Retinoblastoma: An update on genetic origin, classification, conventional to next-generation treatment strategies.

The most prevalent paediatric vision-threatening medical condition, retinoblastoma (RB), has been a global concern for a long time. Several conventional therapies, such as systemic chemotherapy and focal therapy, have been used for curative purposes; however, the search for tumour eradication with the least impact on surrounding tissues is still ongoing. This review focuses on the genetic origin, classification, conventional treatment modalities, and their combination with nano-scale delivery systems for active tumour targeting. In addition, the review also delves into ongoing clinical trials and patents, as well as emerging therapies such as gene therapy and immunotherapy for the treatment of RB. Understanding the role of genetics in the development of RB has refined its treatment strategy according to the genetic type. New approaches such as nanostructured drug delivery systems, galenic preparations, nutlin-3a, histone deacetylase inhibitors, N-MYC inhibitors, pentoxifylline, immunotherapy, gene therapy, etc. discussed in this review, have the potential to circumvent the limitations of conventional therapies and improve treatment outcomes for RB. In summary, this review highlights the importance and need for novel approaches as alternative therapies that would ultimately displace the shortcomings associated with conventional therapies and reduce the enucleation rate, thereby preserving global vision in the affected paediatric population.

von Hippel-Lindau Syndrome and Secondary Hypertension: A Case Report.

von Hippel-Lindau (VHL) syndrome (OMIM #193300) is an autosomal dominant disorder with incomplete penetrance occurring due to a mutation in the VHL gene present on chromosome 3. We present the case of a 21-year-old male with a history of retinoblastoma presenting with intermittent headaches for one month. He was a known hypertensive and his blood pressure on presentation was 180/100 mmHg. A secondary cause for his hypertension was sought. Multiple cysts in his pancreas, both his kidneys, and a mass in the right suprarenal fossa were detected on an abdominal ultrasonogram and a subsequent computed tomography scan of the abdomen. VHL and a pheochromocytoma were suspected, and a positron emission tomography-computed tomography scan was done which collaborated with the above findings. The presence of multiple cystic lesions in the pancreas and kidneys, especially in an individual with a family history of VHL syndrome, should alert the physician to the possibility of VHL syndrome. The need for evaluation of causes for hypertension, especially in young individuals with resistant hypertension, is also highlighted.

In vivo movement of retinoblastoma-related protein (RBR) towards cytoplasm during mitosis in Arabidopsisthaliana.

Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.

Wnt/ß-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment.

The evolutionarily conserved Wnt signaling has a significant and diverse role in maintaining cell homeostasis and tissue maintenance. It is necessary in the regulation of crucial biological functions such as embryonal development, proliferation, differentiation, cell fate, and stem cell pluripotency. The deregulation of Wnt/ß-catenin signaling often leads to various diseases, including cancer and non-cancer diseases. The role of Wnt/ß-catenin signaling in adult tumors has been extensively studied in literature. Although the Wnt signaling pathway has been well explored and recognized to play a role in the initiation and progression of cancer, there is still a lack of understanding on how it affects pediatric tumors. This review discusses the recent developments of this signaling pathway in pediatric tumors. We also focus on understanding how different types of variations in Wnt signaling pathway contribute to cancer development and provide an insight of tissue specific mutations that lead to clinical progression of these tumors.

Molecular Biomarkers Detected Using Fluorescence in situ Hybridization in a Filipino with Retinoblastoma.

Background and Objective: Retinoblastoma is one of the most common intraocular cancers among children usually caused by the loss of retinoblastoma protein function. Despite being a highly heritable disease, conventional diagnostic and prognostic methods depend on clinical examination, with limited consideration of cancer genetics in the standard of care. CD133, KRT19, and MUC1 are commonly explored genes for their utility in liquid biopsies of cancer including lung adenocarcinoma. To date, there are few extensive molecular studies on retinoblastoma in Filipino patients. To this end, the study aimed to describe the copy number of CD133, KRT19, and MUC1 in retinoblastoma samples from a Filipino patient and quantitate the respective expression level of these genes. Methods: Hematoxylin & Eosin (H&E) staining was utilized to characterize the retinoblastoma tissue while fluorescence in situ hybridization (FISH) using probes specific to CD133, KRT19, and MUC1 was performed to determine the copy number of genes in retinoblastoma samples from a Filipino patient (n = 1). The gene expression of CD133, MUC1, and KRT19 was quantitated using RT-qPCR. Results: The H&E staining in the retinoblastoma tissue shows poorly differentiated cells with prominent basophilic nuclei. CD133 was approximately 1.5-fold overexpressed in the retinoblastoma tissue with respect to the normal tissue, while MUC1 and KRT19 are only slightly expressed. Multiple intense signals of each probe were localized in the same nuclear areas throughout the retinoblastoma tissue, with high background noise. Conclusion: These findings suggest that CD133 is a potential biomarker for the staging and diagnosis of retinoblastoma in Filipino cancer patients. However, further optimization of the hybridization procedures is recommended.

Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family.

Retinoblastoma is the most common eye cancer in children. It is caused by pathogenic alterations of both alleles of the tumor suppressor gene RB1. In heritable retinoblastoma, a constitutional RB1 variant predisposes the cells to tumor formation, and loss of the other allele is a prerequisite for the development of retinoblastoma. Heritable retinoblastoma is inherited in an autosomal dominant manner; however, the majority of cases are the result of a de novo pathogenic RB1 variant. Penetrance is usually high (>90%), but with marked inter-familial variability. In some families, penetrance is incomplete and family members who develop tumors tend to remain unilaterally affected. Moreover, some families with low penetrance also show a parent-of-origin effect. We describe a patient with unilateral retinoblastoma caused by a previously unreported likely pathogenic RB1 variant (c.1199T>C) that disrupts a highly conserved amino acid residue within the A-box functional domain. Segregation analysis showed that the variant had unusually low penetrance as nine non-affected family members carried the same variant. We emphasize the use of genetic analysis on tumor DNA for classifying the RB1 variant, and underline the challenges in clinical management and counseling of families carrying the specific RB1 variant.

Single cell transcriptomics reveals early photoreceptor states, cell-specific transcript isoforms, and cancer-predisposing features.

Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin. Here, we used deep full-length single-cell RNA-sequencing to distinguish post-mitotic cone and rod developmental states and cone-specific features that contribute to retinoblastomagenesis. The analyses revealed early post-mitotic cone- and rod-directed populations characterized by higher THRB or NRL regulon activities, an immature photoreceptor precursor population with concurrent cone and rod gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Unexpectedly, both L/M cone and rod precursors co-expressed NRL and THRB RNAs, yet they differentially expressed functionally antagonistic NRL isoforms and prematurely terminated THRB transcripts. Early L/M cone precursors exhibited successive expression of lncRNAs along with MYCN, which composed the seventh most L/M-cone-specific regulon, and SYK, which contributed to the early cone precursors' proliferative response to RB1 loss. These findings reveal previously unrecognized photoreceptor precursor states and a role for early cone-precursor-intrinsic SYK expression in retinoblastoma initiation.

Bmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP.

Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

Molecular Biological Research on the Pathogenic Mechanism of Retinoblastoma.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature.

Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.

Ciliary Madarosis Secondary to Intra-Arterial Chemotherapy for Retinoblastoma Treatment.

Background: Retinoblastoma is the most common intraocular tumor in the pediatric population. Its main therapeutic objectives are to avoid fatal outcomes and preserve vision as much as possible. Intra-arterial chemotherapy (IAC) improves drug delivery and reduces possible systemic adverse effects. This modality allows direct administration of chemotherapeutic agents to intraocular malignancies via the ophthalmic artery (OA), proving to be a feasible and effective method for globe salvage. Most side effects of IAC are local, including eyelash loss of the nasal portion of the eyelid. Summary: We performed a comprehensive review to analyze data regarding ciliary madarosis in patients diagnosed with retinoblastoma treated with IAC. We describe 9 studies with a total of 637 eyes with retinoblastoma that underwent IAC, of which 45 cases presented madarosis. In chemotherapy-induced alopecia, there is hair shaft thinning and breakage. On trichoscopy, the remaining end of the fractured hair will be observed as black dots. Differential diagnoses must include alopecia areata and trichotillomania. Key Messages: Ciliary madarosis secondary to IAC, although transitional, may cause discomfort in patients and family members. Physical examination, as well as a trichoscopic evaluation of the affected area, can help in reaching a prompt diagnosis and prognosis for this particular alopecia.

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 data though on demographics, clinical profile, treatment options, and outcomes in the country are from the National Capital Region. Objectives: This study aimed to describe the demographics, clinical profile, treatment done, and outcomes of retinoblastoma 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<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.

ALYREF/THOC4 expression and cell growth modulation in retinoblastoma.

In this study, we tested the hypothesis that ALYREF/THOC4, a poor prognostic factor in different cancer types, has potential as a drug target and prognostic biomarker for retinoblastoma (RB). Immunostaining (IHC), Western blot, and RT-qPCR analyses detected overexpression of ALYREF in the RB cell lines Y79, RB143, WERI-RB1, and RB116. IHC analysis on RB tumor array showed that 11/14 of RB tumors were ALYREF+ to varying degrees, with eight tumors at maximum 3+ intensity. The IHC analysis also detected ALYREF+ cells in normal retina, mainly in the inner nuclear and ganglion cell layer, while some tumor-bearing human eyes were ALYREF+ in the optic nerve suggesting a role in optic invasion/tumor invasion. The expression of ALYREF within the tumor itself, in the optic nerve, as well as in adjacent "normal" retina, suggest that this pattern of expression may lead to ALYREF being a potentially useful prognostic indicator for RB, as it is for other tumors. siRNA knockdown of ALYREF resulted in a 40 % decrease in cell growth in both WERI-RB1 and Y79 cells (p<0.05) and this was associated with decreased expression of mRNAs for the cell proliferation markers Ki67 and PCNA (p<0.005). These results suggest a role for ALYREF in RB cell growth regulation and its potential as both a target and a biomarker for tumor growth inhibition by anti-cancer therapies.

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.

Personalized treatment approaches in intraocular cancer.

Background: Intraocular malignant tumors represent a severe disease that threatens vision as well as life. To better extend the life of the patient, preserve visual function, and maintain ocular aesthetics, selecting the appropriate timing and methods of treatment becomes crucial. Main text: With the continuous advancement of medical technology, the techniques and methods for treating intraocular malignant tumors are constantly evolving. While surgery was once considered the optimal method to prolong patient survival and prevent local recurrence, the discovery and application of various treatments such as radiotherapy, laser therapy, chemotherapy, cryotherapy, and monoclonal antibodies have led to a greater diversity of treatment options. This diversity offers more possibilities to develop personalized treatment plans, and thereby maximize patient benefit. This article reviews the various treatment methods for intraocular malignant tumors, including indications for treatment, outcomes, and potential complications. Conclusions: Differentiating small intraocular malignant tumors from pigmented lesions is challenging, and ongoing monitoring with regular follow-up is required. Small to medium-sized tumors can be treated with radiotherapy combined with transpupillary thermotherapy. Depending on the tumor's distance from the optic disc, surgery with partial resection may be considered for distant tumors, while proximal tumors may require complete enucleation. Systemic chemotherapy has been widely applied to patients with retinal tumors, lymphomas, and intraocular metastatic cancers, but has limited efficacy in patients with choroidal melanoma. Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) drugs can improve patient vision and quality of life, while the efficacy of immunotherapy and molecular targeted therapy is still under research.

Focused cancer pathway analysis revealed unique therapeutic targets in retinoblastoma.

Retinoblastoma (RB) is a pediatric cancer of the eye that occurs in 1/15000 live births worldwide. Albeit RB is initiated by the inactivation of RB1 gene, the disease progression relies largely on transcriptional alterations. Therefore, evaluating gene expression is vital to unveil the therapeutic targets in RB management. In this study, we employed an RT2 Profiler™ PCR array for a focused analysis of 84 cancer-specific genes in RB. An interaction network was built with gene expression data to identify the dysregulated pathways in RB. The key transcript alterations identified in 13 tumors by RT2 Profiler™ PCR array was further validated in 15 tumors by independent RT-qPCR. Out of 84 cancer-specific genes, 68 were dysregulated in RB tumors. Among the 68 genes, 23 were chosen for further analysis based on statistical significance and abundance across multiple tumors. Pathway analysis of altered genes showed the frequent perturbations of cell cycle, angiogenesis and apoptotic pathways in RB. Notably, upregulation of MCM2, MKI67, PGF, WEE1, CDC20 and downregulation of COX5A were found in all the tumors. Western blot confirmed the dysregulation of identified targets at protein levels as well. These alterations were more prominent in invasive RB, correlating with the disease pathogenesis. Our molecular analysis thus identified the potential therapeutic targets for improving retinoblastoma treatment. We also suggest that PCR array can be used as a tool for rapid and cost-effective gene expression analysis.

Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma.

OBJECTIVE: Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in the RB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavity or in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predicted early, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumors separately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separating miRNAs in blood serum from invasive and non-invasive RB patients. MATERIALS AND METHODS: In this experimental study, selected three gene expression omnibus (GEO) datasets. Two were related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression. Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidate miRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma. RESULTS: Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373, and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. Only MiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomas increased serum miR-20a and miR-191. CONCLUSION: Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma.

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Evidence in Focus: The Sparse Landscape of Randomized Trials on Retinoblastoma Treatment.

Background: Retinoblastoma, although rare, is one of the most common intraocular malignancies worldwide. Its prognosis has improved significantly in the past few decades, thanks to modern treatments, like systemic, intra-arterial, and intravitreal chemotherapy. However, regarding survival, there are significant differences between high- and low-income countries, eye salvage is still a challenge worldwide, and treatment-related toxicity needs to be carefully and sufficiently managed. Summary: To appraise the strength of supporting evidence, we performed a systematic review of randomized controlled trials investigating any therapeutic protocol for retinoblastoma. Four trials with 174 participants (188 eyes) were eligible, all pertaining to different intravenous chemotherapy regimens. Vincristine, etoposide, and carboplatin (VEC) appear superior to a 5-drug combination for stage III retinoblastoma. Moreover, etoposide and carboplatin as neoadjuvant chemotherapy followed by thermochemotherapy seem to offer better local control than vincristine and carboplatin. However, increasing carboplatin dose in the VEC protocol failed to improve treatment efficacy. Key Messages: Retinoblastoma is a success story of modern medicine. However, only intravenous chemotherapy has been studied through randomized trials, while evidence for the most novel retinoblastoma treatments has mainly stemmed from observational studies. International collaborations for multicenter randomized trials could overcome difficulties and increase certainty and precision in the field.

Optimizing Surgical Management for Rhegmatogenous Retinal Detachment in Eyes with Active Retinoblastoma: A Safety-Driven Approach.

Introduction: Intraocular surgeries are conventionally contraindicated for patients with active retinoblastoma (Rb) due to the potential risk of tumor dissemination. However, surgery is occasionally necessary to preserve vision in patients with a single eye when the eye is complicated by rhegmatogenous retinal detachment (RRD). Objective: This study aims to evaluate the outcomes of surgical repair for RRD in pediatric patients with active Rb utilizing a non-drainage scleral buckling approach. Results: This cohort included six eyes from six patients who harbored active Rb and presented with RRD; one had a concurrent tractional component. All eyes (100%) had active intraocular Rb and were undergoing active therapy (systemic chemotherapy, cryotherapy, and thermal laser therapy) when RRD developed. RRD consistently manifested at the site of recent cryotherapy in all cases. RRD repair in the affected eyes was performed by scleral buckling without subretinal fluid drainage. Five of the six eyes (83%) achieved complete retinal reattachment. One eye (17%) with a tractional component exhibited partial reattachment and was eventually enucleated due to persistent active disease. At a median follow-up of 15 months (range 12-180 months) after scleral buckling, all five eyes had persistent retinal attachment, and no case developed orbital or distant metastasis. Conclusions: Our study demonstrates that nondrainage scleral buckling is an effective and safe method for the surgical repair of RRD in eyes harboring active Rb, as most cases achieved persistent complete retinal reattachment without the risk of tumor spread.