Retinoblastoma - A comprehensive review, update and recent advances.

Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas can be unilateral (60%-70%) or bilateral (30%-40%); bilateral tumors are always heritable and present at an earlier age as compared to unilateral ones (18-24 months vs. 36 months in India). High prevalence rates, delayed presentation, and inaccessibility to healthcare lead to worse outcomes in developing countries. The past few decades have seen a paradigm change in the treatment of retinoblastomas, shifting from enucleation and external beam radiotherapy to less aggressive modalities for eye salvage. Multimodality treatment is now the standard of care and includes intraarterial or intravenous chemotherapy along with focal consolidation therapies such as transpupillary thermotherapy, cryotherapy, and laser photocoagulation. Intravitreal and intracameral chemotherapy can help in controlling intraocular seeds. Advanced extraocular or metastatic tumors still have a poor prognosis. Genetic testing, counseling, and screening of at-risk family members must be incorporated as essential parts of management. A better understanding of the genetics and molecular basis of retinoblastoma has opened up the path for potential targeted therapy in the future. Novel recent advances such as liquid biopsy, prenatal diagnosis, prognostic biomarkers, tylectomy, and chemoplaque point to promising future directions.

Strategies to improve diagnosis and access to treatment of retinoblastoma in low- and middle-income countries: A systematic review.

Retinoblastoma, the most common intraocular tumor in childhood, still faces challenges in diagnosis and treatment, particularly in low- and middle-income countries. Identifying strategies to improve the time to diagnosis and access to treatment is crucial to enhance survival rates and preserve ocular health. We conducted a systematic review to identify interventions that have demonstrated potential in addressing these challenges. We performed a comprehensive search across databases until March 2023. Out of the studies reviewed, 21 met the inclusion criteria and were categorized into five main areas: surveillance strategies, genetic counseling, education, public assistance, and international partnership. Despite the obstacles faced, the initiatives identified in this review present acts toward improving the time to diagnosis and access to treatment for retinoblastoma. Based on the extracted data, we propose a comprehensive chain of initiatives. We firmly believe that implementing this chain of initiatives can lead to improved clinical outcomes for retinoblastoma patients.

'It's not meant to be for life, but it carries on': a qualitative investigation into the psychosocial needs of young retinoblastoma survivors.

OBJECTIVE AND DESIGN: Retinoblastoma (Rb) is a rare childhood eye cancer, with 45% of individuals impacted by heritable disease and the remainder impacted non-heritably. The condition can leave survivors with life-long psychological and social challenges. This qualitative study examined the psychosocial needs of teenagers and young adults living beyond Rb. SETTING: A qualitative, exploratory study was conducted using focus groups with teenagers and interviews with young adults. Participants were recruited via the Childhood Eye Cancer Trust and the two national Rb treatment centres in the UK. Reflexive thematic analysis was used to analyse data using exploratory and inductive methods. PARTICIPANTS: 32 young survivors of Rb (10 heritable, 21 non-heritable, 1 unknown; 23 unilateral, 9 bilateral) aged between 13 and 29 years (12 male, 20 female). RESULTS: Data were rich and spanned the life course: three key themes were generated, containing eight subthemes. Theme 1 describes participants' experiences of childhood and trauma, including survivor guilt, memories from treatment and impact on personality. Theme 2 focuses on the challenges of adolescence, including the psychological impact of Rb, the impact on identity, and the sense of normality and adaptation to late effects. The third theme considered adulthood and the development of acceptance, a state of being widely considered unachievable during childhood, as well as the 'work' needed to feel supported, including seeking out information, peer support and therapeutic strategies. CONCLUSIONS: This study provides in-depth insight into the experiences of life beyond Rb. Findings highlight the need for specific psychosocial interventions informed by codesign.

Recent progress in retinoblastoma: Pathogenesis, presentation, diagnosis and management.

Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for survival and preservation of visual acuity hinges upon the disease severity at the time of initial diagnosis. Notably, retinoblastoma has played a crucial role in unraveling the genetic foundations of oncogenesis. The process of tumorigenesis commonly begins with the occurrence of biallelic mutation in the RB1 tumor suppressor gene, which is then followed by a cascade of genetic and epigenetic alterations that correspond to the clinical stage and pathological features of the tumor. The RB1 gene, recognized as a tumor suppressor, encodes the retinoblastoma protein, which plays a vital role in governing cellular replication through interactions with E2F transcription factors and chromatin remodeling proteins. The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

Vasoproliferative Tumor Secondary to Sarcoidosis-Associated Intermediate Uveitis.

We report the visual and clinical outcomes of a middle-aged woman who presented with exudative retinal detachment (ERD) secondary to a vasoproliferative tumor (VPT) in an eye with sarcoidosis-associated intermediate uveitis. A 55-year-old woman previously diagnosed with sarcoidosis presented with decreased vision in the left eye (LE). Visual acuity in the LE was counting fingers. She had active vitritis, and a peripheral retinal vascular mass was noted in the superotemporal periphery. The mass was associated with ERD involving the posterior pole. The patient was managed with systemic and intravitreal steroids, and cyclosporine was subsequently added as a steroid-sparing agent. Because of recurrence of ERD, the patient underwent pars plana vitrectomy, and cryotherapy and laser photocoagulation were applied to the VPT. Two months postoperatively, visual acuity in the LE improved to 6/10. There was marked regression of the VPT and total resolution of the ERD. In conclusion, we report a favorable visual and clinical outcome in a patient with VPT-associated ERD who responded to a combination of medical therapy and surgical intervention. VPT may lead to different remote complications, so timely diagnosis of these tumors and proper management of their complications is warranted.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics.

Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO2 nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn2+ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

Role of apparent diffusion map in the evaluation of retinoblastoma.

PURPOSE: This study aimed to analyze the association between magnetic resonance imaging apparent diffusion coefficient map value and histopathological differentiation in patients who underwent eye enucleation due to retinoblastomas. METHODS: An observational chart review study of patients with retinoblastoma that had histopathology of the lesion and orbit magnetic resonance imaging with apparent diffusion coefficient analysis at Hospital de Clínicas de Porto Alegre between November 2013 and November 2016 was performed. The histopathology was reviewed after enucleation. To analyze the difference in apparent diffusion coefficient values between the two major histopathological prognostic groups, Student's t-test was used for the two groups. All statistical analyses were performed using SPSS version 19.0 for Microsoft Windows (SPSS, Inc., Chicago, IL, USA). Our institutional review board approved this retrospective study without obtaining informed consent. RESULTS: Thirteen children were evaluated, and only eight underwent eye enucleation and were included in the analysis. The others were treated with photocoagulation, embolization, radiotherapy, and chemotherapy and were excluded due to the lack of histopathological results. When compared with histopathology, magnetic resonance imaging demonstrated 100% accuracy in retinoblastoma diagnosis. Optic nerve invasion detection on magnetic resonance imaging showed a 66.6% sensitivity and 80.0% specificity. Positive and negative predictive values were 66.6% and 80.0%, respectively, with an accuracy of 75%. In addition, the mean apparent diffusion coefficient of the eight eyes was 0.615 × 103 mm2/s. The mean apparent diffusion coefficient value of poorly or undifferentiated retinoblastoma and differentiated tumors were 0.520 × 103 mm2/s and 0.774 × 103 mm2/s, respectively. CONCLUSION: This study revealed that magnetic resonance imaging is useful in the diagnosis of retinoblastoma and detection of optic nerve infiltration, with a sensitivity of 66.6% and specificity of 80%. Our results also showed lower apparent diffusion coefficient values in poorly differentiated retinoblastomas with a mean of 0.520 × 103 mm2/s, whereas in well and moderately differentiated, the mean was 0.774 × 103 mm2/s.

Captains on call: A qualitative investigation of an intervention to support children with retinoblastoma undergoing regular eye examinations.

BACKGROUND: Retinoblastoma is a rare childhood ophthalmic cancer that requires frequent eye examinations under anaesthesia and painful or distressing procedures. This can cause significant anxiety for children and their families. OBJECTIVE: We evaluated a Starlight Children's Foundation programme, 'Captains on Call', at the Queensland Children's Hospital, which aims to provide positive distraction and reduce stress, anxiety and pain during the perioperative journey for children in the retinoblastoma treatment pathway. This study examined the impact of the programme on the perioperative experience of the children and their families, using a qualitative design. METHODS: This study was conducted in a paediatric operating suite at a tertiary-level children's hospital in Australia. We interviewed a parent from 20 families (from a cohort of 40 families, including 44 children), whose children received treatment or screening for retinoblastoma, focusing on the programme's impact on the child and family at various stages during the perioperative journey. We undertook a thematic analysis of transcribed interviews. RESULTS: We identified two themes, each with two sub-themes: (1) the programme positively contributed to the overall treatment journey, by addressing different needs at different times, and helping to reframe a traumatic medical experience, and (2), the programme supported the whole family unit by empowering children through play, and adopting a family systems approach which recognised the impact of cancer treatment on the whole family. CONCLUSION: This study highlights the value of the Captains on Call programme in supporting children with retinoblastoma and their families during perioperative visits. The Captains, particularly as non-medicalised professionals in a healthcare setting, built trust and rapport with the children through play over repeated episodes of care. The interprofessional collaborative approach with a reflective cycle of practice extended it beyond a programme providing simple distraction. Other retinoblastoma services may benefit from implementing a similar approach.

Comparing overall survival between pediatric and adult retinoblastoma with the construction of nomogram for adult retinoblastoma: A SEER population-based analysis.

BACKGROUND: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. METHODS: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. CONCLUSION: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients' prognoses.

Updated retinoblastoma incidence and outcome in children in Taiwan from 1980 to 2019: a 40-year nationwide study.

BACKGROUND: Retinoblastoma is a potentially fatal disease, and its incidence and mortality varies among different countries and periods. METHODS: This is a nationwide population-based retrospective study from January 1980 to December 2019 in Taiwan. Patients diagnosed as retinoblastoma were identified from the Taiwan National Cancer Registry. To update the literature on retinoblastoma incidence, mortality and trends in Taiwan, we analysed changes in incidence and survival rates over time according to sex, diagnostic age, laterality and treatment. RESULTS: During 1980-2019, the incidence of retinoblastoma in Taiwan was 1 per 16 489 live births (95% CI: 13 415-19 564). The diagnostic age decreased from 2.21 ± 0.26 during 1980-1984 to 1.24 ± 0.26 during 1985-2019. Compared with that observed during 1980-1989, the incidence rate observed after 1990 increased significantly in children aged <10 years (RR: 1.62-2.40, P = 0.0049 to < 0.0001). From 1980 to 2019, the incidence rate for the 0-4-year age group increased and that for the 5-9-year age group remained constant. The mean diagnostic age for bilateral retinoblastoma (0.36 ± 0.47 years) was significantly less than that for unilateral retinoblastoma (1.37 ± 0.35 years) during 2007-2019 (P < 0.0001). The 10-year survival rate was highest in the enucleation group (89.8%) compared with radiotherapy (52.2%) and others (70.0%; P < 0.0001). CONCLUSIONS: During 1980-2019 in Taiwan, the incidence of retinoblastoma increased significantly, and the diagnostic age decreased, which are similar to the ones from other developed countries. However, the survival rate was still lower than that of most developed countries.

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma.

Retinoblastoma (RB) is a rare malignant tumor that arises in the developing retina in one or both eyes of children. Pathogenic variants of the RB1 tumor suppressor gene drive the majority of germline and sporadic RB tumors. Considering the risk of tumor spread, the biopsy of RB tumor tissue is contraindicated. Advancement of chemotherapy has led to preservation of more eye globes. However, this has reduced access to tumor material from enucleation specimens. Recently, liquid biopsy of aqueous humor (AH) has advanced the RB tumor- or eye-specific genetic analysis. In particular, nucleic acid analysis of AH demonstrates the genomic copy number profiles and RB1 pathogenic variants akin to that of enucleated RB eye tissue. This advance reduces the previous limitation that genetic assessment of the primary tumor could be done only after enucleation of the eye. Additionally, nucleic acid evaluation of AH allows the exploration of the genomic landscape of RB tumors at diagnosis and during and after treatment. This review explores how AH sampling and AH nucleic acid analysis in RB patients assist in diagnosis, prognosis, and comprehending the pathophysiology of RB, which will ultimately benefit individualized treatment decisions to carefully manage this ocular cancer in children.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Familial retinoblastoma: variations in clinical presentation and management based on paternal versus maternal inheritance.

BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.

Global retinoblastoma studies: A review.

In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in underdeveloped nations. The understanding of similarities and disparities between various nations across the world aids in achieving comparable outcomes. With dissolving geographic barriers and evolving collaboration, global collaborative studies on RB are becoming increasingly common. They provide real-world, robust evidence on several aspects of RB. This review discusses insights gained from global RB studies regarding the demographics, certain aspects of etiopathogenesis and epidemiology, international travel burden, disparities in clinical presentations based on national income levels, management protocols, pathology, treatment outcomes, and the effect of COVID-19 on RB care across the world. These insights are likely to impact individual practice as well as inform policy reforms.

Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation.

PURPOSE: To examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation. DESIGN: Cross-sectional study. METHODS: Children (age <18 years) treated for retinoblastoma at a tertiary care center between January 2000 and May 2023 were included. Residential census tract was used to determine the overall and domain-specific COI score for each child. Collected variables included age, sex, race/ethnicity, insurance type, and the International Classification of Retinoblastoma (ICRB) Group at initial examination. The primary outcome was Group D or E retinoblastoma at presentation. Mixed effects regression models were used to estimate the association of COI scores with disease severity at presentation. RESULTS: This study included 125 children (51.2% male). Median age at diagnosis was 13 months (IQR, 5-24 months). One hundred nine (87.2%) children presented with Group D or E retinoblastoma and 33 (26.4%) resided in low or very low opportunity neighborhoods. Children residing in neighborhoods with low overall COI scores (OR, 1.62; 95% CI, 1.01-2.58; P = .044) and low education COI scores (OR, 1.77; 95% CI, 1.13-2.79; P = .013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors. CONCLUSION: Children residing in low opportunity neighborhoods-particularly low education opportunity-more often presented with advanced stage retinoblastoma than children residing in neighborhoods with higher opportunity scores. Efforts to improve preventative vision care and access to eye specialty care for children residing in low-resource areas are needed to reduce existing disparities in retinoblastoma.

Significance of Social Determinants of Health in Tumor Presentation, Hospital Readmission, and Overall Survival in Ocular Oncology.

PURPOSE: To evaluate the association between social determinants of health (SDH) with presentation and outcomes in patients with ocular cancer. METHODS: The National Cancer Database was queried for primary clinical tumor (cT) classifications of T1 to T4 N0M0 uveal melanoma, conjunctival melanoma, or retinoblastoma diagnosed between January 2006 and December 2017. Pearson χ2 analysis assessed differences in SDH-related characteristics between cancer cohorts. Binary logistic regression with adjusted odds ratios (aORs) and multivariate Cox proportional hazards ratios (HRs) with 95% confidence intervals (CIs) were performed. DESIGN: Cross-sectional with a nationally representative sample. RESULTS: Three thousand nine hundred sixty-eight uveal melanoma cases, 352 conjunctival melanoma cases, and 480 retinoblastoma cases were included. Differences in race, primary payer status, income quartile, population density, facility location, Charlson-Deyo comorbidity score, history of malignancy, cT classification at presentation, surgical treatment, radiotherapy, chemotherapy, 30-day readmission, and overall survival (OS) were observed among the cancers. Female sex (aOR 0.819 [95% CI 0.689-0.973]) and top income quartile (aOR 0.691 [95% CI 0.525-0.908]) had decreased likelihood of advanced cT classification at presentation. No insurance (aOR 1.736 [95% CI 1.159-2.601]) and Medicaid primary payer status (aOR 1.875 [95% CI 1.323-2.656]) had increased likelihood of advanced cT classification. Patients in rural areas (aOR 7.157 [95% CI 1.875-27.320]) were more likely to be readmitted within 30 days after initial treatment. Increased age was associated with decreased 5-year OS (HR 1.040 [95% CI 1.033-1.047]). CONCLUSIONS: SDH may influence advanced cT classification at presentation and 30-day readmission compared with OS in patients with ocular cancer, highlighting the need for ophthalmologists and public health efforts to address disparities in SDH.

Retinoblastoma Outcomes in the Americas: A Prospective Analysis of 491 Children With Retinoblastoma From 23 American Countries.

PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income [LIC], lower-middle income [LMIC], upper-middle income [UMIC], and high income [HIC]) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval [CI] 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients >4 years of age (vs ≤4 years, HR = 0.45 [95% CI 0.27-0.78], P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 × 109 [95% CI 1.25 × 109-1.72 × 1010], P < .001) and females (vs males, HR = 1.98 [95% CI 1.27-3.10], P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 [95% CI 2.36-10.5], P < .001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.