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Background Malpositioned orbital implants are an underappreciated source of significant postoperative morbidity, often necessitating revision surgery. Decision-making regarding practical frameworks to guide revision remains challenging and is not well standardized or characterized. Objective To analyze clinical presentations, radiographic failure patterns, multidisciplinary surgical strategies, and outcomes of patients undergoing revision surgery for malpositioned orbital implants. Methods A single-center retrospective consecutive case series was conducted of patients who underwent removal or replacement of malpositioned orbital implants. Patient demographics, presenting symptoms, radiographic findings, surgical approaches, implant management strategies, and postoperative outcomes were reviewed. Most cases were co-managed by plastic/reconstructive and oculoplastic surgeons. Descriptive statistics were used to summarize findings. Results Five of seven patients (71.4%) were female, with a median age of 60 years (range 29–78). Diplopia was the most common presenting symptom (5/7, 71.4%) along with pain or swelling (5/7, 71.4%) followed by globe malposition (3/7, 42.9%). CT demonstrated implant protrusion into orbital soft tissue in 4/7 patients (57.1%) and peri-implant inflammatory collections in 3/7 (42.9%). Out of our 7 revision cases, four patients (57.1%) underwent explantation alone, and three (42.9%) underwent secondary reconstruction with custom or semi-custom implants. At follow-up, diplopia improved or resolved in 4/5 affected patients (80%), and pain, swelling, and globe position improved in all symptomatic patients. Conclusion Malpositioned orbital implants demonstrate heterogeneous failure mechanisms that require individualized surgical management. A multidisciplinary approach can guide decision-making regarding implant removal versus revision of reconstruction, enabling safe revision surgery and favorable clinical outcomes. Additionally, virtual surgical planning and intraoperative navigation are enablers of safe and precise revision orbital surgery.

Abstract Purpose: To explore the potential of the metaverse, a three-dimensional platform merging physical and virtual realities (VRs), in advancing the field of ophthalmology. This study examines its applications in areas such as VR-based surgical training, augmented reality (AR)-assisted surgeries, artificial intelligence (AI)-driven diagnostics, and teleophthalmology. This review builds upon previous literature by integrating recent evidence and technological advancements, offering a more comprehensive analysis of particular applications and barriers in ophthalmology. Methods: Academic literature published between 2019 and 2024 was identified through searches in the PubMed database and Google Scholar search engine using relevant keywords. This review focused on studies discussing the application of the metaverse in health care and ophthalmology, with particular attention to key trends, emerging uses, technological features, and associated challenges. Results: A total of 60 studies were deemed relevant for inclusion in this review. The infrastructure supporting the Metaverse comprises technologies such as the Internet of Things, digital twins, mirror worlds, nonfungible tokens, blockchain technology, and lifelogging. Together, these technologies create immersive environments that users can access through VR headsets, AR glasses, and handheld controllers. The metaverse presents promising opportunities in ophthalmology, particularly in enhancing clinical training through simulators such as the EyeSi™ surgical simulator, VRmagic EyeSi Slit Lamp, and the HelpMeSee™ VR simulator. In addition, it facilitates remote consultations and improves diagnostic and treatment options, exemplified by tools such as the Vivid Vision™ system for amblyopia, the Microsoft HoloLens™ for navigating complex anatomical structures, and AI-based platforms for the early detection of diseases such as glaucoma and diabetic retinopathy. Furthermore, the metaverse may enhance patient education by simulating the visual effects of ophthalmic conditions and visualizing postoperative outcomes. However, challenges, including financial limitations, data security concerns, and cultural acceptance, must be addressed. Conclusions: A gradual and context-specific integration of the metaverse is essential, particularly in underdeveloped regions. As the metaverse evolves, it holds significant potential to transform the field of ophthalmology by promoting global collaboration and innovation, complementing traditional practices, and ensuring equitable access to advanced healthcare solutions.

LBA2 Background: Dedifferentiated liposarcoma (DDLS) remains a difficult disease to treat with limited systemic therapy options. Approved drugs offer modest benefit such as trabectedin (median progression-free survival [mPFS] 2.2 months [m]) or eribulin (mPFS 2.0m). The Cyclin-dependent kinase 4 (CDK4) oncogene is ubiquitously amplified in DDLS and is a rational therapeutic target. In single-arm phase 2 studies, treatment with selective CDK4 inhibitors resulted in mPFS 4.2m with palbociclib and mPFS 7.7m with abemaciclib. We hypothesized that treatment with abemaciclib would improve PFS compared to placebo in patients with recurrent or metastatic DDLS. Methods: SARC041 was a phase 3 randomized double-blind study of abemaciclib versus placebo. The study was open at 9 academic medical centers in the USA. Eligible patients (pts) had recurrent or metastatic DDLS (purely well-differentiated liposarcoma excluded), progression of disease by RECIST 1.1 in the 6 months prior to study entry, any number of prior systemic therapies, and adequate organ function and performance status. Pts were stratified by prior lines of therapy (0 vs 1 or more) and randomized 1:1 between abemaciclib 200 mg PO twice a day or matching placebo. Scans were every 6 weeks (every 12 weeks after week 36) and pts with progression of disease on placebo could cross over to open label abemaciclib. The primary endpoint was PFS. The design provided 80% power with two-sided 10% significance level to detect a hazard ratio of 0.6 by log-rank test. Secondary endpoints were overall response rate (ORR), PFS and response rate after crossover, and overall survival (OS). Data cutoff was March 1, 2026. Results: In total, 108 pts were randomized to receive abemaciclib (n = 54) or placebo (n = 54). Demographic/baseline characteristics were generally similar across treatment arms. Abemaciclib demonstrated a statistically significant improvement in PFS at 9.67m vs placebo at 1.52m (hazard ratio [HR] 0.39; 95% confidence interval [CI], 0.25–0.59; p < 0.001). ORR was 9.3% for abemaciclib vs 0% for placebo (p = 0.057). mOS was not reached with abemaciclib vs 25.45m with placebo (HR 0.55; 95% CI, 0.28–1.07; p = 0.077). mPFS after crossover from placebo to abemaciclib was 3.44m (95% CI 2.66, 6.84). ORR after crossover was 4.3% (95% CI 0.53%, 15%). mOS after crossover was 24.03m (95% CI: 11.7, NA). Grade 3 or higher adverse event rates were similar in both arms (p > 0.99). No new safety signals were observed. Conclusions: Abemaciclib demonstrated a statistically significant improvement in PFS vs placebo in pts with dedifferentiated liposarcoma, with an encouraging OS trend. These results support abemaciclib as a new treatment option for dedifferentiated liposarcoma. Clinical trial information: NCT04967521 .

TPS11592 Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with about 120 cases diagnosed in the US per year. Although it is commonly considered an indolent disease, in its aggressive form clinical outcomes are poor. Molecularly, EHE is characterized by the presence of oncogenic fusions with HIPPO pathway effectors TAZ or YAP; TAZ-CAMTA1 or YAP-TFE3. YAP/TAZ are modulators of mTORC1 in preclinical models, suggesting that mTOR inhibition may be an effective treatment mechanism for EHE. Nab-sirolimus is albumin bound sirolimus, which achieves higher intratumoral accumulation compared to oral sirolimus and has demonstrated increased antitumor activity in preclinical cancer models compared to the oral mTOR inhibitors sirolimus and everolimus. This is an open label, multi-center, single arm, phase II clinical trial with a two-stage design, testing nab-sirolimus for progressing or symptomatic EHE. The primary objective is to determine ORR of nab-sirolimus in patients with EHE who require systemic treatment. We hypothesize that nab-sirolimus will have significant clinical efficacy for EHE as measured by the primary endpoint of objective response rate, as well as by secondary outcomes including progression free survival benefit over historical controls and by improvement in patient reported outcomes (PROs). If positive, this trial could lead to a new standard of care for treating EHE. Methods: This is a single arm, multi-center, phase 2 study with a two-stage design. Key inclusion criteria include histologically or cytologically confirmed EHE that is either progressing or clinically symptomatic, not a candidate for curative intent surgery, and requires systemic therapy in the opinion of the investigator, radiographically evaluable disease by RECIST v1.1, age ≥18 years, ECOG performance status ≤ 2, and adequate end organ function. With a Simon two-stage optimal design with one sided alpha 0.10, power 90%, assuming a historical control ORR 5% to detect an ORR of 20% (alternative hypothesis), 12 patients will be included in the first stage. If there is ≥ 1 response, an additional 25 patients will be enrolled to a total of 37 patients. ≥ 4 responses are needed for a significant result. The total planned accrual is 41 patients to account for unevaluable patients who may be enrolled, 10% above the required evaluable patients. Planned post hoc subgroup analyses will include outcomes by fusion type and presence of serosal effusions at the time of study enrollment. The trial is registered at clinicaltrials.gov NCT07104331. Clinical trial information: NCT07104331 .

e20761 Background: The prognostic role of serial circulating tumor DNA (ctDNA) dynamics during osimertinib treatment has been described mainly in Asian and European populations; however, it remains poorly defined in Hispanic patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC). Our aim was to determine whether serial plasma EGFR testing identifies patients at high risk of early mortality. Methods: This multicenter, retrospective study included 64 Hispanic patients with stage IIIB–IV EGFR-mutant NSCLC treated with first-line osimertinib between 2018 and 2023. Tumor tissue genotyping was performed using hybrid-capture next-generation sequencing. Plasma EGFR mutations were assessed at baseline, week 8, and week 24. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox models adjusted for p53 status, RAF-pathway alterations, and metastatic burden. Results: The cohort had a median age of 61 years, with 65.6% of patients being female and 56.2% being never-smokers. Sensitizing EGFR mutations consisted mainly of exon 19 deletion (59.4%) and L858R (39.1%). Relevant co-mutations were identified in TP53 (29.7%) and RAF-pathway genes (6.2%). Plasma ctDNA remained positive in 42.2% of patients at week 8 and 22.0% at week 24. Week-8 ctDNA persistence was strongly associated with an inferior OS (HR 9.36, 95% CI 3.80–23.03, p < 0.001) after multivariable adjustment. Week-24 positivity also predicted worse OS (HR 3.34, 95% CI 1.13–9.89, p = 0.02). ctDNA status at week 8 or 24 was not significantly associated with PFS. Patients with TP53 or RAF pathway mutations demonstrated higher rates of molecular persistence. Conclusions: In Hispanic patients receiving Osimertinib, ctDNA positivity at 8-24 weeks is able to identify patients with poor survival outcomes. ctDNA monitoring may provide an early, non-invasive biomarker to guide treatment intensification and trial enrollment in EGFR-mutant NSCLC.

Background: The purpose of this study was to describe, and report the outcomes of, a surgical technique that combines reverse shoulder arthroplasty (RSA) using an allograft-prosthetic composite (APC) with a lower trapezius transfer (LTT) to the infraspinatus of the allograft extended with the inferior capsule. Methods: Between 2019 and 2023, 2 surgeons performed a total of 27 RSAs using an APC in conjunction with an LTT. Once the RSA APC reconstruction had been performed, cuff-capsule allograft tissue was passed posterior to the glenosphere and secured to the harvested lower trapezius. One shoulder was resected for periprosthetic joint infection; the remaining 26 shoulders were followed for a minimum of 2 years (mean, 2.7 years; range, 2 to 5 years). Results: The rate of revision or reoperation for humeral complications was 15% and included secondary bone grafting (2 shoulders), resection for infection (1 shoulder), and internal fixation of a periprosthetic fracture (1 shoulder). Other complications requiring surgery included hematoma treated with evacuation (2 shoulders), dislocation (1 shoulder), and glenosphere disassociation (1 shoulder). Preoperatively, 11 shoulders presented with pseudoparalysis, and the mean active elevation of the remaining 16 shoulders was 43°, with only 1 shoulder demonstrating >90° of active elevation. At the most recent follow-up, 3 shoulders were pseudoparalytic, 11 had <90° of active elevation, 8 had >90° of active elevation, and 3 had active elevation to 90°. The overall mean active elevation of the 25 shoulders that could be assessed was 79°. Preoperatively, only 4 (15%) of the 27 shoulders demonstrated active external rotation past neutral; at the most recent follow-up, 80% of surviving shoulders had active external rotation past neutral. Conclusions: LTT at the time of RSA using an APC has the potential to restore active external rotation in shoulders with proximal humeral bone loss and posterosuperior cuff deficiency. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.