Search Results (81)

Purpose: The objective of this study was to evaluate the implementation of a Multidisciplinary Tumor Board (MDTB) strategy in the treatment of patients with uveal melanoma. Methods: A retrospective analysis was conducted on the implementation of MDTB meetings over a 24-month period. During this time, 72 intraocular tumors were discussed, including 59 confirmed cases of uveal melanoma. The MDTB involved a core group of specialists (e.g., ophthalmologists, oncologists, and radiologists), with other experts included when clinically appropriate. To assess patient satisfaction with the MDTB approach, a structured questionnaire was administered, including items on clarity of communication, perceived quality of care, and overall satisfaction, which were ranked on a 5-point scale. Results: A total of 319 patients with ocular, periocular, or orbital tumors were discussed during the study period, of which, 72 had intraocular tumors. A total of 13 (18%) were diagnosed to have choroidal metastases, whereas 59 (82%) had uveal melanomas. The average time between patient care and MDTB discussion was 15.9 days (IQR: 7.5–16.5). The mean time between the case discussion and the implementation of recommendations (diagnostic, therapeutic, or referral decisions) was 14.8 days (IQR: 6.0–23.75). Overall, 4 (7%) patients were classified as Stage I, 16 (27%) as Stage IIa, 18 (31%) as Stage IIb, 7 (12%) as Stage IIIa, 2 (3%) as Stage IIIb, and 12 (20%) as Stage IV. Regarding the satisfaction questionnaire, all patients (100%) agreed to have the clinical case discussed at the TB even though this could result in a delay in diagnostic/therapeutic implementation. However, only 60% of patients perceived they had been directly involved in the decision-making process. Conclusions: In selected cases of uveal melanoma and other types of cancer, MDTBs should be recognized as a gold standard in cancer care, allowing for comprehensive decision-making that draws on a wide range of highly specialized expertise. Full article

Background/Objectives: To determine if the results of cytogenetic analyses of choroidal melanoma biopsies after ruthenium-106 plaque brachytherapy (RPB) are affected by this procedure. Methods: A retrospective study was conducted on 368 patients with choroidal melanoma treated with RPB who underwent cytogenetic testing at the Liverpool Ocular Oncology Centre (LOOC) between May 2012 and November 2024. Data on demographics, tumor characteristics, treatment date, biopsy timing (pre- or post-RPB), and cytogenetic results were extracted from the LOOC database. Statistical analysis included descriptive statistics, binary, and multinomial logistic regression to assess associations between biopsy timing and biopsy success rates. Results: Biopsies were performed before RPB in 58.7% (216/368) cases, and post-PBR in 41.3%. Cytomorphological identification and molecular genetic testing were successful in 96.4% and 85.1% cases, respectively. Timing of biopsy, patient demographics, and tumor characteristics did not significantly influence cytogenetic test outcomes. Molecular testing could not be performed on 6.8% (25/368) cases as the DNA was insufficient in these samples. Genetic testing success slightly declined beyond three months post-RPB, though a few cases had delayed biopsy (n = 8). Pre-RPB biopsies more frequently demonstrated monosomy 3, whereas post-RPB biopsies had higher rates of disomy 3 (χ², p < 0.05). Conclusions: Prognostic biopsies post-RPB provide reliable cytomorphological and molecular genetic results using MLPA or MSA. Test failure is not significantly influenced by biopsy timing, patient or tumor characteristics, biopsy modality, or genetic technique. Insufficient DNA yield remains a key limitation, emphasizing the importance of obtaining adequate tissue samples. Biopsies within three months are preferable to optimize success in molecular testing. Full article

Background/Objectives: This study aims to evaluate whether fine-needle aspiration biopsy (FNAB) of melanocytic uveal tumors (MUTs) using 27-gauge (27G) needles yields aspirates like those obtained using 25-gauge (25G) needles for cytology. Methods: A retrospective review was conducted on 32 primary uveal melanomas (PUMs). Tumors were sampled at three adjacent sites, first using a 27G needle for gene expression profile (GEP) testing, second and third with 27G and 25G needles for cytology. The endpoints evaluated were the sufficiency of aspirates for cytopathology and GEP. Results: Among the 32 patients, 17 tumors were choroidal, 6 ciliochoroidal, 7 iridociliochoroidal, and 2 exclusively iridic. Tumor diameter ranged from 3.3 mm to 23 mm (mean 13.2 mm), and thickness ranged from 0.5 mm to 12 mm (mean 6.4 mm). Aspirates from both needle sizes were sufficient for cytopathological diagnosis and GEP in 31 of 32 cases (96.9%). The single insufficient aspirate was insufficient with both the 27G and 25G needles. The cytopathology was identical in all other cases. The tumors were Class 1 in 22 cases (71.0%) and Class 2 in 9 cases (29.0%). Conclusions: FNAB aspirates of MUTs using 27G needles appear sufficient for cytology and GEP in most cases, showing a similar diagnostic yield compared to 25G needles. Full article

Background and Objectives: Uveitis-masked syndromes or masquerade syndromes (UMSs) are a group of ocular conditions with several systemic underlying causes, malignant or nonmalignant, that mimic the inflammatory status of the uvea. They are often difficult to detect and diagnose with traditional techniques, such as ophthalmic exams. Ocular B (bidimensional)-ultrasound (OBU) is a non-invasive, repeatable, rapid ultrasound method effective in indirect signs that lead back to systemic diseases. It is comparable in effectiveness with other imaging tools. The cause of UMSs can often be serious, and therefore early diagnosis and prompt treatment are critical. This study aimed to identify the sonographic signs of these forms, which can help physicians discover the cause underlying UMS. Materials and Methods: This was a consecutive, retrospective, nonrandomized study. This study was conducted at the University Hospital Polyclinic of Bari, Italy, from January 2022 to December 2024. A total of 186 patients were included, from 10 to 85 years old. They all underwent B-scan ultrasonography (Quantel Medical ABSolu Ocular Ultrasound). Results: All patients reported blurred vision, which could be accompanied by visual reduction (<20/40, Snellen charts), photophobia, floaters, flashes, proptosis, and redness. In all cases, we noted peculiar ultrasonographic signs, which allowed us to discriminate the underlying systemic diagnosis, such as vitreous corpuscles, choroid thickening, and primitive or metastatic solid tumors. Finally, we identified different diseases, such as primary intraocular lymphoma (PIOL), other lymphoproliferative conditions, orbital plasmacytoma, uveal melanoma, metastasis, endogenous endophthalmitis, retinal detachment, central serous retinopathy, metallic foreign bodies, ocular amyloidosis, and drug-induced UMSs. The sensitivity and specificity of ocular ultrasound compared to multimodal ocular imaging in UMSs were as follows: for primary intraocular lymphoma (PIOL) and other lymphoproliferative conditions, 0.98 (95% CI, 0.80–1) and 0.68 (90% CI, 0.40–0.92), respectively; for orbital plasmacytoma, 0.64 (92% CI, 0.52–0.86) and 0.66 (93% CI, 0.48–0.89), respectively; uveal melanoma, 1.00 (98% CI, 0.88–1.00) and 0.98 (95% CI, 0.86–0.98), respectively; metastasis, 0.75 (95% CI, 0.53–0.85) and 0.85 (95% CI, 0.48–0.98), respectively; endogenous endophthalmitis, 1.00 (95% CI, 0.50–1.00) and 0.83 (95% CI, 0.48–0.98), respectively; retinal detachment, both were 1.00 (95% CI, 0.87–1.00 and 0.84–0.97, respectively); central serous retinopathy, 0.60 (80% CI, 0.41–0.88) and 0.85 (95% CI, 0.52–0.98), respectively; metallic foreign bodies, 1.00 (95% CI, 0.78–1.00) and 0.99 (95% CI, 0.99–1.00), respectively; ocular amyloidosis, 0.77 (82% CI, 0.52–0.90) and 0.83 (80% CI, 0.49–0.88), respectively; and drug-induced UMSs, 0.64 (95% CI, 0.49–0.88) and 0.85 (95% CI, 0.52–0.98), respectively. Conclusions: Diagnosing UMS accurately can be quite challenging, and many of its different types frequently go undetected. This complexity in identification often leads to underdiagnosis, meaning it is essential to improve awareness and understanding of the condition in order to achieve better recognition and treatment. Early detection of these forms is imperative. The use of OBU can help diagnose indirect signs of these forms early and treat them promptly. It compares well with other diagnostic imaging techniques, such as MRI, but this does not mean that it replaces them; it can offer added value in multimodal imaging. Full article

Background and Clinical Significance: Choroidal nevi are common benign growths originating from pigment cells in the fundus of the eye. They are typically up to 5 mm in diameter, asymptomatic, and incidentally discovered during routine ophthalmological examinations. Case Presentation: We present the case of a 48-year-old woman with presbyopic complaints and an incidental finding of a large, pigmented, slightly raised tumor in the fundus of the left eye. Examinations revealed normal visual acuity in both eyes and normal intraocular pressure. Ophthalmoscopy of the left eye identified a large, pigmented lesion measuring 11.55 mm in diameter, with drusen-like deposits along the superior nasal vascular arch. Fluorescein angiography showed atrophic changes in the retinal pigment epithelium without evidence of a pathological vascular network. Ultrasound revealed dimensions of 10.21 mm at the base and 0.57 mm prominence, with no changes observed during a one-year follow-up. Optical coherence tomography (OCT) did not detect any subretinal fluid. The right eye appeared normal. Based on these findings, a giant choroidal nevus in the left eye was suspected, and the clinical approach involved monitoring at 3- to 6-month intervals. Discussion: This case highlights the diagnostic challenges associated with a large, pigmented fundus lesion in a relatively young patient. Giant choroidal nevi, defined as lesions larger than 10 mm at the base, may clinically mimic malignant melanoma. However, features such as drusen and atrophic changes in the retinal pigment epithelium suggest a chronic process. Differentiating between giant choroidal nevi and malignant melanoma is essential due to differing therapeutic approaches. Since some choroidal nevi can undergo malignant transformation, close monitoring for signs of malignancy is crucial. Conclusions: The size of pigmented nevi is a significant risk factor for malignant transformation, underscoring the importance of long-term follow-up for affected patients. Full article

This review examines the role of artificial intelligence (AI) in differentiating choroidal nevus (CN) from choroidal melanoma (CM), focusing on diagnosis, classification, segmentation, and prediction of malignant transformation. A literature search was performed in PubMed, Google Scholar, and Science Direct up to December 2024. Eight studies met all the inclusion criteria, evaluating machine learning (ML) and deep learning (DL) applications for CN and CM assessment using various ophthalmic imaging modalities. Performance varied across AI models. U-Net achieved 100% sensitivity and an AUC of 0.88, while DenseNet121 reached an AUC of 0.9781, LASSO logistic regression an AUC of 0.88, RETFound (a self-supervised learning model) had an AUCROC of 0.92, and ResNet50 an accuracy of 92.65% in classification tasks. DeepLabv3 achieved Dice scores of 0.87 (melanoma) and 0.81 (nevi) in lesion-based segmentation, while nnU-Net yielded a Dice score of 0.78 and a recall of 0.77 for pigmented lesion segmentation. SAINT (XGBoost-based) demonstrated a strong predictive performance (AUC: 0.910), confirming its effectiveness in ophthalmic imaging. These results highlight the potential of AI models as effective diagnostic tools in ocular oncology. However, further research is needed to improve model generalizability, enhance dataset diversity, and facilitate clinical integration. Full article

Purpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5–15 Cobalt-Gray-Equivalent (CGE) of the eyes of female C57Bl6/J (Cx3cr1^+/+), Cx3cr1^gfp/+ and Cx3cr1^gfp/gfp mice mimicking the clinical situation and evaluated the structure, function and cellular composition of the retina up to 24 weeks after irradiation. Results: Proton beam irradiation of the eye with 15 CGE leads to cataract formation after 24 weeks without affecting the gross anatomy of the retinal vasculature as shown by Fundus imaging in all genotypes respectively. However, 10 and 15 CGE, lead to a significant decrease in NG2 positive cell numbers and all three dosages induced an increase in GFAP immunoreactivity. At 24 weeks a dosage of 15 CGE resulted in functional impairment and a decrease of NG2 positive cells in both WT and Cx3cr1 animals. Iba1 cell immunoreactivity was increased in all genotypes. However, in the Cx3cr1 animals the invasion of Iba1 cells into the deep vascular layer was partially prevented. This was accompanied by a less severe functional impairment in the irradiated Cx3cr1^gfp/gfp vs. WT. Conclusions: Although the gross anatomy of the retina does not seem to be affected by proton beam irradiation, the cellular composition and retinal function changed significantly in both WT and Cx3cr1 mice reflecting the clinical situation. Moreover, cataract formation was one of the major long-term effects of irradiation. We conclude that the murine model (WT and Cx3cr1 genotype) can be used to investigate proton-beam associated side effects in vivo as well as to test prospective interventions. Moreover, the loss of Cx3cr1 seems to be partially protective. Full article

Objectives: The aim of this study was to establish the concordance between conventional 20 Mhz ultrasonography and an ultrawide-field (UWF) imaging system (Optos^® California) in the measurement of basal diameters of melanocytic choroidal tumors. Methods: A retrospective study comparing diagnostic tests was conducted in patients with untreated melanocytic choroidal lesions (either nevus or melanoma) who had undergone both UWF imaging and ultrasonography. Only cases with a clear visualization of tumor borders in both imaging modalities were included. Longitudinal and transversal base diameters of the melanocytic tumors were measured by 20 MHz US (one observer) and UWF fundus photography (two observers). Interobserver agreement was assessed for UWF imaging first to validate the technique. Then, UWF imaging measurements were compared with 20 MHz US results. Results: In total, 106 patient images were reviewed, of which 61 were excluded due to unclear visualization of tumor margins. We found excellent concordance (from ICC and defined Bland–Altman plots) for interobserver and inter-technique agreement in estimating basal diameters when using pseudocolor composite and red laser images by comparing them with 20 MHz US results. Conclusions: UWF fundus imaging, when complete visualization of the tumor margins is possible, could be as reliable as ultrasonography in the measurement of the basal diameters of choroidal melanocytic tumors. Full article

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. Full article

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. Full article

Plaque radiotherapy is an effective treatment modality for medium-sized ocular tumors such as uveal melanoma. The authors review the available literature and concisely summarize the current state of the art of ophthalmic plaque brachytherapy. The choice of radioisotope, which includes Ruthenium-106 and Iodine-125, depends on the intended treatment duration, tumor characteristics, and side effect profiles. Ophthalmic plaques may be customized to allow for the delivery of a precise radiation dose by adjusting seed placement and plaque shape to minimize collateral tissue radiation. High dose rate (HDR) brachytherapy, using beta (e.g., Yttrium-90) and photon-emitting sources (e.g., Ytterbium-169, Selenium-75), allows for rapid radiation dose delivery, which typically lasts minutes, compared to multiple days with low-dose plaque brachytherapy. The efficacy of Ruthenium-106 brachytherapy for uveal melanoma varies widely, with reported local control rates between 59.0% and 98.0%. Factors influencing outcomes include tumor size, thickness, anatomical location, and radiation dose at the tumor apex, with larger and thicker tumors potentially exhibiting poorer response and a higher rate of complications. Plaque brachytherapy is effective for selected tumors, particularly uveal melanoma, providing comparable survival rates to enucleation for medium-sized tumors. The complications of plaque brachytherapy are well described, and many of these are treatable. Full article

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. Full article

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024. Full article

Background: The purpose of this study is to analyze the long-term evolution of patients with small choroidal melanocytic tumors (SCMTs) undergoing observation, and to assess their rate of transformation into melanomas and survival. Methods: A retrospective single-cohort study of patients with SCMTs (1–3 mm in height and 5–10 mm in base) diagnosed from January 1992 to February 2023 was carried out, with observation as the initial treatment. The main criterion for a transformation into melanoma is considered to be an increase in size of more than 1 mm in height and/or more than 1 mm in base measured on an ultrasound/retinography, recorded in two consecutive visits separated by one to three months. Results: 243 patients were included with a mean age of 65.3 years and a mean follow-up of 7.9 years (6 months–27.9 years); 27 patients showed tumor growth. The probabilities of growth at 5, 10, and 15 years are 10%, 14%, and 17%, respectively. Regarding survival, 22 patients died and only 3 deaths were due to melanoma metastasis. Survival rates at 5 and 10 years are 99% and 97%. Conclusions: Observation is a viable therapeutic option for SCMTs, avoiding the side effects of treatment, considering the majority of these tumors do not progress to melanoma. With close monitoring, patients can be treated promptly upon detecting a transformation. Additionally, the findings confirm that small melanocytic tumors can lead to metastatic disease, albeit at a low rate. Full article

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. Full article