Search

BackgroundGraves’ 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.MethodsProspective 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.ResultsBesides 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; pConclusionGO 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.

Differentiated thyroid cancer (DTC) is generally associated with an excellent prognosis. However up to 20% of DTC patients have disease events during subsequent follow-up; rarely patients present an aggressive disease with distant metastases (DM), mainly in the lung and bone. Metastases at unusual sites may also occur, generally in patients with disseminated disease. Orbital localization is rare and only few cases have been described so far.A 36 years-old man, treated with chemo and radiotherapy during childhood for non-Hodgkin lymphoma, was referred for suspicious lymph node (LN) and multiple lung metastases. Total thyroidectomy and latero-cervical (LC) lymphadenectomy were performed: papillary thyroid cancer (PTC), 25 mm, 11/17 LN metastases; pT2N1bM1. Post-treatment total body scan with I-131 showed LN and lung uptake. Eighteen months from diagnosis he presented progressive diplopia, proptosis and right exophthalmos due to an 18 mm orbital metastasis. Hence, due to I-131 refractoriness for structural disease progression despite I-131 therapy, he started therapy with Lenvatinib for 6 months, with initial partial response followed by disease progression, and then with Cabozantinib, which he stopped after 6 months for adverse events and disease progression after therapy reduction. Currently, the patient is receiving Lenvatinib, rechallenge therapy, with disease stabilization and biochemical response. Molecular analysis, performed on both primary and relapsed tumor didn't show any significant pathogenic alteration.This case of DTC with an unusual metastasis in the orbit, may suggest that patient's exposure to chemo- and radiotherapy during pediatric age might have played a role in the subsequent development of this unusually aggressive tumor, reinforcing the recommendation of long-term and intensive follow-up of these patients.

Graves’ disease (GD) is an autoimmune thyroiditis often associated with Graves’ orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats.

BACKGROUND: European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add-on mycophenolate to methylprednisolone in comparison with methylprednisolone alone in patients with moderate-to-severe Graves' orbitopathy.METHODS: MINGO was an observer-masked, multicentre, block-randomised, centre-stratified trial done in two centres in Germany and two in Italy. Patients with active moderate-to-severe Graves' orbitopathy were randomly assigned to receive intravenous methylprednisolone (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) either alone or with mycophenolate (one 360 mg tablet twice per day for 24 weeks). The prespecified primary endpoints were rate of response (reduction of at least two parameters of a composite ophthalmic index [eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and eye muscle motility] without deterioration in any other parameter) at 12 weeks and rate of relapse (a worsening of symptoms that occurred after a response) at 24 and 36 weeks. Rates of response at week 24 and sustained response at week 36 were added as post-hoc outcomes. Prespecified primary outcomes and post-hoc outcomes were assessed in the modified intention-to-treat population (defined as all patients assigned to treatment who received at least one infusion of methylprednisolone, when outcome data were available), and safety was assessed in all patients who received at least one dose of study drug. This trial is registered with the EU Clinical Trials Register, EUDRACT number 2008-002123-93.FINDINGS: 164 patients were enrolled and randomised between Nov 29, 2009, and July 31, 2015. 81 were randomly assigned to receive methylprednisolone alone and 83 to receive methylprednisolone with mycophenolate. In the intention-to-treat population at 12 weeks, responses were observed in 36 (49%) of 73 patients in the monotherapy group and 48 (63%) of 76 patients in the combination group, giving an odds ratio (OR) of 1·76 (95% CI 0·92-3·39, p=0·089). At week 24, 38 (53%) of 72 patients remaining in the monotherapy group and 53 (71%) of 75 patients remaining in the combination therapy group had responded to treatment (2·16, 1·09-4·25, p=0·026). At week 24, relapse occurred in four (11%) of 38 patients in the monotherapy group and four (8%) of 53 patients in the combination group (OR 0·71, 0·17-3·03, p=0·72). At week 36, relapse occurred in an additional three (8%) patients in the monotherapy group and two (4%) patients in the combination group (0·65, 0·12-3·44, p=0·61). At week 36, 31 (46%) of 68 patients in the monotherapy group and 49 (67%) of 73 patients in the combination group had a sustained response (OR 2·44, 1·23-4·82, p=0·011). 23 patients had 24 serious adverse events, with 11 events in ten patients in the combination group and 13 events in 13 patients in the monotherapy group. Mild and moderate (grade 1-2) drug-related adverse events occurred in 16 (20%) of 81 patients receiving monotherapy and 21 (25%) of 83 patients receiving combination therapy (p=0·48).INTERPRETATION: Although no significant difference was seen in the rate of response at 12 weeks or rate of relapse at 24 and 36 weeks, post-hoc analysis suggested that addition of mycophenolate to treatment with methylprednisolone improved rate of response to therapy by 24 weeks in patients with active and moderate-to-severe Graves' orbitopathy.FUNDING: Novartis, Germany.

AIM: To provide age- and gender-specific reference values for orbital fat and muscle volumes in Caucasian adults. METHODS: Computed Tomographic (CT)-scans of 160 orbits from 52 men and 55 women, aged 20 to 80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and muscle volume (MV) were calculated by a previously validated method using the software program Mimics(R).Ratios of fat volume to orbital bony volume (FV/OV) and of muscle volume to orbital bony volume (MV/OV) were determined. RESULTS: OV, FV and MV were all significantly larger in men than in women (p

Ideally the planning of decompression surgery should be adequate to the severity of the orbitopathy, its possible “lipogenic” or “myopathic” variants, the patient’s specific orbital osteology and possible previous surgeries. Due to surgeon’s experience and local traditions, however, a standardized rather than a tailored approach is often offered to the patient. An inferior fornix incision can be used for infero medial bony decompression and/or for removing fat from the medial and lateral inferior orbital quadrants. Through the same route a lateral osteotomy can also be performed although an upper skin crease incision offers a wider access to the lateral orbital wall. As an alternative the swinging eyelid technique, offering an adequate access to the bony orbit and to the orbital fat compartments is a versatile technique that can virtually be used as a standard approach for the greatest majority of patients needing decompression surgery. Orbital decompression by coronal incision is an invasive technique an...

Introduction: Rhabdomyosarcomas in the orbit form a major challenge in terms of cure without severe side effects in childhood cancer. Our specifically developed approach consists of applying brachytherapy to the tumor area using a mold. Analysis of its results for 20 patients was performed. Methods and Materials: Thirteen patients were referred for brachytherapy if complete remission was not reached after chemotherapy (Group I) and 7 in case of relapse (Group II). In total, 20 patients were treated between 1991 and 2007. Four were female and 16 male; their ages varied from 1.1 to 16.5 years, with an average of 8.5 years. After macroscopically radical tumor resection, molds with holes drilled to hold flexible catheters were placed into the orbit. The dose to the clinical target volume was 40-50 Gy. Results: Three patients of Group I and 1 patient of Group II developed local recurrence and underwent exenteration. The progression-free survival in Group I is 71.9% (95% CI 0.44-1.0), in Group II 85.7% (95% CI 0.60-1.0), the overall 5-year survival rate of the entire group is 92% (95% CI 0.76-1.0). During treatment, no serious side effects were observed. The late complications encountered in this series were cataract in 2 patients, 1 of whom also developed mild retinopathy. Two patients with ptosis needed surgical correction. No facial asymmetries or bone growth anomalies were observed. Conclusions: This entire procedure of brachytherapy with a mold offers a tailor-made treatment for orbital rhabdomyosarcomas with only few signs of late toxicity. (C) 2010 Elsevier Inc

ObjectiveFor many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as ‘Lorenzo's oil’. Recently, bone marrow transplantation (BMT) has also been used.Case reportWe report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards.Evidence synthesisA boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I131 (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up.ConclusionsThis case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.

BACKGROUND: In agreement with the systemic nature of Graves' disease, Graves' ophthalmopathy (GO) presents as a symmetric bilateral eye disease in the vast majority of patients. However, asymmetric involvement of both eyes is frequently observed. We hypothesized that sleeping position might be involved in asymmetric GO; when, for example, the preferred sleeping position is on the right side, retrobulbar pressure might be somewhat higher in the right than in the left orbit, resulting in more severe eye changes in the right eye. METHODS: A prospective study in 75 consecutive untreated patients with GO, in whom eye changes and sleeping position were assessed independent of each other. Criteria for asymmetric eye changes were differences between both eyes in the presence of retrobulbar pain or of > or =1 grade in soft tissue involvement, and/or of > or =2 mm in exophthalmos, and/or > or =8 degrees in elevation. Preferred sleeping position was determined by questionnaire. RESULTS: All patients had bilateral GO. Eye changes were symmetrical in 50 patients, and asymmetrical in 25 patients based on differences in proptosis and elevation. Sleeping position did not differ between symmetric and asymmetric GO. Preferred sleeping position was on the left side in 23%; on the right side in 31%; and on the back, on the belly, or unknown in 46%. In patients with asymmetric GO, the most affected ("worst") eye was not related to preferred sleeping position on the right or left side. CONCLUSION: Slight asymmetry of eye changes between both eyes in patients with bilateral GO is not related to preferred sleeping position on either the right or left side

BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy

Objective To present and discuss three cases of apparent reactivation of Graves' orbitopathy (GO) after orbital decompression and to evaluate the incidence of this phenomenon. Design Observational case series and retrospective follow-up study. Participants A few weeks after surgery 2 patients with GO (patients 1 and 2), treated at our institution with rehabilitative bony orbital decompression during the static phase of the disease showed clinical and radiologic evidence of reactivated orbitopathy. After this observation, a sample of 249 patients who had consecutively undergone the same treatment for the same reason before the second of the 2 observed patients was selected for this study. Methods The records of the selected patients were retrospectively reviewed searching for cases presenting with clinical and radiologic evidence of GO reactivated as a consequence of any type of bony orbital decompression. Patients treated with perioperative systemic glucocorticoids or who had concurrent periorbital diseases, injuries, or surgeries, or who had immunocompromised conditions or a follow-up of ≤2 months, were excluded. Main Outcome Measures Incidence of reactivation. Clinical history, clinical and radiologic characteristics, treatment modalities, and time course of the reactivation in patients presenting with this phenomenon. Results Decompression surgery took place between 1994 and 2000. Eleven patients were excluded for having been treated with perioperative glucocorticoids. Only 1 patient (patient 3) presented with reactivation. The incidence of the phenomenon that we regard as reactivation of GO after rehabilitative bony orbital decompression was therefore 1.3% (3/239). In all 3 patients, the reactivation took place a few weeks after surgery, after an early normal convalescence period and could be controlled with systemic immunosuppression or orbital radiotherapy. None of the patients we report developed further episodes of reactivation during the follow-up period (mean, 7.5 years). Conclusions Based on its clinical characteristics, we suggest naming our observation delayed decompression-related reactivation and we propose using its acronym DDRR when referring to it. Although DDRR appears to be a rare event, it is important for physicians and patients to be aware of its possible occurrence with rehabilitative decompression surgery.

Purpose To determine if early rehabilitative orbital decompression in Graves' orbitopathy (GO) leads to a more effective postoperative outcome than the same intervention performed at a later, more likely, fibrotic stage. Design Retrospective comparative case series. Participants The medical records of all GO patients treated with a 3-wall orbital decompression at our institution between 1990 and 2000 were reviewed retrospectively. Only patients operated bilaterally for aesthetic rehabilitation, without preoperative diplopia, were included. They were divided into group 1 (duration of GO Methods and Main Outcome Measures The 2 groups were compared for demographics, smoking habits, preoperative characteristics (immunosuppressive treatments, Hertel values, score in NOSPECS [no signs or symptoms, only signs, soft tissue involvement with symptoms and signs, proptosis, extraocular muscle involvement, corneal involvement, sight involvement] class 2, degree of extraocular muscle enlargement), and surgical outcome (mean reduction of exophthalmos, symmetry of exophthalmos reduction, reduction in upper and lower lid retraction, any persistent periorbital swelling requiring cosmetic eyelid surgery, postdecompression diplopia). Results The medical records of 125 of 376 patients were selected for this study. There were no differences between group 1 (n = 70) mean GO duration (2.2±0.8 years) and group 2 (n = 55) mean GO duration (9.0±5.4 years) with respect to demographics, smoking habits, and preoperative characteristics except for the degree of extraocular muscle enlargement, which was significantly greater in group 1 ( P = 0.039). There was no difference in surgical outcomes between the 2 groups, with the exception of postdecompression diplopia, which was significantly more frequent in group 1 than in group 2 (29% vs. 13%, P = 0.033). Conclusions In GO, early rehabilitative orbital decompression does not improve surgical outcome and is associated with a higher risk of postdecompression diplopia.

Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

Summary objectives The importance of facial disfigurement in many diseases necessitates a reliable and valid measure of disfigurement severity for clinical studies. The hypothesis is that a universal concept of disfigurement exists and can be measured in a reliable way. The objectives of this study were to investigate if persons, in particular patients and physicians, can agree on facial disfigurement severity; and to determine the relative contribution of predefined clinical characteristics of patients with Graves’ ophthalmopathy (GO) to the overall rating of facial disfigurement severity. design A panel study was carried out in four different panels, each consisting of four members. patients We randomly selected 100 slide pairs of GO patients from four available study populations, involving mild, moderate and severe GO patients (mean age 49 years, 76% female) who were treated with either radiotherapy, sham-irradiation, prednisone or orbital decompression. measurements All panel members individually scored the disfigurement severity of 100 GO patients shown on standardized slides on a Visual Analog Scale. In total, 1600 ratings were collected. We calculated within- and between-panel agreement of disfigurement severity and identified determinants of disfigurement. results Agreement within a panel varied from 0·65 to 0·79 and was highest within the panel of ophthalmologists. Between-panel agreement was 0·67 and was highest between ophthalmologists and laypersons. Compared with the global average, patients overrated and endocrinologists underrated disfigurement severity. Female panellists rated the patients, on average, more disfigured than male panellists. Important determinants of disfigurement were eyelid retraction, severe eyelid swelling and proptosis. Their relative importance was consistent across panels and in contrast to current measures of GO severity. conclusion Facial disfigurement severity can be measured in a reliable way using panels of panellists. Except for some systematic differences between panellists, facial disfigurement does not seem to be in the eye of the beholder.

Summary OBJECTIVE The Graves’ ophthalmopathy quality of life questionnaire (GO-QOL) is the first instrument available to measure health-related quality of life (HRQL) of patients with Graves’ ophthalmopathy. The main objective of this study was to define a minimal clinically important difference (MCID) in score on the GO-QOL that can be considered an important improvement in HRQL by examining changes in GO-QOL scores in patients who subjectively report improvement from their treatment. A secondary objective was to test the longitudinal validity of the GO-QOL, using prespecified hypotheses about expected treatment effects.

Hintergrund. Durch eine Befragung wurde die Meinung von Okularisten zu Orbitaimplantaten, sekundaren Korrektureingriffen, Zufriedenheit der Patienten sowie Kooperation zwischen Ophthalmologen und Okularisten ermittelt. Methode. Allen 29 in Deutschland und 4 in den Niederlanden tatigen Okularisten wurde ein Erhebungsbogen vorgelegt. Ergebnisse. Primare Orbitaimplantate werden empfohlen, bevorzugt Dermis-Fett-Transplantat und “Baseball”-Implantat. Operationsmethode und postoperativer Verlauf wurden fur das Ergebnis als wichtig erachtet. Gegenuber sekundaren Korrekturen eines Postenukleationssyndroms besteht Skepsis. Die Zusammenarbeit zwischen Okularist und Augenarzt wird von der Mehrzahl als mangelhaft beurteilt, ebenso die Informationsvermittlung der Augenarzte an die Patienten. Schlussfolgerungen. Okularisten fordern optimale Operationsmethoden bei der Enukleation und die Verwendung von Orbitaimplantaten. Unbedingt verbesserungsbedurfig ist die Kooperation zwischen Okularisten und Augenarzten. Die Umfrageergebnisse deuten auf erheblichen Handlungsbedarf bei der Betreuung anophthalmischer Patienten hin.

The purpose of this paper was to evaluate the appearance and location of the healed intranasal ostium and the internal aperture of the common canaliculus after uncomplicated external dacryocystorhinostomy (DCR). In 21 patients who underwent uncomplicated external DCR, the distances between the lacrimal puncta and the internal aperture of the common canaliculus were measured during surgery. The measurements were taken with a 1 mm diameter Bowman probe graded in millimeters. These measurements were recorded and considered the landmarks for the spatial localization of the internal aperture of the canaliculus. After surgery, under endoscopic control, the same method was used to measure the distance between the lacrimal puncta and the internal ostium, which was defined as the aperture through which it was possible to visualize the very first protrusion of the probe into the nose. The intra- and post-operative measurements were compared. Endoscopic photos of the healed endonasal ostium were also taken. The photos showed that when DCR procedures were not complicated by scarring or mucosal adhesions, the lacrimal sac became a depression perfectly integrated within the nasal mucosa. The scar at the site of junction between the nasal and the lacrimal sac mucosa appeared as a large-diameter pearl-like colored frame that surrounded the depression. In the context of the depression a small aperture, which presented a diameter of around 2 mm, could be easily visualized. The spatial location of this aperture corresponded to the internal aperture of the common canaliculus (p < 0.05).

Background: Secondary orbital implants are used for the correction of the post-enucleation socket syndrome (PESS). This study evaluates retrospectively the post-operative course, complications, additional surgery, long-term cosmetic and functional results, and patient's satisfaction after secondary orbital implants.

Purpose To present and discuss the occurrence of a traumatic neuroma subsequent to inferomedial orbital decompression surgery in Graves' orbitopathy. Methods Case report. Results Approximately 1 month after surgery, a patient who underwent bilateral rehabilitative inferomedial orbital decompression developed a mass with clinical and radiologic characteristics compatible with a traumatic neuroma of the left infraorbital nerve. The lesion, which was thought to be the result of unnoticed nerve trauma at the time of surgical dissection of the infraorbital canal, remained stable in shape and other imaging characteristics during the 39-month follow-up period. Symptoms of trigeminal neuralgia could be only partially controlled with medical therapy (oral pregabalin 75 mg 3 times daily). Conclusions The second branch of the trigeminal nerve may be damaged in the course of orbital floor removal decompression for Graves' orbitopathy. This may potentially induce the formation of traumatic or amputation neuromas. Such lesions should be included in the potential complications of decompressions when counseling patients about to undergo this type of surgery, as they are difficult to treat and may cause persistent and disabling pain.

Objective To investigate the value of somatostatin receptor scintigraphy (SSRS) in the diagnosis of optic nerve sheath meningiomas (ONSMs). Design Prospective, comparative case series. Participants SSRS was used to investigate 68 orbits in 61 patients diagnosed with an orbital tumor. Methods Patients were injected intravenously with 200 MBq of indium-111 ( 111 In)-octreotide. SSRS with single photon emission computed tomography (SPECT) was performed 24 hours after injection. Main Outcome Measures The 111 In-octreotide uptake in orbital lesions was determined by semiquantitative uptake-ratio analysis (lesion/brain) on attenuation-corrected transverse SPECT slices. Results All orbital meningiomas, including 14 ONSMs and 12 spheno-orbital meningiomas, showed high median 111 In-octreotide uptake ratios of 7.2 (range, 4.6–15.4) and 16.3 (range, 4.6–15.4), respectively. In 7 patients with a diagnosis of ONSM, the SSRS uptake ratio was significantly decreased 2.7 (1–6.8) after treatment with 54 Gy of radiotherapy. Median uptake ratios of other tumors were vascular anomalies/vascular tumors, 1.2 (range, 0.5–3.3); non-Hodgkin lymphomas, 2.9 (range, 0.9–4.2); optic nerve gliomas, 1.5 (range, 0.2–3.3); and idiopathic orbital inflammation, 1.6 (range, 1.4–1.9). By using a threshold uptake ratio of 5.9, the sensitivity of SSRS with 111 In-octreotide for ONSM was 100%, with a specificity of 97.2%. Conclusions SSRS is a useful additional tool in diagnosing ONSM and has 100% sensitivity and 97% specificity at a threshold uptake ratio of 5.9. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Exophthalmos and eyelid retraction are typical symptoms of many orbital or systemic diseases, Graves' orbitopathy being the commonest. Independently from the cause, both may increase evaporation with drying of the ocular surfaces resulting in pain, tearing, and photophobia. The structural integrity of the cornea may also be damaged with possible compromise of the visual function. Acute onset of exophthalmos and/or eyelid retraction deserves maximum attention. In order to avoid corneal decompensation and waiting for a more definitive treatment, eye lubricants, moisture chambers, swimming goggles, temporary tarsorrhaphies or blepharorrhaphies represent the measures of choice. Exophthalmos depending on neoplastic, vascular, infectious, inflammatory or malformative causes is, in the majority of cases, amenable of medical or surgical causative treatment while, for endocrine exophthalmos the commonest treatment is surgical and symptomatic and consists of orbital bone decompressions. Eyelid retraction due to active inflammatory processes can be treated medically while for persistent eyelid retraction the treatment is surgical and based on lengthening of the anterior, and/or posterior, and/or mid-eyelid lamellae. Exophthalmos and eyelid retraction due to Graves' orbitopathy, their influence on ocular surface disorders and the treatment of these conditions will be specifically analysed in this chapter.

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

PURPOSE. There is no consensus as how to calculate orbital soft tissue volume based on CT or MRI scans. The authors sought to validate their technique and to assess the intraobserver and interobserver variability of their calculations of bony orbital volume (OV), orbital fat volume (FV), and extraocular muscle volume (MV) on CT scans of humans. METHODS. The authors calculated these volumes with the use of a manual segmentation technique on CT scans with commercially available software. Two observers (one of them masked) calculated the orbital soft tissue volumes in a CT scan of a phantom constructed of dry skull, butter, and chicken muscle. These calculations were compared with previously taken standard volume measurements of these materials. Repetitive calculations on one CT scan by the same observer were compared. Soft tissue volumes taken from 10 orbital CT scans were calculated by two observers and compared. From the data acquired, intraobserver and interobserver variability was calculated. RESULTS. Outcomes of these calculations using this software approximated the volumes of the phantom measured with standardized techniques. Accuracy of the phantom calculations between the two observers varied from +0.7% to -0.7% for FV and between -1.5% and -2.2% for MV. Mean differences between the repeated calculations were smaller than 5%. The intraclass correlation coefficient varied from 0.961 to 0.999. CONCLUSIONS. Calculating orbital soft tissue volume using a manual segmentation technique for CT scans is a reliable and accurate tool.

Purpose To investigate whether orbital irradiation influences the outcome of decompression surgery in Graves orbitopathy. Design Retrospective, comparative case series. Methods The medical records of all the patients with Graves orbitopathy treated with a three-wall orbital decompression through a coronal approach at our institution between January 1, 1990 and December 31, 2000 were reviewed. Only patients who underwent bilateral surgery for aesthetic rehabilitation, without preoperative diplopia, and who, in the active phase of the disease, had received orbital radiotherapy alone (20 Grays (Gy) in 10 daily fractions of two Gy over a period of two weeks; group R), systemic glucocorticoids alone (daily administration for more than three months independently from the dosage; group G), or both radiotherapy and glucocorticoids (group RG) were selected. Groups were compared for demographics, smoking habits, preoperative characteristics, and surgical outcome (mean reduction of exophthalmos, reduction of lid retraction, persistence of periorbital swelling requiring cosmetic eyelid surgery, onset of diplopia within 20 degrees of the central position of gaze, and variations in the peripheral field of diplopia). Results Sixty-one of 376 patients were selected for this study. There were no differences between group R (n = 29), group G (n = 15), and group RG (n = 17) with respect to demographics or predecompression characteristics, whereas the number of smokers was significantly greater in group RG (P= .019). We could not find differences in surgical outcome by comparing the three groups. Conclusions The total radiation dose, fraction size, and irradiated volume commonly used to treat active Graves orbitopathy do not adversely interfere with the outcome of rehabilitative decompression surgery.

Exophthalmos and eyelid retraction are typical symptoms of many orbital or systemic diseases, Graves’ orbitopathy being the commonest. Independently from the cause, both may increase evaporation wit

Summary Objective Only a small percentage of Graves’ ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first-line treatment, thus preventing treatment with steroids. Design and subjects We performed a randomized trial in 15 patients with very active GO and optic neuropathy. Six patients were treated with surgical decompression, and nine with methylprednisolone i.v. pulses for 2 weeks, followed by oral prednisone for 4 months. The primary outcome was determined by changes in visual acuity. If the eye disease deteriorated despite treatment or did not improve sufficiently, patients were switched to the other treatment arm. Results The severity and activity of GO in both groups were similar at baseline. The Clinical Activity Score (CAS) was 6·3 ± 0·8 in the surgical group vs. 6·0 ± 0·5 in the steroids group and the Total Eye Score was 24 ± 6 vs. 25 ± 6. In the surgery group, 5/6 patients (82%) did not respond because of insufficient improvement in vision (n = 3) or persistent chemosis (n = 2), and all needed further immunosuppression. In the steroids group, 4/9 patients (45%) did not improve in visual acuity (P = 0·132 vs. surgery group), and these needed decompressive surgery. All patients in whom therapy failed were switched to the other treatment arm and visual acuity improved in almost all patients. Visual acuity improved from 0·36 (0·02–0·40) to 0·90 (0·63–1·0) in the surgery group and from 0·50 (0·32–0·63) to 0·75 (0·32–1·0) in the steroids group at 52 weeks. At long-term follow-up in the surgery group 3/6 patients required squint surgery and 5/9 patients in the steroids group. Eyelid surgery was performed in 5/6 patients in the surgery group and in 4/9 patients in the steroids group. Conclusion Immediate surgery does not result in a better outcome and therefore methylprednisolone pulse therapy appears to be the first-choice therapy.

To determine if early rehabilitative orbital decompression in Graves' orbitopathy (GO) leads to a more effective postoperative outcome than the same intervention performed at a later, more likely, fibrotic stage.Retrospective comparative case series.The medical records of all GO patients treated with a 3-wall orbital decompression at our institution between 1990 and 2000 were reviewed retrospectively. Only patients operated bilaterally for aesthetic rehabilitation, without preoperative diplopia, were included. They were divided into group 1 (duration of GO4 years) and group 2 (durationor = 4 years).The 2 groups were compared for demographics, smoking habits, preoperative characteristics (immunosuppressive treatments, Hertel values, score in NOSPECS [no signs or symptoms, only signs, soft tissue involvement with symptoms and signs, proptosis, extraocular muscle involvement, corneal involvement, sight involvement] class 2, degree of extraocular muscle enlargement), and surgical outcome (mean reduction of exophthalmos, symmetry of exophthalmos reduction, reduction in upper and lower lid retraction, any persistent periorbital swelling requiring cosmetic eyelid surgery, postdecompression diplopia).The medical records of 125 of 376 patients were selected for this study. There were no differences between group 1 (n = 70) mean GO duration (2.2+/-0.8 years) and group 2 (n = 55) mean GO duration (9.0+/-5.4 years) with respect to demographics, smoking habits, and preoperative characteristics except for the degree of extraocular muscle enlargement, which was significantly greater in group 1 (P = 0.039). There was no difference in surgical outcomes between the 2 groups, with the exception of postdecompression diplopia, which was significantly more frequent in group 1 than in group 2 (29% vs. 13%, P = 0.033).In GO, early rehabilitative orbital decompression does not improve surgical outcome and is associated with a higher risk of postdecompression diplopia.

To compare the extent of mucosal margins remaining unsutured at the end of external dacryocystorhinostomy (DCR) using single or double flap techniques and to evaluate the influence on outcome.Prospective, consecutive case series.The number and length of mucosal margins remaining unsutured at the end of external DCR were evaluated in 64 patients. Mucosal anastomosis was performed using either a conservative (group 1) or extended (group 2) double flap, or a single flap (group 3) dissection. Patients were selected for group 1 if the regional anatomy permitted the desired dissection. All other patients were randomized to group 2 or 3. The mean length of unsutured mucosal margins was calculated for each group. Subjects were followed up to 12 months, with final success rate recorded.In groups 1, 2, and 3 respectively: 11, 24 and 29 patients were recruited; four, 12, and 10 mucosal margins remained unsutured; and the mean length of unsutured mucosal margins was 16.36 mm (SD = 2.8), 70.66 mm (SD = 9.3), and 62.00 mm (SD = 6.0). The mean length of unsutured mucosal margins was significantly different, although groups 1 and 2 collectively did not have a significantly different mean length of unsutured mucosal margin from group 3. Mean follow-up was 11 months (SD = 2.2), 63 patients (98.43%) had a successful outcome with no significant difference among groups (P = .429).Different patterns of mucosal dissection in external DCR create a different number and extent of unsutured mucosal margins which do not appear to adversely affect the success rate of external DCR.

The importance of facial disfigurement in many diseases necessitates a reliable and valid measure of disfigurement severity for clinical studies. The hypothesis is that a universal concept of disfigurement exists and can be measured in a reliable way. The objectives of this study were to investigate if persons, in particular patients and physicians, can agree on facial disfigurement severity; and to determine the relative contribution of predefined clinical characteristics of patients with Graves' ophthalmopathy (GO) to the overall rating of facial disfigurement severity.A panel study was carried out in four different panels, each consisting of four members.We randomly selected 100 slide pairs of GO patients from four available study populations, involving mild, moderate and severe GO patients (mean age 49 years, 76% female) who were treated with either radiotherapy, sham-irradiation, prednisone or orbital decompression.All panel members individually scored the disfigurement severity of 100 GO patients shown on standardized slides on a Visual Analog Scale. In total, 1600 ratings were collected. We calculated within- and between-panel agreement of disfigurement severity and identified determinants of disfigurement.Agreement within a panel varied from 0.65 to 0.79 and was highest within the panel of ophthalmologists. Between-panel agreement was 0.67 and was highest between ophthalmologists and laypersons. Compared with the global average, patients overrated and endocrinologists underrated disfigurement severity. Female panellists rated the patients, on average, more disfigured than male panellists. Important determinants of disfigurement were eyelid retraction, severe eyelid swelling and proptosis. Their relative importance was consistent across panels and in contrast to current measures of GO severity.Facial disfigurement severity can be measured in a reliable way using panels of panellists. Except for some systematic differences between panellists, facial disfigurement does not seem to be in the eye of the beholder.

To improve management of patients with Graves’ orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves’ Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves’ orbitopathy patients. This form was used in this first multi-center study. Aim: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. Methods: Newly referred patients with Graves’ orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. Results: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis $ 21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P , 0:02). There were no important differences among the eight centers regarding the severity and the activity of their patients. Conclusions: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible. European Journal of Endocrinology 148 491–495

Aim—To analyse the extent of bony orbital volume reduction after enucleation in humans. Methods—Volumetric studies on bony orbital volumes based on three dimensional reconstructions acquired from high resolution computed tomograph (CT) scans were performed in 29 patients with acquired anophthalmia and four patients before enucleation (controls). Eight patients (follow up 25‐52 years) were enucleated in childhood aged between 0.4 and 8 years (group I), 21 in adulthood aged between 15 and 53 years. Fifteen of these patients (group IIa) had long standing anophthalmia (follow up 7‐53 years), six patients (group IIb) were enucleated 9 months to 4 years before CT. Results—Bony orbital volumes were reduced in all patients with long standing anophthalmia. The median percentage reduction in enucleated orbits was 7.0% in group I, 3.8% in group IIa, and 1.9% in group IIb. In patients with long standing anophthalmia (I and IIa) the reductions were statistically significantly diVerent (p

Purpose To assess the level of contamination of full-thickness skin grafts stored with or without an antibiotic cover. Methods Full-thickness skin grafts were harvested from 40 bilateral upper lid blepharoplasties. Before surgery the face was sterilised, the head of the patient was packed with sterile, single-use surgical drapes and the whole face was left exposed. The harvested full-thickness skin grafts were conserved in sterile containers at 4 °C for 6 days, rolled in gauze moistened with either 4 ml of sterile saline solution (group I) or with 4 ml of gentamicin solution (2 mg/ml) (group II). The degree of contamination, expressed in colony forming units (CFU), was evaluated on days 2, 3, 4, 5 and 6. Identification of the microorganisms was done to species level following standard procedures and commercial methods. Results In group I 2 grafts (5%) were negative during the whole observation period while the other 38 grafts (95%) presented a degree of contamination ranging from 102 to 104 CFU. Microorganisms isolated were: Staphylococcus epidermidis (24 cases), Staphylococcus aureus (5 cases), Staphylococcus saprophyticus (2 cases), Pseudomonas aeruginosa (4 cases), Serratia liquefaciens (1 case) and Klebsiella oxytoca (2 cases). In group II, 26 grafts (65%) were negative during the whole observation time while in 14 cases (35%) a few colonies (3 to 6) of Candida albicans were isolated on day 2 and remained constant in number for the whole observation time. Conclusions The storage of full-thickness skin graft with an antibiotic cover is more reliable than the storage of full-thickness skin graft without an antibiotic cover.

The prognosis of primary choroidal malignant melanoma (PCMM) is fatal if no early reliable diagnosis is performed. Any incisional biopsy is impossible, and diagnosis is only based on instrumental examinations. The purpose of this study is to evaluate the reliability of ultrasonography, fluorescein videoangiography (FV), indocyanine green videoangiography (ICGV), magnetic resonance (MR) and radioimmunoscintigraphy (RIS) in the diagnosis of PCMM in a series of 12 eyes in which the tumor was suspected. A presumed diagnosis of PCMM was made when a positive result was obtained with 3 or more methods. The presumed diagnosis was then compared with histological findings (true value) in 4 enucleated eyes. The sensitivity and specificity of every single method were evaluated comparing its results with the final presumed diagnosis and with the histological findings. Sensitivity and specificity of every single method have been expressed as percentage of correspondence with the presumed diagnosis. Sensitivity was 100% for ultrasonography, MR, FV, ICGV and 67% for RIS. Specificity was 92% for ultrasonography, 87% for RIS, 83% for MR and 82% for FV and ICGV. This study indicates that the ophthalmologist can obtain a good diagnostic reliability in the case of PCMM using only ultrasonography, FV and ICGV. Besides MR and RIS are important adjunctive methods to ophthalmological investigations for the diagnosis of PCMM.

PURPOSE: To evaluate the contribution of maximal removal of the deep lateral wall of the orbit to exophthalmos reduction in Graves' orbitopathy and its influence on the onset of consecutive diplopia. DESIGN: Case-control study. METHODS: The medical records of two cohorts of patients affected by Graves' orbitopathy with exophthalmos >= 23 mm, without preoperative diplopia, were retrieved at random from the pool of patients decompressed for rehabilitative reasons at our institution (01/1990 to 12/2003), and retrospectively reviewed. They had been treated with an extended (cases, group 1, n = 15) or conservative (controls, group 2, n = 15) 3,wall orbital decompression performed through a coronal approach. The deep portion of the lateral wall had been removed in the extended decompression group while preserved in the conservative decompression group. Demographics, preoperative characteristics, and surgical outcome were compared. The difference in mean exophthalmos reduce tion between groups 1 and 2 was considered to be the contribution of the deep lateral wall to reduction of exophthalmos. RESULTS: Groups 1 and 2 were drawn from a pool of 37 and 335 patients, respectively. Demographics and preoperative characteristics of the two groups were not significantly different. The mean contribution of the deep lateral wall to exophthalmos reduction was 2.3 mm. The onset of consecutive diplopia was not significantly differ, ent between the two groups (case n = 2/15, controls n = 5/15; P = .203). Diplopia resolved spontaneously in all the patients of group 1, while all the patients of group 2 required surgery. CONCLUSIONS: Removal of the deep lateral orbital wall as part of a coronal-approach, 3-wall decompression, enhances the degree of exophthalmos reduction without increasing the risk of consecutive diplopia. (Am J Ophthalmol 2005. (c) 2005 by Elsevier Inc. All rights reserved.)