Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

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.

A Survey on the Management of Thyroid Eye Disease Among American and European Thyroid Association Members.

Background: The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. Methods: We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. Results: Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227). Conclusions: There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.

Predictive score for the development or progression of Graves' orbitopathy in patients with newly diagnosed Graves' hyperthyroidism.

OBJECTIVE: To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). DESIGN: Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. METHODS: 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. RESULTS: GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2-10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91 (95% CI 0.87-0.94) respectively. CONCLUSIONS: In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

Results after En Bloc Lateral Wall Decompression Surgery with Orbital Fat Resection in 111 Patients with Graves' Orbitopathy.

Purpose. To evaluate the effect of en bloc lateral wall decompression with additional orbital fat resection in terms of exophthalmos reduction and complications. Methods. A retrospective, noncomparative case series study from 1999 to 2011 (chart review) in Graves' orbitopathy (GO) patients. The standardized surgical technique involved removal of the lateral orbital wall including the orbital rim via a lid crease approach combined with additional orbital fat resection. Exophthalmos, diplopia, retrobulbar pressure sensation, and complications were analyzed pre- and postoperatively. Results. A total of 111 patients (164 orbits) with follow-up >3 months were analysed. Mean exophthalmos reduction was 3.05mm and preoperative orbital pressure sensation resolved or improved in all patients. Visual acuity improved significantly in patients undergoing surgery for rehabilitative or vision threatening purposes. Preoperative diplopia improved in 10 patients (9.0%) but worsened in 5 patients (4.5%), necessitating surgical correction in 3 patients. There were no significant complications; however, one patient had slight hollowing of the temporalis muscle around the scar that did not necessitate revision, and another patient with a circumscribed retraction of the scar itself underwent surgical correction. Conclusions. The study confirms the efficiency of en bloc lateral wall decompression in GO in a large series of patients, highlighting the low risk of disturbance of binocular functions and of cosmetic blemish in the temporal midface region.

PREGO (presentation of Graves' orbitopathy) study: changes in referral patterns to European Group On Graves' Orbitopathy (EUGOGO) centres over the period from 2000 to 2012.

BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. METHODS: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. RESULTS: The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). CONCLUSIONS: These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Functional and esthetic outcome after bony lateral wall decompression with orbital rim removal and additional fat resection in graves' orbitopathy with regard to the configuration of the lateral canthal region.

PURPOSE: To investigate whether en bloc resection of the lateral orbital wall, including the orbital rim, during lateral wall decompression surgery in patients with Graves' orbitopathy (GO) potentially influences the esthetic and functional aspects of the lateral canthal region. METHODS: Lateral wall decompression was performed in 30 orbits of 18 patients using an upper lidcrease approach involving complete removal of the lateral orbital wall combined with additional orbital fat resection. Patients undergoing surgery before January 2010 were evaluated retrospectively for exophthalmos, vertical lid aperture, lagophthalmos and eye motility. Patients undergoing surgery after January 2010 were evaluated prospectively in addition for horizontal lid aperture, pupillary distance, lateral movement of the lateral canthus, and the disease-specific GO-QOL questionnaire, including subjective and objective assessments of the appearance of the lateral canthal region. RESULTS: A mean exophthalmos reduction of 3.0 mm was achieved, accompanied by a significant reduction in vertical lid aperture but without significant influence on horizontal eye movements. GO-QOL scores disclosed significant improvements with regard to both visual and psychosocial functioning. Although 3 out of 18 patients reported some temporal hollowing, this was confirmed objectively in only one patient. CONCLUSIONS: Our analysis did not demonstrate any impairment of lateral canthal stability or motility functions. Slight scar retraction was objectively confirmed in only one patient, allaying concerns about significant temporal hollowing. Given the good overall esthetic and functional results of this surgical technique, we advocate lateral wall decompression with resection of the orbital rim in GO patients with mild-to-moderate exophthalmos.