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This work revisits the melting behaviour of neptunium dioxide, an actinide compound which can be produced in the nuclear fuel during operation, and which has an important impact on the nuclear fuel and waste radioactivity especially on the very long term. The present experimental approach employs remote laser heating under controlled atmosphere and fast pyrometry. This technique circumvents problems encountered by more traditional heating techniques, in particular, the reaction between sample and containment at temperatures beyond 2500 K. In addition, only a small amount of sample material is required, which is an advantage with respect to the radioactivity and limited availability of neptunium. The NpO2 melting/freezing temperature has been measured to be 3070 K ± 62 K, much higher than previous values (around 2830 K) obtained by more traditional thermal analysis methods. The large amount of experimental data collected allowed a consistent statistical analysis. It seems likely, although not fully evident from the present results, that the high oxygen potential at temperatures around melting leads to a slightly hypo-stoichiometric congruent melting composition, as already observed in other actinide (ThO2, PuO2) and lanthanide oxides (e.g., CeO2). Finally, a recently developed phase-field model was used for the simulation of the observed thermograms, allowing a deeper insight in material properties that are difficult to directly measure. For example, a polaron contribution to the high-temperature thermal conductivity, well accepted for the commonly studied actinide oxide UO2, is shown here to likely be present in NpO2. [ABSTRACT FROM AUTHOR]

A laser heating technique is employed to study the melting behaviour of cerium dioxide, CeO2, a refractory compound with very high oxygen pressure. The strong tendency of cerium dioxide to reduce to hypostoichiometric compounds, even in the presence of trace amounts of oxygen, leads to discrepancies in the measured melting temperature depending on whether an oxidising, neutral or reducing atmosphere is used during the experiment. The purpose of this study is to measure the melting temperature of initially stoichiometric Ce O2 under different controlled atmospheres: reducing or oxidizing. A high pressure cell was used to limit the oxygen losses while measuring the melting behaviour of initially stoichiometric cerium dioxide samples. The results confirm a strong influence of the atmosphere on the melting temperature: when reducing conditions were simulated a melting temperature of (2675 ± 47) K was measured, in oxidizing conditions it was measured (2743 ± 33) K. The measured values are in line with existing literature data obtained under different conditions. Only under a high buffer gas pressure. He at 15 MPa the highest reported temperature of 3000 K was observed here, although with poor repeatability. [ABSTRACT FROM AUTHOR]

New metrological facilities for high temperature measurements of thermophysical properties have been recently developed by European National Metrology Institutes (NMIs). This work, performed in the framework of the joint research project “MetroFission”, aims to provide reliable measurements up to 2000^\circ C for materials having thermal properties similar to those required for design of new generations of fission reactors. This will enable to improve the traceability to the International System of Units (SI) of measurements performed by nuclear research laboratories. The validation of these reference apparatuses was done at high temperature by measuring the thermal diffusivity and normal spectral emissivity of an isostatic graphite and pure tungsten. [ABSTRACT FROM PUBLISHER]

No real new treatment has been developed in the last decade for thyroid eye disease (TED). Glucocorticoids (GC), orbital radiotherapy (OR) or a combination of both, are most frequently used in the treatment of TED for the iv immunosuppressive effects. However, we now have novel information regarding the when and how corticosteroids should be used. In general, the iv route of GC administration is preferable to the oral use. iv GC should be used at much lower doses than previously (4.5 to 6 g cumulative dose), possibly with a small dose of oral prednisone (or equivalent) in the interpulse period and for a few weeks after completion of iv treatment. Careful assessment of patients before treatment for identification of possible risk factors of liver toxicity is mandatory. Finally, monitoring of patients, particularly for liver function, is warranted during and after treatment. Although OR's effectiveness was disputed by a study few years ago, more recent studies have reconfirmed its beneficial role in TED and shown that it still has a positive role to play in patients with active TED. Finally, although Somatostatin-analogs (SM-as) gave the impression some years ago that might represent an effective weapon for TED management and initial, mostly uncontrolled and non-randomized trials with small number of patients supported this notion, newer randomized, double-blind studies with larger number of patients have not confirmed the first optimistic results. The question after that is if SM-as should be considered as a rubber bullet in the treatment of TED and we have to forget about them. The answer should be “no yet,” especially in the light that the role of SM-as may be revitalized by the use of analogs with higher affinity for all somatostatin receptors subtypes. Such analogs are now available and under investigation in different diseases with very promising results. [ABSTRACT FROM AUTHOR]

The work has been presented at The Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Fort Lauterdale, Florida, May 1999.Purpose To evaluate inter- and intraobserver variability of the R/D score in assessing the iris configuration in Pigment Dispersion Syndrome patients.Methods Fifty-seven high-resolution ultrasound biomicroscopy images were obtained by a single ophthalmologist. All images were examined twice by each of three ophthalmologists, the second assessment being at least 2 weeks after the first. Each observer was masked to their colleagues’ and their previous measurements. R/D scores were calculated at each examination. Agreement between and amongst observers was assessed using Bland–Altman plots. In addition, the R/D scores were categorised and reassessed using the Kappa statistic.Results Intraobserver variability was small, the average differences between first and second scores of each observer being less than 0.01 units. Agreement within observers was 89% or higher, with Kappa values of 0.8 or higher, indicating almost perfect agreement. Interobserver variability was, however, greater. Although there was substantial agreement between two of the observers (87% agreement, first assessment; 80%, second assessment with respective kappa statistics of 0.78 and 0.66), they only moderately agreed with the other observer (kappa statistics between 0.55 and 0.68).Conclusions This study suggests that when using R/D scores to demonstrate changes in iris configuration, assessments should preferably be made by the same observer.Eye (2002) 16, 722–726. doi:10.1038/sj.eye.6700116 [ABSTRACT FROM AUTHOR]

Introduction: The management of Graves' ophthalmopathy is shared between endocrinologists and ophthalmologists. Assessment and treatment of the active inflammatory stage is based on the clinical activity and disease severity scores, often without detailed eye examination by the treating endocrinologist. Materials and Methods: We report a case of acute viral keratoconjunctivitis occurring during immunosuppressive treatment for Graves' ophthalmopathy which masked the signs, symptoms and response to treatment of the orbitopathy, posing a differential diagnostic challenge. Results: The apparent worsening of the ophthalmopathy and the increased clinical activity score led the treating endocrinologist to alter the management decisions. Ophthalmic examination confirmed the diagnosis of viral keratoconjunctivitis and immunosuppressive treatment was continued with significant final improvement of Graves' ophthalmopathy. Discussion: Ocular surface conditions, unrecognised by the treating physician, may complicate the assessment of thyroid ophthalmopathy when detailed eye examination is not performed. The diagnostic challenge of Graves' ophthalmopathy requires a combined approach by an endocrinologist and an ophthalmologist working as a team. [ABSTRACT FROM AUTHOR]

Background: Graves' 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.Conclusion: GO 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. [ABSTRACT FROM AUTHOR]

TaC, HfC and their solid solutions are promising candidate materials for thermal protection structures in hypersonic vehicles because of their very high melting temperatures (>4000 K) among other properties. The melting temperatures of slightly hypostoichiometric TaC, HfC and three solid solution compositions (Ta1−xHfxC, with x = 0.8, 0.5 and 0.2) have long been identified as the highest known. In the current research, they were reassessed, for the first time in the last fifty years, using a laser heating technique. They were found to melt in the range of 4041-4232 K, with HfC having the highest and TaC the lowest. Spectral radiance of the hot samples was measured in situ, showing that the optical emissivity of these compounds plays a fundamental role in their heat balance. Independently, the results show that the melting point for HfC0.98, (4232 ± 84) K, is the highest recorded for any compound studied until now. [ABSTRACT FROM AUTHOR]

Aim: To study possible ocular surface and lacrimal drainage changes in women being on adjuvant chemotherapy with 5-Fluorouracil 600 mg/m2, Epirubicin 60-90 mg/m2, Cyclophosphamide 600 mg/m2 (FEC) regimen for breast cancer. Methods: Sixty one consecutive women with early stage breast cancer (median age 58 years - interquartile range 22) were included in this study. They all underwent mastectomy followed by 6 cycles of tri-weekly administration of FEC regimen and were free of ocular surface, eyelid and tear film symptomatic disease at baseline. None of them had pre- or coexisting treatment with other chemotherapeutic agent or radiotherapy. Slit lamp examination of the ocular surface, Schirmer test I (without topical anesthesia) and tears Break up Time test (BUT) were performed before the initiation of treatment and immediately after the third therapeutic cycle. Results: From 61 women 39.34% had significant conjunctival hyperemia, 41.0% lid margin abnormalities, 4.92% blepharitis, 6.56% madarosis, 3.28% punctate epithelial keratopathy and 4.92% oedema of the lower punctum mucosal opening after three chemotherapeutic cycles. Mean BUT measures were found lower after the third chemotherapeutic cycle (p=0.001) but mean Schirmer test I values were higher after the third chemotherapeutic cycle (p=0.001). Conclusions: Women on chemotherapy with FEC regimen are more susceptible to develop ocular surface and tear film alterations, within the first three cycles of chemotherapy for breast cancer, and thus, prompt ophthalmological evaluation may be proven beneficial for early diagnosis and management of the induced ocular disease. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to evaluate early visual and refractive outcomes of Descemet''s stripping endothelial keratoplasty (DSAEK). Method: Nine eyes of 7 male and 2 female patients, mean age 73 years, were treated with DSAEK. Eight had pseudophakic bullous keratopathy and 1 had advanced Fuch''s syndrome. Patients were followed up for a mean of 11.4 months (range, 4–26). The DSAEK technique consisted of stripping Descemet''s membrane and endothelium from a recipient cornea and transplanting the posterior stroma and endothelium of a donor cornea using the Tan EndoGlide. The mean operating time was 61.89 minutes (standard deviation [SD], 9.3). Results: The median donor diameter was 8.375 mm (range, 8.25–8.75) and the mean donor thickness was 114.4 μm (range, 98–129). Mean preoperative sphere was −2.41 that changed postoperatively in −1.21. Mean endothelial cell loss was 25% (range, 23%–45%) at 6 months after surgery. Corneal pachymetry was reduced from 796.6 μm preoperatively to 535.5 μm postoperatively. Best corrected vicual acuity (BCVA) was 20/40 or better postoperatively and exceeded the preoperative BCVA in all eyes. No graft failure was present. Two partial graft dislocations (1st and 5th postoperative day) were observed. One graft was successfully attached after reinjecting an air bubble (rebubbling) in the anterior chamber and the other graft was reattached with 4 10/0 nylon sutures after failed rebubbling. Conclusions: The key to successful endothelial transplantation is the protection and preservation of as many donor endothelial cells as possible. The TAN EndoGlide is a device that consistently delivers a donor lenticule through a small incision with minimal endothelial loss, while making the insertion procedure relatively reliable and consistent, with the surgeon in full control of the donor at all stages of insertion. The endothelial cell loss during this technique is comparable (if not better) with other endothelial graft insertions systems. [Copyright &y& Elsevier]

We measure the thermal conductivity of solid and molten tungsten using steady state temperature differential radiometry. We demonstrate that the thermal conductivity can be well described by application of Wiedemann-Franz law to electrical resistivity data, thus suggesting the validity of Wiedemann-Franz law to capture the electronic thermal conductivity of metals in their molten phase. We further support this conclusion using ab initio molecular dynamics simulations with a machine-learned potential. Our results show that at these high temperatures, the vibrational contribution to thermal conductivity is negligible compared to the electronic component.

Purpose: To validate the Democritus Digital Acuity and Reading Test (DDART) as a distance VA (dVA) test against a series of prevalent conventional distance vision charts., Setting: Ophthalmology Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece; Ophthalmology Department, AHEPA University Hospital, Thessaloniki, Greece; and Ophthalmica Institute of Ophthalmology & Microsurgery, Thessaloniki, Greece., Design: Prospective multicenter validation study., Methods: The distance best spectacle-corrected visual acuity (dBSCVA) was compared in normal (NVG) and low (LVG) vision participants against 4 prevalent conventional distance vision charts (ETDRS, Snellen, Landolt C, and Tumbling E) by a predefined 2.5-symbol noninferiority margin and intraclass correlation coefficients (ICCs). DDART's test-retest (TRT) reliability was assessed with ICCs., Results: 534 participants (471 and 63 with normal and low vision, respectively) were included in the study. The mean difference between dBSCVA measured with DDART and conventional charts ranged between -0.84 and +0.85 symbols, without exceeding the 2.5-symbol noninferiority margin. ICCs indicated an excellent level of agreement for all patient groups (from 0.848 to 0.985). TRT reliability indicated differences below 1 symbol both for the NVG and LVG, with ICCs ranging between 0.912 and 0.964 for the 4 DDARTs., Conclusions: DDART was a valid web-based dVA test that provided reliable measurements in clinical and telemedical settings, both for normal and low vision patients., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

The primary objective of this study was to objectively compare the visual performance of patients following premium pseudophakic presbyopia corrections in different light combinations for near- and intermediate-vision activities of daily living (ADLs). This is a prospective, comparative study. A total of 75 patients populated three study groups: G1-patients with bilateral trifocal implantation, G2-patients with bilateral bifocal implantation, and G3-patients with bilateral monofocal implantation. All participants addressed 10 ADLs in nine combinations of light temperature (3000 K, 4000 K, and 6000 K) and light intensity (25 fc, 50 fc, and 75 fc) and declared their subjectively optimal light combination while reading. G2 and G3 had the best total ADL scores in 6000 K/75 fc, while G1 had the best total ADL score in 4000 K/75 fc. Total ADL, easy ADL, and moderate difficulty ADL scores were significantly better in G2, while difficult ADL score was significantly better in G1. The majority of all groups selected 6000 K/75 fc as the most comfortable light combination, and no group selected 3000 K and 25 fc. In conclusion, trifocal patients benefit from intense daylight, while bifocal and monofocal patients benefit from intense, cold lighting. Trifocal patients present superior near-vision capacity in difficult near-vision daily tasks, while bifocal patients present superiority in easy and moderate-difficulty ADLs.

Objective: To describe a clinical entity of upper eyelid margin and meibomian gland inversion (MGI) sequential to meibomian gland dysfunction (MGD), in the absence of eyelash ptosis, trichiasis or manifest marginal entropion. We highlight its clinical features, surgical management and outcomes., Methods: We performed a retrospective analysis of symptomatic MGI cases refractory to conservative management who underwent surgery in our centre over a 4-year period. Anatomical correction, resolution of symptoms and possible complications are reported., Results: A total of 21 eyelids of 13 patients (mean age: 68.5 ± 15.4, range: 32-88 years) were analysed. Symptomatic MGI patients were operated only if they have noted immediate comfort when we corrected the lid margin position with a cotton tip. Those with refractory superior punctate corneal staining (n = 14 eyes), blink-related discomfort (n = 8) and pseudo-blepharospasm (n = 3) reported complete postoperative resolution. Milder symptoms showed partial improvement: gritty feeling (79%), sore eye (80%) and watery eye (86%). However, symptoms of dry eye disease (DED) persisted in 88% of patients. One case recurred in 6 weeks and was offered revision surgery. Median follow-up was 5 (range: 3-12) months., Conclusion: Meibomian gland inversion (MGI) is a subtle clinical entity that can be easily overlooked. Symptoms are often attributed to DED or MGD alone. It is likely that MGI represents early upper lid margin anatomical changes secondary to MGD before cicatricial marginal entropion becomes clinically apparent. Recommended treatment is conservative with intensive lid hygiene and topical MGD management. However, refractory symptomatic cases who respond positively to a 'cotton-tip test' (reversal of lid margin malposition with a rolling cotton-tip) may benefit from surgical intervention with favourable anatomical and functional outcome., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Non-melanoma skin cancer (NMSC) is the commonest malignancy worldwide (>80% located in the head and neck area). The aim of this study was to assess risk factors predisposing to local recurrence of NMSC of the middle third of the face (MTF). This was a single-centre retrospective analysis of patients with NMSC of the MTF treated during 1995-2010. Data on epidemiological and tumour characteristics were collected. Survival analysis was performed and log-rank tests were used to compare differences in survival for each variable. A total of 531 patients with basal cell carcinoma (BCC) of the MTF were identified. Most tumours were nodular type (28.4%), located on the nose (34.3%), and confined to the dermis (75.5%). Negative margins were achieved in 91% of cases. Median follow-up time was 35 months and 15.2% of patients developed local recurrence. Incomplete excision was the only variable predisposing to local recurrence. The cohort also included 114 patients with squamous cell carcinoma (SCC). Most tumours were well differentiated (43.9%), located at the zygomatic area (49.1%), excised with negative margins (93%), and confined to the dermis (67.8%). At a median follow-up time of 42 months, local recurrence occurred in 15.7% of patients. Tumour size, depth of invasion, and prior history of head and neck SCC were risk factors for local recurrence. The variables predictive of recurrence of BCC were incomplete excision and for SCC tumour size, depth of invasion, and a prior history of head and neck SCC.

Purpose: The pathogenesis of Graves' disease (GD) and orbitopathy (GO) is not completely elucidated. On the other hand, vitamin D receptor (VDR) gene polymorphisms have been associated with vulnerability to a plethora of chronic autoimmune diseases. The primary aim of this study was to synthesize evidence on the association between VDR gene polymorphisms and GD. Secondary aim was to investigate their association with GO., Methods: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to December 8, 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was quantified with I 2 index., Results: Ten studies were included in the qualitative and quantitative analysis. TT subtype of TaqI polymorphism was associated with an increased risk of GD compared with Tt and tt polymorphisms (OR: 1.42; 95% CI, 1.05-1.94, p = 0.025), whereas tt was associated with a lower risk of GD, compared with TT and Tt polymorphisms (OR: 0.79; 95% CI, 0.62-0.99, p = 0.043). No association was found for ApaI, BsmI, and FokI polymorphisms. The bb subtype of BsmI polymorphism was associated with a lower risk in Asian, but with a higher GD risk in Caucasian populations, compared with BB/Bb subtypes. No eligible study was found regarding the association between VDR gene polymorphisms and the risk of GO., Conclusions: The TT subtype of the TaqI polymorphism was associated with a higher susceptibility for GD compared with Tt and tt. Regarding BsmI, the bb subtype was associated with increased GD risk in Caucasians, whereas it is protective in Asians.

Intravenous (i.v.) glucocorticosteroids (GCs) constitute the first-line treatment for active and moderate-to-severe Graves' orbitopathy (GO). In cases of persistent disease, rituximab, a monoclonal anti-CD20 antibody, may be used, although studies have yielded conflicting results. In case 1, a 50-year-old female heavy smoker presented with severe bilateral disfiguring eyelid edema of four months, bilateral exophthalmos and a clinical activity score (CAS) of 5/7. Laboratory investigation showed thyrotoxicosis and high thyroid-stimulating immunoglobulin (TSI) levels [32 IU/L (normal <1.75]. After minor improvement by i.v. methylprednisolone and standard retrobulbar radiotherapy (20 Gy), her visual acuity progressively declined to "hand motion". Rituximab was administered (two pulses of 500 mg, two weeks apart), with significant response. At 3 1/2 years of follow-up, CAS is 0/7 and CD20+ lymphocytes remain at the lower normal range. In case 2, a 78-year-old non-smoker male was referred for management of severe active GO, one month after total thyroidectomy for Graves' thyrotoxicosis (TSI: 6.74 IU/L). Over the preceding two-three months, severe GO manifested with chemosis, constant diplopia, loss of color vision and acuity of 1/10 bilaterally (CAS: 7/7). Following partial response to i.v. methylprednisolone and concomitant radiotherapy, rituximab (two pulses of 500 mg each, two weeks apart), was administered. Vision partially recovered and GO remains in remission one year later, even after 131 I (100 mCi) administration for papillary thyroid carcinoma (TSI: 0.9 IU/L and CD20+ count at the lower normal range). In conclusion, rituximab may be an effective second-line therapy in GO patients, providing long-lasting remission.

Major and severe accidents have occurred three times in nuclear power plants (NPPs), at Three Mile Island (USA, 1979), Chernobyl (former USSR, 1986) and Fukushima (Japan, 2011). Research on the causes, dynamics, and consequences of these mishaps has been performed in a few laboratories worldwide in the last three decades. Common goals of such research activities are: the prevention of these kinds of accidents, both in existing and potential new nuclear power plants; the minimization of their eventual consequences; and ultimately, a full understanding of the real risks connected with NPPs. At the European Commission Joint Research Centre's Institute for Transuranium Elements, a laser-heating and fast radiance spectro-pyrometry facility is used for the laboratory simulation, on a small scale, of NPP core meltdown, the most common type of severe accident (SA) that can occur in a nuclear reactor as a consequence of a failure of the cooling system. This simulation tool permits fast and effective high-temperature measurements on real nuclear materials, such as plutonium and minor actinide-containing fission fuel samples. In this respect, and in its capability to produce large amount of data concerning materials under extreme conditions, the current experimental approach is certainly unique. For current and future concepts of NPP, example results are presented on the melting behavior of some different types of nuclear fuels: uranium-plutonium oxides, carbides, and nitrides. Results on the high-temperature interaction of oxide fuels with containment materials are also briefly shown.

Dry eye disease (DED) results in tear film instability and hyperosmolarity, inflammation of the ocular surface and, ultimately, visual disturbance that can significantly impact a patient's quality of life. The effects on visual acuity result in difficulties with driving, reading and computer use and negatively impact psychological health. These effects also extend to the workplace, with a loss of productivity and quality of work causing substantial economic losses. The effects of DED and the impact on vision experienced by patients may not be given sufficient importance by ophthalmologists. Functional visual acuity (FVA) is a measure of visual acuity after sustained eye opening without blinking for at least 10 s and mimics the sustained visual acuity of daily life. Measuring dynamic FVA allows the detection of impaired visual function in patients with DED who may display normal conventional visual acuity. There are currently several tests and methods that can be used to measure dynamic visual function: the SSC-350 FVA measurement system, assessment of best-corrected visual acuity decay using the interblink visual acuity decay test, serial measurements of ocular and corneal higher order aberrations, and measurement of dynamic vision quality using the Optical Quality Analysis System. Although the equipment for these methods may be too large or unaffordable for use in clinical practice, FVA testing is an important assessment for DED., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients. In mild GO, a watchful strategy is usually sufficient, but a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms. High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO. The optimal cumulative dose appears to be 4.5-5 g of methylprednisolone, but higher doses (up to 8 g) can be used for more severe forms. Shared decision-making is recommended for selecting second-line treatments, including a second course of intravenous GCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab or watchful waiting. Rehabilitative treatment (orbital decompression surgery, squint surgery or eyelid surgery) is needed in the majority of patients when GO has been conservatively managed and inactivated by immunosuppressive treatment.

Background: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy., Methods: We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score., Results: At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems., Conclusions: Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).

Glucocorticoids (GCs) are used for Graves' ophthalmopathy (GO) in two different clinical settings: 1) moderately severe to severe eye disease; and 2) mild eye disease, for which radioiodine therapy is given to treat concomitant hyperthyroidism. Intravenous pulse corticosteroids have a small but statistically significant advantage in terms of response rate compared with oral corticosteroids and cause significantly fewer adverse events. Steroids should be used for as short a period of time as possible. The need for large doses of steroid over a long period of time is a hint that other treatment modalities need to be explored. Combination treatment with oral steroids and ciclosporin, another immunosuppressant, are more efficacious than use of either agent alone. The same applies to combination treatment with oral steroids and orbital radiotherapy. Somatostatin analogues (SM-as) have marginal clinical efficacy and are expensive. More potent analogues, like SOM230, could prove to be the treatment of choice in moderately severe cases of GO. The latter, in contrast to the thus far used analogues, has a rather high affinity for all SM receptors except SM receptor 4.

Although pediatric Graves' disease is an uncommon condition, children have about the same (or slightly increased) risk as adults to develop Graves' ophthalmopathy (GO) once they have contracted Graves' hyperthyroidism. GO occurs in the same proportion between sexes but with a milder clinical presentation compared with adults. Lid lag, soft tissue involvement and proptosis are the commonest manifestations, whereas restricted eye muscle motility, severe strabismus and optic neuropathy are practically absent. Genetic, immunologic and environmental factors may be associated with the different appearance of GO in children and adolescents. Interestingly, manifestation of GO begins to resemble the adult findings more closely when adolescence approaches. This could be explained by increasing smoking prevalence with age as long as smoking is a proven to be a risk factor for GO, and the odds increase significantly with increasing severity of GO. Management of hyperthyroidism is essential for the control of complications and seems to offer improvement of eye changes upon restoration of euthyroidism. Antithyroid drugs are the first choice treatment. Lasting remission rates though are achieved in less than 30% of cases. Long periods of therapy are needed and risk for side effects (often serious) increases. In resistant or severe cases early radical treatment with surgery or radioiodine is needed. Both can be equally effective and safe in selected cases. Identification of subjects prone to relapses is critical for optimal management. Regarding treatment of thyroid eye disease in childhood, most physicians who are dealing with such cases prefer a 'wait-and-see' policy. Pharmacological intervention, predominantly with steroids, is considered appropriate in case of deterioration or no improvement of eye changes when the patient has become euthyroid. It has been shown that somatostatin analogs (SM-as) might be of therapeutic value in the treatment of active eye disease in adults. Newer generations of SM-as that target a wider range of somatostatin receptors may show markedly superior results in the treatment of ophthalmopathy. Surgical orbital decompression is hardly ever necessary due to the mild nature of the disease, while retrobulbar irradiation, which has been proved beneficial in adults, has no place in the treatment of juvenile GO, in view of the theoretical risk of tumor induction.