Importance:Ocular surface malignancies pose risks to vision and survival yet are frequently misdiagnosed as benign lesions because of their subtle presentation and the lack of widely accessible screening tools, potentially resulting in treatment delays and the need for extensive surgical intervention. Objective:To develop and validate a smartphone-based, media-facilitated artificial intelligence (AI) system for proactive self-screening of ocular surface malignancies in the general population. Design, Setting, and Participants:A nonrandomized clinical trial was conducted across China from December 2022 to June 2023. A deep learning model was initially trained and validated using 12 years of multicenter slitlamp images. The system was then optimized for smartphone-based photography and deployed through a widely disseminated mobile application. Data analysis was performed from July 2023 to June 2024. Intervention:Participants used the CaptureTumor standardized smartphone application, incorporating real-time AI-guided photography instructions, to capture images of suspected lesions. The application provided immediate binary (benign vs malignant) and multiclass risk stratification and triaged high-risk cases for expedited clinical referral. Main Outcomes and Measures:The primary outcome was area under the receiver operating characteristic curve (AUC) for differentiating malignant from benign lesions. Secondary outcomes included sensitivity, specificity, and the number of histopathologically confirmed malignancies detected. Results:Multimedia outreach via television, social media, and internet hospitals reached 256 053 individuals, with 614 completing at-home self-screening through the app. Of these participants, the median (IQR) age was 46 (11) years (range, 4-87 years); 301 (49%) were female and 313 (51%) male. After optimizing the image quality, the smartphone-based CaptureTumor achieved an AUC of 0.905 (95% CI, 0.837-0.973), comparable with the performance of the slitlamp-based model (AUC = 0.945; 95% CI, 0.918-0.972). During real-world screening, 20 malignancies were pathologically confirmed among the 614 participants, with 19 of 20 participants (95%) newly diagnosed, and no cases requiring enucleation. At the population level, CaptureTumor demonstrated an AUC of 0.977 (95% CI, 0.964-0.990), a sensitivity of 89.3% (95% CI, 86.7%-91.9%), and a specificity of 95.9% (95% CI, 94.2%-97.6%). Conclusions and Relevance:This trial found that the integration of smartphone-enabled imaging, AI-driven diagnostics, and targeted media outreach established a scalable, accessible, and potentially clinically effective strategy for population-level screening of rare ocular malignancies. This closed-loop mobile health model potentially addresses gaps in early detection and equitable care delivery for vision- and life-threatening rare diseases. Trial Registration:ClinicalTrials.gov Identifier: NCT05645341.

This nonrandomized clinical trial reports data from developing and validating a smartphone-based, media-facilitated artificial intelligence system for self-screening for ocular surface malignancies in the general population. QuestionCan a smartphone-based artificial intelligence system integrated with mass media outreach enable large-scale screening for rare ocular surface malignancies in the general population?FindingsIn this nonrandomized clinical trial, the smartphone-optimized CaptureTumor application achieved diagnostic accuracy comparable with that of specialist-graded slitlamp evaluation. This application demonstrated accuracy for malignancy detection and identified cases with 5-fold greater efficiency than conventional hospital-based referral pathways.MeaningThese findings suggest that combining smartphone photography, artificial intelligence, and media-facilitated public engagement can establish a scalable and accessible model for population screening of rare sight and life-threatening ocular tumors, advancing early detection and health equity for underrecognized conditions. ImportanceOcular surface malignancies pose risks to vision and survival yet are frequently misdiagnosed as benign lesions because of their subtle presentation and the lack of widely accessible screening tools, potentially resulting in treatment delays and the need for extensive surgical intervention.ObjectiveTo develop and validate a smartphone-based, media-facilitated artificial intelligence (AI) system for proactive self-screening of ocular surface malignancies in the general population.Design, Setting, and ParticipantsA nonrandomized clinical trial was conducted across China from December 2022 to June 2023. A deep learning model was initially trained and validated using 12 years of multicenter slitlamp images. The system was then optimized for smartphone-based photography and deployed through a widely disseminated mobile application. Data analysis was performed from July 2023 to June 2024.InterventionParticipants used the CaptureTumor standardized smartphone application, incorporating real-time AI-guided photography instructions, to capture images of suspected lesions. The application provided immediate binary (benign vs malignant) and multiclass risk stratification and triaged high-risk cases for expedited clinical referral.Main Outcomes and MeasuresThe primary outcome was area under the receiver operating characteristic curve (AUC) for differentiating malignant from benign lesions. Secondary outcomes included sensitivity, specificity, and the number of histopathologically confirmed malignancies detected.ResultsMultimedia outreach via television, social media, and internet hospitals reached 256 053 individuals, with 614 completing at-home self-screening through the app. Of these participants, the median (IQR) age was 46 (11) years (range, 4-87 years); 301 (49%) were female and 313 (51%) male. After optimizing the image quality, the smartphone-based CaptureTumor achieved an AUC of 0.905 (95% CI, 0.837-0.973), comparable with the performance of the slitlamp-based model (AUC = 0.945; 95% CI, 0.918-0.972). During real-world screening, 20 malignancies were pathologically confirmed among the 614 participants, with 19 of 20 participants (95%) newly diagnosed, and no cases requiring enucleation. At the population level, CaptureTumor demonstrated an AUC of 0.977 (95% CI, 0.964-0.990), a sensitivity of 89.3% (95% CI, 86.7%-91.9%), and a specificity of 95.9% (95% CI, 94.2%-97.6%).Conclusions and RelevanceThis trial found that the integration of smartphone-enabled imaging, AI-driven diagnostics, and targeted media outreach established a scalable, accessible, and potentially clinically effective strategy for population-level screening of rare ocular malignancies. This closed-loop mobile health model potentially addresses gaps in early detection and equitable care delivery for vision- and life-threatening rare diseases.Trial RegistrationClinicalTrials.gov Identifier: NCT05645341

BACKGROUND:Graves' orbitopathy (GO) is an autoimmune disorder characterized by orbital inflammation, fibrosis, and adipogenesis. circulating exosomesomes, critical mediators of intercellular communication, are implicated in autoimmune pathologies through miRNA cargo delivery. However, their direct role in GO pathogenesis and mechanisms driving systemic-to-local disease progression remain unexplored. METHODS:Plasma-derived exosomes from patients with Graves' orbitopathy (GO-Exos) and healthy controls (Con-Exos) were isolated and characterized. Functional assays assessed their impact on primary human orbital fibroblasts (OFs). A GO model was established via weekly intravenous administration of GO-Exos. Disease progression was evaluated through thyroid function tests, histopathology, MRI, and single-cell RNA sequencing. Mechanistic studies focused on miR-221-5p and its downstream CACNG4/AMPK pathway. RESULTS:In vitro, GO-Exos reprogrammed OFs into proinflammatory, profibrotic, and adipogenic phenotypes, while upregulating disease-associated receptors IGF-1R and TSHR, suggesting a feedforward mechanism for sustained autoimmunity. Strikingly, stable-phase GO-Exos retained bioactivity, inducing comparable cytokine elevations in control OFs. In vivo, weekly intravenous administration of GO-Exos in BALB/c mice over 150 days recapitulated human disease hallmarks, including thyroid dysfunction, exophthalmos, orbital adipose hyperplasia, and collagen deposition, validated by histopathology and MRI. Mechanistically, miR-221-5p was identified as a key driver of orbital remodeling via suppression of CACNG4/AMPK. Partial rescue of pathogenic phenotypes by miR-221-5p inhibition confirmed its functional centrality. Single-cell RNA sequencing revealed exosome-mediated cellular reprogramming, including TREM2+ macrophage enrichment and CD8+ T cell infiltration. CONCLUSION:Our findings establish circulating exosomesomes as novel pathogenic drivers in GO and provide a foundational resource for understanding exosome-mediated immunopathogenesis in autoimmune orbitopathies.

Recent advances in the surgical management of restrictive strabismus caused by thyroid-associated orbitopathy (TAO) demonstrate a clear trend toward precision and individualization. This review synthesizes current literature, highlighting innovations in preoperative evaluation, surgical techniques, and outcome assessment over the past decade. Preoperative assessment has evolved from clinical observation alone to a comprehensive model incorporating serological markers and high-resolution imaging, significantly improving the accuracy of surgical timing decisions. Surgical techniques have been refined to address a range of complex scenarios, enhancing predictability, success rates while reducing reoperation rates. Outcome measures now prioritize functional vision and patient-reported outcomes alongside ocular alignment. Furthermore, emerging therapies, including biologics, offer novel non-surgical options for active-phase disease management and perioperative care. Based on the evidence synthesized herein, the field is moving toward a more personalized approach; however, high-level prospective trials evaluating surgical strategies remain limited. Surgeons are encouraged to base decisions on comprehensive assessments to optimize functional and quality-of-life outcomes. Future directions may involve the integrating evolving biologic therapies with advanced data analytics, an approach that holds promise for further personalization.

OBJECTIVE:To analyze the pathological composition ratio of orbital space-occupying lesions in a large single-center cohort and to assess differences across age groups and decades. DESIGN:A retrospective observational study. PARTICIPANTS:A total of 7 515 patients with histopathologically confirmed orbital space-occupying lesions who underwent surgical excision at Zhongshan Ophthalmic Center from January 2000 to March 2021. METHODS:Demographic and histopathological data were reviewed. Lesions were classified by biological behavior (benign/borderline vs malignant), tissue origin, and age group (0-14, 15-59, and ≥60 years). Temporal trends were compared between 2000-2009 and 2010-2021. RESULTS:Among 7 515 patients, 3 717 (49.5%) were male. Benign or borderline lesions comprised 78.0%, and malignant lesions comprised 22.0%, with mean ages of 36 and 49 years, respectively (p < 0.05). The leading histopathologic types were vasculogenic (22.3%), lymphoproliferative (16.4%), inflammatory (16.0%), and cystic (11.9%) lesions. Idiopathic orbital inflammatory pseudotumour was the most common benign entity, and mucosa-associated lymphoid tissue (MALT) lymphoma was the most frequent malignancy. Malignancy increases with age, reaching 43.6% in the elderly. Over 2 decades, vasculogenic lesions declined, while lymphoproliferative and malignant lesions rose. CONCLUSIONS:The pathological spectrum of orbital space-occupying lesions in southern China is dominated by inflammatory and vascular lesions in younger patients and by lymphoproliferative malignancies in the elderly. Over the past two decades, vascular lesions have decreased, whereas lymphoproliferative and malignant lesions have become more prevalent, reflecting demographic aging and advances in diagnostic pathology. These findings provide updated epidemiologic evidence to guide the differential diagnosis and management of orbital tumours.

BACKGROUND:Thyroid eye disease (TED) is characterized by orbital inflammation and fibrosis, with a hypoxic microenvironment implicated in disease pathogenesis. OBJECTIVE:To determine whether hypoxia-inducible factor-1α (HIF-1α) mediates hypoxia-induced inflammation and fibrosis in TED, and whether the HIF-1α inhibitor digoxin suppresses these processes. METHODS:Serum HIF-1α was measured by ELISA in TED patients (n = 12) and healthy controls (n = 7). Primary orbital fibroblasts (OFs) from TED patients were transduced with lentiviral HIF-1α or exposed to hypoxia (1% O2). Inflammatory and fibrotic markers were assessed by qRT-PCR, western blotting, and ELISA. STAT3 phosphorylation and GSDME-mediated pyroptosis were examined. Digoxin (1.5-6 nM) was tested for its ability to reverse HIF-1α-induced changes. RESULTS:Serum HIF-1α was significantly elevated in TED patients. HIF-1α overexpression recapitulated hypoxia-induced effects, upregulating IL-6, IL-8, CCL2, CCL8, CXCL1, CXCL2, IL-1β, TIMP1, α-SMA, and COL1A1, increasing STAT3 phosphorylation and activating GSDME-mediated pyroptosis. Digoxin dose-dependently suppressed HIF-1α-driven inflammatory and fibrotic responses, reduced STAT3 phosphorylation, and attenuated cleaved caspase-3 and GSDME-NT expression. CONCLUSIONS:HIF-1α is a critical downstream mediator of hypoxia-induced inflammation and fibrosis in TED, acting through STAT3 and GSDME-mediated pyroptosis. Pharmacological inhibition of HIF-1α by digoxin reverses these changes, positioning digoxin as a promising therapeutic candidate for TED.

Objective Surgical outcomes for the orbital-cavernous sinus schwannomas are limited. Therefore, the current study aims to present and evaluated surgical strategies and clinical outcomes in orbital-cavernous sinus schwannomas in our center. Methods A retrospective analysis was conducted in patients with orbital-cavernous sinus schwannomas who underwent surgery via the pterional approach combined with orbital osteotomy at our center between January 2016 and December 2024. Clinical data, extent of resection, postoperative neurological function and surgical complications were evaluated. Results A total of 32 patients were included in the current study. Gross total resection was achieved in 28 cases (87.50%) and subtotal resection was achieved in 4 cases (12.50%). After surgery, visual acuity was improved in 6 patients (18.75%), remained unchanged in 24 patients (75.00%), and worsened in 2 patients (6.25%). Proptosis improved in 32 patients (100%). Ptosis occurred in 11 patients, with 9 patients fully recovered during the follow-up and the remaining 2 patients experienced partial recovery. 2 patients experienced impaired ocular abduction, and were recovered within 3 months post-surgery. Conclusion Surgical intervention plays an important role in the treatment of orbital-cavernous sinus schwannomas. The pterional approach combined with orbital osteotomy achieved high resection rate, symptom relief, and a low incidence of complications.

·Nonspecific orbital inflammation(NSOI)is an orbital inflammation that is not associated with an infection.Even though it's often considered the most common diagnosis in orbital biopsies,it's still an exclusionary diagnosis that means systemic illnesses and other possible causes have to be ruled out.Though it is always an excluded clinical diagnosis,acute orbital symptoms such discomfort,exophthalmos,periorbital edema,chemosis,diplopia,and vision impairment are commonly associated with NSOI.Clinical diagnosis and management of NSOI provide a substantial difficulty.There are presently no recognized diagnostic criteria or standard treatment strategy for NSOI,and the clinical symptoms and histological features show significant variation.This guide was formulated under the auspices of the Ocular Oncology Committee of the Opthalmology Branch of the Chinese Medical Doctor Association,Opthalmology Committee of International Association of Intelligent Medicine,Opthalmology Committee of International Association of Translational Medicine making a detailed summary of the definition,classification,diagnosis and treatment of the NSOI,with a view to aiding clinicians to improve diagnostic efficiency and formulate a better treatment plan for patients.

To explore the clinicopathological characteristics and prognosis of orbital alveolar soft part sarcoma (ASPS), providing a basis for its diagnosis and treatment. Patients diagnosed with primary orbital ASPS at the Zhongshan Ophthalmic Center of Sun Yat-sen University from 2014 to 2024 were included. A retrospective analysis of clinical data, imaging findings, pathological features, immunohistochemistry results, etc., was conducted. Follow-up data were also analyzed. A total of 7 patients (7 eyes) were included in the study, consisting of 4 males and 3 females, aged between 2 and 47 years (median age 27 years), with follow-up period range from 16 to 201 months. Orbital protrusion was the most common presenting symptom (5/7), with one case involving invasion of the paranasal sinuses. During follow-up, all patients survived, and two patients experienced recurrence, all localized to the orbit. Recurrence was more common in younger patients, with an average recurrence time of 10 months post-surgery. High Ki67 expression was significantly associated with local recurrence (P = 0.047). Primary orbital ASPS generally exhibits indolent biological behavior, and complete surgical excision can lead to long-term control. However, patients with high Ki67 expression should be closely monitored due to the higher risk of recurrence.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease characterized by inflammation and tissue remodeling, with fibrosis being a predominant and often irreversible feature in type II TAO. While immunosuppressive therapies offer limited efficacy, there remains a critical need to identify effective molecular targets for fibrotic TAO. Circular RNAs (circRNAs) have emerged as key regulators in various diseases, yet their roles in TAO are largely unexplored. In this study, we identified hsa_circ_0007006 as significantly downregulated in fibrotic TAO tissues through high-throughput RNA sequencing. Functional assays in orbital fibroblasts revealed that circ-0007006 suppresses fibrosis by downregulating COL1A1, α-SMA, HAS1, and HAS2, and inhibiting SMAD2/3 phosphorylation. Mechanistically, circ-0007006 functions as a competing endogenous RNA for miR-383-3p, thereby stabilizing HBEGF expression. Rescue experiments showed that exogenous HBEGF alleviates the pro-fibrotic effects induced by circ-0007006 knockdown. These findings identify the circ-0007006/miR-383-3p/HBEGF axis as a novel regulatory pathway in TAO fibrosis and support circ-0007006 as a potential therapeutic target for the fibrotic subtype of TAO.

Purpose:To evaluate the role of transglutaminase 2 (TGM2) in fibroblasts of Graves' orbitopathy (GO) and explore its potential mechanisms in orbital fibrosis. Methods:A key gene selection model for GO was established through bioinformatics and machine learning. Orbital fibroblasts (OFs) were cultured from orbital connective tissue samples. Subsequently, three-dimensional spheroid models were developed. Lentiviral transduction was used to establish TGM2 overexpression and knockdown models. Fibrosis levels were assessed using Western blot, PCR, and collagen contraction assays. TGM2 activity was evaluated by FITC-cadaverine staining and the colorimetric assay. The canonical and truncated TGM2 isoforms were selectively introduced to restore expression. TGF-β1 levels in cell culture supernatants were measured by ELISA. Results:The results of bioinformatics and machine learning indicate that TGM2 is a key characteristic gene in GO. Knockdown of TGM2 markedly suppresses the expression of fibrosis-related genes and reduces the proliferation, migration, and adhesion capabilities of fibroblasts. TGF-β1 can upregulate TGM2 expression and induces the production of both the canonical and truncated TGM2 forms. Similar results were observed in GO tissues. Restoration of TGM2_V2 expression following knockdown can prevent the inhibitory effects on guanosine triphosphate (GTP). Additionally, TGM2 is involved in the autocrine loop of TGF-β1. TGM2 inhibitors significantly reverse the fibrotic response induced by TGF-β1 in OFs. Conclusions:TGM2 is highly expressed in GO fibroblasts and plays a key role in the TGF-β1 autocrine feedback loop. TGF-β1 induces more truncated TGM2 variants that bypass GTP inhibition, exacerbating fibrosis. Inhibiting TGM2 activity significantly reduces fibrosis markers.

Objectives:To characterize tear cytokine profiles in patients with idiopathic orbital inflammation (IOI) and analyze the expression of altered cytokines in blood and involved tissues. Methods:This case-control study enrolled 18 IOI patients and 11 age-/sex-matched controls. Ocular Surface Disease Index (OSDI), corneal fluorescent staining, tear film breakup time (TBUT), Schirmer I test, and other clinical and laboratory parameters were obtained from all participants. Concentrations of cytokines in tear fluid, blood, and tissues were determined using a multiplex bead immunoassay system, enzyme-linked immunosorbent assay, and immunohistochemistry. Results:Significantly elevated levels of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 (both p < 0.05) were found in IOI tear fluid. The area under receiver operating characteristic curve was 0.73 and 0.74 for IL-8 and MCP-1, respectively. IL-8 and MCP-1 were overexpressed in orbital tissues from patients with IOI, while the plasma levels of IL-8 and MCP-1 in the IOI group were parallel to the control group. Conclusions:The dysregulation of tear cytokine profiles provides a new insight into the potential immunologic mechanism for IOI. The elevated IL-8 and MCP-1 may represent candidate biomarkers of IOI.

Abstract Purpose Myeloid sarcoma (MS) is a rare extramedullary tumor of myeloid origin, often underdiagnosed or misdiagnosed, particularly in children. This study aims to evaluate the clinicopathological features, immunophenotypes, therapeutic approaches, and prognosis to enhance patient management. Methods This retrospective, single-center case series examined 14 patients diagnosed with myeloid sarcoma through pathological analysis. Results The median age at diagnosis was 7 years, with a male-to-female ratio of 8:6. The median disease duration at diagnosis was 1 month, and all patients had unilateral eye involvement. The most common presentation was proptosis, followed by restricted eye movement and eyelid swelling. Immunohistochemical analysis revealed that MPO (myeloperoxidase) and lysozyme were the most frequently expressed markers, followed by CD56, α1-antitrypsin (AACT), and CD34. Eleven patients were treated with chemotherapy according to the acute myeloid leukemia (AML) regimen. The median follow-up time for these patients was 13 months. No relapses occurred; one patient died, and three were lost to follow-up. The Kaplan–Meier survival analysis estimated a 5-year overall survival (OS) and event-free survival (EFS) rate of 87.5%. Conclusion Diagnosing myeloid sarcoma (MS) is often challenging. An adequate tumor biopsy and comprehensive immunohistochemical analysis are essential for an accurate diagnosis. Early and consistent systemic chemotherapy can result in long-term survival.

Purpose:This study aimed to investigate the characteristics and molecular mechanisms of orbital fibroblasts under three-dimensional (3D)-culture conditions. Methods:Orbital connective tissue was collected from patients with thyroid eye disease (TED) and normal controls. Primary fibroblasts were cultured and used to generate 3D microspheres via the hanging drop. These spheroids were cultured for nine days, followed by biomechanical testing, transmission electron microscopy (TEM), and RNA sequencing for transcriptomic analysis. Multiplex immunofluorescence staining was used to assess fibrosis markers, and quantitative PCR validated gene expression changes. TED and normal control (NC) tissues, as well as primary cultured fibroblasts, were also subjected to transcriptomic sequencing. Results:TED-3D microspheres exhibited enhanced contractility, denser fiber deposition, and a characteristic fibrous ring at the periphery. TEM revealed more extracellular matrix (ECM) deposition and stronger tissue remodeling in TED-3D. Fibrosis markers (α-SMA, COL1A1, FN1) increased significantly in TED-3D. Biomechanical testing showed higher stiffness in TED-3D compared to NC-3D. Transcriptomic analysis revealed significant differences, with genes involved in ECM remodeling and fibrosis pathways enriched in TED-3D. Transcriptomic comparison of TED-tissue, TED-2D, and TED-3D revealed that TED-3D is closer to tissue than TED-2D. Conclusions:The 3D culture of orbital fibroblasts from TED induces in vivo-like tissue remodeling and fibrosis features. Compared to traditional two-dimensional culture, the expression pattern of TED-3D is closer to tissue, making it a more effective model for studying the mechanisms of TED-related fibrosis.

Background and Objectives:Opioid-minimizing strategies are making their appearance in enhanced recovery after surgery. This study is aimed to explore the potential advantages of opioid-free analgesia (OFA) compared to opioid-sparing analgesia (OSA) in patients undergoing orbital fracture reconstruction. Methods:In this prospective, single-center, randomized controlled study, we randomly recruited 122 patients undergoing orbital fracture reconstruction under general anesthesia. Patients received total intravenous anesthesia with a flexible laryngeal mask airway, and multimodal analgesia with either OSA or OFA methods. The OSA group (n = 61) received low doses of fentanyl and nonsteroidal anti-inflammatory drugs (NSAIDs), and the OFA group (n = 61) received medial canthus peribulbar block (MCPB) combined with NSAIDs. The primary outcomes consisted of area-under-the-curve (AUC) of the numerical rating scale (NRS) pain score, and the incidence of postoperative nausea and vomiting (PONV) through the first 24h. Results:Compared to the OSA group, the OFA group demonstrated non-inferiority in postoperative analgesia through the first 24 postoperative hours (difference of the medians, -6; 95% confidence interval [CI], -12 to 6), but failed to meet the non-inferiority criterion in the incidence of PONV (difference ratio, 3%; 95% CI, -7% to 14%). The Quality of Recovery-40 questionnaire (QoR-40) scores on postoperative day 1 was significantly higher in group OFA compared to group OSA (188 [178 to 196] vs 181 [169 to 191], respectively; P = 0.005). Conclusion:In orbital fracture reconstruction, both OFA and OSA strategies provide effective postoperative pain relief, but OFA using MCPB combined NSAIDs enhances the quality of early postoperative recovery. Registered:Chinese Clinical Trial Registry ChiCTR1900028088.

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.

BACKGROUND:Only 2% to 6% aneurysmal bone cyst (ABC) involve the cranial region, and even fewer show sphenoid and orbital involvement. The spheno-orbital ABC is prone to misdiagnosis and can result in intraoperative bleeding and residual lesions. The study was to summarize the clinical and therapeutic characteristics of patients with spheno-orbital ABC in children. METHODS:We retrospectively analyzed three childhood-onset spheno-orbital ABC cases at our hospital. A literature review was conducted and the spheno-orbital ABC cases were retrieved. The characteristics of clinical manifestations, treatment outcomes, and follow-ups were analyzed. RESULTS:All three cases involved the sphenoid and orbital bones, and had a history of surgery or biopsy before being transferred to our hospital. Two of them were terminated due to severe bleeding. The surgeries were performed through frontotemporal craniotomy, where the masses and the surrounding suspected diseased bones were removed. The pathological diagnosis was ABC. All the patient's eye symptoms improved. A review of the literature reveals that ABC typically presents as bone destruction, with some lesions containing fluid levels. Tumors that significantly enhance on contrast-enhanced magnetic resonance imaging are often misdiagnosed. ABC is more prevalent in children. The ABC can lead to excessive intraoperative bleeding and residual lesions. Gross total resection is the treatment of choice. CONCLUSIONS:Spheno-orbital ABC should avoid transorbital approach in favor of craniotomy. It is imperative to remove as much of the affected bone as possible and to intensify subsequent monitoring. It is essential to prepare blood prior to surgery to manage potential severe bleeding.