International Intraocular Retinoblastoma Classification Research Articles

Evolving criteria for group E retinoblastoma: impact on outcomes

ObjectiveTo assess the impact of evolving criteria for group E retinoblastoma on ocular survival outcomes. DesignA retrospective observational study. MethodsSingle-institution consecutive case series of patients with advanced intraocular retinoblastoma (groups D and E) were classified based on International Intraocular Retinoblastoma Classification (IIRC) and International Classification of Retinoblastoma (ICRB) criteria. The main outcomes measured were ocular survival, frequency of histopathologic risk factors (HRF), and the need for adjuvant therapy. ResultsA total of 332 eyes of 298 patients were classified into group D (150, 45%) and E eyes (182, 55%) based on IIRC criteria. ICRB classification resulted in upstaging of 57 group D eyes (17%) to group E. Eyes that were upstaged to group E from D in the ICRB classification (E1) differed significantly, with a greater proportion undergoing primary enucleation (17 of 57, 30%) than those that were not (10 of 93, 11%) (p = 0.003). Similar significant differences were observed between group E2 and E3 eyes (p < 0.0001). Ocular survival according to Kaplan–Meier estimates at 12 months of 79%, 59%, 49%, and 1% differed significantly between all groups (ICRB D, E1, E2, and E3, respectively). ConclusionProposed new subgrouping of group E eyes into E1, E2, and E3 based on clinical criteria is based upon natural history of tumor progression and is predictive of ocular survival. Preservation of the existing lower boundaries for group E by ICRB and IIRC offers the possibility of reanalyzing existing published data.

The Impact of Tumor Laterality (Unilateral vs. Bilateral) on Presentation and Management Outcome in Patients with Retinoblastoma.

Background: This study compares the outcomes of managing retinoblastoma between patients with unilateral and bilateral presentations. Methods: The study, conducted at the King Hussein Cancer Center in Amman, Jordan, retrospectively analyzed cases of retinoblastoma treated between March 2003 and December 2019. Evaluation criteria included clinical features, disease stage, treatment methods, and overall management outcomes. Results: The study comprised 697 eyes from 478 patients with retinoblastoma, with 52% being males. Bilateral disease was observed in 70% of patients, and a family history of retinoblastoma was more prevalent in cases with bilateral disease (20%) compared to those with unilateral disease (4%). Unilateral cases had a median age at diagnosis of 28 months, whereas bilateral cases were diagnosed at a median age of 6 months. Extra-ocular retinoblastoma was detected in 1% of eyes. According to the International Intraocular Retinoblastoma Classification (IIRC), 88% of unilateral cases presented with advanced disease (IIRC group D/E), compared to 46% in bilateral cases. Primary enucleation was performed in 29% of unilateral cases and 16% of bilateral cases (p-value 0.0007). Eye salvage rates were 31% in unilateral cases and 68% in bilateral cases (p-value < 0.0001). At 120 months of follow-up, 5% of patients died from secondary neoplasms or metastases, 81% were alive, and 14% were lost to follow-up. There was no significant difference in metastasis, secondary neoplasms, or mortality between patients with unilateral and bilateral retinoblastoma. Conclusions: This study highlights the nuanced differences in clinical characteristics and outcomes between unilateral and bilateral retinoblastoma, emphasizing the necessity of customized management and early detection strategies. It demonstrates that while bilateral retinoblastoma benefits from earlier detection and has a higher rate of eye salvage, there is no significant difference in metastasis or mortality rates when compared to unilateral cases. The critical roles of primary enucleation in advanced cases, along with effective communication and patient education, are also underscored to improve treatment adherence. Overall, these findings point to the importance of tailored approaches in optimizing outcomes for the diverse patient population affected by retinoblastoma.

Outcome of 6 Cycles of Primary Intravenous Chemotherapy of Retinoblastoma Patients in Terms of Recurrence in a Tertiary Health Care Hospital

Objective: To determine the frequency of recurrence after 6 cycles of primary intravenous chemotherapy of retinoblastoma patients in a tertiary health care hospital.&#x0D; Materials and Methods: This study was conducted at the Department of Ophthalmology, Lahore General Hospital, Lahore from March 15, 2020 to September 15, 2020. A total of 81 patients were selected randomly from outpatient department. Performa designed was used to collect data including name, age, gender, registration number, laterality, age at diagnosis, group of disease, treatment given and outcomes of given treatment. International Intraocular Retinoblastoma Classification (IIRC) was used for classification of the disease. The chemotherapy regimen used was vincristine, etoposide and carboplatin (VEC). A total of 6 cycles were given at 3 weekly intervals. Serial monitoring of the tumors was done to rule out any local recurrence or side effects of therapy.&#x0D; Results: Total 81 children presenting with retinoblastoma were enrolled in this study. There were 52(64.2%) male and 29(35.8%) female. The mean age of patients was 3.41±1.45 year. Unilateral disease was in 61 (75.30%) patients while 20 (24.70%) patients had bilateral retinoblastoma. Among 81 children, 20(24.7%) had recurrence of the disease.&#x0D; Conclusion: Development of recurrence after intravenous chemotherapy was noted in 24.7 % of all retinoblastoma eyes. Younger patients with more advanced, posteriorly located tumors and subretinal seeds at presentation were at increased risk, but recurrence can often be managed with globe-sparing therapy.

Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.

Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.

Study of the Efficacy of Indocyanine Green Enhanced Transpupillary Thermotherapy as a Treatment Modality for Retinoblastoma

Background Retinoblastoma represents approximately 4% of all pediatric malignancies and is the most common ocular malignancy in children. It has one of the highest survival rates among all pediatric malignancies owing to improving treatment methods over the years. Objectives The purpose of our work was to evaluate the efficacy of intravenous indocyanine green dye injection combined with diode laser transpupillary thermotherapy (TTT) as a treatment modality for Group (B) intraocular retinoblastoma compared to the standard protocol of treatment. Patients and Methods A prospective interventional comparative study was conducted in the Ocular Oncology Clinic, Ophthalmic Department, Ain Shams University Hospital in the period from August 2017 to December 2020. The study was conducted on twenty tumors, classified as Group (B) retinoblastoma according to International Classification of Intraocular Retinoblastoma (ICRB). It includes; Tumors &amp;gt;3 mm (in basal dimension or thickness), tumors located in the macula (≤3 mm to foveola), juxta-papillary tumors (≤1.5 mm to disc) or tumors surrounded by subretinal fluid (≤5 mm from the tumor margin). They were divided into two main groups: Group I: It included ten (10) tumors; newly diagnosed or recurrent. This group was treated with systemic chemotherapy plus ICG enhanced diode laser TTT, Group II (control group): It included ten (10) tumors; newly diagnosed or recurrent. This group was treated with systemic chemotherapy plus conventional diode laser TTT. Results The study found that ICG has significantly improved uptake of diode laser, eliminating the need for increasing the laser power to the photocoagulation levels which would disrupt the inner retinal layers. ICG-TTT allowed rapid tumor regression and decreased the number of laser sessions needed to achieve tumor regression.ICG-TTT was successful with 3 challenging recurrent masses on a hypopigmented scar and achieved complete regression. There was no statistically significant difference between the two groups as regards the disease-free survival curves using Kaplan Meier analysis. During the period of post chemotherapy follow up, 3 tumors in Group I (30%) and 2 tumors in group II (20%) developed recurrence. And one case in group I (10%) developed a new mass in a remote site. Conclusion The study concluded that ICG-TTT is both efficient and safe despite some potential complications.

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated.

Although biopsy is contraindicated in retinoblastoma (RB), the aqueous humor (AH) is a robust liquid biopsy source of molecular tumor information, facilitating biomarker discovery. Small extracellular vesicles (sEVs), promising biomarker candidates across multiple cancers, were recently identified in RB AH, but relationships between sEVs and RB clinical features are unknown. We analyzed sEVs in 37 AH samples from 18 RB eyes of varying International Intraocular Retinoblastoma Classification (IIRC) groups and explored clinical correlations. Ten samples were collected at diagnosis (DX) and 27 during treatment (Tx). Unprocessed AH underwent Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS) analysis for fluorescent particle count and tetraspanin immunophenotyping; counts were subsequentially converted to percentages for analysis. Comparing DX and Tx samples, a higher percentage of CD63/81+ sEVs was found in DX AH (16.3 ± 11.6% vs. 5.49 ± 3.67% P = 0.0009), with a more homogenous mono-CD63+ sEV population seen in Tx AH (43.5 ± 14.7% vs. 28.8 ± 9.38%, P = 0.0073). Among DX samples, CD63/81+ sEVs were most abundant in group E eyes (n = 2) compared to group D (n = 6) by count (2.75 × 105 ± 3.40 × 105 vs. 5.95 × 103 ± 8.16 × 103, P = 0.0006), and to group A+B (n = 2) by count (2.75 × 105 ± 3.40 × 105 vs. 2.73 × 102 ± 2.59 × 102, P = 0.0096) and percentage (32.1 ± 7.98% vs. 7.79 ± 0.02%, P = 0.0187). CD63/81+ sEVs enrich AH from RB eyes before treatment and those with more significant tumor burden, suggesting they are tumor-derived. Future research into their cargo may reveal mechanisms of cellular communication via sEVs in RB and novel biomarkers.

Abstract 6717: Extracellular vesicles in diagnostic retinoblastoma aqueous humor correlate with disease stage and clinical outcome: a pilot study

Abstract Introduction: Retinoblastoma (RB), a pediatric retinal malignancy, is unique in that it cannot be biopsied, impeding biomarker discovery. Aqueous humor (AH) is an ocular fluid that is an established source of tumor information, serving as a surrogate liquid biopsy. Extracellular vesicles (EVs) are promising biomarker candidates, and were recently established in RB AH. EVs are membrane-enclosed secretory vesicles carrying bioactive molecular information, which can be phenotyped using validated tetraspanin protein markers. Currently, relationships between EVs and RB clinical features are unknown, but establishing such relationships is necessary to determine the utility of EVs as RB biomarkers. Methods: We quantified and phenotyped EVs in 37 AH samples from 18 RB eyes with varying International Intraocular Retinoblastoma Classification (IIRC) stages and explored clinical correlations. Samples were collected from 10 eyes at diagnosis (DX) and 27 eyes during treatment (Tx). By outcome, 6 DX eyes were enucleated and 4 were salvaged. DX samples were collected from one A, one B, six D and two E eyes by IIRC group. 10μL of unprocessed AH underwent Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS) (Exoview R100) analysis for fluorescent-based particle count and immunophenotyping of tetraspanin expression (CD63/81/9). Counts were converted to percentages. Statistics were done with Mann-Whitney U, ANOVA, and Tukey’s tests. Results: Samples from DX eyes (n=10) contained a higher number of EVs than samples from Tx eyes (n=27) (1.68 x 107 ± 4.28 x 107 per mL vs. 2.10x 106 ± 1.33 x 106 per mL) by SP-IRIS analysis. By percentage, DX samples were enriched with CD63/81+ EVs (P&amp;lt;0.001) while Tx samples had more homogenous mono-CD63+ dominant EV populations (P=0.007). Enrichment of CD63/81+ EVs was significantly higher in enucleated AH (n=6) than salvaged AH (n=4) when compared by count (P=0.038) and marginally higher when compared by percentage (P=0.067). The CD9/81+ EV population percentage was significant in salvaged eyes (P=0.01). By IIRC, CD63/81+ EVs were most abundant in Group E eyes (n= 2) when compared to Group D eyes (n=6) by count (P&amp;lt;0.001), and when compared to Group A+B eyes (n=2) by count (P=0.01) and percentage (P=0.019). Group A+B eyes had a larger percentage of CD9/81+ EVs than did Group E eyes (P=0.043). Conclusions: EV quantity in RB AH decreases with treatment, and phenotypic expression profiles vary by treatment status and clinical outcome. TheCD63/81+ EV subpopulation is higher in eyes with advanced Group E disease and those requiring enucleation, while the CD9/81+ subpopulation is higher in eyes with less advanced Group A+B disease and those salvaged with treatment. Our data suggests that EV phenotypes correlate with RB clinical features, and further research into these subpopulations offers the prospect of establishing critical RB biomarkers. Citation Format: Sarah Pike, Chen-Ching Peng, Paolo Neviani, Jesse L. Berry, Liya Xu. Extracellular vesicles in diagnostic retinoblastoma aqueous humor correlate with disease stage and clinical outcome: a pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6717.

EPIDEMIOLOGICAL AND CLINICAL ASPECTS OF RETINOBLASTOMA IN DEVELOPING COUNTRY

Introduction: &#x0D; Retinoblastoma is the most common intraocular tumor in child. Treatment depend on stadification and classification of retinoblastoma. The aim of this study was to describe epidemiological and clinical aspects of retinoblastoma in Madagascar.&#x0D; Method: We report in this retrospective study 44 cases found during 5 years, from January 2015 to December 2019. We have collected information about epidemiological and clinical aspect, delay of diagnosis. Classification of retinoblastoma was done with Reese Ellsworth classification and International Classification of Intra-ocular Retinoblastoma (ICRB). Data was collected with excel software and analysis was done with R-studio 4.2.2 software. The quantitative variables were expressed as an average and the qualitative variables as a proportion and percentage.&#x0D; Result: We had collected 44 cases. The incidence was 8.8 cases per year. Sex ratio was 1.3. Mean age was 40 months. Exophthalmos was found in 35% (n=12) of cases. Leukocoria was found in 24% (n=11) children. The delay time before diagnosis was 13 months. In 97.7% of cases, the retinoblastoma was unilateral. Intraocular form was found in 23 patients (52.3%). Among intraocular form 13 patients (57%) presented with grade E, including one patient with meningeal extension 9 patients (39%) with grade D, 1 patient (4%) in grade B. Extra ocular form was found in 21 patients (47.7%) : 17 (77%) had orbital invasion (stage III), 4 (23%) were metastatic (stage IV).&#x0D; Conclusion: Diagnosis of retinoblastoma was made in advanced stage. Most of patients had extraocular form. Prognosis was worse in Madagascar. Making diagnosis early is necessary to prevent loss of life.

Intravitreous Chemotherapy as Adjuvant Treatment for Vitreous Seeding in Retinoblastoma: A Philippine Tertiary Hospital Experience

Background. Intravitreal chemotherapy has been an effective addition in treating vitreous seeding in retinoblastoma. However, it was only in 2020 that it was used in the Philippines. There is no literature on its use in multiple Filipino retinoblastoma patients.Objectives. To describe the clinical course of the four patients who are the first to undergo intravitreal chemotherapy for vitreous seeding of retinoblastoma in the Philippine tertiary hospital.Methods. A case series of four eyes of four patients with retinoblastoma who underwent intravitreous injectionof melphalan and topotecan for vitreous seeding at the Department of Ophthalmology and Visual Sciences of aPhilippine tertiary hospital.Results. Two eyes, with International Intraocular Retinoblastoma Classification (IIRC) Group C with vitreous seeding, responded well to intravitreous melphalan and topotecan. One eye had recurrent vitreous seeding despite 10 intravitreal injections. One eye with IIRC Group E, did not respond to intravitreous chemotherapy and was eventually enucleated.This is the first case series on the local use of intravitreous chemotherapy in the country for vitreous seeding inretinoblastoma. The control of 50% achieved in this case series is lower than in other series due to longer treatment interval from poor follow-up and the presence of advanced disease.Conclusion. The use of intravitreous melphalan and topotecan can be an effective adjuvant for systemic chemotherapy in controlling vitreous seeding in eyes with IIRC Group C. It is not effective in controlling IIRC Group E disease.

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

Effectiveness of Intra-Arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma: Relevance of a Multidisciplinary Setting.

We aim to report about effectiveness and safety in the context of our centers' setting in the management of retinoblastoma with intra-arterial chemotherapy (IAC) in a 5-year retrospective analysis of the Portuguese population. Retrospective analysis of consecutive cases of retinoblastoma selected to initiate IAC between 2015 and 2020, at the Portuguese National Reference Center. All included patients underwent complete ophthalmological evaluation under anesthesia with fundus photography. Diagnosis and classification of retinoblastoma was made according to the International Classification of Intraocular Retinoblastoma (ICRB). The patients were further divided into two groups: Group I for primary IAC and Group II for secondary IAC. Tumor recurrence or relapses, systemic metastasis and deaths were documented. Main efficacy outcome included ocular salvage and recurrence-free survival rates estimated using the Kaplan-Meier method. Twenty-eight eyes (19 eyes included in Group I and 9 eyes included in Group II) were eligible and a total of 130 IAC procedures were performed, with a median number of sessions of 4 (range 1-8) for each treated eye, during a median follow-up of 21 months (range 4-64). Of the included eyes, 22 (78.6%) were preserved. An overall survival of 100% was achieved. Considering the preserved eyes, the overall median decimal visual acuity achieved at the last visit was 0.15 (range 0.02-0.8). Three patients had permanent adverse events related to IAC (cataract, vitreous hemorrhage and choroidal ischemia). Considering the survival analysis of recurrence, the mean survival without recurrence was 84.2% for Group I and 66.7% for Group II, and the mean survival without enucleation was 78.6% (no events in Group II). IAC has been shown to be an effective and safe treatment for children with intraocular retinoblastoma. This study demonstrates that IAC is effective even in moderate sample sizes, when a multidisciplinary approach is available.

Favourable Response to Chemotherapy in Ora-Located Intraocular Retinoblastoma Grade B, C, and D: A Case Series

Background: We aim to analyze which tumor location gives more favorable chemotherapy response in intraocular retinoblastoma grade B, C, and D as well as to report the first case series in Indonesia. Methods: Six boys with age ranging from 10 weeks to 47 months old were recruited into the study from April 2019 to January 2020 at National Eye Centre, Cicendo Eye Hospital, and Hasan Sadikin General Hospital, Bandung, West Java, Indonesia. Retinoblastoma (RB) patients underwent examination under anesthesia (EUA). Tumor size and location were evaluated by using RetCam pre and post 2 cycles of chemotherapy. The tumors were classified according to the International Intraocular Retinoblastoma Classification. Results: There were two patients with unilateral RB and four patients with bilateral RB. All patients had leukocoria and sought medical advice within 12 months of onset. There were one tumor in the macular zone, six tumors in the equatorial zone, and two tumors in the ora zone. Two cycles of intravenous vincristine, etoposide, and carboplatin (VEC) were administered and the tumor diameter was re-evaluated afterwards. The tumor size was decreased following 2 cycles of chemotherapy. Conclusions: Ora zone showed a more favorable chemotherapy response.

Primary Macular Retinoblastoma: Clinical Presentation and Treatment Outcomes.

Purpose: To describe the clinical features and treatment outcomes in eyes with primary macular retinoblastoma (RB). Methods: Patients with primary macular RB were analyzed. Results: Of 41 patients (47 eyes), 20 (49%) were boys and 21 (51%) were girls. The mean age at diagnosis was 16 months (range, 1-60 months). The RB was bilateral in 6 patients (15%). At presentation, the macula was completely covered with the tumor in 22 eyes (47%) and partially covered with the fovea spared in 13 eyes (28%) and the fovea involved 12 eyes (25%). Based on the International Classification of Intraocular Retinoblastoma, 25 (53%), 15 (32%), and 7 (15%) of tumors were in Group B, Group C, and Group D, respectively. The tumor had exophytic features in 36 eyes (77%). The mean tumor basal diameter was 10.0 mm and the mean thickness, 5.6 mm. Associated features included subretinal seeds (10 eyes; 21%) and surrounding subretinal fluid (16 eyes; 34%). Forty-three eyes (92%) were treated with intravenous chemotherapy, 2 (4%) with intra-arterial chemotherapy, and 2 (4%) with transpupillary thermotherapy. Local tumor control was achieved in 45 eyes (96%), with 33 eyes (70%) showing a type III regression pattern. Over a mean follow-up of 23 months (range, 3-48 months), the macular tumor recurred in 5 eyes (11%), the globe was salvaged in all eyes with associated foveal atrophy (36 eyes; 77%), and 1 patient (2%) died. Conclusions: Macular RB has a good prognosis for globe salvage while vision salvage might be compromised as a result of associated foveal atrophy.

Clinicopathological Presentation of Retinoblastoma in Ethiopia

Introduction: The presenting symptoms of retinoblastoma in Ethiopia, as well as their relationship to the stage of the disease, are poorly understood, but they could be important as background knowledge for creating early detection initiatives. This study aimed to describe the clinical and histopathological characteristics of retinoblastoma among Ethiopian patients. Methods: A hospital-based cross-sectional analysis of all children with newly diagnosed retinoblastoma during the study period of May 2015 to December 2019, inclusive, who presented to a tertiary referral center during were included. Demographic, clinical, and histological characteristics were collected and descriptive statistics were done using SPSS Version 20.0 software. Results: A total of 217 patients (unilateral 84.3%, bilateral 15.7%) were studied. The median age at presentation was 29 months (34 months vs. 19.5 months in unilateral and bilateral cases, respectively, p < 0.001). Among all patients, 57.8% were male. Leukocoria was the most common presenting sign (37.3%) and followed by fungating mass (31.8%). Tumors were extraocular in 40.1% of cases. From the intraocular cases, 73.3% were advanced International Intraocular Retinoblastoma Classification Group D or E disease. Sixty-two (54.4%) of the eyes had high-risk pathological features. The median lag time was significantly shorter for intraocular versus extraocular cases (5 months vs. 12 months, respectively, p < 0.001). Conclusion: Our results show that the majority of Ethiopian children with retinoblastoma have delayed presentation and late stage at diagnosis. This suggests that national health promotion campaigns to increase public knowledge on the presenting signs of retinoblastoma may be critical to achieving early diagnosis. Furthermore, the development of standard management guidelines informed by this study will be helpful in managing the complex and advanced cases currently observed.

Outcomes of patients with unilateral retinoblastoma: A report from the RIVERBOAT Consortium.

10046 Background: Retinoblastoma (RB) is the most common tumor of the eye in childhood. Intraocular RB cure rates approach 100%. Therefore, treatment now focuses on globe salvage preserving functional vision. The Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient health outcomes, including vision, in the contemporary therapy era. Methods: Patients with RB treated at consortium centers from 2007 to present were identified. Medical record abstraction was performed for disease presentation, treatment, and outcomes. A subset of the patients returned to centers and completed functional vision questionnaires (Child Vision Function Questionnaire - ages 0 – 7 and Cardiff Visual Ability Questionnaire for Children - ages &gt; 8) and had visual acuity assessed. For participants who could not yet return for a study evaluation, medical record abstraction alone was performed. Results: Among 463 participants enrolled to date, 270 (58%) had unilateral disease. One patient with metastatic RB did not survive, resulting in overall survival of 99.6. There was one case of secondary leukemia. The eye group distribution (International Intraocular Retinoblastoma Classification) was 0.4% A, 5.6% B, 7.0% C, 36.0% D, 49.0% E and 2.0% not classified. 131 (49%) patients underwent primary enucleation and are not included in further analyses. Among the remaining 139 patients, 3% were treated with local ophthalmic therapy only, 22% with intravenous chemotherapy (IV) only, 53% with intra-arterial chemotherapy (IAC) only, 22% with IV and IAC, and 35% required secondary enucleation. Globe salvage after chemotherapy was successful in 100% A, 93% B, 82% C, 72% D, and 48% E eyes. This salvage was achieved with IV only, IAC only, or both in 22%, 58% and 20% respectively. The mean percentage of patients receiving IAC per year increased from 13% (2008 – 2013) to 21% (2014 – 2017) to 28% (2018 – 2022). In 29 patients without enucleation who reported functional vision to date, the mean scores (survey theoretical ranges) were 0.72 for &lt; 3 years (0.57 to 0.87), 0.82 for 3 -7 years (0.56 to 0.94) and -2.72 for &gt; 8 years (-2.53 to -0.51), all considered good functional vision. In 20 of these 29 patients, 4 eyes had normal vision (20/20-20/40) across A to D groups. Moderate vision loss (&gt; 20/40 – 20/70) was noted in 3 D eyes and low vision (&gt; 20/70 - &lt; 20/200) in 1 D eye. Twelve B through E eyes met criteria for a legally blind eye (&gt;20/200). Conclusions: In this cohort of RB patients with unilateral disease treated from 2007 - 2022, 66% required primary or secondary enucleation. Among 29 patients with globe salvage, self-reported functional vision was good, but 12 eyes in 20 of the patients were legally blind. IAC only or IV plus IAC was most used in those who avoided secondary enucleation. With ongoing cohort accrual and increased IAC use, it will remain to be determined if globe salvage with functional vision will improve.

Outcomes of patients with bilateral retinoblastoma: A report from the RIVERBOAT Consortium.

10045 Background: Retinoblastoma (RB) is the most common tumor of the eye in childhood. Intraocular RB cure rates approach 100%. Therefore, treatment advances have focused on globe salvage preserving functional vision. The Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient health outcomes, including vision, in the contemporary therapy era. Methods: Patients with RB treated at consortium centers from 2007 to the present were identified. Medical record abstraction was performed for disease presentation, treatment, and outcomes. A subset of the patients returned to centers and completed functional vision questionnaires (Child Vision Function Questionnaire for ages 0 – 7 and Cardiff Visual Ability Questionnaire for Children for ages &gt;8) and had visual acuity assessed. For participants who could not yet return for a study evaluation, medical record abstraction alone was performed. Results: Among 463 participants enrolled to date, 193 (42%) had bilateral disease. Two each had metastatic RB, trilateral RB, and secondary osteosarcoma. One patient each with metastatic RB and trilateral RB is deceased, with overall survival for the cohort of 99%. The eye group distribution (International Intraocular Retinoblastoma Classification) was 14% A, 22% B, 14% C, 28% D, 19% E and 3% not classified. Primary enucleation was performed in 43 (22%), secondary enucleation in 48 (25%) and bilateral enucleation in 1(0.5%). Intravenous chemotherapy (IV) alone was administered in 58%, intra-arterial chemotherapy (IAC) alone in 4%, with 31% receiving both. Among 145 patients who did not require secondary or bilateral enucleation, the distribution was 16% A, 21% B, 16% C, 28% D, 15% E, and 4% non-classified eyes. This salvage was achieved with IV alone, IAC alone, or both in 55%, 5% and 30% respectively and with ophthalmic therapy only in 10%. The mean percentage of patients receiving IAC per year increased from 6% in 2008 – 2013 to 11% in 2014 – 2022 and was stable at 11% in 2018 – 2022. Among 53 patients who have reported functional vision to date, the mean scores were 0.81 for &lt; 3 years 0.80 for 3-7 years and -1.31 for those &gt;8 years, all considered to be good functional vision. Among 50 eyes in 37 of these 53 patients, 33 had normal vision (20/20-20/40) across A to E groups. Moderate vision loss (&gt; 20/40 – 20/70) was noted in 1 C and 1 B eye and low vision (&gt; 20/70 - &lt; 20/200) in 6 group B, C or D eyes. Nine B or D eyes were legally blind (&gt;20/200). No patients had two legally blind eyes. Conclusions: In this cohort of RB patients with bilateral disease treated between 2007 and 2022, 52% have been successfully treated without enucleation. Self-reported functional vision in 53 of these patients with all group eyes was good. Only 6 of 50 eyes in 37 patients met criteria for legal blindness and 66% of eyes had normal vision. With cohort accrual ongoing, we will determine if these promising outcomes continue.

Bilateral enucleation for retinoblastoma: A study of 14 patients

PURPOSE:To study the clinical profile of patients who underwent bilateral enucleation for retinoblastoma (RB).METHODS:Retrospective study of 14 cases.RESULTS:Of >3000 RB cases, 14 (<1%) underwent bilateral enucleation for treatment of RB. The mean age at diagnosis of RB was 26 months (median, 24 months; range, 5–72 months). All patients had bilateral RB at presentation. Intraocular RB was evident in 23 (82%) eyes and orbital tumor extension was noted in 5 (18%) eyes. Based on the International Classification of Intraocular RB, tumors were classified as Group B (n = 1; 4%), D (n = 4; 14%), or E (n = 14; 50%) at presentation. Based on the International RB Staging System, tumors were classified as Stage 1 (n = 23; 82%) or Stage 3 (n = 5; 18%). Two patients (four eyes with intraocular RB) had undergone prior treatment before presenting to us and thus could not be classified. Primary treatment included systemic chemotherapy (n = 27; 96%) or enucleation (n = 1; 4%). Five patients were lost to follow-up for a mean duration of 15 months (median, 12 months; range, 7–24 months) during treatment and presented with the orbital extension of RB in one (n = 4; 29%) or both (n = 1; 7%) eyes. Secondary enucleation was performed in 27 (96%) eyes. Over a mean follow-up period of 49 months (median, 29 months; range, 3–340 months), there was no evidence of metastasis and 1 (7%) child died due to pneumonia.CONCLUSION:Bilateral enucleation is rare in the treatment of RB. Advanced tumor presentation or noncompliance to treatment necessitates bilateral enucleation.

Scenario of Retinoblastoma Among Bangladeshi Children – A Single Center Experience of 10 Years

Background: Retinoblastoma is the most common intraocular tumor of childhood and most detected cases are from Indian subcontinent. Here we explore the presentation of retinoblastoma with its histopathological features and treatment outcome in a tertiary eye care center in Bangladesh. Method: This was a retrospective study of 70 eyes of 60 patients in a ten years period from 2006 to 2016 who had met the criteria regarding demographic profile, clinical presentation, management and histopathology. Tumor was classified based on IIRC (International Intraocular Retinoblastoma Classification) for intraocular tumor and IRSS (International Retinoblastoma Staging System) for extraocular tumor by reviewing the data revealed from EUA, imaging and histopathology. Result: The mean age of presentation was (Table 1) 31.3 ± 21.68 months, range was 4 months to 96 months and the most frequent presenting age was 12 months. Fifty three percent of children presented between 13 months and 59 months. Mild male predominance was 53.3% (n = 32). Unilateral cases were 71.3% (n = 43) and 6.7% (n = 4) of patients had positive family history. The most common presenting sign was leucocoria (85%) followed by strabismus (18.3%) and proptosis (13.3%). Fifty five (91.6%) children presented with intraocular tumor and 64.9% were with Group E. Enucleation (91.6%) was the prime treatment modality and histopathological risk factor was positive in 51.7% cases among 63.3% cases of primary enucleation. Fifty percent of treated children were in regular follow up. Conclusion: Most children presented delayed and prime treatment modality was enucleation. Only half of the patients were in regular follow up. Generation of awareness, proper referral, information regarding treatment availability and early detection of cases can increase the survival rate and globe salvage.

Retinoblastoma in Calabar Nigeria: An 18-Month Retrospective Review of Clinical Presentation at a Tertiary Eye Center

Background: Retinoblastoma, although rare, is the most frequently occurring primary intraocular tumor of childhood. While a cure is often achieved where appropriate treatment is instituted early in the disease, late presentation often leads to unsuccessful treatment interventions. Aim: The aim of this study is to provide baseline information on the clinical presentation of retinoblastoma as seen in a tertiary pediatric eye care facility in Calabar, Nigeria. Materials and Methods: A retrospective review of case files of children presenting to the Calabar Children's Eye Center (CCEC) with retinoblastoma over 18 months from January 1, 2018 to June 30, 2019 was done. Results: Data were collected from 39 children with retinoblastoma who met the inclusion criteria. There were 22 (56.4%) males and 17 (43.6%) females, and the age range was 7–41 months, with a mean age of 25.6 (±9.0) months. Unilateral disease was seen in 27 (69.2%) participants, whereas 12 (30.8%) had bilateral disease. Although multiple symptoms were seen in many participants protrusion of eye was the most frequently occurring first symptom, (17, 44.0%) followed by red eye (13, 33.0%), whitespot in eye (5, 13.0%), and abnormal alignment (4, 10.0%) among study participants. The lag time from recognition of symptoms to initial consultation ranged from 1 to 25 months, with a mean lag time of 9.13 ± 5.68 months. The ICRB classification system was most frequently used, 27 (69.2%), followed by cTNMH 11 (28.2%), and International Intraocular Retinoblastoma Classification 1 (2.6%). The International Retinoblastoma Staging System was representative. Of the 78 eyes studied, (51, 65.3%) had different stages of retinoblastoma with the majority presenting as advanced retinoblastoma (46, 90.2%). Conclusions: Retinoblastoma is seen at the CCEC. Although the most frequent symptom was protrusion of eye, the lag time was often several months long. Most patients presented late with advanced ocular retinoblastoma and or extraocular disease.

Scenario of Retinoblastoma Among Bangladeshi Children – A Single Center Experience of 10 Years

Background: Retinoblastoma is the most common intraocular tumor of childhood and most detected cases are from Indian subcontinent. Here we explore the presentation of retinoblastoma with its histopathological features and treatment outcome in a tertiary eye care center in Bangladesh. Method: This was a retrospective study of 70 eyes of 60 patients in a ten years period from 2006 to 2016 who had met the criteria regarding demographic profile, clinical presentation, management and histopathology. Tumor was classified based on IIRC (International Intraocular Retinoblastoma Classification) for intraocular tumor and IRSS (International Retinoblastoma Staging System) for extraocular tumor by reviewing the data revealed from EUA, imaging and histopathology. Result: The mean age of presentation was (Table 1) 31.3 ± 21.68 months, range was 4 months to 96 months and the most frequent presenting age was 12 months. Fifty three percent of children presented between 13 months and 59 months. Mild male predominance was 53.3% (n = 32). Unilateral cases were 71.3% (n = 43) and 6.7% (n = 4) of patients had positive family history. The most common presenting sign was leucocoria (85%) followed by strabismus (18.3%) and proptosis (13.3%). Fifty five (91.6%) children presented with intraocular tumor and 64.9% were with Group E. Enucleation (91.6%) was the prime treatment modality and histopathological risk factor was positive in 51.7% cases among 63.3% cases of primary enucleation. Fifty percent of treated children were in regular follow up. Conclusion: Most children presented delayed and prime treatment modality was enucleation. Only half of the patients were in regular follow up. Generation of awareness, proper referral, information regarding treatment availability and early detection of cases can increase the survival rate and globe salvage.