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Importance: To improve diagnostics of cancer predisposition syndromes (CPSs) in children with cancer, it is essential to evaluate the effect of CPS gene sequencing among all children with cancer and compare it with genetic testing based on clinical selection. However, a reliable comparison is difficult because recent reports on a phenotype-first approach in large, unselected childhood cancer cohorts are lacking., Objective: To describe a national children's cancer center's experience in diagnosing CPSs before introducing routine next-generation sequencing., Design, Setting, and Participants: This retrospective cohort study was conducted at the National Retinoblastoma Treatment Center (Amsterdam, the Netherlands) and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands) and included Dutch pediatric patients with a new diagnosis of neoplasm between June 1, 2018, and December 31, 2019. Follow-up was at least 18 months after neoplasm diagnosis. Data analysis was conducted from July 2021 to February 2022., Exposures: As part of routine diagnostics, pediatric oncologists and ophthalmologists checked for characteristics of CPSs and selected children for referral to clinical geneticists and genetic testing., Main Outcomes and Measures: Detected cancer predisposition syndromes., Results: A total of 824 patients (median [range] age at diagnosis 7.5 [0-18.9] years; 361 girls [44%]) were assessed, including 335 children with a hematological neoplasm (41%) and 489 (59%) with a solid tumor. In 71 of 824 children (8.6%), a CPS was identified, of which most (96%) were identified by a phenotype-driven approach. Down syndrome and neurofibromatosis type 1 were the most common CPSs diagnosed. In 42 of 71 patients (59%), a CPS was identified after these children developed a neoplasm. The specific type of neoplasm was the most frequent indicator for genetic testing, whereas family history played a minor role., Conclusions and Relevance: In this cohort study of children with a neoplasm, the prevalence of CPSs identified by a phenotype-driven approach was 8.6%. The diagnostic approach for identifying CPSs is currently shifting toward a genotype-first approach. Future studies are needed to determine the diagnostic value, as well as possible disadvantages of CPS gene sequencing among all children with cancer compared with the phenotype-driven approach.

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.

Objective: To validate the conclusion of our previous prospective study of 250 patients with isolated posterior vitreous detachment: follow-up visits are only necessary if patients mention symptoms of flashes in combination with multiple floaters or a curtain or cloud at the initial examination, or an increase in number of floaters after the initial examination., Methods: Prospective study of 270 consecutive patients with symptomatic isolated posterior vitreous detachment. All patients completed a questionnaire detailing their symptoms and had a full eye examination at the initial examination and at follow-up visits. Logistic regression with backward elimination was used for statistical analysis. We also performed pooled analysis of our previous and present study data., Results: New retinal breaks developed in 10 patients (3.7%). Multiple floaters, a curtain or cloud, hemorrhages (retinal or vitreous) at the initial examination, and an increase in the number of floaters after the initial examination were found to be predictive factors for the development of new retinal breaks. These factors were also the only significant predictors after pooled analysis of both studies (520 patients, 23 breaks)., Conclusions: We assume we can formulate a safe policy for scheduling patients with isolated posterior vitreous detachment: only patients with multiple floaters, a curtain or cloud, or hemorrhages (retinal or vitreous) at the initial examination should be scheduled for reexamination. All other patients should return only if the number of floaters increases.

Objective: To investigate the effect of glycosylated hemoglobin, age, sex, hypertension, body mass index, waist-hip ratio, serum lipid levels, and smoking on the incidence of retinopathy in persons with normal and abnormal glucose metabolism., Methods: The incidence of retinopathy was determined in 233 individuals, aged 50 to 74 years, by ophthalmoscopy and fundus photography at baseline and after an average follow-up of 9.4 years. Relative risks for retinopathy, estimated by odds ratios, were calculated for tertiles of cardiovascular risk factors at baseline. Logistic regression analysis was used, without and with adjustment for age, sex, hypertension, and glucose metabolism., Results: The cumulative incidences of retinopathy among individuals with normal, impaired, and diabetic glucose metabolism were 7.3%, 13.6%, and 17.5%, respectively. Adjusted odds ratios for retinopathy were 2.36 (95% confidence interval, 1.02-5.49) for hypertension and 3.29 (95% confidence interval, 1.11-9.72) and 8.67 (95% confidence interval, 1.85-40.60) for the highest tertiles of glycosylated hemoglobin level and waist-hip ratio, respectively. No consistent or statistically significant associations with retinopathy were present for age, sex, body mass index, smoking, and serum levels of triglycerides and total, high-density lipoprotein, and non-high-density lipoprotein cholesterol (P>.05 for all)., Conclusion: Glycemia, hypertension, and abdominal obesity are determinants for retinopathy in a general population.