BACKGROUND:Despite advances in diagnostic techniques, determining the etiology of uveitis remains a clinical challenge. In addition to infectious causes, neoplastic entities, such as intraocular lymphoma can mimic inflammatory diseases. Aqueous humor sampling enables direct detection of infectious pathogens and can provide clues to underlying neoplastic diseases. PURPOSE:To evaluate the diagnostic utility of aqueous humor sampling in patients with uveitis in the clinical routine of a tertiary university referral center. METHODS:In this retrospective single-center study 59 aqueous humor samples obtained between 2015 and 2020 at the Department of Ophthalmology, University Hospital Essen, were analyzed. The cohort included anterior, intermediate, posterior and panuveitis cases. Demographic data, clinical course, pretreatment status, virological and microbiological findings from aqueous humor analysis as well as complementary findings from vitreous body or tissue biopsies were recorded. RESULTS:An etiologically relevant finding was identified in 18 cases (30.5%), including direct detection of infectious pathogens in 16 aqueous humor samples and 2 intraocular lymphomas confirmed during follow-up by vitreous body or tissue biopsy. Toxoplasmagondii and herpesviruses were the most frequently detected pathogens. Descriptively, comparable detection rates were observed between pretreated and treatment-naïve patients. In selected clinical cases aqueous humor polymerase chain reaction (PCR) enabled early etiological classification of herpes simplex virus type 1 (HSV-1)-associated retinitis and detection of cytomegalovirus (CMV)-associated uveitis with immediate therapeutic consequences. CONCLUSION:Aqueous humor sampling represents a valuable diagnostic tool in the evaluation of uveitis and can facilitate targeted therapy, particularly in infectious diseases. In atypical or treatment-refractory cases, it can contribute to the detection of tumor-associated intraocular disease within a stepwise diagnostic approach.

IntroductionUveal melanoma (UM) is a rare tumor entity and the predominant primary intraocular malignancy in adulthood. Despite high local tumor control rates, metastatic disease remains frequent and systemic therapeutic options are limited. Electrochemotherapy (ECT) with bleomycin enhances intracellular drug uptake through electroporation (EP), thereby increasing targeted antitumor activity. This study investigated the effects of bleomycin-based ECT delivered using a custom bipolar electrode in UM patient-derived xenografts (PDX).MethodsUM PDX were analyzed in both in ovo and ex vivo experimental settings. Tumor grafts were treated with EP alone at voltage settings of 750 V or 1000 V, or with ECT combined with bleomycin at concentrations of 1 μg/mL or 2.5 μg/mL. Histological evaluation and immunofluorescence analyses were performed to assess tumor morphology, melanoma-associated marker expression, vascularization, proliferative activity and treatment-induced cell death pathways.ResultsECT caused pronounced tumor disruption and decreased tumor size parameters compared with untreated controls, with statistically significant reductions in tumor area following EP at 750 V alone or combined with 2.5 μg/mL bleomycin and in tumor perimeter across all groups treated with EP at 750 V in ovo, while changes in the ex vivo model were not statistically significant. Expression of melanoma-associated markers, including a melanoma marker cocktail and Sox10, decreased following treatment, with significant differences observed in multiple in ovo and selected ex vivo conditions. Analysis of cell death markers indicated involvement of multiple cell death mechanisms, with statistically significant treatment-associated changes in markers of apoptosis, pyroptosis, necrosis and necroptosis detected in ovo, whereas gasdermin D expression did not reach statistical significance ex vivo. Treatment responses differed between experimental models and EP conditions, suggesting model-dependent cellular responses.DiscussionBleomycin-based ECT using a custom bipolar electrode induces substantial tumor damage in UM PDX in ovo and ex vivo. These findings support the potential application of bipolar electrode-based ECT for intraocular tumor treatment and provide a basis for further optimization of electrode design and translational investigation.

Introduction:This case highlights the complexity of managing highly refractory, recurrent pterygium. Despite numerous prior surgeries by experienced anterior segment surgeons, the patient developed persistent fibrosis, symblepharon formation, and functional limitations. This underscores the need for a tailored, multidisciplinary approach, a strategy not widely documented in current literature. Case Presentation:Over 6 years, the patient underwent ten previous interventions, including conjunctivoplasty with ipsilateral free conjunctival flap and mitomycin C (MMC), amniotic membrane transplantation, symblepharolysis, and tenonplasty. The most recent surgery had been performed 6 months before referral to our clinic. Despite these attempts, each procedure was followed by significant fibrosis, scarring, and recurrent symblepharon formation involving the fornices. Following comprehensive multidisciplinary discussion and literature review, reconstructive surgery was undertaken. This included conjunctivoplasty with a free limbal-conjunctival autograft from the contralateral eye, adhesiolysis of the extraocular muscles, muscle belly plasty with amniotic membrane grafting, and placement of barrier sutures to reduce adhesion recurrence. During 12 months of follow-up, the patient exhibited notable clinical improvement, including enhanced ocular motility, resolution of diplopia in primary gaze, and improved visual acuity. Conclusion:This case emphasizes the importance of individualized, innovative surgical planning for advanced recurrent pterygium. A long-term, multidisciplinary strategy can offer sustained anatomical and functional restoration in patients with extensive prior surgical failure and severe ocular surface disease.

Die ätiologische Abklärung der Uveitis bleibt trotz moderner diagnostischer Verfahren eine klinische Herausforderung. Neben infektiösen Ursachen können Tumorerkrankungen wie intraokulare Lymphome entzündliche Krankheitsbilder imitieren. Das Vorderkammeraspirat ermöglicht den direkten Erregernachweis und kann Hinweise auf Tumorerkrankungen liefern. Ziel dieser Studie war es, den diagnostischen Nutzen des Vorderkammeraspirats bei Patienten mit Uveitis im klinischen Alltag eines tertiären universitären Zentrums zu evaluieren. In einer retrospektiven monozentrischen Studie wurden 59 Vorderkammeraspirate analysiert, die zwischen 2015 und 2020 an der Universitätsaugenklinik Essen durchgeführt wurden. Die Kohorte umfasste anteriore, intermediäre und posteriore Uveitiden sowie Panuveitiden. Erfasst wurden demografische Daten, klinischer Verlauf, Vorbehandlung sowie virologische und mikrobiologische Befunde des Vorderkammeraspirats und ergänzende Befunde aus Glaskörper- oder Gewebebiopsien. In 18 Fällen (30,5

BackgroundGraves’ disease (GD) is an autoimmune condition that can extend beyond the thyroid, leading to thyroid eye disease (TED), a disorder marked by orbital inflammation and tissue remodeling.MethodsWe explored the therapeutic potential of maraviroc, a CCR5 antagonist, in a mouse model of TED triggered by immunization with the human TSH receptor (hTSHR) A-subunit. Mice received pTriEx1.1neo-hTSHR A-subunit plasmid immunizations, and a subset were treated with maraviroc via drinking water. We assessed thyroid function, orbital tissue changes, immune cell infiltration, and lipid metabolism through serological testing, histology, immunohistochemistry, and untargeted lipidomics.ResultsMaraviroc did not significantly affect anti-TSHR antibody production nor the degree of hyperthyroidism, though it modestly improved thyroid histopathology. Notably, it reduced key signs of orbital disease, including brown adipose tissue expansion, CCL5-positive immune cell infiltration, CD4+ T-cell infiltration and the presence of F4/80+ macrophages. Lipidomic profiling revealed distinct metabolic changes in treated mice, with reduced triacylglycerols and elevated carnitines, indicative of enhanced fatty acid utilization. Composite Z-score analysis reinforced maraviroc’s beneficial effects on orbital inflammation and remodeling.ConclusionMaraviroc shows promise as a targeted therapy for TED in the context of GD, offering anti-inflammatory and anti-adipogenic benefits while sparing thyroid autoimmunity. These preclinical findings support further clinical investigation into its role in managing TED.

OBJECTIVE:The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls. METHODS:Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM's genetic architecture. RESULTS:We identify nine linkage disequilibrium (LD)-independent loci (three novel) with an IVW P value of less than 5 × 10-8. TWAS analysis indicates five potential target genes, including MOB3B, RBAK, and MTSS1, which have established links to multiple cancer types. We note a significant genetic correlation (rg = 0.31, P = 0.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg = 0.25, P = 0.08). CONCLUSIONS:This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation.

A 59-year-old woman presented with a four-month history of progressive visual loss and floaters in her left eye. Her medical history included hypothyroidism, psoriasis, and type 2 diabetes. Fundus examination revealed choroidal folds, an amelanotic lesion temporal to the fovea, and an exudative retinal detachment. Optical coherence tomography (OCT) demonstrated a choroidal mass without subretinal fluid, while indocyanine green angiography (ICGA) showed a hypocyanescent lesion with no intrinsic vascularity. B-scan ultrasonography revealed an inhomogeneous choroidal mass with retrobulbar fluid (positive T-sign). Blood tests revealed elevated C-reactive protein (CRP) and liver enzymes levels, together with positive antinuclear antibodies (ANA), while the chest X-ray was normal. The overall clinical and imaging findings were consistent with nodular granulomatous scleritis. Choroidal melanoma, uveal lymphoma, primary vitreoretinal lymphoma, and choroidal hemangioma were excluded based on their imaging characteristics. Treatment with systemic corticosteroids resulted in rapid visual improvement and complete resolution of the lesion. This case demonstrates how inflammatory choroidal lesions can mimic intraocular tumors. Recognizing characteristic multimodal imaging features (choroidal folds, preserved choroidal vasculature on ICGA, positive T-sign on ultrasonography) can enable a confident diagnosis without biopsy, avoiding unnecessary treatment and delays in cancer diagnosis.

OBJECTIVE:To analyse the data of a cohort of patients with conjunctival melanoma in order to analyse risk and guarding factors and to investigate the impact on metastatic disease with and without adjuvant therapy. METHODS AND ANALYSIS:We have retrospectively analysed the impact of clinical aspects and adjuvant therapies after tumour excision or biopsy in 167 patients cared for at the University Hospital Essen and the University Hospital Tübingen, Germany. Clinical as well as histopathological data and therapeutic approaches were analysed with regard to regional (lymphatic) and/or distant (haematogenous) spread during follow-up. The Kaplan-Meier estimate method was used to analyse survival and the Cox regression hazard model to define the probability of metastases depending on different factors. P value of <0.05 was considered statistically significant. RESULTS:167 cases of malignant conjunctival melanoma were retrospectively analysed. The patients received treatment and were followed up for 78.3±67.5 months. Local tumour recurrence occurred in n=79 patients (47.3%) after a mean of 41.5±70.33 months. 30 patients (37.9%) with a recurrence had not received adjuvant therapy. The overall rate of metastasis was 24.5% (n=41). In n=31 cases, regional lymphatic metastases were found after a follow-up of 48.9±63.5 months; in n=24 cases, distant metastases were found, occurring after 55.5±67.4 months. In n=14, the metastatic disease took both pathways. Ruthenium-106 brachytherapy performed in localised melanoma of the bulbar conjunctiva showed a relevant effect of decreasing the risk for haematogenous metastases by 74% (HR=0.256, p=0.003). 4 out of 54 patients developed distant metastases. CONCLUSION:In conjunctival melanoma, it is important to perform an adjuvant therapy after excision. This reduces not only local recurrences but also significantly the risk for haematopoietic spread.

BACKGROUND:Thyroid eye disease (TED) is characterized by orbital inflammation, fibroblast activation, and pathological tissue remodeling. While autoimmunity to the thyrotropin receptor (TSHR) initiates disease, the contribution of proinflammatory cytokines, such as tumor necrosis factor (TNFα), to fibroblast differentiation and extracellular matrix (ECM) remodeling remains incompletely understood. METHODS:A mouse model of TED was generated by immunization with a plasmid encoding the human TSHR A-subunit. Orbital tissues were analyzed for immune cell infiltration and cytokine expression. Primary murine orbital fibroblasts (mOFs) from TSHR- and control β-Gal-immunized mice were treated with TNFα or IFNγ. The expression of cytokines, chemokines, adiponectin, TGFβ, hyaluronic acid (HA), and hyaluronan synthase 2 (HAS2) was assessed by ELISA, qPCR, and western blotting. RESULTS:TSHR-immunized mice displayed marked orbital macrophage infiltration accompanied by elevated TNFα levels. TNFα induced a strong proinflammatory response in mOFs, with robust IL-6 and IL-8 secretion and an IL-6-dominant profile in TSHR-derived cells. TNFα also upregulated CCL2, CCL20, and CXCL10, supporting enhanced immune cell recruitment. Moreover, TNFα reduced adiponectin while increasing TGFβ in TSHR mOFs, indicating activation of profibrotic pathways. TNFα significantly increased HA production and HAS2 expression, particularly in TSHR-derived fibroblasts, demonstrating enhanced ECM synthesis under autoimmune conditions. CONCLUSION:These findings identify TNFα as a central regulator linking inflammation to adipogenic suppression, profibrotic signaling, and ECM remodeling in a TSHR-immunized mouse model of TED. Enhanced HA/HAS2 induction underscores a disease-specific sensitivity of orbital fibroblasts to TNFα. Targeting TNFα or its downstream IL-6/TGFβ-ECM axis may offer a promising therapeutic strategy to limit pathological tissue remodeling in TED.

BACKGROUND:Uveal melanoma (UM), the most common adult primary intraocular malignancy, has its highest frequency in Europe. Because of the current diagnostic and therapeutic practices, calculating UM incidence can be error prone. Using cancer registry data, the aim here was to estimate UM incidence in Germany and North Rhine-Westphalia (NRW), its largest federal state. METHODS:All UM cases from the German Centre for Cancer Registry Data (RKI) in 2019-2021 were analyzed. Data were compared to the 2019-2022 data of NRW's cancer registry. We calculated crude incidence and age-standardized rates (ASR) using the 2013 European standard population. RESULTS:Overall, 2047 German and 830 NRW UM cases were included. In both datasets, the mean age at diagnosis was 65 years; men and women were equally affected. Ciliary body and iris melanomas represented 11-13% of total cases. In Germany (RKI dataset), ASR was 7.4 per million person-years (pyrs). Highest ASR was in the North (Schleswig-Holstein: 16.6 per million pyrs), followed by North-Eastern federal states (ASR: 11-13 per million pyrs in Brandenburg, Berlin, Saxony-Anhalt, Mecklenburg-Western Pomerania), and ASR was 4-8 per million pyrs in the remaining federal states. ASR in NRW was 6.2 (RKI dataset) but 10.6 per million pyrs using the state's cancer registry data. CONCLUSION:Determining UM incidence in Germany remains challenging. High incidence variations between both datasets and German federal states point to a probable incompleteness of the RKI UM-dataset. Incidence is likely higher than previously assumed, but similar to rates observed in Northern Europe (around 10-12 per million pyrs).

Tebentafusp, a T-cell receptor-bispecific molecule targeting glycoprotein 100-derived peptide presented by HLA class I molecule and CD3, is standard of care for patients with unresectable or metastatic uveal melanoma who are positive for HLA-A*02:01. Mechanisms of resistance to tebentafusp are unknown. We report a patient with metastatic uveal melanoma who acquired resistance to tebentafusp after 30 months of treatment. Genomic loss of the HLA-haplotype carrying the HLA-A*02:01 restriction element was detected in a progressive metastasis, resulting in loss of presentation of tebentafusp's target antigen. Understanding mechanisms of resistance against synthetic cancer immunotherapies will be key to monitoring disease control and development of early intervention strategies towards cure.

Eine 59-jährige Patientin stellte sich mit seit vier Monaten progredienter Visusminderung und Mouches volantes am linken Auge vor, ohne Augenbewegungsschmerzen oder Gelenkbeschwerden. Anamnestisch bestanden Hypothyreose, Psoriasis und Diabetes mellitus Typ II. Funduskopisch zeigten sich am linken Auge Aderhautfalten, eine amelanotische, temporal der Fovea gelegene Läsion sowie eine exsudative Ablatio retinae. Die optische Kohärenztomographie (OCT) zeigte eine choroidale Raumforderung ohne subretinale Exsudation, die Indocyaningrünangiographie (ICGA) eine hypocyaneszente, gefäßfreie Läsion. Sonographisch fand sich eine inhomogene Raumforderung mit retroskleraler Flüssigkeit (positives T-Zeichen). Laborchemisch bestanden ein erhöhtes C-reaktives Protein (CRP), erhöhte Leberwerte und positive antinukleäre Antikörper (ANA). Der Röntgen-Thorax war unauffällig. Diese Befunde stützten die Verdachtsdiagnose einer nodulären granulomatösen Skleritis. Differentialdiagnostisch wurden Aderhautmelanom, uveales Lymphom, primäres vitreoretinales Lymphom und chorioidales Hämangiom erwogen. Unter Kortisontherapie mit Prednisolon zeigten sich rasche Visusbesserung und vollständige, stabile Rückbildung der Läsion. Der Fall verdeutlicht, dass die Abgrenzung entzündlicher von neoplastischen intraokularen Raumforderungen zu den schwierigsten Situationen der Ophthalmoonkologie zählt und klinische Erfahrung sowie konsequente multimodale Bildgebung erfordert, um Übertherapie und Verzögerungen der Tumordiagnostik zu vermeiden. Das Vorliegen von wichtigen Befunden in der multimodalen Diagnostik (Aderhautfalten, normalen Aderhautgefäßen in der ICGA, T-Zeichen im Ultraschall) können die korrekte nicht-invasive differentialdiagnostische Einordnung ermöglichen.

Choroidal tumors comprise a heterogeneous group of intraocular lesions ranging from benign entities such as choroidal nevus and circumscribed choroidal hemangioma to malignant tumors including uveal melanoma and choroidal metastasis. Accurate differentiation is crucial, as management and prognosis exhibit significant variations. Choroidal nevi are the most prevalent benign intraocular tumors and are generally asymptomatic. However, a small subset of these nevi carries a risk of malignant transformation into melanoma. Risk stratification utilizing multimodal imaging criteria, such as the TFSOM-DIM and MOLES systems, is pivotal in clinical decision-making. Uveal melanoma represents the most common primary intraocular malignancy in adults and is associated with high metastasis rates, particularly to the liver. Prognosis depends on tumor size, location, histopathologic features, and molecular alterations such as monosomy 3 or BAP1 loss. Treatment options range from globe-preserving radiotherapy to adjuvant or neoadjuvant surgical resection and enucleation in advanced cases. Choroidal hemangioma is a benign vascular tumor that can lead to visual impairment due to exudative retinal detachment. Photodynamic therapy is currently considered the preferred treatment in symptomatic cases.Choroidal metastases represent the most prevalent intraocular malignancies, with a primary origin in breast or lung carcinoma. Multimodal imaging is essential for diagnosis and monitoring, and management requires interdisciplinary coordination. A structured multimodal diagnostic approach is crucial for accurate classification, risk assessment, and individualized therapeutic planning in patients with choroidal tumors.

Abstract Background Choroidal naevi (CN) are small, and mostly asymptomatic choroidal lesions. Despite their benignity, identification and follow-up of CN is required as malignant transformation is possible. CN prevalence was shown to vary greatly depending on ethnical descent, but data from European countries are rare. The aim of this study was to estimate the prevalence of CN based on fundus images from participants of the prospective German BiDirect study. Methods Observational cross-sectional study of participants aged 37–68 years separated into three cohorts: patients with (1) depression, (2) acute cardiovascular disease, (3) participants of the general population. Participants with at least one 45°-wide macula-centred image of both eyes were included. General health indicators and eye function were assessed. The prevalence of posteriorly localised CN was calculated. Age-standardization was performed using the European Standard Population of 2013 (ESP2013) and the U.S. 2000 Standard Population (US2000). To estimate the entire fundus prevalence of CN, we applied a correction factor of 2.5 based on the assumption that 40% of all CN were detected by the study’s method. A sensitivity analysis was also performed. The association between CN presence and health indicators was investigated using logistic regression. Results 1170 participants were included. When fundus image was acquired, participants were aged 37–68 years (mean ± standard deviation: 54 ± 7.8) and 49% were females. Mean visual acuity was 0.20 ± 0.2 LogMAR on both eyes. At least one CN was detected in 36 participants. Thus, the crude prevalence of posterior CN was 3.1% (95% confidence interval: 2.1–4.1). After age-standardization, ESP2013-prevalence was 2.6% (95% CI: 2.2-3.0). A sensitivity analysis was performed to explore the potential prevalence of CN in the entire fundus; if 40% of CN were detected by our method, the entire fundus prevalence would be 7.7% (95% CI: 6.1–9.3). No association between CN and age, sex, or general health indicators was identified; the presence of CN did not impact visual acuity. Conclusions In regions with demographics like those in the German BiDirect study, posteriorly localised CN can be expected in approximately 3.1% of the population. However, the prevalence of CN across the entire fundus remains difficult to determine.

INTRODUCTION:Metastatic uveal melanoma (MUM) has a poor prognosis, but hepatic arterial infusion chemotherapy (HAIC) may improve outcomes in patients with hepatic metastases. To identify reliable prognostic factors for patient stratification and treatment allocation, we analyzed the clinical and imaging data from a large single-center cohort using machine learning (ML) models. METHODS:Pre- and post-first treatment clinical data of 235 patients with MUM treated with HAIC between 2009 and 2019 were retrospectively analyzed using Cox regression to identify prognostic factors for overall survival (OS) and time to change treatment strategy (TTCS). Furthermore, ML models were trained on clinical and computed tomography (CT) data for endpoint prediction. RESULTS:Pre-treatment multi-variate analysis identified elevated lactate dehydrogenase (LDH) (OS: 6.5 vs. 16.4 months, hazard ratio [HR]) = 1.87, P = 0.006) and gamma-glutamyl transpeptidase (GGT) (OS: 7.6 vs. 16.4 months, HR = 1.67, P = 0.012) as prognostic factors for inferior OS. Decreased albumin (TTCS: 1.3 vs. 6.1 months, HR = 6.26, P < 0.001) and elevated LDH (TTCS: 2.9 vs. 7.6 months, HR = 1.72, P = 0.011) and alanine aminotransferase (ALT) (TTCS: 3.7 vs. 6.4 months, HR = 1.65, P = 0.004) predicted shorter TTCS. Scoring enhanced the power of the prognosticators for OS and TTCS. Post-first treatment multi-variate analysis emphasized the importance of inflammation management and liver protection. ML models incorporating radiomics features from baseline CT imaging were not superior to models based on pre-treatment clinical data alone. CONCLUSION:We identified independent but synergistic prognostic factors for outcome stratification to guide treatment decisions and optimize patient management. ML-based radiomics features did not significantly enhance prognostic performance.

Die rhegmatogene Netzhautablösung (Amotio retinae) ist ein ophthalmologischer Notfall mit steigender Inzidenz in Deutschland. Trotz etablierter Methoden bleibt die perioperative Lagerung, insbesondere bei immobilen Patienten, eine Herausforderung, die Erfolg und Komplikationsrate maßgeblich beeinflusst. Eine Analyse der aktuellen Trends in der chirurgischen Behandlung und perioperativen Versorgung der Amotio im Vergleich zu 2018 ist essenziell. Online-Umfrage mit 5 hypothetischen Fällen akuter rhegmatogener Amotio wurde an vitreoretinale Chirurg*innen des retina.net gesendet; 27 Fragebögen wurden hinsichtlich demografischer Daten, Operationsmethoden, Anästhesieform, perioperativer Lagerung und Nachsorgestrategien ausgewertet. Es waren 50

Metastatic risk stratification is critical for uveal melanoma (UM) management, as approximately up to half of patients develop metastatic disease. Current prognostication for patients undergoing eye-preserving therapies relies on tumor staging and molecular analysis of tumor tissue obtained through potentially invasive biopsy, which can be challenging. While liquid biopsy using cell-free DNA (cfDNA) has emerged as a less invasive alternative for other cancers, studies have shown limited utility of blood-derived cfDNA in UM due to low tumor DNA fractions. This study investigates the potential of aqueous humor (AH) and vitreous body (VB) aspirates as alternative sources of tumor DNA for molecular prognostication in UM patients at the time of diagnosis. In this prospective study, AH and/or VB samples were collected from 96 consecutive UM patients undergoing enucleation, transretinal endoresection or transretinal biopsy. DNA was extracted from the ocular fluids and analyzed for the presence of tumor-derived DNA using deep amplicon sequencing targeting mutations in GNAQ and GNA11. This approach achieved an average read depth of 120,000, enabling highly sensitive detection of tumor-specific variants. Tumor DNA was detected in at least one ocular fluid (AH or VB) in 43 of 88 evaluable patients (49%), with variant allele fractions (VAFs) ranging from 0.3 to 50%. Of these positive cases, tumor DNA was identified in VB only in 22 patients, AH only in 5 patients, and both fluids in 16 patients. Importantly, tumor DNA in AH was almost exclusively observed in patients with monosomy 3 UM. No significant correlation was found between the presence of tumor DNA in either ocular fluid and primary tumor size or location. Liquid biopsy of AH and VB offers a promising, minimally invasive strategy for obtaining tumor DNA in nearly half of UM patients at diagnosis. The strong association between detectable tumor DNA in AH and monosomy 3 status warrants further investigation and may offer valuable insights into UM biology and dissemination mechanisms. This approach may improve risk stratification and inform personalized treatment strategies for patients with UM.