Global Retinoblastoma Study Group 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 PARTICIPANTSA 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 MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe 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,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis 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.

BACKGROUND AND PURPOSE: Intra-arterial chemotherapy for retinoblastoma is not always a straightforward procedure, and it may require an adaptable approach. This study illustrates strategies used when the ophthalmic artery is difficult to catheterize or not visible, and it ascertains the effectiveness and safety of these strategies.

ABSTRACT.Purpose: To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. Methods: From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission ⁄ relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes). Results: Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus ⁄ exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7 ⁄ 16 (43%) newly diagnosed retinoblastomas and 1 ⁄ 22 (4.5%) retinoblastomas undergoing partial remission ⁄ relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission ⁄ relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively. Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents.

Survival of orbital RMS has improved due to advances in chemotherapy and radiotherapy. Posttreatment complications, including side effects of radiotherapy and secondary orbital malignancies, as well as visual dysfunction, occur more often and present new challenges due to improved long-term survival.

From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree) Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support for parents when neonatal retinoblastoma has been diagnosed.

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When properly searched, anastomoses between the ophthalmic artery and the external carotid artery are almost constant in children. Depending on the clinical scenario, they can represent dangers or valuable alternative routes for collateral circulations and intraarterial chemotherapy.

BackgroundOphthalmic artery chemosurgery [OAC, intra-arterial chemotherapy (IAC)] was introduced in 2006 as treatment modality for intraocular retinoblastoma. The purpose of this commentary is to retrospectively review the incidence of metastatic deaths in retinoblastoma patients treated with OAC worldwide over a 10 year period. Retrospective data regarding metastatic deaths was collected from six international retinoblastoma centers (New York City USA, Philadelphia USA, Sao Paulo Brazil, Siena Italy, Lausanne Switzerland and Buenos Aires Argentina). All retinoblastoma patients from these centers (naive and recurrent, unilateral and bilateral) treated with OAC/IAC since 2006 have been included in this study. Data regarding number of patients, number of OAC/IAC infusions, number unilateral and bilateral, number treated for naive disease or salvage and number of metastatic deaths have been assessed. Over a 10-year period of time 1139 patients received OAC/IAC for 4396 infusions. At last follow-up there were only three metastatic deaths (all treated in Buenos Aires).ConclusionThe current survey assessed the recorded risk of metastatic deaths in six retinoblastoma centers worldwide in children with retinoblastoma (unilateral or bilateral) treated with OAC/IAC as primary or secondary therapy. Overall, the observed risk for metastatic deaths from retinoblastoma was <1% in OAC/IAC treated children.