Search Results (443)

Objective: To provide a comprehensive literature review of original work on artificial intelligence in ocular oncology. Methods: Scoping review of PubMed-indexed original articles (n = 94) on the use of artificial intelligence in ocular oncology, retrieved during the month of February 2026 and independently screened by two ocular oncologists. Results: Most of the literature on artificial intelligence (AI) in ocular oncology focuses on uveal melanoma and its differentials (n = 39, 41%), followed by retinoblastoma (n = 14, 15%) and orbital tumors (n = 12, 13%). The purpose of using the AI models was to screen, diagnose, and classify the disease (n = 59, 62%) and to treat, predict outcomes, and monitor the disease (n = 35, 37%). Most literature (n = 32, 34%) on AI in ocular oncology originates from China. Datasets comprised images in 78% (n = 73) of the studies, clinical parameters in 14% (n = 13), and omics data in 12% (n = 11). Most studies worked on developing AI models (n = 83, 88%), of which two reached a deployment stage. Few studies evaluated or incorporated pre-existing models (n = 11, 12%). Supervised learning strategy was most commonly employed (n = 75, 80%). Among studies that developed AI models, traditional machine learning architectures were used in 36, deep learning in 39, and a combination in 8. Most studies (n = 59, 63%) were at a Clinical AI Readiness Evaluator Technology Readiness Level 4, i.e., at the prototype development stage. Conclusions: Despite the limitation of a single database search, a surge in AI applications in ocular oncology after 2020 is evident. Most studies are in the model development stage, and few have been deployed in the real world for clinical implementation. Very few models have proven effective in real-world clinics and the community, holding promise for the future. Full article

Background/Objectives: Uveal melanoma (UM) is the most common primary intraocular malignant tumor among adults and has a high risk of metastasis. Recently, artificial intelligence (AI) tools have been developed to support the management of UM across different clinical tasks. The definition of ground truth, the reference standard that models use in training and development, greatly influences the performance and clinical relevance of the models. Currently, there is limited consensus regarding which ground truth methods are most appropriate for each clinical application. This review aims to evaluate the advantages and limitations of available ground truth options in UM and proposes task-specific recommendations based on clinical utility, feasibility, and cost. Methods: A narrative review of the existing literature was conducted to identify and evaluate commonly used ground truth methods for UM AI applications based on factors such as time, cost, invasiveness, and required level of expertise. Results: Each ground truth method offers distinct benefits and drawbacks in relation to biological precision, invasiveness, availability, cost, and turnaround time. No single ground truth is universally optimal across all applications. Instead, the ideal choice depends on the intended clinical task, and practical alternatives exist to mitigate the constraints that result from limited time and institutional resources. Conclusions: The selection of ground truth for AI models in UM should be chosen based on the specific clinical task to balance predictive relevance with feasibility of implementation. The adoption of task-specific ground truth standards may improve the development of clinically meaningful AI tools and facilitate their integration into real-world practice. Full article

Background/Objectives: Loss of nuclear BAP1 (BRCA1-associated protein 1) expression is a well-established adverse prognostic marker in uveal melanoma (UM). However, data from Central and Southeastern European populations are limited. This descriptive study aimed to evaluate BAP1 immunohistochemical expression in a Croatian enucleation-based UM cohort, characterize its associations with clinicopathological parameters, and contextualize the findings within the published literature. Methods: Formalin-fixed, paraffin-embedded tumor tissue from 58 consecutive patients with primary choroidal and ciliary body melanoma treated with enucleation at University Hospital Centre Zagreb (2006–2016) was analyzed immunohistochemically for BAP1 nuclear expression. Associations with clinicopathological parameters were assessed using chi-square and Fisher’s exact tests. Survival analysis was performed using Kaplan–Meier estimation, log-rank tests, and Cox proportional hazards regression with a median follow-up of 11.2 years. Results: Loss of nuclear BAP1 expression was observed in 53/58 (91.4%) specimens, resulting in a severely imbalanced distribution (53 versus 5 patients) precluding meaningful comparative survival analysis. Five-year and 10-year overall survival rates were 72.4% and 51.7%, respectively, with a median overall survival of 14.5 years. BAP1 loss was associated with longer disease-free survival (log-rank p = 0.020); however, this finding likely reflects a statistical artifact attributable to the extremely small BAP1-retained group (n = 5) harboring concurrent adverse features and should not be interpreted biologically. The study was underpowered to draw prognostic inferences regarding BAP1 status. Exploratory survival analyses are presented for transparency but should not be interpreted inferentially. Conclusions: The exceptionally high prevalence of BAP1 loss reflects the selection bias inherent in enucleation-based cohorts, which are enriched for large, molecularly high-risk tumors. This study provides the first comprehensive BAP1 immunohistochemical data from Croatia, contributing to the growing evidence that enucleation cohorts represent a distinct, biologically high-risk subgroup in which BAP1 immunohistochemistry offers limited discriminatory value. The extended follow-up of 11.2 years confirms the prolonged natural history of UM. Future multi-center studies incorporating molecular validation and diverse treatment modalities are needed to establish the prognostic utility of BAP1 across the full spectrum of UM disease. Full article

As the executive leadership of the Collaborative Ocular Oncology Group (COOG), which has conducted the largest prospective clinical studies ever performed in patients with uveal melanoma, we read with concern the recent report by Rivas, Samlowski and McCannel, which claims that brachytherapy combined with vitrectomy and silicone oil injection results in an “unexpectedly low rate” of metastasis and death in patients with uveal melanoma [...] Full article

Uveal melanoma (UM) lacks minimally invasive and reproducible biomarkers to support clinical risk stratification, motivating the need for molecular profiling of aqueous humor (AH) as an alternative to fine-needle tumor aspiration (FNAB). This study aimed to generate a calibrated AH protein concentration map to identify tumor-associated signals present at clinically measurable levels and assess their associations with established molecular and clinical features. AH samples from 70 UM eyes were analyzed using next-generation sequencing-based proximity extension assays (PEAs), and leftover AH from 27 samples was further assessed using qPCR-based PEA to obtain reference concentration values. Regression models derived from overlapping proteins enabled extrapolation of calibrated pg/mL-level concentrations across the full cohort. Twenty-three proteins had median modeled concentrations above 5 pg/mL and were examined for clinical relevance and translational feasibility. Several proteins, including CXCL8, CXCL10, VEGFA, HGF, PDCD1, FLT1, FLT3LG, and CCL2, showed progressive increases from GEP1/PRAME− to GEP2/PRAME+ tumors and from AJCC Stage I/II to Stage III/IV, with Stage IV tumors demonstrating significant elevations in CXCL8, VEGFA, and PDCD1. Pathway analysis revealed activation of inflammatory and tumor microenvironment pathways, and upstream regulator analysis identified VEGFA and CCL2 as potential drivers. These findings demonstrate that calibrated AH proteomic profiling can identify clinically measurable protein changes associated with UM risk and stage, supporting its potential utility for biomarker development. Full article

Uveal melanoma (UM) represents an uncommon intraocular malignancy with high aggressiveness. Dysregulation of ferroptosis has been associated with UM progression. Dihydroartemisinin (DHA), a natural derivative of Artemisia annua, exhibits potent antitumor activity with a favorable safety profile, yet its role in ferroptosis regulation in UM remains unclear. Here, we showed that DHA significantly reduced the proliferation and invasiveness of UM cells—both primary and secondary—with effects intensifying over time and dose. Transcriptomic analysis indicated that DHA may exert antitumor effects by modulating the ferroptosis-related pathway, characterized by upregulating heme oxygenase-1 (HO-1) and downregulating the SLC7A11 (xCT)/GPX4 axis, leading to iron accumulation, increased ROS and lipid peroxidation, and mitochondrial dysfunction. Iron chelators and pancaspase inhibitors partially reverse these effects, whereas HO-1 inducers enhance them. Overall, our results suggest that DHA suppresses UM progression by inducing ferroptosis and mitochondrial dysfunction, while the HO-1 and xCT/GPX4 pathways may contribute to these effects. DHA may represent a potential therapeutic approach for UM, warranting further investigation. Full article

Background/Objective: Although most melanocytic lesions are diagnosed as benign or malignant by histopathologic evaluation, with or without the aid of immunohistochemistry, diagnosis may remain uncertain in a minority of cases. Assessment of copy number abnormalities (CNAs) may provide sufficient additional evidence to favor either a benign or malignant diagnosis in both pediatric and adult cases and in melanocytic lesions of various subtypes, including Spitzoid, mucosal, and acral. CNAs are common in melanomas, while they are rare, with few exceptions, in benign lesions. Detection of CNAs by fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA) has been well established for melanocytic lesions, with advantages and disadvantages for each. The objective of this meta-analysis was to evaluate the utility of CNA testing for the diagnosis of melanoma, across subtypes, when a lesion remains ambiguous after histopathologic and immunohistochemical assessment. In addition, the utility of CNAs to determine prognosis in established diagnoses of melanoma was also evaluated. Methods: The Cancer Genomics Consortium Working Group for Melanocytic Lesions reviewed published data from January 1998 through September 2022 of CNAs in melanocytic lesions detected by either FISH or CMA and conducted a meta-analysis of the findings. Results: Specific abnormalities common in primary cutaneous melanomas of various subtypes and uveal melanomas were enumerated. Differences in CNAs found in primary versus metastatic lesions were also determined, and published evidence for prognosis was summarized. Conclusions: The working group established evidence-based recommendations for the use of CNA testing for evaluation of ambiguous melanocytic lesions. Full article

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and remains associated with a high risk of metastatic spread and poor survival once metastasis occurs. Despite advances in the molecular characterization of UM, progress in effective therapeutic strategies has been limited, partly due to the lack of preclinical models that accurately recapitulate the tumor’s complex biology and microenvironment. Traditional two-dimensional (2D) culture systems fail to reflect key features of UM, including cellular heterogeneity, extracellular matrix interactions, and immune modulation. In recent years, three-dimensional (3D) models have emerged as powerful tools to overcome these limitations and to better mimic in vivo tumor architecture and behavior. This review provides a comprehensive overview of the current landscape of 3D UM models, including spheroids and organoids. We discuss their applications in studying UM pathogenesis, tumor–microenvironment interactions, metastatic mechanisms, and therapeutic responses. Advancing 3D modeling approaches holds promise for improving translational research and accelerating the development of effective therapies for uveal melanoma. Full article

Background: The aim of this study was to evaluate the influence of demographic, clinical and physical factors on the occurrence of ocular complications after ruthenium-106 (Ru-106) brachytherapy, iodine-125 (I-125) brachytherapy and proton therapy of uveal melanoma. Methods: A retrospective analysis of 300 patients’ electronic and paper medical records treated for uveal melanoma at the Department of Ophthalmology and Ocular Oncology, University Hospital in Krakow, Poland, from May 2014 to December 2016 was performed. The created database, which includes numerous parameters characterizing patients, tumors, applied treatments and their effects, with particular emphasis on the occurrence of ocular complications, was subjected to detailed analysis. The influence of selected factors on the occurrence of identified complications was checked by performing a univariable Cox proportional hazards regression analysis, and then the factors that were statistically significant were included in a multivariable Cox proportional hazards regression analysis which gave the final results. Results: Of the 300 patients, 125 (41.67%) were treated with Ru-106 brachytherapy (87 (29%) with CCB plaque and 38 (12.67%) with COB plaque), 102 (34%) with I-125 brachytherapy and 73 (24.33%) with proton therapy. Mean follow-up was 88.63 months (median 89, range: 20–127). The occurrence of cataract was associated with the older age of patients. Maculopathy was associated with female sex, younger age, use of I-125 brachytherapy, tumor location involving the macula and/or optic disc and moderate tumor pigmentation. Diagnosis of systemic hypertension was associated with a lower risk of maculopathy. Retinopathy was associated with younger age, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Optic neuropathy was associated with younger age, greater tumor largest base diameter, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Secondary glaucoma was associated with baseline best corrected visual acuity (BCVA) weaker than 0.5, greater tumor thickness, involvement of the left eye and the use of I-125 brachytherapy. Vitreous hemorrhage was associated with greater tumor thickness, tumor location including the macula and/or optic disc and mushroom-shaped tumor. Conclusions: Our study demonstrated an association between demographic, clinical, and physical factors and the occurrence of ocular complications after radiotherapy for uveal melanoma. Full article

Background: Early identification of small choroidal melanomas is important, as metastatic risk increases with tumor size. However, distinguishing small melanomas from benign choroidal nevi is challenging and may lead to unnecessary referrals and overtreatment. Both the MOLES scoring system and the deep learning algorithm MelAInoma have been developed to support assessment of pigmented choroidal lesions in non-expert settings. This study aims to compare the association between MOLES and MelAInoma scores and to assess their relative association with expert melanoma versus nevus diagnosis. Methods: In this retrospective cohort study, 86 patients with small pigmented choroidal lesions (29 melanomas and 57 nevi) diagnosed at a national ocular oncology referral center were included. MOLES scores were assigned by ocular oncologists based on multimodal examination, whereas MelAInoma scores were generated solely from color fundus photographs. Associations between scores were assessed using linear regression and the Jonckheere–Terpstra test. Univariable and multivariable binary logistic regression was used to evaluate associations with melanoma diagnosis. Results: MelAInoma scores increased monotonically with higher MOLES categories (p = 0.0001). Linear regression showed a statistically significant association between MOLES and MelAInoma scores, but with substantial dispersion (R² = 0.16). In univariable logistic regression, both MOLES and MelAInoma scores were associated with increased odds of melanoma diagnosis. MelAInoma showed a stronger association with diagnosis than MOLES (R² = 0.38 vs. 0.27). In multivariable analysis including both scores, each remained independently associated with melanoma diagnosis. Conclusions: Both MOLES and MelAInoma are effective for differentiating small choroidal melanomas from nevi. Although the scores are statistically associated, they capture partly distinct information. MelAInoma demonstrates slightly stronger association with melanoma diagnosis and provides fully reproducible output, supporting its role as a complementary aid in lesion triage. Full article

Background/Objectives: The primary objective of this systematic review is to synthesize the available evidence regarding the safety of the various treatment options for advanced uveal melanoma. A thorough understanding of a drug’s safety profile enables early identification and management of adverse reactions, thereby preventing clinical deterioration and minimizing the need for dose reduction, treatment delays, or therapy discontinuation. Methods: In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) guidelines, this review included all clinical studies that examined the most common adverse events associated with all available systemic treatments for metastatic uveal melanoma. Following the study selection process, nine studies were considered eligible and were included in the review. Results: Treatment with the bispecific antibody was associated with a favorable toxicity profile. The most severe adverse event observed was limited to cutaneous toxicity. Analysis of treatment-related adverse events (TRAEs) of grade ≥3 showed that patient cohorts receiving trametinib, selumetinib, and darovasertib experienced the lowest incidence of severe events (with the exception of creatine phosphokinase elevation observed with selumetinib), suggesting a comparatively more favorable safety profile for these agents. At present, the most robust efficacy data in the metastatic uveal melanoma setting are available for tebentafusp and darovasertib. Conclusions: This study provides the most comprehensive analysis of TRAEs in randomized trials of UM, delineating the toxicity and safety profiles of current therapies to guide personalized treatment decisions. Full article

Background: Although blinded independent central review (BICR) can reduce assessment variability, it introduces additional financial and logistical burdens to trial operations. This study analyzed the discrepancy indexes (DIs) to evaluate differences between progression-free survival (PFS) assessments by local investigators (LIs) and BICR in randomized clinical trials (RCTs) of patients with metastatic melanoma. Methods: A comprehensive literature search was conducted on PubMed, Embase, and Cochrane databases up to 30 June 2024. The primary outcome was the DI, which was calculated for each trial as a ratio of the hazard ratios (HR)_BICR by HR_LI. The agreement between PFS HRs was also evaluated using the intraclass correlation coefficient (ICC) and Pearson’s correlation coefficient (r). Results: Twelve studies comprising 4915 patients were included in this study. Of these, 10 (83%) were Phase III, 11 (92%) were cutaneous melanoma, one was uveal, and all identified PFS as the primary endpoint. Most (86%) of the PFS comparisons yielded the same statistical inference by both BICR and LIs. The overall combined DI was calculated at 1.08 (95% CI: 1.01–1.15), indicating a statistically significant, numerically small difference in PFS evaluations driven primarily by the uveal Phase III double-blinded study, while there was a strong overall correlation [(ICC: 0.87, p < 0.001); (r = 0.89, 95% CI 0.67–0.96, p < 0.0001)]. Cutaneous melanoma trials demonstrated strong agreement between BICR and local investigator assessments. Conclusions: In randomized trials of metastatic cutaneous melanoma, LI-assessed PFS closely aligns with BICR and provides equivalent trial-level conclusions in most cases. These findings support the use of LI-assessed PFS as a valid and practical primary endpoint, without routine requirement for BICR. Central review should be reserved for selected scenarios. Full article

Background: Chromosome 3p (chr3p) is frequently deleted in multiple cancers, indicating the presence of shared tumor suppressors. In aggressive uveal melanomas (UVM), this deletion often co-occurs with chr8q amplification (8q+), suggesting strong selection pressure during UVM evolution. Methods: To understand the pattern of genomic alterations mediated by chr3p deletion, we have developed an algorithm for detecting isochromosomes in 10,632 TCGA cancer patients. We further perform integrative genomics analysis to investigate how chr3p deletion could affect subsequent cancer genome evolution and synthetic lethality in UVM. Results: Analysis of genomic alterations in 33 different cancer types implicates the deletion or deleterious mutations of SET-domain-containing 2 (SETD2) at chr3p21 in significantly facilitating the formation of isochromosomes, thereby promoting genomic instability conducive to rapid cancer genome evolution. Fracturing of dicentric isochromosomes during cell division is pervasive and follows the dynamic fragmentation pattern of solids under impulse. In the most aggressive UVM subtype, chr3 deletion includes MITF, a master regulator of melanocyte survival and differentiation, and co-occurs with 8q+. We demonstrate that MITF is a master transcriptional regulator of GNAQ/GNA11 and associated synthetic-lethal genes in UVM. MITF maintains MAPK and calcium homeostasis in UVM, and its hemizygous deletion is thus accidental, likely creating an early crisis during oncogenesis. We further show that MITF, MYC, and GNAQ/GNA11 form coupled regulatory feedback loops in the melanocyte lineage, and MITF deletion in UVM creates acute dependency on MYC-mediated rescue via 8q+. The discovered feedback loops predict both overall and relapse-free patient survival within the most aggressive UVM subtype, explain sensitivity to therapeutic gene perturbations, and inform effective combinatorial therapies. Conclusions: SETD2 deletion potentiates isochromosome formation across diverse cancers. Combinatorial targeting of MITF together with a previously identified synthetic lethal gene may benefit UVM patients harboring both chr3 deletion and 8q+. Full article

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver mutation in GNAQ and GNA11 G-alpha proteins. Methods: Several DNA constructs encoding mutated GNAQ were developed and tested for activation of UM-reactive T cells in HLA-A2/Hd transgenic mice and human T cells ex vivo. Results: Constructs containing immune-enhancing PADRE and VP22-derived epitopes boosted T cell responses against mutant GNAQ, which correlated with reduced experimental lung metastases. Ex vivo dendritic cell-mediated T cell activation with vaccine constructs containing optimized structure produced cytolytic T cells that secreted IFN gamma and killed mutated GNAQ-expressing UM cells in vitro. Conclusions: These findings propose the utility of the fusion DNA vaccines in eliciting T cell immunity against UM cells bearing the Q209L mutation in GNAQ/GNA11 protein to prevent the establishment and progression of metastatic disease. Full article