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.

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.

A multi-institutional feasibility study of intra-arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1).

BACKGROUND: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies. OBJECTIVE: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma. METHODS: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions. Eligible patients older than six months of age were enrolled. The feasibility of delivering three injections of melphalan into the ophthalmic artery every 28 days was assessed. RESULTS: Nine institutions participated in this trial. Fourteen patients were enrolled, two of whom were unevaluable for feasibility. Four patients experienced a feasibility failure. In two patients, the ophthalmic artery could not be accessed for the second IA injection, in one the artery could not be accessed for the first injection, and one patient experienced grade 4 hypotension during the procedure. CONCLUSION: Delivery of prescribed therapy within the context of this study did not meet the feasibility goals of the study with only a 67% feasibility success rate. These results should caution centers that plan to initiate this treatment and suggest investment in training to achieve technical expertise or referral to centers with expertise.

Factors related to central nervous system involvement of primary vitreoretinal lymphoma.

PURPOSE: This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). METHODS: Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. RESULTS: Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). CONCLUSION: Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.

SILICONE FINE-NEEDLE ASPIRATION RETINAL BIOPSY: A Novel Surgical Technique for Vitreoretinal Lymphoma.

PURPOSE: To describe a 41-gauge silicone fine-needle aspiration biopsy (S-FNAB) technique and assess its value in diagnosing primary vitreoretinal lymphoma (PVRL). METHODS: Retrospective review of seven consecutive patients who underwent vitreous biopsy (VB) and 41-gauge S-FNAB of retinal/subretinal lesions in a single tertiary center between January 2012 and March 2023. RESULTS: Of seven patients, S-FNAB confirmed the diagnosis of PVRL in six patients. In five of those patients, both VB and retinal/subretinal S-FNAB (performed at the same procedure) yielded positive results, with the retinal thickness at the biopsy site as small as 231 µm. Four of these five patients had one or more previous negative VB. In one patient, S-FNAB yielded positive results despite a negative VB. Silicone fine-needle aspiration biopsy failed to confirm positive VB for PVRL in the remaining patient. The time from symptom onset to diagnosis of PVRL ranged from 18 days to 26 months. There were no severe complications associated with the procedure. CONCLUSION: Silicone fine-needle aspiration biopsy might be a valuable method for obtaining a sufficient sample of viable cells to diagnose PVRL. It can be performed as a primary procedure along with VB. Further studies are warranted to determine where this technique could be most advantageous.

Retinoblastoma patients treated in Sri Lanka from 2014 to 2020: epidemiology, clinical status and correlates of lag time in seeking tertiary care services.

BACKGROUND: Retinoblastoma (RB) is a tumour of children < 5 years with a incidence of 1 in 20,000. Around 20 RB cases are diagnosed yearly in Sri Lanka, a lower middle-income country with high literacy levels and healthcare free at point of delivery. Incidence, local and systemic severity and mortality related to RB are reportedly high in low- and middle- income countries in comparison to higher income countries. Aims of this study were to describe demographic, socioeconomic, and clinical characteristics of Sri Lankan RB patients attending the designated RB unit at the Lady Ridgeway Hospital (LRH), Colombo between January 2014 to December 2020, and determine correlates of lag time (LT) for first tertiary care visit after detecting the first symptom/sign. METHODS: Two descriptive cross-sectional studies (DCSS) were conducted, one on 171 RB patients with demographic and clinical data collected between 2017 and 2020. In 2021, the second DCSS took place where socioeconomic and further demographic data were collected using telephone interviews, recruiting a subgroup of 90 (53%), consenting and contactable RB patient/ parent pairs. Bivariate and multivariable analyses were applied to determine correlates of LT of > 4 weeks for first tertiary care visit. Results were expressed as odds ratios and 95% confidence intervals. RESULTS: LRH survey (N = 171): Median age at diagnosis was 15 months (range 1-94 months; IQR: 8-27); 89 (52%) were females. Groups D and E tumours were 25.7% (n = 44) and 62.6% (n = 107) respectively with 121 (71%) enucleations. The number of deaths were 2 (1.2%). Telephone survey (N = 90): Proportion with LT of > 4 weeks for first tertiary care visit was 58% (n = 52). None of the putative risk factors (ethnicity, parental educational level, socioeconomic status, distance from residence to tertiary care unit and receiving financial assistance) were associated with LT in both analyses. CONCLUSION: Despite a high proportion with groups D and E tumours and enucleations, mortality rate was low, most likely due to availability of designated tertiary care. No correlates for LT of > 4 weeks for tertiary care presentation were identified. Early RB detection needs rigorous implementation of screening strategies and increased awareness among primary care health workers and parents.

Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

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.

Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma.

PURPOSE: To investigate the expression of nuclear receptor subfamily 1 group D member 1 (NR1D1) and nuclear receptor subfamily 2 group E Member 3 (NR2E3) in retinoblastoma (RB) and their correlation with the clinical and pathological features of RB. METHODS: Immunohistochemical (IHC) assays were performed to detect and evaluate the expression levels of NR1D1 and NR2E3 in paraffin-embedded tissue samples. The relationship between the expression levels and clinicopathological characteristics of RB patients was analyzed using the χ2 test or Fisher exact test. RESULTS: A total of 51 RB patients were involved in this research. The expression levels of NR1D1 (P = 0.004) and NR2E3 (P = 0.024) were significantly lower in RB tumor tissues than in normal retina. The expression levels of NR1D1 and NR2E3 were less positive in RB patients with advanced stages (P = 0.007, P = 0.015), choroidal infiltration (P = 0.003, P = 0.029), and optic nerve infiltration (P = 0.036, P = 0.003). In addition, a low expression level of NR2E3 was associated with high-risk pathology (P = 0.025) and necrosis (P = 0.035) of RB tissues. CONCLUSION: The expression levels of NR1D1 and NR2E3 were decreased in RB and closely associated with the clinical stage and high invasion of the disease. These findings provide new insights into the mechanism of RB progression and suggest that NR1D1 and NR2E3 could be potential targets for treatment strategies.

[Isolated primary vitreoretinal lymphoma (case report)]. / Izolirovannaya pervichnaya vitreoretinal'naya limfoma (klinicheskoe nablyudenie).

This case report presents the diagnostic features of isolated primary intraocular lymphoma, which was initially misdiagnosed as neovascular age-related macular degeneration. A comprehensive examination using ultrasound, optical coherence tomography, and fundus autofluorescence revealed changes characteristic of vitreoretinal lymphoma. Molecular genetic analysis of the vitreous body showed the presence of a MYD88 gene mutation and B-cell clonality by immunoglobulin heavy chain (IGH) gene rearrangement tests, which confirmed the diagnosis.

Role of optical coherence tomography angiography in retinal tumors: A narrative review.

Intraocular tumors constitute a small subset of cases in ophthalmologic practice. Proper diagnosis of intraocular tumors is crucial because some pose threat to vision and life, while others may indicate underlying systemic disorders. Intraocular tumors comprise benign and malignant lesions affecting the retina, choroid, optic disc, iris, and ciliary body. Retinal tumors can be classified as vascular, neural, glial, and retinal pigment epithelial tumors. Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality employed in diagnosis and management of retinal and choroidal vascular diseases, and has enhanced our knowledge in better understanding of the vascular physiology and pathology. Multiple case reports and small series evaluating the role of OCTA in retinal tumors are published in literature. OCTA helps in better understanding of the vascularity of intraocular tumors. In addition to this, OCTA has its role in clinical practice. It helps in identification of small retinal capillary hemangioblastoma (RCH), assessment of treatment response, and identification of tumor recurrence in RCH. It aids in identification of retinal astrocytic hamartoma missed on clinical examination and differentiating retinal astrocytic hamartoma and presumed solitary circumscribed retinal astrocytic proliferation. It helps in assessment of risk of tumor recurrence in retinoblastoma. It helps in differentiating tumors of retinal pigment epithelium (RPE) origin from pigmented tumors of the choroid. It also helps in detection of choroidal neovascular membrane in combined hamartoma of the retina and RPE.

Vitreoretinal Lymphoma Masquerading as Central Serous Chorioretinopathy.

The following is a case of vitreoretinal lymphoma masquerading as central serous chorioretinopathy (CSCR). A 74-year-old man presented with blurred vision in the left eye with unilateral subretinal fluid in the setting of exogenous corticosteroid use, which was diagnosed as CSCR and resolved with corticosteroid cessation. He later experienced a similar self-limited episode in the right eye. Subsequently, he developed bilateral vitritis with yellow-white subretinal pigment epithelial infiltrates. Vitreous biopsy confirmed a diagnosis of large B-cell lymphoma. Vitreoretinal lymphoma can masquerade as a number of ocular pathologies, including CSCR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:467-470.].

Three-Dimensional Ultrasound Imaging of Retinoblastoma and Its Correlation With Pathology.

BACKGROUND AND OBJECTIVE: Monitoring the response of retinoblastoma to globe-salvaging therapies is based on subjective assessments of changes determined by fundoscopy, ultrasound, and optical coherence tomography. Advances in organ-preserving therapies have increased the need for objective, quantitative estimates of tumor response to treatment. Primary tumor volume is a metric that can be objectively determined as a surrogate measure of treatment response. PATIENTS AND METHODS: We evaluated the correlation of objective, quantitative estimates of tumor volume made with two-dimensional (2D) and three-dimensional (3D) ultrasound with gold standard pathological tumor volumes derived by analysis of enucleation specimens. RESULTS: Twelve eyes in 12 patients undergoing primary enucleation were evaluated by 2D and 3D ultrasound during ophthalmic examination under anesthesia prior to enucleation. 2D- and 3D-ultra-sound measurements of tumor volume were both strongly correlated with pathological estimates of tumor volume (r = 0.69, P = 0.018; and r = 0.66, P = 0.027, respectively). CONCLUSIONS: 2D- and 3D-ultrasound measurements of retinoblastoma primary tumor volume are highly correlated with pathological estimates. 3D measurements are easy to perform with volumetric probes and consider the irregular morphology of the tumor. Further study should be undertaken to evaluate the performance of these metrics as surrogate markers of tumor response to treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:136-140.].

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.

The association between race and age of diagnosis of retinoblastoma in United States children.

PURPOSE: To explore the associations between race and retinoblastoma diagnosis in United States children. METHODS: In this analytical nonconcurrent cohort study, we used 1988-2018 data from the Surveillance, Epidemiology, and End-Results (SEER) database. Children ages 0-17 with retinoblastoma were included (n = 758); those with missing data were excluded (n = 11; final cohort: n = 747). The exposure variable was race (White, Black, Asian/Pacific Islanders, American Indian/Alaska Native), and the outcome variable was diagnosis of retinoblastoma before versus after 2 years of age. Covariates included sex, rural-urban continuum, ethnicity, decade of diagnosis, and laterality of disease. Unadjusted and adjusted logistic regression analyses were performed to calculate odds ratios and 95% confidence intervals. RESULTS: No statistically significant association was found between racial/ethnic groups (OR = 0.61-0.99; P = 0.92) and age at diagnosis (OR = 0.86; P = 0.66). Females were more likely to be diagnosed earlier than males (OR = 0.62; 95% CI, 0.44-0.88; P = 0.042). No association was found between urban versus rural subjects (OR = 1.02; 95% CI, 0.60-1.75) or between decades (OR = 0.81; 95% CI, 0.54-1.22 and OR 0.96; 95% CI, 0.62-1.47). CONCLUSIONS: We found no statistically significant difference between racial/ethnic groups for diagnosis of children with retinoblastoma after 2 years of age. Future studies could explore why females are more likely than males to be diagnosed before 2 years of age.