OBJECTIVE:To explore the impact of radiation dosage on vital ocular structures to identify target dosage for vision preservation in patients with uveal melanoma treated with Eye Physics plaque brachytherapy. DESIGN:Retrospective study. SUBJECTS:Patients with choroidal melanoma treated with I-125 brachytherapy between 2017 and 2021 with at least 1-year follow up. METHODS:Retrospective chart review was performed. Time-to-event analysis was used to evaluate the effect of total dosage on ophthalmic structures. Other parameters analyzed include initial visual acuity, presence or absence of radiation retinopathy, tumor thickness, and tumor proximity to the fovea and optic nerve. Evaluation was based on 2 events: final best visual acuity of ≤20/200 and visual loss ≥5 lines from baseline. Univariate and multivariate Cox proportional hazards models were used for analysis. MAIN OUTCOME MEASURES:Visual acuity at baseline and each follow up visit. RESULTS:One hundred thirty-six patients met inclusion criteria. Initial visual acuity was 20/20-20/40 in 71%, and ≤20/200 in 7% of patients. At final visit, 27% patients had 20/20-20/40 and 50% had ≤20/200. Higher total dose and average dose rate to the optic disc, fovea, lens, opposite retina and sclera were associated with worse visual outcomes. Foveal dosage <35 Gy resulted in the greatest proportion of patients maintaining useful vision followed by a dose of <27.5 Gy to the optic nerve. CONCLUSIONS:<35 Gy to the fovea and <27.5 Gy to the optic disc results in >50% of patients maintaining useful vision and may represent dose target values and are important when considering neoadjuvant treatments prior to definitive plaque brachytherapy.

PURPOSE:To describe the clinical, histologic, and molecular features of a rare case of orbital synovial sarcoma and to provide a comprehensive literature review. METHODS:The authors present a case report and up-to-date literature review of orbital synovial sarcoma. Variables analyzed included patient demographics, clinical presentations, imaging findings, histopathologic features, molecular diagnostics, treatment, and outcomes. RESULTS:A 25-year-old female presented with a left orbital mass causing swelling, tearing, and mild vision impairment. Imaging identified a mass in the inferior orbit, which was subsequently confirmed by pathology as a monophasic spindle cell synovial sarcoma. Notably, initial fluorescence in situ hybridization testing for the SS18 rearrangement was negative; however, next-generation sequencing later identified an SS18-synovial sarcoma X breakpoint protein 2 fusion. The patient underwent complete surgical resection, followed by proton beam radiotherapy and chemotherapy. A PubMed and Medline search revealed 10 prior cases of orbital synovial sarcoma. Most patients were female (90.9%) and presented with painless swelling, lacrimation, and headaches. All tumors were localized at diagnosis. Surgical resection was the primary treatment in 81% of cases, with adjuvant radiation or chemotherapy each administered in 36% of cases. No recurrence or metastasis was observed on follow-up (average 11.6 months). CONCLUSIONS:Orbital synovial sarcoma is rare and typically localized at diagnosis. This is the first reported orbital synovial sarcoma with an SS18-synovial sarcoma X breakpoint protein 2 fusion identified by next-generation sequencing after negative fluorescence in situ hybridization. The case underscores the diagnostic value of molecular profiling when standard testing is inconclusive.

PURPOSE:The authors describe a case of Indeterminate cell histiocytosis, a rare disease of histiocytic proliferation on the spectrum of Langerhans cell histiocytosis. METHODS:Data were collected through retrospective chart review. RESULTS:The authors present a novel case of congenital Indeterminate cell histiocytosis with multisystem disease, including significant pan-ocular involvement. The neonate was successfully treated with the BRAF-kinase inhibitor dabrafenib, local anti-VEGF, and corticosteroid. CONCLUSIONS:The present case expands on the current ocular presentations of Indeterminate cell histiocytosis.

Purpose: We describe the diagnostic challenge by melanocytomas originating from locations other than the optic nerve.Methods: This is a retrospective case report of two patients who presented with vitreous hemorrhage with underlying melanocytomas.Results: Both patients had hemorrhage obscuring indeterminant uveal masses; fine-needle aspiration biopsies confirmed melanocytoma with necrosis and atypia and, in one case, concern for malignant transformation.Conclusion: Melanocytomas are rare, benign melanocytic lesions that resemble nevi. In contrast to optic nerve melanocytoma, those involving the choroid and ciliary body lack specific clinical characteristics. Vitreous hemorrhage is an underrecognized complication, and uveal melanocytoma must be included in the differential diagnosis of vitreous hemorrhage with associated ciliary body or choroidal mass. Biopsy is required for definitive diagnosis and to identify malignant transformation of the lesion, a rare but possible occurrence.

e15037 Background: Uveal melanoma (UM) is a rare and aggressive intraocular malignancy, with up to half of patients developing metastatic disease. Surveillance approaches depend on gene expression profiling and radiographic imaging, but these methods do not address detection of subclinical disease. Circulating tumor DNA (ctDNA), derived from tumor nucleic acids in plasma, has emerged as a tumor marker for disease burden and treatment response, but currently limited in UM to matched tumor-informed assays in the metastatic setting. Here we assess the utility of a novel tumor-agnostic ctDNA assay, to be used for early detection in the surveillance setting as well as for metastatic disease monitoring. Methods: We conducted a prospective study of 42 UM patients at Columbia University Irving Medical Center, stratifying them into surveillance (n = 24) and metastatic (n = 18) cohorts. The Columbia University Division of Personalized Genomic Medicine developed blood based ctDNA assay using genetic alterations common to uveal melanoma (a 30 gene panel including GNAQ, GNA11, BAP1, and PLCB4). ctDNA level was measured in copies/mL and variant allele frequency (VAF %). Surveillance patients had ctDNA collected at 3-6 month intervals, while metastatic patients were sampled throughout a variety of investigational and standard treatments including liver-directed therapy. Results: In the surveillance cohort, all 24 patients had negative ctDNA at baseline and follow-up. This included two patients with undetectable ctDNA, both of whom developed radiographic evidence of liver metastasis, confirmed by biopsy within 2 weeks of a negative ctDNA. In the metastatic cohort, 10 of 18 (56%) patients had detectable ctDNA. ctDNA VAF correlated with imaging and clinical treatment responses in 6 of 7 (86%) patients in whom longitudinal samples were collected. As example, 3 patients showed rising ctDNA levels during radiographic disease progression; 1 patient exhibited decrease in ctDNA with positive treatment response on targeted clinical trial; 2 demonstrated stable disease by all metrics; and 1 exhibited stability in ctDNA levels despite rapid and overt disease progression while on trametinib. Overall, GNAQ Q209 were the most common mutations detected by ctDNA. Conclusions: Our findings show that tumor-agnostic ctDNA represents a useful biomarker for active disease monitoring in metastatic UM, in conjunction with radiographic and clinical assessment. Within the surveillance setting, our assay showed limited sensitivity for early disease detection with common false negative results. Additional development of novel, noninvasive biomarker driven assays are necessary to improve early detection of metastatic UM.

e23324 Background: Due to the hepatotropic pattern of metastasis in uveal melanoma (UM), liver directed therapies (LDT) are commonly used for the treatment of advanced disease. The PUMMA meta-analysis (Khoja et al, 2019) assessed patients (pts) with metastatic UM (mUM) treated on trials conducted from 2000-2016 and suggested improved outcomes for those treated with LDT. Methods: Using data from 7 centers in the US, Canada, the UK and Australia collected between as part of the Ocular Melanoma Natural History (OMNi) study, we assessed this finding in a more contemporary dataset and investigated potential global variations in practice patterns. Analysis was performed on data entered as of May 2024. Results: Of 985 pts enrolled, 283 developed mUM and received at least 1 line of treatment (tx; 77-US; 160-Canada; 30-UK; 16-Australia). 164 received regional (R) tx (LDT, surgery, radiation; 41% US pts, 35% Canadian pts, 46% UK pts, 55% Australian pts), with 130 treated in the first-line (1L) setting. 212 received systemic (S) tx (51% US pts, 55% Canadian pts, 51% UK pts, 55% Australian pts), with 137 treated in the 1L setting. Concurrent (C; any R tx delivered while a S tx was ongoing) was administered in 50 patients (18% US pts, 10% of Canada pts, 3% UK, pts 5% Australian pts), with 16 treated in the 1L setting. At the time of 1L tx, median age was 63 (range, 25-92), 62 (range, 24-88), and 64 (range, 42-83) years for those treated with S, R, and C tx, respectively. 47%, 50% and 25% were female of those treated with S, R, and C tx, respectively. Mean diameter of the largest tumor lesion and percentage of cases with stage M1b/c disease at time of 1L tx were 1.5cm and 20%, 1.1cm and 19%, and 0.6 cm and 0% for those treated with S, R or C tx, respectively. There was no significant difference in proportion of patients with liver-only disease who received 1L S or R/C tx (61 vs 62%, respectively). Median overall survival (OS) was 32, 24 and 32 months for those treated with S, R or C tx, respectively, with no significant difference observed across groups (p = 0.09). Conclusions: The use of C tx was more common in the US and Canadian centers when compared with those in the UK and Australia. Patient and tumor characteristics were similar between those treated with 1L S and R therapies, with no difference in OS observed in this dataset based upon initial tx strategy. Clinical trial information: NCT04588662 . Therapy Pts Receiving 1L Systemic Therapy (n = 137) Pts Receiving 1L Regional Therapy (n = 130) Pts Receiving 1L Concurrent Therapy (n = 16) Systemic Regional Checkpoint Blockade 104 (76%) n/a 10 (62%) n/a Targeted Therapy 22 (16%) n/a 6 (38%) n/a Other Systemic Therapy 11 (8%) n/a 0 (0%) n/a Surgery or Radiofrequency Ablation n/a 62 (48%) n/a 3 (18%) Radiotherapy n/a 22 (17%) n/a 4 (25%) Other Liver Directed Therapy n/a 34 (26%) n/a 6 (38%) Radioembolization or Chemoembolization n/a 9 (7%) n/a 2 (12%) Percutaneous Hepatic Perfusion n/a 3 (2%) n/a 1 (6%)

Tumors of the eye, orbit, and ocular adnexa can arise in the pediatric population. These entities can be both vision- and life-threatening and may be associated with systemic disease. Given their relative rarity, pediatricians must be aware of these conditions and understand what findings warrant immediate referral to an ophthalmologist for initiation of further testing. We aimed to review these conditions and highlight clinical features to promote awareness and expedite diagnosis. Tumors are subdivided into the following categories for review: anterior tumors of the eyelid and ocular surface, orbital tumors, and intraocular tumors.

PURPOSE:To describe two cases of retinal hemangioblastoma regression following treatment with belzutifan in patients with von Hippel-Lindau syndrome.METHODS:Clinical information was extracted from the charts and tumor imaging of two patients with von Hippel-Lindau-associated retinal hemangioblastoma.RESULTS:In Case 1, a 40-year-old man was treated with belzutifan for spine hemangioblastomas after diagnosis of a 2.0 × 2.0 × 1.3 mm left-eye retinal hemangioblastoma temporal to the macula associated with intraretinal edema, subretinal fluid, and mild retinal traction. In Case 2, a 66-year-old woman presented with a right eye 2.0 × 1.5 × 1.3 mm juxtapapillary lesion with subretinal fluid, intraretinal fluid, and nasal traction, and a 4.0 × 3.5 × 1.1 mm inferior midperiphery lesion with subretinal fluid, intraretinal fluid, and active exudation. She was treated for 2.5 years with belzutifan for renal cell carcinoma on the National Institutes of Health trial. The patient in case 1 demonstrated a 10% reduction in largest tumor diameter and 8% reduction in thickness, along with improving subretinal fluid, intraretinal edema, and retinal traction, after 4 weeks of treatment. After 2.5 years of treatment, the patient in Case 2 demonstrated similar margins of her now fibrotic-appearing juxtapapillary lesion with a 45% reduction in thickness, along with resolved subretinal fluid and greatly improved intraretinal fluid and traction. The inferior lesion demonstrated 12.5% reduction in largest diameter, 36% reduction in thickness, and was without active subretinal fluid or exudation. Neither patient demonstrated new lesions while on treatment.CONCLUSION:Belzutifan is a promising treatment for retinal hemangioblastoma with the potential for both rapid and sustained tumor regression.

Introduction: Schimmelpenning-Feurstein-Mims Syndrome (SFMS) is a rare neurocutaneous disorder. Herein, we describe a novel case and review the phenotypic spectrum and molecular findings of SFMS from an ophthalmology perspective.Methods: Clinical case including presentation, management, pathology, and genetic analysis is described. A literature search on Schimmelpenning-Feuerstein-Mims and its synonyms, Linear nevus sebaceous syndrome, Organoid nevus syndrome, Jadassohn nevus phacomatosis, and Solomon syndrome, was conducted. An updated review and description of published cases with identified genetic mutations are described.Results: A 13-year-old boy with SFMS presented with acute right eye pain and an enlarging orbital mass. Excisional biopsy of the mass revealed an orbital choristoma. Genetic analysis of the orbital tumor confirmed a KRAS c.35 G>A, p.G12D mutation. A literature search revealed 19 cases of SFMS with mutations in the RAS-pathway. KRAS, HRAS, and NRAS mutations were identified in 74%, 21%, and 5% of patients, respectively. Ophthalmic pathology was seen in 83% of patients. Systemic findings varied and involved the skin, central nervous system, and eyes most commonly.Discussion: SFMS, a rare neurocutaneous disorder, results from postzygotic mosaic mutations in the RAS/MAPK pathway. Patients present with various systemic findings and ophthalmic manifestations occur in most cases. This is the first case description of a KRAS mutation identified in an orbital choristoma in SFMS. The disease is described under various names in the literature, and we propose that all syndromic cases with mosaic RAS mutations be reported under the eponym, SFMS.

The authors present two cases of conjunctival pediatric- type follicular lymphoma. A 14-year-old Black boy and 14-year-old Black girl were each referred for evaluation of a painless salmon-colored conjunctival lesion. Both patients underwent excisional biopsy. Histopathology demonstrated follicles with germinal centers composed of atypical B-cells with high Ki67 proliferation index, positive staining for CD20, CD10, and BCL6, and negative for BCL2. This series contributes two cases to the limited literature and presents the first case reported in a female. [ J Pediatr Ophthalmol Strabismus. . 2024;61(4):e33-e38.]

PURPOSE Validated 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 METHODS This 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). RESULTS 15-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. CONCLUSION In 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.

Introduction: Proper plaque positioning is essential for effective episcleral plaque brachytherapy and can be verified using ultrasound. In this study, we show our center’s protocol for intraoperative ultrasound verification of plaque placement and present our single-center local recurrence data in patients with primary UM involving the choroid and/or ciliary body. We also indicate our center’s distance metastasis rate for patients presenting with primary UM. Methods: All patients who presented to our institution with UM of the choroid and/or ciliary body between May 2017 and March 2022 and treated with plaque brachytherapy were enrolled. Endpoints include the 24-month local recurrence-free rate (primary) and 24-month metastasis rate (secondary), both estimated using the Kaplan-Meier method (KM). Results: Local Recurrence: 176 patients met the study criteria with median follow-up of 23.2 months. The 24-month recurrence-free probability for this cohort was estimated at 99.1% (95% confidence interval: 0.974–1.00). Metastatic Recurrence: 136 of these patients underwent at least one follow-up surveillance scan. The 24-month metastasis-free survival probability in our cohort was estimated at 87% (95% confidence interval: 81–94%). Conclusions: We show improved local control utilizing ultrasound verification compared to historical controls who received TTT and brachytherapy without intraoperative ultrasound confirmation.

Purpose: The authors aim to describe the ophthalmologic manifestations of pediatric Erdheim-Chester disease (ECD). Methods: The authors describe a novel case of ECD presenting as isolated bilateral proptosis in a child and provide a comprehensive review of the documented pediatric cases to observe overall trends and ophthalmic manifestations of disease. Twenty pediatric cases were identified in the literature. Results: The mean age at presentation was 9.6 years (1.8–17 years) with a mean time of symptom presentation to diagnosis of 1.6 years (0–6 years). Nine patients (45%) had ophthalmic involvement at diagnosis, 4 who presented with ophthalmic complaints: 3 with observable proptosis and 1 with diplopia. Other ophthalmic abnormalities included eyelid findings of a maculopapular rash with central atrophy on the eyelids and bilateral xanthelasmas, neuro-ophthalmologic findings of a right hemifacial palsy accompanied by bilateral optic atrophy and diplopia, and imaging findings of orbital bone and enhancing chiasmal lesions. No intraocular involvement was described, and visual acuity was not reported in most cases. Conclusions: Ophthalmic involvement occurs in almost half of documented pediatric cases. Typically presenting with other symptoms, the case highlights that isolated exophthalmos may be the only clinical sign, and ECD should be included in the differential diagnosis of bilateral exophthalmos in children. Ophthalmologists may be the first to evaluate these patients, and a high index of suspicion and an understanding of the varied clinical, radiographic, pathologic, and molecular findings are critical for prompt diagnosis and treatment of this unusual disease.

Vasoproliferative tumors (VPT) are benign retinal lesions that may cause epiretinal membrane proliferation and tractional retinal detachments (TRD). We describe a case of a 71-year-old woman who presented with a macula involving TRD in the setting of a VPT. Given the limited number of publications on the management of these cases, we aim to articulate some principles we believe may be helpful in planning a surgical approach that maximizes postoperative anatomic and functional outcomes. We hope that our video provides useful guidance in preparing the vitreoretinal surgeon for managing this uncommon entity. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:485–488.]

9590 Background: Metastatic uveal melanoma (mUM) is characterized by a hepatotropic pattern of spread and poor outcomes. Tebentafusp, the only FDA approved therapy, is restricted to patients (pts) with the HLA-A*02:01 genotype. As a result, a variety of liver-directed therapies (LDT) are commonly used for management of hepatic metastases. Methods: Pts with mUM with hepatic metastases who underwent LDT, including radiofrequency ablation, microwave ablation, hepatic metastatectomy, Yttrium-90 radioembolization (SIRT), transarterial chemoembolization (TACE), bland embolization, and immunoembolization (IE), were identified from an institutional database. Data collected included: age, gender, tumor location and size, baseline liver function tests (LFT) and lactate dehydrogenase (LDH), molecular tumor characteristics (where available), type(s) of LDT received, systemic therapies received, and vital status. Time from onset of hepatic metastasis until death (Liver-OS), as well as time from initial diagnosis of primary uveal melanoma until death (Ocular-OS) were calculated. Results: A total of 119 pts were identified. The median age at diagnosis was 53.8 years (range 26-83), 47% were female. At the time of LDT initiation, 33% had bilobar disease and 16% had extrahepatic metastasis. 18% pts had elevated LFTs and 55% had elevated LDH. 72% of pts had M1a disease, 24% had M1b and 4% had M1c disease. 45% of pts received more than one form of LDT. SIRT (31%) was the commonly administered initial LDT, followed closely by IE (26%) and TACE (9%). 86% of pts received systemic therapy including 42% who received immune checkpoint blockade overlapping with LDT. Molecular profiling in 26 pts revealed recurrent mutations in BAP1 (n = 18) and SF3B1 (n = 8). The median ocular-OS across all pts was 71.0 months (95% confidence intervals (CI), 62.8-99.4). The median liver-OS across all pts was 31.8 months (95% CI 25.2-35.3). In pts who received TACE, IE, or SIRT exclusively (n = 44), the median Liver-OS was 15.2 months (95% CI 12.8-NA) for TACE (n = 8), 23.3 months (95% CI 15.8-NA) for SIRT (n = 28), and 28.2 months (95% CI 22.6-NA) for IE (n = 8). Conclusions: Our results provide additional support for the utilization of LDT in pts with mUM, as demonstrated by improved OS compared to historical survival data.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

PURPOSE:1% topical 5-fluorouracil (5-FU) is a treatment for ocular surface squamous neoplasia (OSSN) due to its effectiveness, low cost, and tolerable side effect profile. To our knowledge there is no reported sight-threatening corneal complication of 1% 5-FU for the treatment of OSSN.OBSERVATIONS:We report a 78 year-old man with bilateral conjunctival intraepithelial neoplasia (CIN) who developed bilateral corneoscleral ulceration and corneal perforation of the left eye after 1% 5-FU topical treatment.CONCLUSIONS AND IMPORTANCE:Our case report describes serious potential complications of 1% 5-FU, reviews possible risk factors associated with poor outcomes, and discusses our treatment approach.

Purpose: To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. Methods: Retrospective case report. Results: A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. Conclusions: Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice. We aimed to determine the true rate of BM in mUM and to clarify the clinical and genomic risk factors associated with BM patients through a collaborative multicenter, retrospective research effort. Data collected from 1,845 mUM patients in databases across four NCI-designated comprehensive cancer centers from 2006-2021 were retrospectively analyzed to identify patients with BM. Brain imaging in most cases were performed due to onset of neurological symptoms and not for routine surveillance. An analysis of demographics, therapies, gene expression profile, tumor next generation sequencing (NGS) data, time to metastasis (brain or other), and survival in the BM cohort was completed. 116/1,845 (6.3%) mUM patients were identified with BM. The median age at time of UM diagnosis was 54 years old (range: 18-77). The median time to any metastasis was 4.2 years (range: 0-30.8). The most common initial metastatic site was the liver (75.9%). 15/116 (12.9%) BM patients presented with BM at the time of initial metastatic diagnosis. Median survival after a diagnosis of BM was 7.6 months (range: 0.4-73.9). The median number of organs involved at time of BM diagnosis was 3 (range: 1-9). DecisionDX-UM profiling was completed on 13 patients: 10-Class 2, 2-Class 1B, and 1-Class 1A. NGS and cytogenetic data were available for 34 and 21 patients, respectively. BM was identified in 6.3% of mUM cases and was associated with high disease burden and a median survival of under 8 months once diagnosed. Since most patients in this cohort were symptomatic, the incidence of asymptomatic BM remains unknown. These data suggest the use of routine brain imaging in all mUM patients at risk for developing BM for early detection.