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.

PurposeTo assess the optical coherence tomography angiography (OCTA) retinal vessel density and foveal avascular zone (FAZ) in children with type 1 diabetes (T1D) and compare potential pathologic early changes in this population to healthy age-matched controls.MethodsThis study included 130 pubescent children: 94 with T1D (188 eyes) and 36 of their age-matched control group (60 eyes). OCTA was performed using AngioVue (Avanti, Optivue). FAZ area (mm2) in superficial plexus, whole superficial capillary vessel density (wsVD), fovea superficial vessel density (fsVD), parafovea superficial vessel density (psVD), whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea deep vessel density (pdVD), foveal thickness (FT) (μm) and parafoveal thickness (PFT) (μm) were taken into analysis. Among the studied patients with T1D there were assessed codependences regarding the investigated foveal and parafoveal parameters and selected potential predictors, i.e. patient’s age (years), diabetes duration time (years), age of onset of the disease (years), mean level of glycated hemoglobin (HbA1C) (%), and concentration of serum creatinine (mg/dL).ResultsNone of the abovementioned OCT and OCTA parameters was statistically significantly different between the groups. The patient’s age statistically significantly did not influent any of the OCT and OCTA parameters. Yet an elevated level of HbA1C tended to reduce the parafovea superficial vessel density (p = 0.039), and parafoveal thickness (p = 0.003) and an increased serum creatinine level correlated with the decreased whole deep vessel density (p < 0.001). The parafovea deep vessel density in the diabetic patients decreased when the serum creatinine level (p = 0.008), age of onset of the disease (p = 0.028), and diabetes duration time (p = 0.014) rose.ConclusionsVessel density, both in superficial and deep plexuses, and FAZ area are normal in pubescent children with T1D comparing to healthy subjects. An elevated level of HbA1C correlated with reduced psVD and PFT. Longitudinal observation of these young patients is needed to determine if any of these OCTA measurements are predictive of future DR severity.

Aim To assess the retinal and choroidal thickness and ganglion cell complex (GCC) in pubescent children with type 1 diabetes (T1D) without diabetic retinopathy (DR), using spectral domain optical coherence tomography (SD-OCT). Materials and Method Sixty-four right eyes of 64 subjects with T1D and 45 right eyes of 45 age-matched healthy volunteers (control group) were enrolled in this study. The mean age of the subjects and controls was 15.3 (±SD = 2.2) and 14.6 (±SD = 1.5), respectively. SD-OCT was performed using RTVue XR Avanti. Ganglion cell complex (GCC), GCC focal loss volume (FLV), GCC global loss volume (GLV), choroidal thickness (CT), foveal (FT) and parafoveal thickness (PFT), and foveal (FV) and parafoveal volume (PFV) data were analyzed. Results There was no significant difference between subjects and controls in the CT in the fovea and nasal, temporal, superior, and inferior quadrants of the macula. There were no significant correlations between CT, duration of diabetes, and HbA1C level (p = 0.272 and p = 0.197, resp.). GCC thickness did not differ significantly between the groups (p = 0.448), but there was a significant difference in FLV (p = 0.037). Significant differences between the groups were found in the PFT and PFV (p = 0.004 and p = 0.005, resp.). There was a significant negative correlation between PFT, PFV, and HbA1C level (p = 0.002 and p = 0.001, resp.). Conclusions Choroidal thickness remains unchanged in children with T1D. Increased GCC FLV might suggest an early alteration in neuroretinal tissue. Parafoveal retinal thickness is decreased in pubescent T1D children and correlates with HbA1C level. OCT can be considered a part of noninvasive screening in children with T1D and a tool for early detection of retinal and choroidal abnormalities. Further OCT follow-up is needed to determine whether any of the discussed OCT measurements are predictive of future DR severity.

BackgroundThe travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

Aim. To evaluate the influence of metabolic parameters and the treatment method in children with type 1 diabetes (T1D) on the optical coherence tomography angiography (OCTA) results as early markers of diabetic retinopathy (DR). Material and Methods. This prospective study enrolled 175 consecutive children with T1D. OCTA was performed using AngioVue (Avanti, Optovue). Whole superficial capillary vessel density (wsVD), fovea superficial vessel density (fsVD), parafovea superficial vessel density (psVD), whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea deep vessel density (pdVD), foveal thickness (FT), parafoveal thickness (PFT), and foveal avascular zone (FAZ) in superficial plexus were evaluated and analyzed in relation to individual characteristics, i.e., sex, weight, height, body mass index (BMI), and metabolic factors: current and mean value of glycated hemoglobin A1c (HbA1c). Furthermore, the analysis concerned the diabetes duration, age at the T1D onset, and type of treatment—multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII). Results. In the study group, we did not identify any patient with DR in fundus ophthalmoscopy. Age at the onset of diabetes correlated negatively with FAZ ( r = − 0.17 , p < 0.05 ). The higher level of HbA1c corresponded to a decrease of wsVD ( r = − 0.13 , p < 0.05 ). We found significantly lower fsVD ( 32.25 ± .1 vs. 33.98 ± .1 , p < 0.01 ), wdVD ( 57.87 ± .1 vs. 58.64 ± .9 , p < 0.01 ), and pdVD ( 60.60 ± .2 vs. 61.49 ± .1 , p < 0.01 ) and larger FAZ area ( 0.25 ± .1 vs. 0.23 ± .1 , p < 0.05 ) in the CSII vs. MDI group. Conclusion. The metabolic parameters, age of the onset of diabetes, and treatment method affected the OCTA results in children with T1D. Further studies and observation of these young patients are needed to determine if these findings are important for early detection of DR or predictive of future DR severity.