Multicenter external validation of the liverpool uveal melanoma prognosticator online: An OOG collaborative study

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3’s performance using discrimination and calibration methods. LUMPO3’s ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Retinal emboli after cervicopetrous junction internal carotid artery pseudoaneurysm stenting.

PurposeTo describe acute and chronic retinal ischemic changes following an internal carotid artery pseudoaneurysm stenting procedure, and to review current evidence for risk factors and management of post-procedural retinal ischemic events.ObservationA 50-year-old man presented with a 3-month history of pulsatile tinnitus, headache, and intermittent blurry vision. A CT angiogram of head and neck showed bilateral cervicopetrous internal carotid artery (ICA) pseudoaneurysms. The patient underwent successful repair with angioplasty and stenting of the flow-limiting high-grade (>95%) stenosis of his left high cervical ICA. On post-operative day 1, the patient reported monocular vision loss with a large central scotoma. He was found to have a central macular area of retinal whitening and multiple areas of perivascular retinal whitening on exam, concerning for retinal artery occlusions secondary to peri-procedural emboli. Dual antiplatelet therapy was started and a stroke evaluation was performed. Two months later, his visual acuity in the affected eye was counting fingers and his left eye fundus examination was notable for multiple areas of scattered hemorrhages, microaneurysms, and retinal exudates in the distribution of prior retinal ischemia. OCT imaging revealed atrophic changes in the left macula. Subsequently, the patient completed stage-2 repair of the left ICA pseudoaneurysm followed by uncomplicated repair of the right ICA. Four months later, his left eye visual acuity and retinal findings remained stable.Conclusions and importancePost-procedure retinal emboli and ischemia are important, vision threatening possible ocular complications for patients undergoing carotid vascular and endovascular procedures

Retinal emboli after cervicopetrous junction internal carotid artery pseudoaneurysm stenting.

PurposeTo describe acute and chronic retinal ischemic changes following an internal carotid artery pseudoaneurysm stenting procedure, and to review current evidence for risk factors and management of post-procedural retinal ischemic events.ObservationA 50-year-old man presented with a 3-month history of pulsatile tinnitus, headache, and intermittent blurry vision. A CT angiogram of head and neck showed bilateral cervicopetrous internal carotid artery (ICA) pseudoaneurysms. The patient underwent successful repair with angioplasty and stenting of the flow-limiting high-grade (>95%) stenosis of his left high cervical ICA. On post-operative day 1, the patient reported monocular vision loss with a large central scotoma. He was found to have a central macular area of retinal whitening and multiple areas of perivascular retinal whitening on exam, concerning for retinal artery occlusions secondary to peri-procedural emboli. Dual antiplatelet therapy was started and a stroke evaluation was performed. Two months later, his visual acuity in the affected eye was counting fingers and his left eye fundus examination was notable for multiple areas of scattered hemorrhages, microaneurysms, and retinal exudates in the distribution of prior retinal ischemia. OCT imaging revealed atrophic changes in the left macula. Subsequently, the patient completed stage-2 repair of the left ICA pseudoaneurysm followed by uncomplicated repair of the right ICA. Four months later, his left eye visual acuity and retinal findings remained stable.Conclusions and importancePost-procedure retinal emboli and ischemia are important, vision threatening possible ocular complications for patients undergoing carotid vascular and endovascular procedures

Choroidal Lymphoma Discovered on Ultrasound in a Patient with Suspected Corneal Tumor.

Background/aimsTo report the case of a 77-year-old male with a blind, painful eye, referred for suspected corneal mass, with finding of choroidal B-cell lymphoma on pathology of enucleated globe.MethodsThis is a retrospective case report of a single patient.ResultsA 77-year-old male with a longstanding history of poor vision in the left eye was referred for a scarred, vascularized corneal mass. The patient had reported occasional mild ocular discomfort in the left eye and loss of light perception over the last year. Visual acuity was 20/20 in the right eye and no light perception in the left eye. Intraocular pressure was 32 mm Hg in the left eye. Fundoscopic visualization was not possible due to corneal opacity. B-scan ultrasound showed an infiltrative, low-reflective choroidal lesion and inferior retinal detachment. Pathology from the enucleated globe revealed diffuse sheets of CD20+ small B cells replacing the choroid, characteristic of a low-grade small B-cell extranodal marginal zone lymphoma.ConclusionThis is an unusual presentation of choroidal lymphoma in an eye with severe corneal opacification and scarring, and underscores the diagnostic value of ultrasonography in examination of eyes without view to the posterior segment

Choroidal Lymphoma Discovered on Ultrasound in a Patient with Suspected Corneal Tumor.

Background/aimsTo report the case of a 77-year-old male with a blind, painful eye, referred for suspected corneal mass, with finding of choroidal B-cell lymphoma on pathology of enucleated globe.MethodsThis is a retrospective case report of a single patient.ResultsA 77-year-old male with a longstanding history of poor vision in the left eye was referred for a scarred, vascularized corneal mass. The patient had reported occasional mild ocular discomfort in the left eye and loss of light perception over the last year. Visual acuity was 20/20 in the right eye and no light perception in the left eye. Intraocular pressure was 32 mm Hg in the left eye. Fundoscopic visualization was not possible due to corneal opacity. B-scan ultrasound showed an infiltrative, low-reflective choroidal lesion and inferior retinal detachment. Pathology from the enucleated globe revealed diffuse sheets of CD20+ small B cells replacing the choroid, characteristic of a low-grade small B-cell extranodal marginal zone lymphoma.ConclusionThis is an unusual presentation of choroidal lymphoma in an eye with severe corneal opacification and scarring, and underscores the diagnostic value of ultrasonography in examination of eyes without view to the posterior segment

Metastatic Cutaneous Melanoma Presenting with Choroidal Metastasis Simulating Primary Uveal Melanoma

PurposeTo report a case of metastatic cutaneous melanoma presenting with choroidal metastasis simulating primary uveal melanoma.DesignCase report.MethodPresentation of clinical, radiographic, histopathologic, and tumor genetic findings in a patient with cutaneous melanoma with choroidal metastasis.ResultsA 50-year-old man with a remote history of stage 1A cutaneous melanoma presented with eye pain, peripheral vision loss, floaters, red eye, and choroidal mass that was originally diagnosed as a primary uveal melanoma at an outside institution; however, subsequent imaging and clinical evaluation demonstrated that this choroidal mass was the first manifestation of widely metastatic cutaneous melanoma (liver, pancreas, lung, bone, brain, and orbit lesions). Histopathologic analysis of the tumor after enucleation was consistent with cutaneous melanoma, and tumor genetic testing was positive for BRAF V600E mutation, confirming the choroidal lesion to be a cutaneous melanoma metastasis rather than a primary choroidal melanoma.ConclusionsMetastatic cutaneous melanoma to the orbit or globe occurs rarely. Tumor genetic testing may help differentiate metastatic cutaneous melanoma from primary uveal melanoma in cases where the diagnosis is uncertain, and can also inform therapy and prognostic counseling

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features

PurposeTo determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma.DesignCohort study.ParticipantsThirty-two children with retinoblastoma.MethodsWe performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing.Main outcome measuresPresence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features.ResultsGermline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease.ConclusionsComprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features

Practice Considerations for Proton Beam Radiation Therapy of Uveal Melanoma During the Coronavirus Disease Pandemic: Particle Therapy Co-Operative Group Ocular Experience.

Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment