Retinoblastoma Group Research Articles

Evolving criteria for group E retinoblastoma: impact on outcomes

ObjectifÉvaluer en quoi la révision des critères du rétinoblastome du groupe E influent sur la survie oculaire. NatureÉtude d'observation rétrospective. MéthodesOn a classé le rétinoblastome intraoculaire avancé (groupes D et E) chez une série de patients consécutifs d'un établissement unique en fonction des critères de la classification internationale du rétinoblastome intraoculaire (IIRC, pour International Intraocular Retinoblastoma Classification) et du système international de stadification du rétinoblastome (ICRB, pour International Classification of Retinoblastoma). Les principaux paramètres de mesure étaient la survie oculaire, la fréquence des facteurs de risque histopathologiques et la nécessité d'administrer un traitement adjuvant. RésultatsSelon l'IIRC, 332 yeux de 298 patients ont été classés dans les groupes D (150, 45 %) et E (182, 55 %). Suivant l'application des critères de l'ICRB, 57 yeux du groupe D (17 %) ont migré vers le groupe E. Les yeux qui sont passés du groupe D au groupe E selon l'ICRB (E1) présentaient des différences significatives : en effet, l'exécution d'une énucléation en première intention a été nécessaire dans une plus grande proportion des yeux ainsi déplacés (17 sur 57; 30 %) que des yeux qui sont demeurés dans le même groupe (10 sur 93; 11 %; p = 0,003). Des différences significatives semblables ont été observées entre les yeux des groupes E2 et E3 (p < 0,0001). D'après la méthode d'estimation de Kaplan-Meyer, la survie oculaire à 12 mois différait significativement entre tous les groupes, s’établissant à 79 %, à 59 %, à 49 % et à 1 %, respectivement, dans les groupes D, E1, E2 et E3 selon l'ICRB. ConclusionLa nouvelle sous-classification suggérée des yeux du groupe E en trois classes distinctes (E1, E2 et E3) en fonction de critères cliniques se fonde sur l’évolution naturelle de la progression tumorale et permet de prédire la survie oculaire. La conservation des limites inférieures actuelles pour le groupe E selon l'ICRB et l'IIRC ouvre la possibilité d'analyser à nouveau les données publiées à ce jour.

Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation

PurposeTo examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation. DesignCross-sectional study. MethodsChildren (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. ResultsThis study included 125 children (51.2% male). Median age at diagnosis was 13 months (IQR, 5-24 months). 109 (87.2%) of 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=0.044) and low education COI scores (OR, 1.77; 95% CI, 1.13-2.79; p=0.013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors. ConclusionChildren 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.

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

BackgroundSeveral 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. MethodsThe clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. ResultsA 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. ConclusionsPatients 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.

Late metastasis in bilateral familial retinoblastoma and review of literature

A 5-year-old female with bilateral familial retinoblastoma (Group A, Group C) was treated with systemic chemotherapy and three cycles of intra-arterial chemotherapy. She was being followed closely and had no evidence of intraocular recurrence for 4 years. She developed isolated femoral metastasis 5 years after initial diagnosis and was treated with high-dose chemotherapy and stem cell transplant. This case emphasizes the need for metastatic monitoring for low-grade retinoblastoma and points toward delayed tumor latency.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Direct medical costs of globe salvage in group C-E retinoblastoma and implications for cost-effectiveness

To determine the direct medical costs and cost-effectiveness of globe salvage compared with primary enucleation in patients with advanced retinoblastoma. Patients with International Classification of Retinoblastoma groups C-E retinoblastoma at a single institution from 2001 to 2021 were categorized into two groups: primary enucleation and globe salvage. Hospital visits and treatments were compared to determine differences in care utilization. Costs per encounter were derived from billing data and multiplied by number of encounters to determine total costs in the first year of treatment. Groups were stratified by unilateral or bilateral retinoblastoma, and visual acuity-based utility values were used to compare quality-adjusted life years to determine cost-effectiveness. Of 74 group C-E eyes of 70 patients, 55 eyes underwent primary enucleation and 19 eyes underwent globe salvage, 12 of which ultimately underwent secondary enucleation. Patients who underwent globe salvage had higher usage of systemic chemotherapy (P=0.001), more examinations under anesthesia (P < 0.001), fewer outpatient visits (P= 0.03), and a higher total cost of care (301,151 vs 104,764 USD [P < 0.001]) in the first year of treatment compared with the primary enucleation group. At an average life expectancy of 76 years, the incremental cost-effectiveness ratio was 118,347 USD per QALY in unilateral retinoblastoma and 32,987 USD per QALY in bilateral retinoblastoma, meeting the <150,000 USD/QALY threshold of cost-effectiveness. Incurring additional costs may save the eye in advanced retinoblastoma, but the possibility of secondary enucleation should be disclosed for informed decision making. Despite this risk, globe salvage was cost-effective in unilateral and bilateral retinoblastoma.

Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Retinoblastoma in the Southern Philippines: Clinical Outcomes of Retinoblastoma Patients in a Davao Tertiary Hospital

Background. Retinoblastoma is the most common intraocular cancer in childhood in the Philippines. Most datathough on demographics, clinical profile, treatment options, and outcomes in the country are from the NationalCapital Region.Objectives. This study aimed to describe the demographics, clinical profile, treatment done, and outcomes ofretinoblastoma patients seen in a public tertiary referral center in Davao from 2011-2020 to make available literature more representative of the status of retinoblastoma in the Philippines.Methods. An analytical cross-sectional study was conducted using the records of retinoblastoma patients seen in a tertiary government hospital located in Davao Region from January 2011 to December 2020.Results. There were 157 patients included in the analysis. Seventy-three (46%) were female with 44% coming from the Davao Region. One hundred seven (69%) patients had unilateral disease. Median age at initial consultation for patients with unilateral disease was significantly older than those with bilateral disease (p&lt;0.003). Tumors were extraocular in 82 (40%) eyes. In the intraocular group, 36% of the eyes belonged to International Classification of Retinoblastoma (ICRB) Groups D and E. Enucleation was the most commonly performed treatment. Survival rate was 28%.This is the first report to provide epidemiologic and clinical data on retinoblastoma in the literature, including survival data, from Mindanao. Advanced stages and extraocular cases of retinoblastoma remain high. Delay of consultation contributed to the prognosis and clinical outcome of the disease.Conclusion. Advanced stages and extraocular cases of retinoblastoma remain significantly high in the country, even in Mindanao.&nbsp;treatment, outcomes, survival rate, Mindanao &nbsp

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma.

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cataracts as the control (Group 5). We found a total of 889 proteins in all samples. Comparative parametric analyses among the different groups revealed three additional proteins expressed in the RB groups that were not expressed in the control group. These were histone H2B type 2-E (HISTH2B2E), InaD-like protein (PATJ), and ubiquitin conjugating enzyme E2 V1 (UBE2V1). Upon processing the data of our study with the OpenTarget Tool software, we found that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and CD44 were more highly expressed in the RB groups. Our results provide a proteome database regarding AH related to RB disease that may be used as a source of biomarkers. Further prospective studies should validate our finding in a large cohort of RB patients.

Epidemiological and Clinical Presentation of Retinoblastoma among Nepalese Children in 2019.

Suresh B.K. RasailyObjectives Retinoblastoma (RB) is rare but potentially fatal if left untreated. This study aimed to evaluate the epidemiological profile, clinical manifestation, classification, and affordability of RB treatment among Nepalese children in the year 2019. Materials and Method A multicentric, multiethnic hospital-based cross-sectional study after ethical approval from the National Health Research Council was conducted from January 2019 to December 2019 by incorporating ophthalmologists all over the nation. Twenty-seven RB centers were selected. All the RB presented in the RB centers either newly diagnosed or ongoing treatment consented to the study were included and failed to consent for the study, RB survivors were excluded from the study. Data based on demographic profile, clinical manifestation, ethnical and geographical distribution, and treatment received were collected in the customized Google Form. Each case was classified at the time of diagnosis as per the International Classification of Retinoblastoma groups and different treatment modalities offered as per grouping and staging. The affordability of treatment was calculated using a catastrophic approach. Statistical Analysis Data were entered into Microsoft Excel 2010 and analyzed using Statistical Package for Social Sciences version 20. Result A total of 34 RB cases, 21 (61.76%) in ongoing treatment group and 13 (38.2%) in newly diagnosed group presented in the RB centers. Out of total, 32 (64.7%) had unilateral and 12 (35.3%) cases had bilateral involvement. The majority of patients was from Province 1 (35.3%) and belonged to the upper caste (38.2%). Leukocoria was the most common presentation (73.9%) followed by proptosis, red eye, and phthisis bulbi. More than 75% patients presented at advanced group D (54%) and E (21%) and stage 0 (90%). More than 90% of patients received systemic chemotherapy, and 42.6% received transpupillary thermotherapy. The average cost of RB treatment was estimated to be 521% of the nonfood expense of the family which is unaffordable to almost all cases (100%). Conclusion Leukocoria is the most common mode of clinical presentation in both unilateral and bilateral RBs. Early diagnosis and appropriate treatment are key to success for saving life, sight, and eye. However, community awareness programs against RB, active referral networks, and the establishment of chemotherapy centers with trained human resources are needed to reduce loss of life, sight, and eye.

Follow-up of intraocular retinoblastoma through the quantitative analysis of conserved nuclear DNA sequences in aqueous humor from patients.

Fundoscopy is the standard method for diagnosis and follow-up of intraocular retinoblastoma, but it is sometimes insufficient to discern whether tumors are inactivated following treatments. In this work, we hypothesized that the amount of conserved nuclear DNA sequences in the cell-free DNA (cfDNA) fraction of the aqueous humor (AH) might complement fundoscopy for retinoblastoma follow-up. To address our hypothesis, we developed highly sensitive droplet digital polymerase chain reaction (ddPCR) methods to quantify highly conserved DNA sequences of nucleus-encoded genes (GAPDH and B4GALNT1) and of a mitochondrial gene, MT-ATP6. We obtained AH samples during intravitreal treatments. We analyzed 42 AH samples from 25 patients with intraocular retinoblastoma and 11 AH from controls (non-cancer patients). According to clinical criteria, we grouped patients as having progression-free or progressive retinoblastoma. cfDNA concentration in the AH was similar in both retinoblastoma groups. Copy counts for nucleus-derived sequences of GAPDH and B4GALNT1 were significantly higher in the AH from patients with progressive disease, compared to the AH from progression-free patients and control non-cancer patients. The presence of mitochondrial DNA in the AH explained that both retinoblastoma groups had similar cfDNA concentration in AH. The optimal cut-off point for discriminating between progressive and progression-free retinoblastomas was 108 GAPDH copies per reaction. Among patients having serial AH samples analyzed during their intravitreal chemotherapy, GAPDH copies were high and decreased below the cut-off point in those patients responding to chemotherapy. In contrast, one non-responder patient remained with values above the cut-off during follow-up, until enucleation. We conclude that the measurement of conserved nuclear gene sequences in AH allows follow-up of intraocular retinoblastoma during intravitreal treatment. The method is applicable to all patients and could be relevant for those in which fundoscopy evaluation is inconclusive.

Health-Related Quality of Life in Adolescent and Young Adult Retinoblastoma Survivors.

Background: Retinoblastoma (RB) is a malignant intraocular tumor diagnosed in early childhood that requires extensive medical and surgical treatment at a young age. Health-related quality of life (HRQOL) is thought to be diminished due to visual impairment, facial deformities, and fear of recurrence or secondary cancer. However, few studies have identified variables associated with HRQOL among those with RB. Purpose: To compare HRQOL of adolescents and young adults (AYAs) with RB to matched controls and to identify predictors of HRQOL in RB survivors. Methods: Using a cross-sectional design, 198 AYAs (101 RBs and 97 controls) completed HRQOL (PROMIS®-29 profile) and psychosocial questionnaires (Rosenberg self-esteem scale, multidimensional scale of perceived social support, and Hollingshead index for socioeconomic status). Clinical variables (age at diagnosis, visual acuity, laterality, heredity, treatment regime, and anesthesia exposure) were extracted from the medical record. Correlates of HRQOL were estimated using linear regression models. Results: RB survivors reported similar HRQOL compared to controls. Physical function (p < .001), social support (p = .013), and self-esteem (p = .028) were lower in the RB group compared to controls. Visual acuity and self-esteem accounted for 52% of the variance in PROMIS physical health summary scores and self-esteem accounted for 38% of the variance in mental health summary scores. Conclusion: Despite deficits in physical function and self-esteem HRQOL in RB survivors was comparable to healthy counterparts. However, the majority of RB survivors in this study had normal visual acuity. Clinicians should explore ways to enhance self-esteem in RB survivors.

Aqueous humor as a surrogate biomarker for retinoblastoma tumor tissue

To demonstrate the feasibility of identifying a germline RB1 pathogenic variant in retinoblastoma (RB) from an aqueous humor (AH) sample. In this pilot case series, peripheral blood, fresh tumor tissue, and AH were obtained from 3 eyes of 3 RB patients who underwent enucleation at a tertiary eye care institute. After isolation of the cell-free DNA (cfDNA), sequence analysis of the RB1 core promoter and of exons 1 through 27, including nearby flanking intronic regions, was performed using a custom targeted hybridization protocol, followed by high-throughput sequencing. The study cohort included 3 enucleated eyes with advanced RB (group E [n = 2], group D [n = 1]). In case 1, deletion of the RB1 promoter to exon 23 (delP->23) on both alleles was identified from tumor as well as AH samples and absent in the blood sample, indicative of absence of a germline RB1 pathogenic variant. In case 2, two heterozygous RB1 nonsense variants, c.610G>T p.(Glu204Ter) and c.751C>T p.(Arg251Ter), were identified in tumor and AH samples (allele frequency of 49% and 45%, resp.) and were absent in the blood sample, indicative of absence of a germline RB1 pathogenic variant. In case 3, a heterozygous c.2326-14T>A substitution on allele 1 and loss of heterozygosity on allele 2 were identified in the tumor and AH (allele frequency of 97%), with the same heterozygous mutation in the blood sample, indicating presence of a germline RB1 pathogenic variant. The pathogenic RB1 variant results from AH in all 3 eyes were concordant with direct tumor DNA sampling, suggesting that AH can serve as a surrogate for tumor tissue. Because the AH can be accessed during treatment, specific testing can be performed even in the absence of enucleation.

Targeted chemotherapy in retinoblastoma: A step forward from patient survival to globe survival.

Despite being the most common intraocular malignancy in childhood, there is a substantial disparity between developing and developed countries in terms of patient and globe survival in retinoblastoma (Rb). The current study intends to determine patient and globe survival before and after the introduction of the new targeted treatment modalities in a developing country. Medical records of 350 patients (516 eyes) with retinoblastoma referred to a tertiary referral center for Rb in Tehran, Iran, were reviewed. In order to compare patient and globe survival before and after the availability of the new treatment modalities, including intra-arterial and intravitreal chemotherapy, the patients were divided into group 1 (2001-2007) and group 2 (2008-2018) based on the calendar period of diagnosis. Two-hundred-twenty-three eyes of 149 patients and 293 eyes of 201 patients were categorized into groups 1 and 2, respectively. The 5-year patient survival was 97% across the current survey, and the overall survival rate was 96% in group 1 and 99% in group 2 (P = 0.08). Overall, 50% of eyes with retinoblastoma underwent enucleation, which was the primary in 63% (116/184) of the unilateral and 30% (99/322) of the bilateral cases. Primary enucleation was significantly lower in group 2 (35%) in contrast to group 1 (50%) (P < 0.001). In addition, globe survival improved significantly in the International Classification of Retinoblastoma Groups D (17% in group 1 vs. 66% in group 2, P < 0.001) and E (1% in group 1 vs. 23% in group 2 P < 0.001) during the two timelines. In enucleated eyes, despite the increased rate of prelaminar involvement in group 2 (13% vs. 2% in group 1, P = 0.003), the rate of high-risk histopathologic findings was similar between the two groups. Similar to developed countries, the application of new targeted treatment modalities, including intra-arterial and intravitreal chemotherapy, has been associated with significantly improved globe survival in Rb patients. However, it should be noted that even with the availability of these novel treatment options, the decision for on-time enucleation should not be deferred.

Determinants of late diagnosis and treatment of children with retinoblastoma. Analytical review of the organizational and methodological department of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia

Introduction . Early diagnosis of oncological diseases is one of the most important tasks of public health, because improves the quality of medical care for patients and the prognosis of the disease. Despite advances in oncology, pediatric tumors continue to be diagnosed at advanced stages, which may be associated with a delayed visit to a doctor and a delay in diagnosis due to several factors. Many foreign articles are devoted to the search and analysis of significant factors of untimely diagnosis of oncological diseases, but few similar works in Russia. Purpose of the study – to identify factors of late diagnosis and treatment of children with retinal tumors using the example of a common childhood tumor of retinoblastoma (RB). Material and methods . A retrospective cohort study of patients diagnosed with RB at the of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia (Research Institute of Pediatric Oncology and Hematology) was performed using the database of the hospital cancer registry. The study group included RB patients from Russia with a first diagnosis in the period from 2016 to 2019 and receiving treatment at the Research Institute of Pediatric Oncology and Hematology. Time intervals were calculated based on the dates of the first symptom of RB, the initial medical consultation, the date of the final diagnosis by an oncologist or ophthalmologist, and the date of the first therapy for a child with RB. The intervals were calculated in days. Results . Data from 197 patients (aged 0 to 15 years) were analyzed, which corresponded to 262 cases and the number of eyes with bilateral or unilateral Rb. The median diagnostic interval for patients with localized RB (groups A and B) was 30 days, for patients with locally advanced RB (groups C, D and E) 41 days. The median treatment initiation interval for localized and locally advanced RB was 15 days. Age (p = 0.0067) and patient gender were statistically significantly correlated with the diagnostic interval. For strabismus, the median diagnostic interval was 91 days (p &lt; 0.0001), and when RB was detected during a preventive medical examination, the median diagnostic interval was 17 days (p &lt; 0.0001). The event-free survival of the eyes depended on the prevalence of the process (in groups A, B, C) and the duration of the doctors’ interval (p = 0.0394). The distance to the cancer center was not statistically significant. Conclusion . Predictors of late diagnosis and initiation of treatment in our study: gender, age of the patient at the time of diagnosis, and the first specific symptom of RB.

Intravitreal chemotherapy in the management of retinoblastoma in a resource-limited setting

Intravitreal chemotherapy (IVitC) in the management of retinoblastoma has increased the rate of globe salvage, specifically in patients with recurrent disease and associated vitreous seeds. A significant number of children with retinoblastoma in developing countries present late, resulting in higher intraocular tumour-stage at presentation. Treatment requirements for such tumours usually include intravenous chemotherapy (IVC) and/or intra-arterial chemotherapy (IAC). While IVC has a long usage track record and a good efficacy, it has been reported to be associated with higher recurrence rates in a significant number of patients. Intra-arterial chemotherapy has the advantage of lower recurrence rates but requires personnel with advanced interventional radiology skills and has limited efficacy in treating intravitreal seeds. Intravitreal chemotherapy has gained popularity recently, largely because of its superior efficacy in the management of vitreous seeds, subretinal seeds and recurrent retinal tumour. An 8-month-old male infant initially presented with bilateral retinoblastoma, International Classification System for Intraocular Retinoblastoma (ICRB) Group E in the right eye and Group B on the left eye. The right eye was enucleated and currently has a prosthesis. The left eye had tumours that initially responded to brachytherapy and transpupillary thermotherapy (TTT). Approximately two years later his tumours recurred with vitreous seeds and were successfully managed with the use of cryotherapy and intravitreal chemotherapy. The simplicity of the technique of IVitC and its efficacy in controlling vitreous seeds and recurrent retinal tumours makes this route of regional chemotherapy a viable one in areas with limited expertise and resources such as South Africa.

Enucleated Pseudoretinoblastoma: A Six-year Review from a Philippine Center.

To evaluate the prevalence, etiologies, demographics, and clinical presentation of enucleated pseudoretinoblastoma. This retrospective study reviewed ocular pathology records of enucleated globes with clinically diagnosed or suspected retinoblastoma submitted to a public university ocular pathology laboratory from 2013 to 2018. Hematoxylin-eosin-stained sections of pseudoretinoblastoma cases were reevaluated, and additional clinical data were taken from hospital charts. Of the 211 enucleated eyes with clinically diagnosed or suspected retinoblastoma, 202 (95.7%) had histologically confirmed retinoblastoma, while 9 (4.3%) had pseudoretinoblastoma. The most common ocular conditions mimicking retinoblastoma were retinal dysplasia (2 eyes) and persistent fetal vasculature (2 eyes). The pseudoretinoblastoma group consisted of 4 females and 5 males, and enucleated were 6 right eyes and 3 left eyes. The mean age at the time of enucleation was 3.65 years, and the mean symptom duration was 17.36 months. Leukocoria, which was noted in 4 patients, was the most frequent initial symptom. No significant difference between the pseudoretinoblastoma group and the retinoblastoma group were found in terms of sex, laterality of the enucleated eye, age at the time of enucleation, and symptom duration. In this retrospective review, the prevalence of pseudoretinoblastoma in enucleated globes clinically suspected or diagnosed with retinoblastoma was 4.3%. Persistent fetal vasculature and retinal dysplasia were the most common pseudoretinoblastomas. Clinicians should perform a thorough clinical evaluation and judiciously utilize the available diagnostic means to differentiate retinoblastoma from pseudoretinoblastoma.

Changes in Treatment Patterns and Globe Salvage Rate of Advanced Retinoblastoma in Korea: Efficacy of Intra-Arterial Chemotherapy.

(1) Background: To analyze changes in treatment patterns for advanced retinoblastoma over time and differences in globe salvage rates; (2) Methods: Retrospective, observational case-control study of 97 eyes of 91 patients with advanced retinoblastoma (Group D and E).; (3) Results: Patients were divided into two groups based on whether they were treated before or after intraarterial chemotherapy (IAC) was introduced in our center in 2010. Before 2010, primary treatment pattern was enucleation, which was performed in 57.6% of cases, whereas primary treatment pattern after 2010 was IAC combined with intravenous chemotherapy (IVC), which was performed in 78.1%. Intravitreal chemotherapy (IVitC) has been performed to treat vitreous and subretinal seeding since 2015. The 5-year globe salvage rate of IVC alone was 24.0% for Group D and 0% for Group E, whereas that of IVC–IAC was 50.4% for Group D and 49.7% for Group E. Whether IVitC was performed or not did not significantly contribute to globe salvage rate. There was one metastatic death in the IVC alone group.; (4) Conclusions: Primary treatment pattern changed from enucleation to IAC-based treatment, which can now save nearly half of eyes with advanced retinoblastoma with excellent safety profile and survival rate.

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank <.001). The OES did not differ significantly between the two treatment groups (plogrank =.77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank <.0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank <.0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1years after diagnosis of retinoblastoma (range 0.1-6.9years). Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.

Clinical picture and grouping of retinoblastoma at first presentation to a tertiary Hospital in Dar es Salaam: Implications for treatment outcomes

Objectives: To assess the clinical picture and grouping of retinoblastoma at first presentation to the oncology ward at Muhimbili National Hospital. Methods: A cross sectional descriptive hospital based study was conducted from April to December 2018. Seventy two patients who presented for the first time to Muhimbili National Hospital (MNH) with a diagnosis of retinoblastoma were consecutively sampled and recruited in the study. Visual acuity, horizontal corneal diameter, intraocular pressure, anterior and posterior segments of the eye were assessed and each eye was classified according to the International Classification of Retinoblastoma (ICRB) group. Ultrasonography, neuroimaging and histology were performed. Results: A total of 72 patients comprising of 90 affected eyes were recruited and analyzed: 39(54.2%) males and 33(45.8%) females. Majority of patients were residents of the Coastal and Lake Zones. Family history of Retinoblastoma was positive in only one patient. Fifty four (75.0%) patients had unilateral disease. Leukocoria (77.8%) and proptosis (41.7%) were the commonest first clinical signs noted by the family and health workers at MNH respectively. At MNH, both bilateral and unilateral cases presented with advanced disease of group E and extra ocular extension where 84(93.3%) eyes were indicated for enucleation. The median lag time from disease onset to presentation at MNH was 4 months. Conclusion: Leukocoria was the commonest first sign of retinoblastoma presentation at home. However, despite early presentation to primary health facilities, most patients presented to the tertiary centre of MNH late with advanced disease. Efforts to raise awareness on retinoblastoma to both health workers and the community are important for early case detection, referral, diagnosis and treatment in order to improve visual outcomes and survival rates of retinoblastoma patients.