[Metachronous bilateral retinoblastoma: a case report].

The patient is a 2-year-old male. The family consulted the Department of Ophthalmology, Shanghai Ninth People's Hospital, after noticing a white reflection in the pupil area of the child's right eye for 6 days. Following a thorough ocular and systemic examination, the patient was diagnosed with retinoblastoma (Group E, cT2bN0M0) of the right eye. The right eye was enucleated and classified as pathological stage pT3cN0M0. Postoperatively, systemic intravenous chemotherapy with the VEC regimen was administered. Genetic testing revealed a germline mutation in the RB1 gene: c.874 (exon9) delT (p.Tyr292fsTer9), necessitating close monitoring of the socket during follow-up visits. Three months after the operation, fundus examination revealed yellow-white lesions in the left eye, and bilateral retinoblastoma was diagnosed (Group E in the right eye, Group C in the left eye). Based on the ICRB and pTNM stages, the patient underwent six rounds of systemic intravenous chemotherapy and three rounds of cryotherapy in the left eye. No recurrence was detected with a 4-year follow-up. The patient was initially diagnosed with unilateral retinoblastoma, but later developed the disease in the contralateral eye during treatment, which was a case of metachronous bilateral retinoblastoma.

Quality of life of Retinoblastoma survivors in tertiary care eye hospital in South India.

PURPOSE: With the increased survival of retinoblastoma (RB) patients, it is important to evaluate the quality of life (QoL) of RB survivors as well as caregivers to provide comprehensive care to the children and caregivers. This study aims to assess the QoL of survivors of RB, as perceived by parents and the self-report by patients, through a pediatric QoL (PEDs-QoL) questionnaire. METHODS: The study cohort included 86 RB survivors, 86 age-matched controls, and their primary carers. PedsQL 4.0 generic core scale and structured interview were administered. QoL in physical, social, emotional, and school health was evaluated and correlated with clinical and sociodemographic parameters. RESULTS: The mean age of the RB survivors was 5.7 years with an M:F ratio of 1.1:1. Disease was bilateral in 79% of cases. About 45% (39/86) underwent enucleation, while others received combination therapy (16; 18%), chemotherapy (30; 34%), and radiation (1; 1%). As reported by parents, the QoL of physical health domain of RB survivors was 70.2 SD ± 27.8 and 96.15 ± 13 SD, emotional health was 72.1 ± 27.4 SD and 94.4 ± 12.5 SD, social health was 80.4 ± 24.9 SD and 98.6 ± 6.2 SD; and school health was 71.9 ± 2 6.5 SD and 96.1 ± 12.2 SD. As per the self-report perception, the QoL of physical health was 68.2 ± 27.8 SD and 96.2 ± 13 SD, emotional health was 66.2 ± 28.4 SD and 95.3 ± 12.5 SD, social health was 69.5 ± 24.9 SD and 98.7 ± 6.2 SD, and school health was 63.5 ± 26.5 SD and 95.1 ± 12.2 SD. There was a significant relationship between enucleation and QoL domains, where χ2 = 67.75, degrees of freedom (df) = 36, and P < 0.01. There was a significant association between vision in the better eye (6/18 or better = 8, 6/18-6/60 = 8, 3/60 or worse = 42) and QoL scores (χ2 = 95.36, df = 62, P < 0.01). There was a substantial association between socioeconomic status and QoL domains, where χ2= 88.5, df = 56, P < 0.01. CONCLUSION: The results of the study showed that the QoL of parents of RB survivors and self-proxy reports were negatively affected in many ways, including physical, social, emotional, and school-related dimensions. Despite the small differences, self-proxy reports indicated a lower QoL than the parents' group. The study findings indicate that there are notable correlations between enucleation and visual acuity less than 6/18, as well as socioeconomic status, with various aspects of QoL domains among individuals who have survived RB.

Hematological Second Primary Malignancy in Pediatric Retinoblastoma: A Case Report and Systematic Review.

PURPOSE: The impact of heredity and treatment modalities on the development of hematologic second primary malignancies (SPMs) is unclear. This study primarily reviewed the literature on patients with hematologic SPMs after retinoblastoma. METHODS: The PubMed and Web of Science databases were searched to identify all cases of hematologic SPMs after retinoblastoma through December 2023 (International prospective register of systematic reviews CRD42023488273). RESULTS: Sixty-one patients from 35 independent publications and our case were included. Within the cohort, 15 patients (51.7%) were male, and 14 patients (48.3%) were female. Of the 43 cases with known heritability status, 27 (62.8%) were classified as heritable and 16 (37.2%) as nonheritable. The median age at diagnosis was 18 months (IQR: 7.00-36.00). The geographic distribution of patients was diverse, with North America accounting for 35.0% (21/60) of cases. The following treatment strategies were used: 11.9% (5/42) of patients received neither chemotherapy nor radiotherapy, 33.3% (14/42) received chemotherapy alone, 11.9% (5/42) received radiotherapy alone, and 42.9% (18/42) received a combination of chemotherapy and radiotherapy. The median delay between retinoblastoma diagnosis and SPM diagnosis was 40 months (IQR: 22.00-85.00). Among the 61 cases, acute myeloid leukemia accounted for 44.3% (27/61), followed by acute lymphoblastic leukemia in 21.3% (13/61), Hodgkin's lymphoma in 11.5% (7/61), non-Hodgkin's lymphoma in 9.8% (6/61), chronic myeloid leukemia in 3.3% (2/61), and acute natural killer cell leukemia in 1.6% (1/61). CONCLUSIONS: Vigilant systemic surveillance for hematologic SPMs in retinoblastoma survivors, especially those treated with systemic chemotherapy and those with hereditary conditions, is warranted to improve management strategies and patient outcomes.

Outcome of Retinoblastoma After Implementation of National Retinoblastoma Treatment Guidelines in South Africa.

PURPOSE: Retinoblastoma, a curable childhood cancer, has been identified as a tracer cancer in the WHO Global Initiative for Childhood Cancer. To document the outcomes of children with retinoblastoma in South Africa, treated as per the first prospective standard national treatment guidelines for childhood cancer in South Africa. PATIENTS AND METHODS: All children diagnosed with retinoblastoma between 2012 and 2016 in five South African pediatric oncology units were treated with a standard treatment on the basis of the International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries guidelines for high-income settings. Treatment included focal therapy with/without chemotherapy, or enucleation with/without chemotherapy, and orbital radiotherapy, depending on enucleated eye histology. The end point was survival at 24 months, using Kaplan-Meier curves with log-rank (Mantel-Cox) and chi-square (χ2) tests with respective P values reported. RESULTS: A total of 178 children were included in the study; 68% presented with unilateral disease. The median age was 27 months (range 0-118 months) with a male:female ratio of 1:0.75. The overall survival was 79% at 24 months with significant association with stage at diagnosis (P < .001) and older age over 2 years as opposed to younger than 2 years (P < .001). Causes of death were disease progression/relapses in 90% (34 of 38) and unknown in 2% (1 of 38), whereas treatment abandonment was 1.7% (3 of 178). CONCLUSION: Efficacy with national treatment guidelines was confirmed, and feasibility of implementing standard national childhood cancer treatment guidelines was documented, involving multidisciplinary teams in South Africa. Outcome was significantly associated with stage at diagnosis and age.

Vitreoretinal large B- cell lymphoma (VR- LBCL): Clinical and pathological features and treatment outcomes.

CONTEXT: Vitreoretinal large B- cell lymphoma (VR- LBCL) is a type of non- Hodgkin lymphoma confined to the eye and central nervous system (CNS). The clinical manifestations of intraocular lymphoma can precede, occur simultaneously with, or follow disease at CNS sites. It differs from other forms of extra-nodal lymphoma; in that it does not involve systemic sites other than CNS. OBJECTIVES: To analyse the clinical and pathological features, and treatment outcomes of a cohort of patients diagnosed with vitreoretinal lymphoma (VRL) in Royal Victoria Eye and Ear Hospital, Ireland between 2010 and 2024. METHOD: Retrospective review of medical records and pathology specimens of patients with ocular involvement in VR- LBCL over 14-year period and a review of the literature. RESULTS: Eight patients were included. All of them underwent pars plana vitrectomy and were confirmed to have VR- LBCL. The median age at diagnosis was 71 years. Three were men and five were women. Six had bilateral disease and two unilateral. Four of four patients had MYD88 L265P mutation present. Four patients showed a high interleukin-10 (IL-10) to interleukins-6 (IL-6) ratio in keeping with the diagnosis of VRL. Three patients had primary CNS lymphoma with subsequent eye involvement, despite systemic chemotherapy treatment. Of the five patients who presented with ocular lymphoma, two patients had CNS involvement after primary vitreoretinal lymphoma was diagnosed. Of those, one was initially treated with local intravitreal chemotherapy. Three patients had no CNS recurrence. At the time of this study, seven patients of eight are alive, four are disease free and two are on a first- line local chemotherapy treatment. One underwent treatment for CNS relapse. One patient died of the disease before commencing targeted therapy. CONCLUSION: This case series demonstrated excellent treatment outcomes for seven patients, alive at the time of the study. Both local radiotherapy and intravitreal chemotherapy achieved good ocular control with acceptable side effects and no significant difference in visual outcome. VRL is a difficult diagnosis and vitreous cytology should be prioritised in cases of vitritis unresponsive to treatment. Analysis of MYD88 L265P mutation and IL- 10: IL- 6 ratio >1 are useful adjuncts in the diagnosis of VR- LBCL, particularly in cases where limited vitreous material makes cytological evaluation challenging.

Clinical, epidemiological, and care profile of hospitalized patients with retinoblastoma in Brazil.

PURPOSE: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. METHODS: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0-19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). RESULTS: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1-14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. CONCLUSIONS: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services.

Polydopamine-Based Targeted Nanosystem for Chemo/Photothermal Therapy of Retinoblastoma in a Mouse Orthotopic Model.

Background: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions. Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus. Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted. Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility. Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.

Evolving criteria for group E retinoblastoma: impact on outcomes.

OBJECTIVE: To assess the impact of evolving criteria for group E retinoblastoma on ocular survival outcomes. DESIGN: A retrospective observational study. METHODS: Single-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. RESULTS: A 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). CONCLUSION: Proposed 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.

Selective ophthalmic arterial injection using a balloon catheter for retinoblastoma: a seven-year clinical evaluation.

PURPOSE: To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber. STUDY DESIGN: Retrospective analysis. METHODS AND PATIENTS: This study was sanctioned by theNational Cancer Center Hospital' Independent Ethics Committee. The surgeon was a general interventional radiologist. After confirming that the distal internal carotid artery was not delineated by balloon occlusion and the ophthalmic artery was visualized using digital subtraction angiography, melphalan was manually administered. Notably, in cases presenting bilateral retinoblastoma, both eyes received treatment in a singular, low-dose procedure. Between July 2015 and December 2021, 125 patients with retinoblastoma (68 boys and 57 girls) underwent SOAI at our facility. The average age at initial treatment was 19.3 months. The study covered 250 procedures, with patients undergoing an average of 3.7 procedures. RESULTS: The success rate of the procedure was 99.2%, with a mean procedure duration of 18.3 min. Two distinct technical failures were recorded: one attributed to an internal carotid artery having a wide lumen and the other due to the ophthalmic artery remaining undetected on angiography post-balloon occlusion of the internal carotid artery. Adverse events were minimal but included bronchospasm post-procedure and severe orbital inflammation in 0.8% and 0.4% of cases, respectively. CONCLUSION: SOAI using the microballoon catheter with the M chamber is a feasible and safe procedure for the treatment of retinoblastoma. The success rate was 99.2%. This system can be recommended as intra-arterial chemotherapy for retinoblastoma.

Retinoblastoma - A comprehensive review, update and recent advances.

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

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

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

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

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

Vasoproliferative Tumor Secondary to Sarcoidosis-Associated Intermediate Uveitis.

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

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

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

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

PURPOSE: To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). METHODS: A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). RESULTS: Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). CONCLUSION: Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.