidal location (75%). Median follow-up among survivors was 30.9 months (IQR: 19–57.9). 67 patients developed metastasis. The 5-year overall survival (OS) was 80% and the 5-year metastasis-free survival (MFS) was 71%. For Class 1 patients, 12-month scan interval was optimal as it had the minimal Euclidean distance to the point (0, 0) with a median of 2.92 months from negative to positive scan with an average of 2.83 scans per patient. For Class 2 patients, a 9-month scan interval was optimal as it minimized the Euclidean distance to the point (0, 0) with an average of 3.09 scans per patients and a median of 2.93 months from negative to positive scans. There was an association between the longer scan interval and size of metastatic lesion (>=6 months versus <6 months, p = 0.002). Conclusions and relevance: Our analysis suggests that the frequency of hepatic imaging for detection of metastasis can be tailored on the risk status to 12 months and 9 months for patients with low and high-risk tumors, respectively. Our study provides a framework for future studies assessing surveillance protocol designs, efficacy, and impact on patient survival.

Background/Objectives: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma. Methods: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, and surgical oncologists from North America. A multidisciplinary steering committee developed statements addressing risk-based surveillance using both molecular and clinical prognostic factors, including gene expression profiling (GEP) and PRAME status. Consensus was defined a priori as ≥70% of panelists rating a statement 7–9 on a 9-point Likert scale. Results: Forty-nine experts were invited, and 41 completed at least one survey round. The panel represented 17 U.S. states, Washington, D.C., and two Canadian provinces. Twelve statements reached stable consensus, including recommendations for imaging modality, frequency, and duration in intermediate- and high-risk patients. Although there was agreement that low-risk patients warrant surveillance, no consensus was reached on the optimal approach for this group. Conclusions: This is the first study to provide consensus-based guidance incorporating GEP and PRAME status into surveillance recommendations for uveal melanoma, offering a standardized framework to guide clinical practice and future research.

Importance: The accuracy of the predicted risk of malignant transformation of a large choroidal nevus or indeterminate melanocytic tumor (IMT) is not known.Objective: To estimate the risk of malignant transformation (predicted risk) in a cohort of patients with IMT of known outcomes (observed status; benign [large nevus] or malignant [small melanoma]).Design, Setting, and Participants: This was a cohort study of patients from a single center. Patients diagnosed with IMTs that were benign (large nevus) or malignant (small melanoma) were included in the analysis. Those lesions classified as large nevus (benign; 0% risk) had documented stability over 24 or more months. IMTs classified as small melanoma (malignant; 100% risk) had quantified growth or confirmatory pathology. Data were analyzed from October to December 2024.Exposures: Prediction of malignant transformation of a large choroidal nevus or IMT.Main Outcomes and Measures: The primary outcome included the predicted 5-year Kaplan-Meier probability of malignant transformation using combinations of risk factors of predictive models, the Collaborative Ocular Melanoma Study (COMS) and Wills Eye Hospital (WEH) model.Results: A total of 123 patients (median [IQR] age, 63 [56-67] years; 89 male [72%]), 62 with large nevus and 61 with small malignant melanoma, were included in this study. The mean predicted 5-year Kaplan-Meier probability of melanoma for observed melanoma was 0.39 (95% CI, 0.32-0.46) by the COMS model and 0.44 (95% CI, 0.39-0.49) by the WEH model. The difference of −0.05 (95% CI, −0.14 to 0.04) was not statistically significant. However, the mean predicted 5-year Kaplan-Meier probability of melanoma for observed nevus was 0.18 (95% CI, 0.12-0.23) by the COMS model and 0.31 (95% CI, 0.24-0.38) by the WEH model. The difference of −0.13 (95% CI, −0.22 to −0.05) was statistically significant. There was a significant difference in mean 5-year Kaplan-Meier probability of melanoma between observed melanoma and nevus of 0.21 (95% CI, 0.12-0.31) by the COMS model and 0.13 (95% CI, 0.05-0.21) by the WEH model. Optimal cut points of 0.18 and 0.34 for the COMS model and the WEH model, respectively, were identified using the Youden index. The sensitivity was lower for the COMS model than the WEH model (−15.2% difference; 95% CI, −25.6% to −4.8%), and the specificity was higher for the COMS model than the WEH model (11.7% difference; 95% CI, 2.0%-21.4%).Conclusions and Relevance: Findings of this cohort study suggest that predicted risk for malignant transformation estimated by 2 different models based on combinations of risk factors was suboptimal and may lead to overtreatment in approximately 30% of patients. These findings support pursuing other methods for prediction that should be validated before use in clinical practice.

Aim To conduct a performance analysis of intra-arterial chemotherapy (IAC). Material and methods Comprehensive data search in MEDLINE from inception until December 2023. Peer-reviewed, English-language, clinical studies (retrospective, prospective, trials, non-randomised) and case series. Two authors abstracted data independently using a standardised form. Study heterogeneity calculation and influence statistics with a leave-one-out analysis were carried out. Globe salvage rates (GSR) (overall, primary and secondary), per international classification of retinoblastoma groups and adjuvant intravitreal chemotherapy were carried out. Performance was assessed using learning curve, experience and study variable effects (site, size and year). Results 416 identified studies met the selection criteria. 43 studies (3174 eyes) were included for random-effects meta-analysis. The statistical test for heterogeneity was significant (p value2020, p value Discussion Improved selection criteria are needed to identify eyes suitable for IAC.