TPS9607 Background: Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Primary UM are effectively treated by plaque radiotherapy or enucleation; however, up to 50% of UM patients ultimately succumb to advanced disease. Tebentafusp-tebn is a bispecific gp100 peptide human leukocyte antigen (HLA)-directed cluster of differentiation 3 (CD3) T-cell engager that became the first FDA approved treatment for unresectable or metastatic UM. Among the metastatic UM patients who received tebentafusp on clinical trial (IMCgp100-01 (n=19), IMCgp100-102 (n=146), and IMCgp100-202 (n=245)), 12 patients had recurrent orbital tumors. All orbital lesions were stable or had achieved shrinkage with tebentafusp. The best percentage changes from baseline were reported as -3 to -40% reduction in intra-ocular target lesions. All intra-ocular non-target lesions were stable or achieved a complete response after tebentafusp treatments. These preliminary data indicate that tebentafusp may have potential for treating surgically unresectable primary UM. Methods: This is an investigator-initiated, prospective, single arm phase II trial evaluating neoadjuvant tebentafusp in patients with locally advanced primary UM [NCT06414590]. Patients must be 18 years or older, HLA-A*02:01 with a primary UM with T3 or T4 category tumor size. Patients cannot have a symptomatic UM that requires immediate ophthalmological intervention such as enucleation. Patients will be treated with up to 8 weeks of neoadjuvant tebentafusp, followed by radioactive plaque or enucleation. Tebentafusp will be administered as follows: 20mcg on Day 1, 30mcg on Day 8, 68 mcg on Day 15, and weekly doses of 68 mcg thereafter. The first three treatments will require inpatient hospitalization for overnight observation. The primary endpoint of the study is regression (defined as ≥ 20% reduction in tumor volume) of primary UM after tebentafusp treatment in 20% of treated patients. Secondary endpoints include toxicity assessment and ctDNA analysis in both blood and aqueous humor. Exploratory endpoints include changes to visual acuity, radiation dose to the fovea, and treatment (enucleation to plaque brachytherapy). The efficacy of this combination treatment will be assessed using the Simon’s two stage design. In stage I, a total number of 8 patients are accrued and if there are 0 responses among these 8 patients, further enrollment of patients may be stopped. Otherwise, an additional 11 patients will be accrued in stage II, resulting in a total sample size of 19 patients. Enrollment began in September 2025 at Thomas Jefferson University Hospital, in conjunction with Wills Eye Hospital. Clinical trial information: NCT06414590 .

To evaluate clinical factors that lead to ≥15-letter visual acuity loss following plaque radiotherapy of posterior uveal melanoma (PUM) in the pre-anti-vascular endothelial growth factor (anti-VEGF) era. We reviewed data on 4000 consecutive patients with plaque-irradiated PUM managed between May 1976 and November 2008 to identify parameters predictive of ≥15-letter vision loss. Data included median patient age (60 years), diabetes mellitus (11%), median tumor diameter (11.0 mm) and thickness (4.5 mm), and median distance to optic disc (4.0 mm) and foveola (3.0 mm). Kaplan-Meier analyses revealed ≥15-letter loss at 1 versus (vs.) 3 vs. 5 vs. 10 years in 30% vs. 60% vs. 73% vs. 82% of patients. Multivariate analyses revealed factors predictive of ≥15-letter loss included greater tumor thickness (p<0.01, hazard ratio [HR] 1.14), shorter distance to foveola (p<0.01, HR 0.93), greater radiation dose to foveola (p<0.01, HR 1.01) and lens (p<0.01, HR 1.01), and presence of diabetes mellitus (p<0.01, HR 1.11). For small PUM, multivariate risk factors included older age (p<0.01), diabetes mellitus (p<0.01), and shorter distance to foveola (p<0.02); for medium PUM, risk factors included greater tumor thickness (p<0.01), shorter distance to foveola (p<0.01), and less (but shorter) radiation dose to foveola (p<0.01); for large PUM, risk factors included greater tumor thickness (p<0.01) only. In the pre-anti-VEGF days, following treatment of PUM with plaque radiotherapy, clinical and treatment factors predictive of ≥15-letter visual acuity loss included greater tumor thickness, shorter distance to foveola, greater radiation dose to foveola and lens, and presence of diabetes mellitus.

Extremely Late Local Recurrence of a Choroidal Melanoma, 51 Years Following Cobalt-60 Plaque Radiation Therapy.

Prospective study of blepharoptosis after plaque radiotherapy.

PurposeTo report a case of an acute rise in blood pressure and acquired cardiac arrhythmia resulting from excessive topical phenylephrine exposure intraoperatively during the surgical insertion of a radioactive plaque for choroidal melanoma.MethodsObservational case report with literature review.ObservationsA 56‐year‐old asymptomatic man with a diagnosis of choroidal melanoma of the right eye underwent routine plaque radiotherapy placement. Due to delayed dilation, additional topical 10% phenylephrine drops were placed on the eye after limited conjunctival peritomy. Shortly thereafter, the patient experienced an acute hypertensive episode with a cardiac arrhythmia and confusion due to the excess phenylephrine used that pooled on the ocular surface. The patient was successfully treated by the anesthesia team and found to have no chronic cardiac conditions. The choroidal melanoma was also successfully treated.Conclusion and ImportanceAdditional mydriatic agents may be used with caution in the postincision setting, but should be thoroughly rinsed to prevent adverse cardiac events, particularly phenylephrine. Open communication is critical between the surgical and the anesthesia team prior to the addition of phenylephrine drops.

To assess the outcomes of pars plana vitrectomy (PPV) in patients with complications related to retinal focal nodular gliosis (FNGs), also known as vasoproliferative tumours. This retrospective case series included 22 patients who underwent PPV for the management of FNG-related complications at Moorfields Eye Hospital between 2012 and 2024. We collected and analysed the patient demographics, clinical features and surgical outcomes. The mean age was 50.59 years (SD 14.5) at presentation and 52.59 years (SD 13.9) at the time of surgery. The most common indications for surgery were epiretinal membrane (n = 9, 40.9%) and vitreous haemorrhage (n = 8, 36.4%). Fifteen eyes (68.2%) were treatment-naïve, while five (22.7%) had previously undergone ruthenium plaque radiotherapy. The median follow-up period was 34 months (IQR 6.0-62.2). The median preoperative visual acuity was 1.15 logMAR (IQR 0.67-2.40), which significantly improved to 0.4 logMAR (IQR 0.17-1.0) at the last follow-up visit (p < 0.01). Postoperative complications were not observed in 14 patients (63.6%), while cystoid macular oedema was the most common complication following vitrectomy (13.6%, n = 3). Three patients required FNG-related re-operation for rhegmatogenous retinal detachment, macular hole, and epiretinal membrane. All FNGs were inactive at the last follow-up visit. Vitreous haemorrhage and epiretinal membrane are the most common indications for surgery in patients with FNG. PPV demonstrates favourable functional and anatomic outcomes, though it is worth noting a 13.6% re-operation rate for complications. Significant visual improvement and effective tumour control are also recorded in the long-term.

BackgroundTo describe the characteristics and outcomes of endoresection in patients with uveal melanoma previously treated with ruthenium brachytherapy or proton beam therapy.MethodsIn this retrospective study, data on the indication to perform endoresection, best-corrected visual acuity, tumor characteristics, surgery details, and characteristics of ruthenium brachytherapy or proton beam therapy were obtained.ResultsA total of 27 patients (12 men and 15 women) were included, with a median age of 63.5 (range 50.5) years. The indication for endoresection was exudative retinal detachment in 20 patients, glaucoma induced by tumor bleeding in 6 patients, and persistent inflammation in 1 patient. Ruthenium brachytherapy was performed in 6 patients, while 21 patients received proton beam therapy. In the ruthenium group, mean visual acuity before endoresection in Snellen was 0.099 ± 0.197, which increased to 0.285 ± 0.302 after endoresection (p = 0.043). In the proton beam group, mean visual acuity before endoresection was 0.030 ± 0.044, which decreased to 0.020 ± 0.036 after endoresection (p = 0.546). Mean change in visual acuity before and after endoresection was +0.186 ± 0.249 in the ruthenium group and −0.009 ± 0.053 in the proton beam group. Enucleation had to be performed in 1 eye in the ruthenium group and 8 eyes in the proton beam group. No surgery-related vascular events were observed.ConclusionsPatients previously treated with ruthenium brachytherapy have favorable post-endoresection outcomes, opposed to those treated with proton beam therapy. Patient-specific counselling is important before endoresection, as there is a wide variety in expected outcomes.

To explore the histopathological characteristics in eyes with uveal melanoma (UM) that had secondary enucleation after iodine-125 plaque radiotherapy (PRT). This study included 243 patients with unilateral UM treated at Beijing Tongren Hospital from 2007 to 2020. Of these, 119 initially received PRT, followed by enucleation 2 months-9 years later. We retrospectively examined the histopathological features of enucleated ocular tissues to investigate microscopic differences based on treatment methods and reasons for secondary enucleation. Compared with 124 primary enucleations, eyes after PRT were more likely to show tumour diffuse distribution; had more tumour cell necrosis and more inflammation. In addition, eyes after PRT had a higher frequency of sclera invasion, optic nerve invasion by the tumour and neovascularisation of the iris. Histopathologically, 55 eyes (46%) were removed due to local control failure. Compared with eyes enucleated because of severe radiotherapy complications, eyes enucleated for local control failure had tumours invading the optic disc and ciliary body more frequently, pathological mitosis and the proportion of tumour diffuse distribution were higher. Eyes with radiotherapy complications had more tumour tissue necrosis and more neovascularisation of the iris. By observing the pathological features, we regrouped the patients who underwent secondary enucleation after PRT. These differences in histopathology may represent tissue effects of radiotherapy radiation or features related to tumour progression and growth. Tumour insensitivity and progression after PRT clearly increased the risk of metastasis-related death. Some pathological microscopic features may be important prognostic indicators of patients with UM.

Uveal melanomas are almost always unilateral. Bilateral presentation is extremely rare, about 1 in 80 million/year. This report presents the case of a 40-year-old man who developed bilateral choroidal melanoma sequentially. The right eye with a de novo juxtapapillary choroidal melanoma was managed with 18-mm notched I125 plaque with full distribution. Eighteen months later, transformation of a choroidal nevus into a melanoma was detected in the fellow eye, and was treated with 12-mm round I125 plaque with full distribution. The patient tested positive for BAP1 germline mutation (c.659+1G >A p.?; rs2153227622). After three years of follow-up, both tumors were regressed and the patient was receiving immunotherapy for related liver metastasis.

Conjunctival melanoma is a rare, potentially lethal cancer that mainly affects fair-skinned individuals. The tumor mostly arises from primary acquired melanosis (PAM) with atypia. The presentation of conjunctival melanoma varies and should be clinically differentiated from an array of ocular surface pigmented and nonpigmented lesions. Mutations in the oncogenes BRAF (V600E) and NRAS, and the tumor suppressor gene NF1, are associated with worse survival. UV signature mutations are frequently observed in the bulbar conjunctival melanoma. The TNM staging classifies conjunctival melanoma according to its location and extent. The treatment of conjunctival melanoma depends on tumor staging. Surgical excision of a localized bulbar or forniceal tumor with the no-tumor-touch technique and margin cryotherapy can be sufficient for local control. Adjunctive radiotherapy options include Proton beam radiotherapy, Plaque radiotherapy for ocular surface melanoma, Orthovoltage (Deep x-ray) radiotherapy for palpebral melanoma, and Megavoltage LINAC-based photon radiotherapy can be used for locally invasive and localized orbital extension of conjunctival melanoma. Topical mitomycin-C eye drops are used for diffuse flat melanoma or PAM with severe atypia. Systemic targeted therapy such as BRAF inhibitors for melanoma with BRAF mutation, and systemic immunotherapy drugs have been recently used for more extensive or metastatic disease. Risk factors for metastasis include: greater tumor thickness, non-bulbar location, low tumor pigmentation, histologic ulceration, >1 mitotic figure per mm2, and adjacent structures invasion. Localized tumors should be excised en block, and incisional biopsy should be avoided, which could lead to local widespread tumor dissemination and subsequent recurrence and metastasis.

Uveal metastasis: clinical characteristics, treatment, and prognostic factors in a cohort of 161 patients in China.

Choroidal melanoma can arise from malignant transformation of choroidal nevus. The Cancer Genome Atlas, a classification system based on the genetic status of chromosomes 3 and 8, can be used to prognosticate metastasis and death in choroidal melanoma. This study explores the impact that growth rates and clinical/imaging (TFSOM-DIM (To Find Small Ocular Melanoma, Doing IMaging)) risk factors have on cytogenetics, metastasis and death in choroidal nevus which transforms into melanoma. A retrospective study was performed on 86 consecutive patients diagnosed with choroidal nevus with transformation into melanoma. Tumour cytogenetic results and TFSOM-DIM risk factors for transformation at the date of initial presentation (DIP) and date of transformation diagnosis (DOT) were recorded. Cytogenetic testing of tumours was offered to patients at DOT and was performed on tumour samples obtained via fine-needle aspiration biopsy prior to plaque radiotherapy initiation. Of 86 patients, 66% were cytogenetically low-risk and 34% were cytogenetically high-risk. At DOT, high-risk tumours possessed more TFSOM-DIM risk factors than low-risk tumours (4.5 vs 3.8, p=0.003). Choroidal nevus with growth in thickness >0.5 mm/year or >20% per year had increased risk for high-risk cytogenetics (relative risk (RR)=1.93, 95% CI 1.09 to 3.43, p=0.027; RR=2.18, 95% CI 1.22 to 3.92, p=0.008, respectively). Choroidal nevus with growth in basal diameter >0.7 mm/year or >10% per year had increased risk for high-risk cytogenetics (RR=2.22, 95% CI 1.25 to 3.93, p=0.007; RR=1.83, 95% CI 1.03 to 3.26, p=0.042, respectively). When monitoring patients with choroidal nevus, clinical risk factors are important in estimating risk for transformation into melanoma. We found that thickness growth >0.5 mm/year or >20% per year, as well as basal diameter growth >0.7 mm/year or >10% per year, were all thresholds that demonstrated increased risk for high-risk cytogenetics. Additionally, tumours with a greater number of TFSOM-DIM risk factors by DOT had significantly increased likelihood of high-risk cytogenetics.

PurposeThis study aimed to assess long-term visual acuity outcomes and multiple secondary factors in fellow eyes of uveal melanoma patients treated with either iodine-125 (125I) plaque radiotherapy (PRT), transpupillary thermotherapy (TTT), or proton beam therapy (PBT).Material and methodsA retrospective chart review of 213 patients treated from 2000 to 2022 was performed, with baseline and post-treatment visual acuity data collected at follow-up time points up to 10 years, when available. Paired t-tests compared changes in visual acuity (VA) and intraocular pressure (IOP) over time for affected and fellow eyes. Spearman’s rho test assessed correlations between melanoma thickness and VA over time, and repeated measures ANOVA determined interactions between time and comorbidities in VA.ResultsFellow eyes VA showed no significant change up to a decade post-treatment regardless of treatment modality, except for a likely false positive improvement at 2 years post-PRT. In contrast, affected eyes had significant VA decline post-PRT and PBT, while TTT used in affected eyes demonstrated no significant change. IOP did not show any significant changes in fellow eyes. Tumor thickness and the presence of diabetes, hypertension, or coronary artery disease, did not correlate with fellow eye VA outcomes.ConclusionsThis study suggests that following uveal melanoma treatment with either 125I PRT, TTT, or PBT, fellow eyes remain stable regarding VA and other outcomes up to 10 years. This provides important information for treatment choice in patients with ocular melanoma, especially as VA can decline in affected eye post-treatment, leading to reliance on contralateral eye.

Purpose: To describe the prevalence of epiretinal membrane (ERM) in eyes with choroidal melanoma. Methods: A retrospective clinical case review was conducted to evaluate the prevalence of ERMs. Examinations included ophthalmoscopy, fundus photography, and optical coherence tomography. Multivariate analysis evaluated ERMs with choroidal melanoma, retinal detachment (RD) before treatment, plaque radiation dose to the fovea, radiation retinopathy, and intravitreal (IVT) antivascular endothelial growth factor (anti-VEGF) treatment. Contralateral eyes were used as controls. Results: The study included 373 patients (746 eyes). ERMs were found in 34% of eyes with choroidal melanoma that were treated and 12.1% of control eyes. A larger tumor size (increasing American Joint Committee on Cancer cT category) was significantly associated with the presence of an ERM at baseline. In addition, a higher radiation dose to the fovea was associated with ERM development. Risk factors determined by multivariate analysis included radiation retinopathy (odds ratio [OR], 3.00), anti-VEGF injections (OR, 2.87), and RD at presentation (OR, 3.19). Conclusions: This study found a significantly higher prevalence of ERMs in eyes with choroidal melanoma. Risk factors contributing to ERM development included the radiation dose, radiation retinopathy, IVT anti-VEGF injections, and RD. Of these factors, the presence of RD at the initial diagnosis was the strongest predictor of the occurrence of a secondary ERM.

To investigate the changes in retinal oxygen kinetics and hemodynamics in patients with choroidal melanoma (CM) within 2 years before and after iodine-125 plaque radiotherapy (PRT) using a novel noninvasive structure-functional imaging analysis system. A novel noninvasive cost-effective imaging analysis system that integrates multimodal structural and functional retinal imaging techniques has been used, which allows rapid acquisition of vascular structural, hemodynamic, and oxygenation metrics using multispectral imaging (MSI) and laser speckle contrast imaging (LSCI) techniques. Follow-ups have been arranged at the time before plaque implantation surgery, and 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after iodine-125 plaque removal. CM patients after PRT demonstrated a significant decrease in retinal arterial oxygen concentration (CO2 a), arterial oxygen saturation (SO2 a), oxygen utilization (SO2 av, CO2 av), and metabolism (oxygen extraction fraction, OEF) over time. However, there was no significant difference in SO2 and CO2 compared with healthy controls. Systolic time (Time_sr), acceleration time index (ATI), and resistivity index (RI) gradually increase over time; ATI and RI were significantly higher than those of the healthy controls. At baseline, mean arterial blood flow velocity (BFVa) and mean arterial retinal blood flow (RBFa) in CM eyes were significantly higher than those in the healthy control group. BFVa and RBFa showed a decreasing trend over time after PRT. In addition, some retinal oxygen kinetics and hemodynamic indicators were also correlated with tumor size, patient gender, and age. CM patients after iodine-125 plaque radiotherapy had significant retinal and vascular changes. Future research should focus on rapidly screening radiation microvascular complications and exploring more timely and effective interventions to protect visual function in CM patients.

The most widespread primary intraocular tumor in adults is called uveal melanoma (UM), if detected early enough, it can be curable. Various methods are available to treat UM, but the most commonly used and effective approach is plaque radiotherapy using Iodine-125 and Ruthenium-106. The authors performed searches to distinguish relevant studies from 2017 to 2024 by three databases (PubMed, Scopus, and Google Scholar). Imaging technologies such as ultrasound (US), fundus photography (FP), optical coherent tomography (OCT), fluorescein angiography (FA), and magnetic resonance images (MRI) play a vital role in the diagnosis and prognosis of UM. The present review assessed the power of different image modalities when integrated with artificial intelligence (AI) to diagnose and prognosis of patients affected by UM. Finally, after reviewing the studies conducted, it was concluded that AI is a developing tool in image analysis and enhances workflows in diagnosis from data and image processing to clinical decisions, improving tailored treatment scenarios, response prediction, and prognostication.

To evaluate tissue glue-assisted plaque placement regarding accuracy, stability, and longer-term outcomes for choroidal tumors with scleral thinning. All patients with tissue glue-assisted plaque radiotherapy at a single ocular oncology center were evaluated for patient demographics, tumor features, surgical details, tumor response, and glue-related complications. There were 13 patients (mean age 72 years) treated with tissue glue-assisted plaque radiotherapy for choroidal melanoma (n = 12) or choroidal metastasis (n = 1). At presentation, the tumor was mean 4.3 mm to the optic disk and 2.0 mm to the foveola with a mean basal diameter of 9.5 mm and a thickness of 4.2 mm. In all cases, the tissue glue-assistance was used due to extreme scleral thinning in the bed of proposed radiation. The plaque size was 15 mm (n = 5), 18 mm (n = 7), or 20 mm (n = 1). At application, there was no immediate glue hypersensitivity, ultrasonography confirmed accuracy of placement, and the glue remained adherent for the entire treatment duration (mean 113 hours) with stable plaque location at removal. At removal, the plaque-glue composite was peeled off the globe without need for glue dissolvent and without scleral disruption. At 12 months, mean melanoma thickness was 2.7 mm (regression 36%). There were no conjunctival, corneal, or scleral complications. Tissue glue-assisted plaque radiotherapy is safe and effective for treatment of choroidal tumors with thin sclera.

Favorable Outcomes of Patients With High-Risk Uveal Melanoma Treated With a Novel Linear Accelerator-Based Frameless Fractionated Stereotactic Radiosurgery.

Abstract The purpose of this report is to highlight the results of iodine-125 episcleral plaque radiotherapy for the treatment of circumscribed choroidal hemangiomas (CCHs) as an alternative to photodynamic therapy. CCH are rare benign vascular hamartomas without systemic associations. We herein describe the treatment of a case of a pediatric patient with CCH associated with an exudative retinal detachment. His treatment consisted of brachytherapy with a plaque loaded with 125 Iodine seeds with a target apex dose of 40 Gy. Preoperative visual acuity (VA) in the affected right eye was 20/800. After treatment and for 24 months of follow-up, the VA improved to 20/200, with no signs of radiation retinopathy or recurrence of subretinal fluid. The favorable visual results, resolution of exudative retinal detachments, and the low rate of side effects lead us to conclude that iodine-125 episcleral brachytherapy should be considered in large tumors, those with a subfoveal location or the presence of extensive subretinal fluid.

Eye plaque radiation therapy is the treatment of choice for small- and medium-sized choroidal melanomas. This study investigated the dose distribution around eye plaques containing 125I seeds to treat ocular melanoma using Monte Carlo N-Particle eXtended (MCNPX) and Plaque Simulator (PS) software. Dosimetry evaluation and comparison of the resulting isodose curves for 125I COMS plaques were performed using the MCNPX code. The isodose curves and dose distributions were calculated using PS treatment planning for a 125I COMS plaque. In the validation, the maximum relative difference between the results of this study and those reported in other literature was approximately 9%-10% for the COMS plaques. The dose distributions of MCNPX were lower than those of PS with a relative difference of approximately 27.7%-35.4%. The dose distribution may differ depending on the 125I source spectra and seed design used in the two methods. In addition, the dose algorithm used in PS made a major contribution to the relative differences between the results. The PS did not provide accurate details of dose distribution near the surface of the plaque insert. The source parameters used in each program should be studied more carefully to determine the source of the differences in the estimated dose values.