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. 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. 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). 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. Queen Elizabeth Diamond Jubilee Trust.

Visual outcome following plaque radiotherapy of choroidal melanoma depends on several factors, including patient age, general health, visual acuity, tumor location/size, subretinal fluid, radioactive isotope, and ultimately radiation retinopathy and papillopathy.¹ In a consecutive case study¹ of 1106 patients with uveal melanoma of random size treated with plaque radiotherapy (in the prebevacizumab era), ultimate visual acuity was poor at 20/200 or worse in 34% at 5 years and 68% at 10 years. Results of the Collaborative Ocular Melanoma Study² for medium-size uveal melanoma in 623 patients at 3 years revealed reduction in visual acuity, from visual acuity greater than 20/200 to visual acuity of 20/200 or less in 43% and loss of at least 6 lines of vision in 49%. These poor visual results extend even to the smallest tumors (≤ 3-mm thickness) in 1780 cases that demonstrated Kaplan-Meier 10-year estimates of poor visual acuity (≤20/200) at 54%, despite low risk for metastasis at 9%.³

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, with favorable local tumor control in the era of plaque radiotherapy but relatively poor systemic outcomes with moderate metastatic risk because of micrometastasis before treatment.^1,2 This insidious behavior has spawned several clinical trials evaluating adjuvant therapy for prevention of metastasis in high-risk patients with UM.^3,4 To best identify patients at high risk, ocular oncologists and medical oncologists have assessed various single or combined parameters as predictors of metastatic disease.^5-7 Among the numerous systems for prediction of UM-related metastasis, some strive for maximal accuracy at the expense of simplicity, while others are easier to use at the expense of precise predictive value.^8-10

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photography, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI. Conclusions: AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma. Translational Relevance: Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes.