Abstract There is an unmet need to identify biomarkers of active thyroid eye disease (TED). scRNAseq revealed that orbital fibroblasts from orbital decompressions in people with TED express high levels of thyroid hormone receptors, growth factor receptors, including insulin-like growth factor 1 receptor (IGF1R), and extracellular matrix proteins including SPARC (osteonectin), whereas orbital fat endothelial cells expressed thyroid peroxidase (TPO). SPARC was significantly raised in the serum of people with thyroid disease compared to healthy controls. Furthermore, those with moderate, severe and sight threatening TED had higher SPARC levels than those with thyroid disease but free of TED or mild TED. Free-triiodothyronine (FT3) levels were positively correlated with SPARC in moderate-sight threatening TED. SPARC and IGF1 were positively correlated across people with thyroid disease alone, as well as TED. Thyroid stimulating hormone (TSH) levels were negatively correlated with SPARC in moderate-sight threatening TED. When participants were followed longitudinally, SPARC decreased after the active phase of TED. At the protein level, immunohistochemistry indicated that SPARC was heterogeneously expressed by fibroblasts in both control and TED orbital fat. SPARC is a key mediator of fibrosis and deposition of extracellular matrix and the correlation of SPARC serum levels to TED status and FT3 make it a promising biomarker of active TED.

Background:Heterozygous c.283+1G>A and c.283G>A variants in the THRB gene, encoding for thyroid hormone receptor (TR)β1 and β2, lead to autosomal dominant macular dystrophy (ADMD). We report the detailed clinical characterization of two first-degree relatives with ADMD, heterozygous for THRB c.283+1G>A, and an unrelated ADMD patient with a novel variant, c.283G>C. The genomic and molecular consequences of both variants were studied. Methods:gDNA and mRNA were obtained from leukocytes. Clinical characterization included biochemistry, bone density and body composition, ECG, echocardiography, ultrasound, audiometry and color-vision. In vitro assays investigated TR function and DNA binding. Results:The patients manifested no resistance to thyroid hormone beta (RTHβ) and had normal FT4 and TSH. Detailed studies in two patients showed no goiter, tachycardia, hypercholesterinemia or hepatic steatosis. Hearing was not impaired. Both had impaired color vision and reduced bone density. RT-PCR from all three patients revealed skipping of exon 4 exclusive to TRβ1, producing a deletion of 87 amino acids in the N-terminal domain (TRβ1ΔNTD). In vitro, DNA-binding affinity of TRβ1ΔNTD to DR4-TRE with or without RXRα was comparable to TRβ1WT. Surprisingly, TRβ1ΔNTD was transcriptionally twice more active than TRβ1WT with a similar EC50 for T3, demonstrating gain-of-function of TRβ1ΔNTD. THRA expression in leukocytes was increased by 3-fold compared to unrelated controls and different from RTHβ patients. Conclusion:These THRB splice site variants produce TRβ1 exon 4 skipping, resulting in a gain-of-function mutant, TRβ1ΔNTD. This explains the dominant ADMD phenotype devoid of RTHβ and suggests a TRβ1 gain-of-function syndrome.

CONTEXT:Interleukin (IL)-17, a key proinflammatory cytokine, drives inflammation and fibrosis in Graves orbitopathy (GO), and elevated IL-17 and Th17 cells correlate with disease activity and severity. OBJECTIVE:The ORBIT study aimed to evaluate the efficacy and safety of secukinumab, an IL-17A inhibitor, in individuals with active, moderate-to-severe GO. METHODS:A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted. Adults with active, moderate-to-severe, non-sight-threatening GO randomly (1:1) received secukinumab 300 mg or placebo subcutaneously over a 16-week double-blind treatment period, followed by an additional 16-week open-label treatment phase for proptosis nonresponders. Safety parameters, thyroid-related hormones, and autoantibodies were also assessed. The primary end point was overall response of reduced Clinical Activity Score (CAS) of 2 or more points and a reduction of 2 mm or greater in proptosis from baseline without worsening in the fellow eye at week 16. RESULTS:Twenty-eight adult GO patients with a CAS of 4 or greater were enrolled (secukinumab, n = 14; placebo, n = 14). None in either the secukinumab or placebo group achieved an overall response at weeks 16 and 32, respectively, when all patients received open-label secukinumab. No clinically meaningful changes were observed in ophthalmic symptoms and signs, proptosis, lid aperture, eye muscle motility, CAS, and health-related quality of life either at week 16 or week 32. No meaningful effect on serum levels of thyroid-related hormones and antibodies was observed. Secukinumab was well tolerated, with mostly mild adverse events. Neither treatment-induced study discontinuation nor new safety signals were registered. CONCLUSION:Secukinumab did not show clinical efficacy vs placebo when treating patients with active, moderate-to-severe GO.

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.

Graves’ orbitopathy (GO) is an autoimmune disease of the orbit that occurs most often in relation to autoimmune. The clinical picture varies and is dependent on many risk factors, especially age, antibody levels and the quality of control of thyroid function. This study aimed to (1) compare the clinical characteristics of pediatric and adult Graves’ orbitopathy (GO), (2) identify factors associated with remission in pediatric GO, and (3) assess the influence of thyroid treatment modality on TRAb dynamics in pediatric patients. We reviewed the medical records of all pediatric patients with GO (< 18 years) and compared the results with those of a random sample of 482 (18–50 years old) adult patients from the Graves’ Orbitopathy Database (GODE), which includes 4260 patients from our tertiary referral center. A subcohort analysis of pediatric GO patients receiving definitive (surgical) thyroid or medical thyroid treatment was conducted. Risk stratification for remission in pediatric GO patients with the help of univariate as well as multiple logistic regression for different variables, including the serological laboratory results of Free Triiodothyronine (FT-3), Free Thyroxine (FT-4), TSH-receptor autoantibodies (TRAb) and antithyroglobulin antibodies (anti-TG), was conducted. Only those with complete data sets were included in the statistical analysis. Clinical presentation varied significantly between pediatric and adult patients, with children showing mostly mild manifestations (81

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:Diplopia is a common symptom of interdisciplinary significance that can lead to marked impairment of function. Its causes range from harmless to life-threatening conditions that must be precisely distinguished. METHODS:For this CME review article, a PubMed search was conducted in an interdisciplinary collaboration of ophthalmologists and neurologists. RESULTS:Systematic history-taking and a structured clinical examination are the basis for topographic-anatomical diagnosis and the differentiation of peripheral and central causes. It is important to distinguish monocular from binocular diplopia. Monocular diplopia persists when one eye is covered and is not dangerous. Binocular diplopia may arise from disturbances at a variety of anatomical levels that can result from many different causes: disturbances of fusion in strabismus, diseases of the eye muscles such as thyroid eye disease or mitochondropathies, orbital trauma, impaired neuromuscular transmission in myasthenia gravis, fascicular or nuclear lesions of the three nerves that supply the extraocular muscles (oculomotor, trochlear, and abducens), supranuclear lesions "above" the cranial nerve nuclei, and cerebellar diseases. The most common causes, together accounting for ca. 70% of cases, are decompensated latent strabismus and cranial nerve palsies, followed by orbital, brainstem, and cerebellar diseases. CONCLUSION:Diplopia can be accurately diagnosed through a systematic approach that includes precise history-taking and clinical examination of eye position and eye movements. On this basis, there can be a targeted and specific search for the various underlying causes. When the patient's leading symptom is isolated diplopia, the ophthalmologist is generally the specialist to whom the primary care physician should turn next.

Patients with active, moderate-to-severe Graves’ orbitopathy require immunosuppressive treatments to reduce inflammation and morbidity. Since 2021 EUGOGO lists Mycophenolate-sodium (MPS) as first-line-treatment, which lead to a change in treatment regimens. In our center MPS was administered mainly for patients at risk for deterioration (e.g. unstable thyroid function, smoker etc.) or as second-line treatment. To augment the limited data we analyzed our real-world cohort retrospectively. We analyzed all consecutive patients of our tertiary referral center (2019–2023) with a complete data set, who either received MPS simultaneously with intravenous methylprednisolone (IVMP), or after a first course of IVMP. We evaluated the data of 172 patients. Ninety-five were eligible for analysis. Clinical Activity Score showed a significant decrease between baseline (BL) and primary endpoint 6 months (3.9 ± 0.9 vs. 2.4 ± 1.4, p < 0.0001). Inactivation was achieved in 60

BACKGROUND:Due to the variable course of thyroid eye disease (TED), treatment should be tailored to disease severity, individual risk factors, and clinical course. This study is based on a retrospective analysis at the orbital centre of the University Eye Clinic Essen and evaluates the efficacy of the IL-6 receptor blocker tocilizumab as a second-line therapy in patients with therapy-refractory TED. PATIENTS/METHODS:After approval of cost coverage, 20 patients were treated with tocilizumab over a mean period of 4.8 ± 2.7 months. The following parameters were assessed: sex, age, underlying thyroid disease, disease activity and severity, prior therapies, visual acuity, intraocular pressure, eyelid position, exophthalmos, monocular excursions, strabismus/diplopia, levels of TSH receptor antibodies (TRAb), and adverse events. RESULTS:The female-to-male ratio was 3 : 1. Mean patient age was 58.2 ± 8.5 years. The majority (90%, n = 18) had Graves' disease; one patient had primary hypothyroidism and one was euthyroid. All patients had previously failed various treatment regimens (median cumulative steroid dose 4.6 g [1.5 - 7.5 g], 55% mycophenolate, 65% orbital apex radiation, 20% balanced orbital decompression). Among 17 patients with detectable TRAb at baseline, mean antibody levels decreased by 48.4%. A reduction of at least 30% was achieved in 70.6% of these patients (n = 17). A decrease in the Clinical Activity Score (CAS) by ≥ 2 points was observed in 70% of cases. The mean inflammation score (maximum 20 points per patient) decreased from 8.8 ± 3.9 to 3.4 ± 2.4. The effect on exophthalmos was moderate: mean reduction was 0.9 ± 1.8 mm (range - 6 mm to + 3 mm). A decrease of ≥ 2 mm was documented in 25% of patients, whereas an increase was noted in 12.5% (0.5 to 3 mm). Improvement in ocular motility was documented in 22.5% of patients, while 10% showed deterioration. DISCUSSION:This cohort exclusively included therapy-refractory patients, some with protracted disease. The significant reduction in inflammation and particularly in TRAb levels, as a biomarker of disease activity, demonstrate the efficacy of tocilizumab in this highly selected population. Tocilizumab may therefore be an important treatment option for patients with high antibody levels and predominantly inflammatory disease manifestations. Further studies are warranted to evaluate whether it reduces the risk of relapse after successful treatment with an IGF-1 receptor blocker.

OBJECTIVE:Surgical treatment of orbital floor fractures (OFF) in Germany is performed by several subspecialties. In an emergency setting, the question of necessity and urgency of surgery is frequently answered without ophthalmological consultation. PURPOSE:The aim of this survey was to investigate the current management of OFF in German centres with emergency care, among the members of the national oculoplastic society (Section Ophthalmoplastic and Reconstructive Surgery [SORC]). METHODS:An 11-question questionnaire was sent to the main ophthalmology departments and members of the Section for Ophthalmic Reconstructive Surgery (SORC). Open (2), semi-open/multiple choice variant with multiple choice (6) and closed/dichotomous questions were used (3). RESULTS:The questionnaire response rate was 36.3% (37/102). Patients with OFF are treated by oral and maxillofacial surgeons at 86.1% of the sites and by ear, nose and throat specialists (in some cases interdisciplinary) at 25% of the sites. When the indication for surgery was made, the orthoptic status was only carried out at 72% of the sites and preoperative imaging was carried out at 75%. At 58.3% of the sites, OFF correction was also performed without any preoperative clarification by an ophthalmologist, predominantly in cases of polytrauma. The time of surgery was between 0 and 25 days, with a median of 7 days after the accident (8 ± 6 days). CONCLUSIONS:In Germany, the initial surgical treatment of OFF is predominantly performed without prior ophthalmologic consultation and not by ophthalmologists. As early reconstruction can cause considerable individual ophthalmologic loss of function, it is important to promote interdisciplinary cooperation and, in particular, the corresponding oculoplastic care expertise in ophthalmology in order more reliably to avoid inadequate indications. The development of an interdisciplinary S2 guideline and the establishment of a national registry for orbital floor fractures appear to be urgently required to improve the quality of care.

Hintergrund: Die chirurgische Versorgung von Frakturen des Orbitabodens (OBF) wird in Deutschland von mehreren Fachdisziplinen vorgenommen. Die Frage der Notwendigkeit und der Dringlichkeit einer Operation wird gerade in der Notfallversorgung auch ohne ophthalmologische Konsultation beantwortet. Fragestellung: Ziel dieser Umfrage war es in Zentren mit augenärztlicher Notfallversorgung und unter den Mitgliedern der DOG-Sektion „Ophthalmoplastische und rekonstruktive Chirurgie“ (SORC) einen Überblick über die Versorgungssituation dieser Patienten in Deutschland zu gewinnen. Methoden: Ein elf Aspekte umfassender standardisierter Fragebogen wurde an die Hauptabteilungen für Augenheilkunde und Mitglieder der Sektion ophthalmoplastisch-rekonstruktive Chirurgie (SORC) versandt. Es wurden offene (2), halboffene/multiple choice Variante mit Mehrfachauswahl (6) und geschlossene/dichotome Fragen verwendet (3). Ergebnisse: Die Fragebogen-Rücklaufquote betrug 36,3 % (37/102). Patienten mit OBF werden an 86,1% der Standorte von Mund-Kiefer-Gesichtschirurgen und an 25% der Standorte durch (z.T. interdisziplinär) Hals-Nasen-Ohrenärzte behandelt. Bei der medizinischen Indikationsstellung zur Operation wurde nur bei 72% der Standorte der orthoptische Status und bei 75% eine präoperative Bildgebung durchgeführt. An 58,3% der Standorte erfolgte eine OBF-Korrektur sogar ohne jegliche präoperative Diagnostik durch einen Augenarzt, überwiegend bei Polytraumata. Der Zeitpunkt der Operation lag zwischen 0 und 25 Tagen im Median 7 Tage nach dem Unfall (86 Tage). Fazit: Die operative Erstversorgung von OBF wird in Deutschland häufig ohne vorherige augenärztliche Konsultation und nicht von Augenärzten durchgeführt. Eine OBF stellt jedoch in aller Regel keine medizinische Indikation zur Notfalloperation dar. Da eine frühzeitige Rekonstruktion in erheblichem Maße individuelle ophthalmologische Funktionseinbußen auslösen kann, gilt es neben der interdisziplinären Zusammenarbeit insbesondere die entsprechende okuloplastische Versorgungskompetenz in der Augenheilkunde zu fördern, um inadäquate Indikationsstellung sicherer zu vermeiden. Die Entwicklung einer interdisziplinären S2-Leitlinie sowie die Etablierung eines nationalen Registers für Orbitabodenfrakturen erscheinen für die Verbesserung der Versorgungsqualität dringend erforderlich. Objective: Surgical treatment of orbital floor fractures (OFF) in Germany are performed by several subspecialties. In an emergency setting, the question of necessity and urgency of surgery is frequently answered without ophthalmologic consultation. Purpose: The aim of this survey was to investigate the current management of OFF in German centers with emergency care among the members of the national oculoplastic society (Section Ophthalmoplastic and Reconstructive Surgery (SORC)). Methods: An eleven-question questionnaire was sent to the main ophthalmology departments and members of the Section for Ophthalmic Reconstructive Surgery (SORC). Open (2), semi-open/multiple choice variant with multiple choice (6) and closed/dichotomous questions were used (3). Results: The questionnaire response rate was 36.3% (37/102). Patients with OFF are treated by oral and maxillofacial surgeons at 86.1% of the sites and by ear, nose and throat specialists (in some cases interdisciplinary) at 25% of the sites. When the indication for surgery was made, the orthoptic status was only carried out at 72% of the sites and preoperative imaging was carried out at 75%. At 58.3% of the sites, OFF correction was also performed without any preoperative clarification by an ophthalmologist, predominantly in cases of polytrauma. The time of surgery was between 0 and 25 days, with a median of 7 days after the accident (86 days). Conclusions: In Germany, the initial surgical treatment of OFF is predominantly performed without prior ophthalmologic consultation and not by ophthalmologists. As early reconstruction can cause considerable individual ophthalmologic loss of function, it is important to promote interdisciplinary cooperation and, in particular, the corresponding oculoplastic care expertise in ophthalmology in order to avoid inadequate indications more reliably. The development of an interdisciplinary S2 guideline and the establishment of a national registry for orbital floor fractures appear to be urgently required to improve the quality of care.

LHON leads to gradual, painless, and permanent vision loss in both eyes, often associated with central scotomas. As the condition progresses, there is a decline in visual function, accompanied by noticeable structural alterations. This study focused on evaluating the clinical characteristics of patients with differing LHON stages, with a specific emphasis on optical coherence tomography (OCT) imaging results. This analysis included 22 individuals with LHON. Patients underwent thorough clinical ophthalmologic assessments, including SD-OCT, Visual evoked potentials, and perimetry. When LHON was suspected, blood samples were obtained to test for the three major mitochondrial mutations (G1178A, T14484C, G3460A), with further sequencing to identify additional known mutations. The data were subsequently examined through descriptive statistical methods. The clinical characteristics of 22 individuals (median age 33, range 9–68) were examined. All participants carried a mutation linked to LHON. The most prevalent mutation was G11778A (55

Introduction Congenital oculomotor nerve palsies occur rarely and are classified according to the localization of the lesion. Clinically, external oculomotor nerve palsy is characterized by strabismus and ptosis. Exophthalmos may occur due to the loss of posterior traction of the rectus muscles.

Purpose: Graves’ orbitopathy (GO) is an autoimmune disorder leading to inflammation, adipogenesis, and fibrosis. The severity of GO can vary widely among individuals, making it challenging to predict the natural course of the disease accurately, which is important for tailoring the treatment approach to the individual patient. The aim of this study was to compare the clinical characteristics, course, treatment, and prognosis of GO patients under 50 years with older patients. Methods: We reviewed the medical records of a random sample of 1000 patients in our GO database Essen (GODE) comprising 4260 patients at our tertiary referral center. Patients were divided into two groups: Group 1 (≤50 years) and Group 2 (>50 years). Only patients with a complete data set were included in the further statistical analysis. Results: The results showed that younger patients (n = 484) presented significantly more often with mild GO (53% vs. 33%, p < 0.0001), while older patients (n = 448) were more likely to experience moderate-to-severe disease (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility, and clinical activity scores (5.9 vs. 2.3 PD/310° vs. 330° both p < 0.0001, CAS: 2.1 vs. 1.7, p = 0.001). Proptosis and occurrence of dysthyroid optic neuropathy (DON) showed no significant difference between groups (both 3%). Multiple logistic regression revealed that the need for a second step of eye muscle surgery was most strongly associated with prior decompression (OR = 0.12, 95% CI: 0.1–0.2, p < 0.0001) followed by orbital irradiation and age. The model showed good fitness regarding the area under the curve (AUC = 0.83). Discussion: In conclusion, younger GO patients present with milder clinical features such as a lower rate of restrictive motility disorders and less pronounced inflammatory signs. Therefore, older patients tend to need more steroids, irradiation, and lid and eye muscle surgery. Still, the risk of DON and the necessity of secondary eye muscle surgery are not or only slightly associated with age, respectively.

INTRODUCTION:Congenital dacryocystoceles are a rare condition caused by nasolacrimal duct obstruction. Symptoms include epiphora, nasal obstruction, and swelling in the medial canthus. Treatment usually entails probing Hasner's valve open and, if necessary, intubating the nasolacrimal duct. We present a minimally invasive, endoscopic procedure with marsupialisation of the endonasal portion of the cele. The operation avoids additional manipulation of the lacrimal duct to prevent iatrogenic injury. METHODS:This retrospective analysis included a total of nineteen infants or young children (21 eyes) aged 3 days to 39 months. Two of the patients were suffering from acute respiratory distress, seven from recurrent infections with persistent epiphora, and twelve from acute dacryocystitis with orbital phlegmon. RESULTS:The endonasal portion of the dacryocele was detected in all cases and resected endonasally using an endoscope. Recurrences required revision surgery involving dacryocystorhinostomy after primary surgery in two patients aged of 22 and 39 months. All other seventeen patients were free of recurrence. SUMMARY:Our results show endoscopic endonasal marsupialisation without additional intubation or probing of the lacrimal ducts to be a successful treatment strategy for congenital dacryocystoceles. This avoids iatrogenic scarring, false passages, or postoperative bacteraemia. The surgical technique presented here shows a lower success rate in older children with a history of inflammation.

Background Solitary fibrous tumours are rare. The aim of this study is to describe the clinical features, therapy and outcome of affected patients and to identify factors associated with recurrence.Methods Retrospective study of a cohort of 20 patients who underwent surgery for orbital solitary fibrous tumour at the University Department of Oral and Maxillofacial Surgery between 2002 and 2023. Demographic, clinical, and therapeutic data as well as tumour follow-up results were collected. Tumour volume and molecular genetic mutations were retrospectively determined.Results The median patient age was 49.5 years at initial surgery. The left orbit was affected in 65% of cases. The most common clinical symptom was proptosis (80%). This was reported with a mean lateral difference of 3.9 mm (range: 1 - 10 mm). The tumours were localised predominantly in the intra- and extraconal space, craniolateral quadrant and middle third. The median tumour volume was 7.66 cm(3) (range 2.15 - 12.57 cm(3)). In all patients, the diagnosis was made by pathological examination. All tumours investigated showed a NAB2-STAT6 mutation. The most frequently detected mutation was the fusion NAB2 exon 4 - STAT6 exon 2. All patients were initially managed with frontolateral orbitotomy. Incomplete resection (R1-status) occurred in 35% (n = 7). The recurrence rate was 25% (n = 5), with a median disease-free interval of 45.5 months (range 23 - 130). 80% (n = 4) of recurrences were initially R1-resected.Conclusion Orbital solitary fibrous tumours are rare tumours and are clinically manifested by signs of displacement of orbital structures. Diagnosis is made by histology and immunohistochemistry and can be proven with the molecular genetic detection of the NAB2-STAT6 mutation. The therapy of choice is complete surgical resection. R1-resection is more likely in the intraconal location as well as in location in the posterior third of the orbit - due to difficult surgical accessibility. The greatest risk factor for the development of recurrence is incomplete surgical excision. Late recurrences are possible, which is why a long-term connection to a specialised clinic is necessary.

Background Graves’ orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves’ Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. Methods Prospective observational multicentre study. All new referrals with diagnosis of GO within September–December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. Results Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0–350) vs 6 (0–552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). Conclusion GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.