Nicola Currò

Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO

Summary of consensus a. All patients with GO should (Fig. 1):Be referred to specialist centers;Be encouraged to quit smoking;Receive prompt treatment in order to restore andmaintain euthyroidism.b. Patients with sight-threatening GO should be treatedwith i.v. GCs as the first-line treatment; if the responseis poor after 1–2 weeks, they should be submitted tourgent surgical decompression.c. The treatment of choice for moderate-to-severe GO isi.v. GCs (with or without OR) if the orbitopathy isactive;surgery(orbitaldecompression,squintsurgery,and/or eyelid surgery in this order) should beconsidered if the orbitopathy is inactive.d. In patients with mild GO, local measures and anexpectant strategy are sufficient in most cases, buttreatment may be justified if QoL is affectedsignificantly. In memoriam This document is dedicated to the memory of MarkPrummel (1956–2005), one of the founders ofEUGOGO, who greatly contributed to expanding ourunderstanding of clinical and therapeutic aspects of GO.

Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy.

Luigi Bartalena, Lelio Baldeschi, Alison J. Dickinson, Anja Eckstein, Pat Kendall-Taylor, Claudio Marcocci, Maarten P. Mourits, Petros Perros, Kostas Boboridis, Antonella Boschi, Nicola Curro, Chantal Daumerie, George J. Kahaly, Gerasimos Krassas, Carol M. Lane, John H. Lazarus, Michele Marino, Marco Nardi, Christopher Neoh, Jacques Orgiazzi, Simon Pearce, Aldo Pinchera, Susanne Pitz, Mario Salvi, Paolo Sivelli, Matthias Stahl, Georg von Arx, and Wilmar M. Wiersinga

Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures

Aim: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves’ orbitopathy (GO) receiving surgery for disfiguring proptosis. Method: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. Results: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. Conclusions: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: Effects on orbital lymphocytic infiltrates

Rituximab (RTX) has been shown in previous work to improve thyroid-associated ophthalmopathy (TAO), but very little data is available on the effects of RTX in the target tissues. We studied the effects of RTX on peripheral lymphocytes and on the intra-orbital infiltrates in one patient with severe TAO who was treated with two cycles of therapy. Intra-orbital tissues derived at decompression from 3 patients with moderate-severe and 1 with severe TAO, treated with standard immunosuppression, were studied as controls. Peripheral blood lymphocytes were analyzed throughout the study period, while intra-orbital tissue lymphocytes at decompression. In the patient treated with RTX visual field and acuity improved in response to peripheral CD 20+ cell depletion, although there was a proportion of persisting CD 19+ cells. After RTX re-treatment the patients optic nerve function improved only transiently. The number of CD 20+ cells was lower in orbital tissues (0-1%) than in the peripheral blood (3%). A greater percentage of CD 19+ was observed in the orbits compared to the periphery, most of which were CD 19+5+ (80%). By immunohistochemistry, orbital tissues from all control patients showed CD 20+ and CD 3+ cells, independently of the duration of TAO and of the treatment with either steroids or radiotherapy. This is the first report on the therapeutic effect of RTX in active, severe TAO associated to the depletion of intra-orbital CD 20+ lymphocytes. After RTX, CD 19+5+ lymphocytes were shown to be 2-3 times more prevalent in the orbital infiltrates, compared to CD 20+ cells. Persistence of autoreactive cells is believed to be related to TAO relapse.

Small Dose of Rituximab for Graves Orbitopathy: New Insights Into the Mechanism of Action

citing role as increased levels of dopamine have been shown to cause choroidal vasodilation. The time course of effusion development in this case is similar to that with topiramate. This suggests that if bupropion use were causative, one of its major active metabolites, hydroxybupropion or theobupropion (both with half-lives similar to that of topiramate), may be responsible. Both metabolites inhibit dopamine and norepinephrine reuptake; thus, norepinephrine could also have a role. Bilateral effusions have been reported with venlafaxine hydrochloride, a norepinephrine and serotonin reuptake inhibitor. Bupropion is a common medication, and it is unclear why other cases have not been reported. If bupropion use were causative in this case, the absence of other similar reports may reflect underreporting; alternatively, this patient may harbor a rare, private polymorphism that causes bupropion or one of its metabolites to become a particularly potent choroidal vasodilator.

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.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement

BackgroundGraves’ orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682).The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves’ hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves’ Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02–1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00–5.00/10,000; unilateral GO 0.50–1.50/10,000.ConclusionGO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Management of mild graveś orbitopathy

Mild GO is usually diagnosed based on the assessment of soft tissue inflammation, in particular eyelid and conjunctival edema and hyperaemia, mild proptosis ( 3 mm above normal for race and gender) and only minor, if any, eye muscle involvement [1] (fig. 1) [see chapter by Dickinson, pp. 1–25]. In a proportion of patients, eye muscles may be significantly involved [2], although motility tests may not reveal the actual degree of inflammation unless orbital imaging is performed [3, 4]. Orbital changes in mild GO are sometimes uniquely limited to eye muscles in the absence of soft tissue inflammation [5]. Recent work has shown that eye muscle enlargement by itself may be more significantly correlated to proptosis than retroocular fat and connective tissue hypertrophy [6].

Declaración de consenso del Grupo europeo sobre la orbitopatía de Graves (EUGOGO) sobre el tratamiento de la orbitopatía de Graves (OG)

LUIGI BARTALENAa, LELIO BALDESCHIb, ALISON DICKINSONc, ANJA ECKSTEINd, PAT KENDALL-TAYLORe, CLAUDIO MARCOCCIf, MAARTEN MOURITSg, PETROS PERROSh, KOSTAS BOBORIDISi, ANTONELLA BOSCHIj, NICOLA CURROk, CHANTAL DAUMERIEl, GEORGE J. KAHALYm, GERASIMOS E. KRASSASn, CAROL M. LANEo, JOHN H. LAZARUSp, MICHELE MARINOf, MARCO NARDIq, CHRISTOPHER NEOHc, JACQUES ORGIAZZIr, SIMON PEARCEs, ALDO PINCHERAf, SUSANNE PITZt, MARIO SALVIu, PAOLO SIVELLIv, MATTHIAS STAHLw, GEORG VON ARXx Y WILMAR M. WIERSINGAy