[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.

FACTORS ASSOCIATED WITH DELAYED DIAGNOSIS IN PATIENTS WITH PRIMARY VITREORETINAL LYMPHOMA.

PURPOSE: To identify demographic and clinical factors associated with delayed diagnosis in patients with primary vitreoretinal lymphoma (VRL). METHODS: Retrospective, tertiary referral center-based cohort study of all patients at Mayo Clinic in Rochester, Minnesota, with a biopsy-proven diagnosis of VRL from January 1, 2000, to October 31, 2022. RESULTS: There were 87 patients included during the 22-year study period with 73 patients (83.9%) diagnosed with VRL upon initial evaluation at the tertiary center, with the other 14 patients (16.1%) diagnosed later. The median referral time was 4.8 months (range: 0-113 months). Patients who received an initial diagnosis of inflammatory uveitis or another incorrect diagnosis elsewhere were referred slower than those initially diagnosed with VRL (P = 0.04). The most common incorrect initial diagnosis from an outside institution was inflammatory uveitis (n = 35, 40.2%). When patients were split into four groups based on referral time, prior use of corticosteroids was associated with a significant delay in referral (P = 0.03). CONCLUSION: Diagnosing VRL continues to be challenging, as months-long delays from initial evaluation to expert referral center evaluation are common. Prior use of corticosteroids was associated with delay in diagnosis and referral time, underscoring the need to increase awareness regarding differences between VRL and uveitis.

INTEREST OF REGULAR ASSAYS OF AQUEOUS HUMOR INTERLEUKIN-10 LEVELS IN MONITORING OF VITREORETINAL LYMPHOMA.

PURPOSE: To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse. METHODS: This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group. RESULTS: A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months. CONCLUSION: The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

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.

PRMT1 mediates the proliferation of Y79 retinoblastoma cells by regulating the p53/p21/CDC2/cyclin B pathway.

Retinoblastoma (RB) is the most common intraocular malignancy among children and presents a certain mortality risk, especially in low- and middle-income countries. Clarifying the molecular mechanisms underlying the onset and progression of retinoblastoma is vital for devising effective cancer treatment approaches. PRMT1, a major type I PRMT, plays significant roles in cancer development. However, its expression and role in retinoblastoma are still unclear. Our research revealed a marked increase in PRMT1 levels in both retinoblastoma tissues and Y79 cells. The overexpression of PRMT1 in Y79 cells promoted their growth and cell cycle progression. Conversely, the suppression of PRMT1 hindered the growth of Y79 cells and impeded cell cycle progression. Mechanistically, PRMT1 mediated the growth of Y79 retinoblastoma cells by targeting the p53/p21/CDC2/Cyclin B pathway. Additionally, the ability of PRMT1 knockdown to suppress cell proliferation was also observed in vivo. Overall, PRMT1 could function as a potential target for therapeutic treatment in individuals with retinoblastoma.

Clinical characterization and long-term postoperative outcomes of retinoblastoma patients receiving enucleation and primary orbital implantation in early infancy: an observational study.

OBJECTIVES: To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0-6 months old). METHODS: The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. RESULTS: Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. CONCLUSIONS: The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

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.

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

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

Injectable Dendrimer Hydrogel Delivers Melphalan in Both Conjugated and Free Forms for Retinoblastoma.

We report the successful synthesis of an injectable dendrimer hydrogel (DH) carrying melphalan, a clinical drug for retinoblastoma treatment, in both conjugated and free forms. Polyamidoamine (PAMAM) dendrimer generation 5 (G5) is surface-modified with an acid-sensitive acetal-dibenzocyclooctyne linker and then undergoes azide-alkyne cycloaddition with melphalan-PEG-N3 conjugate to form G5-acetal-melphalan. During the DH gelation between G5-acetal-melphalan and PEG-diacrylate, free melphalan is added, resulting in a hydrogel (G5-acetal-melphalan-DH/melphalan) that carries the drug in both conjugated and free forms. Melphalan is slowly released from G5-acetal-melphalan-DH/melphalan, with the conjugated melphalan released more quickly at pH 5.3 due to acid-triggered acetal bond cleavage. The formulation's in vitro safety and efficacy were established on human corneal epithelia (HCE-2) and retinoblastoma cells (Y79). In an in vivo Y79 tumor xenograft model of retinoblastoma, intratumorally injected G5-melphalan-DH formulation prolonged tumor suppression. This injectable, multimodal, pH-responsive formulation shows promise for intravitreal injection to treat retinoblastoma.

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.

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.

EIF4A3-induced hsa_circ_0078136 inhibits the tumorigenesis of retinoblastoma via IL-17 signaling pathway.

PURPOSE: Retinoblastoma (RB) is one of the most common intraocular cancers, with the highest prevalence among infants and young children under the age five. Numerous findings across the literature illustrate the involvement and significance of circular RNAs (circRNAs) in human malignancies, including RB. The current investigation attempted to decipher the exact roles and underlying mechanisms of a novel circRNA, hsa_circ_0078136, in RB progression. METHODS: The hsa_circ_0078136 expression was evaluated in RB tumors and cell lines via qRT-PCR. The significance of hsa_circ_0078136 in RB was examined by performing CCK8 assay, transwell assays, western blotting of apoptotic and IL-17 signaling ligand molecules, and a subcutaneous xenograft tumor model. In addition, the interaction of circRNA and eukaryotic translation initiation factor 4A3 (EIF4A3) was determined with bioinformatics, western blot, and RIP assay. RESULTS: The hsa_circ_0078136 expression was reduced in RB tumor samples and cells. Additionally, its overexpression restricted the oncogenic properties of RB cells in vitro. Moreover, hsa_circ_0078136 overexpression lowered the protein levels of cytokine ligand molecules of IL-17 signaling pathway in RB cell lines. In vivo, hsa_circ_0078136 overexpression in subcutaneous tumor xenografts reduced tumor growth. We also observed that EIF4A3 binds to the downstream flanking sequence of hsa_circ_0078136 in the SHRPH pre-mRNA transcript, and EIF4A3 overexpression reduced hsa_circ_0078136 expression, suggesting that EIF4A3 inhibited hsa_circ_0078136 formation. CONCLUSIONS: Our results demonstrate that hsa_circ_0078136 is regulated by EIF4A3 and functions as a tumor suppressor via the IL-17 signaling pathway in RB.

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.

Clinical Case Review of Bilateral Retinal Metastasis.

Bilateral retinal metastasis is a rare disease that represents less than 1% of ocular metastases. Additionally, the prevalence of ocular metastases overall is only 5% to 10%. It is uncommonly found due to the absence of a lymphatic system in the eye. Ocular metastasis is spread hematogenously and the retina only receives 5% of blood flow, contributing to the rarity of this condition. Retinal metastasis has been reported to mimic symptoms of retinitis which include watery eye discharge, conjunctival injection and pain with ocular movement which leads to a harder diagnosis. Treatment options for retinal metastasis include systemic chemotherapy, intravitreal chemotherapy, and plaque radiotherapy. However, despite treatment, retinal metastasis often has a poor prognosis. This is a case of a 65-year-old woman with a history of breast carcinoma status post mastectomy who initially presented with metastatic infiltration of the lung and liver. However, she later developed an interesting case of retinal metastasis, which presented as symptoms of retinitis and indicated widespread dissemination of an unknown primary neoplasm.

Investigating druggable kinases for targeted therapy in retinoblastoma.

Retinoblastoma (RB) is a childhood retinal neoplasm and commonly treated with cytotoxic chemotherapeutic agents. However, these therapeutic approaches often lead to diverse adverse effects. A precise molecular therapy will alleviate these side effects and offer better treatment outcomes. Over the years, kinases have become potential drug targets in cancer therapy. Hence, we aimed to investigate genetic alterations of putative kinase drug targets in RB. Targeted exome sequencing was performed on 35 RB tumors with paired blood samples using a gene panel consisting of 29 FDA-approved kinase genes. Single nucleotide variants were analyzed for pathogenicity using an in-house pipeline and copy number variations (CNVs) were detected by a depth of coverage and CNVPanelizer. The correlation between genetic changes and clinicopathological features was assessed using GraphPad Prism. Three somatic mutations, two in ERBB4 and one in EGFR were identified. Two of these mutations (ERBB4 c.C3836A & EGFR c.A1196T) were not reported earlier. CNV analysis revealed recurrent gains of ALK, MAP2K2, SRC, STK11, and FGFR3 as well as frequent losses of ATM, PI3KCA and ERBB4. Notably, nonresponsive tumors had a higher incidence of amplifications in clinically actionable genes such as ALK. Moreover, ALK gain and ATM loss were strongly correlated with optic nerve head invasion. In conclusion, our study revealed genetic alterations of druggable kinases in RB, providing preliminary insights for the exploration of kinase-targeted therapy in RB.

Comprehensive identification of pathogenic variants in retinoblastoma by long- and short-read sequencing.

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. The causal variants in RB are mostly characterized by previously used short-read sequencing (SRS) analysis, which has technical limitations in identifying structural variants (SVs) and phasing information. Long-read sequencing (LRS) technology has advantages over SRS in detecting SVs, phased genetic variants, and methylation. In this study, we comprehensively characterized the genetic landscape of RB using combinatorial LRS and SRS of 16 RB tumors and 16 matched blood samples. We detected a total of 232 somatic SVs, with an average of 14.5 SVs per sample across the whole genome in our cohort. We identified 20 distinct pathogenic variants disrupting RB1 gene, including three novel small variants and five somatic SVs. We found more somatic SVs were detected from LRS than SRS (140 vs. 122) in RB samples with WGS data, particularly the insertions (18 vs. 1). Furthermore, our analysis shows that, with the exception of one sample who lacked the methylation data, all samples presented biallelic inactivation of RB1 in various forms, including two cases with the biallelic hypermethylated promoter and four cases with compound heterozygous mutations which were missing in SRS analysis. By inferring relative timing of somatic events, we reveal the genetic progression that RB1 disruption early and followed by copy number changes, including amplifications of Chr2p and deletions of Chr16q, during RB tumorigenesis. Altogether, we characterize the comprehensive genetic landscape of RB, providing novel insights into the genetic alterations and mechanisms contributing to RB initiation and development. Our work also establishes a framework to analyze genomic landscape of cancers based on LRS data.

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

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

Electroretinographic changes in the inner and outer retinal layers before and after intravenous chemotherapy for retinoblastoma.

PURPOSE: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). METHODS: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol - light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. RESULTS: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. CONCLUSION: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.