Características clínico-oftalmológicas y evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social, Paraguay / Clinical-ophthalmological characteristics and evolution of patients with moderately severe active thyroid ophthalmopathy treated with methylprednisolone boluses who attended the Central Hospital of the Instituto de Previsión Social, Paraguay

Introducción: La oftalmopatía tiroidea (OT) es un trastorno debilitante en pacientes con enfermedad tiroidea autoinmune, principalmente enfermedad de Graves, que se desarrolla entre el 30 a 50% de los casos. Objetivos: Describir las características clínico-oftalmológicas y la evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social en el tiempo comprendido entre enero de 2018 y setiembre de 2021. Materiales y métodos: Investigación de diseño observacional, con estudio descriptivo, retrospectivo. Resultados: Se revisaron fichas de 34 pacientes con OT activa moderada severa que recibieron bolos de metilprednisolona basado en las guías EUGOGO 2016, de los cuáles se excluyeron 3 pacientes por tener fichas incompletas y otros 3 pacientes ya que requirieron tratamiento de segunda línea previo al término del esquema de 12 sesiones. De los 28 pacientes estudiados, la edad promedio fue de 43,6 ±13,1 años, el 89% de sexo femenino y el 28,5%, fumadores. En cuanto a la función tiroidea de la población previo al tratamiento, se constató hipertiroidismo en el 82%, hipotiroidismo en el 11% y eutiroidismo en el 7%; y posterior al tratamiento, se constató hipertiroidismo en el 78,6% (subclínico), eutiroidismo en el 17,9% e hipotiroidismo en el 3,5%. La mayoría (92.6%) contaba con anticuerpos contra el receptor de TSH positivo, con un promedio de 18 ± 9,9 mIU/Ml. Respecto a la actividad de la oftalmopatía según la escala CAS, se constató un promedio de 4,1 ±1,0 previo al tratamiento y posterior 1,2 ±1,4; de ellos el 46,4% presentó un estado leve según escala de gravedad, 39% sin criterios de gravedad y 14 % persistió en moderada -severa. Se constató mejoría de la agudeza visual tras el tratamiento (57,1%), el promedio de exoftalmía previo al tratamiento fue 22,2 mm y posterior 21,1 mm; se presentó diplopía en el 7,1% previo al tratamiento y en el 3,6% posterior al tratamiento. Conclusión: El tratamiento con glucocorticoides endovenosos en la oftalmopatía de Graves moderada-severa (esquema EUGOGO 2016) fue muy efectivo, revirtiendo la actividad y consecuentemente ayudando a disminuir la gravedad, en la gran mayoría de nuestros pacientes. Esto podría explicarse porque la oftalmopatía era incipiente y por el alto grado de adherencia de los pacientes en el contexto de un manejo multidisciplinar bien protocolizado.

Introduction: Graves' orbitopathy (GO) is a debilitating disorder in patients with autoimmune thyroid disease, mainly Graves' disease, which develops in 30 to 50% of cases. Objectives: To describe the clinical-ophthalmological characteristics and evolution of patients with moderate-to- severe active GO treated with methylprednisolone boluses who attended the Central Hospital of the Institute of Social Security between January 2018 and September 2021. Materials and methods: Observational design research, descriptive, retrospective study. Results: Records of 34 patients with active moderate-to-severe GO who received boluses of methylprednisolone based on the EUGOGO 2016 guidelines, were reviewed, of which 3 patients were excluded due to having incomplete records and another 3 patients since they required second-line treatment prior to end the 12-session scheme. Of the 28 patients studied, the average age was 43.6 ±13.1 years, 89% were female and 28.5% were smokers. Regarding the thyroid function of the population prior to treatment, hyperthyroidism was found in 82%, hypothyroidism in 11% and euthyroidism in 7%; and after treatment, hyperthyroidism was found in 78.6% (subclinical), euthyroidism in 17.9% and hypothyroidism in 3.5%. The majority (92.6%) had positive thyrotropin receptor antibodies, with an average of 18 ± 9.9 mIU/Ml. Regarding the activity of orbitopathy according to the CAS scale, an average of 4.1 ±1.0 was found before treatment and 1.2 ±1.4 after; Of them, 46.4% presented a mild condition according to the severity scale, 39% without severity criteria and 14% persisted in moderate-severe. Improvement in visual acuity was noted after treatment (57.1%), the average exophthalmia before treatment was 22.2 mm and after 21.1 mm; Diplopia occurred in 7.1% before treatment and in 3.6% after treatment. Conclusion: Treatment with intravenous glucocorticoids in moderate-severe Graves' orbitopathy (EUGOGO 2016 scheme) was very effective, reversing the activity and consequently helping to reduce the severity, in the vast majority of our patients. This could be explained because the orbitopathy was incipient and by the high degree of patient adherence in the context of well-protocolized multidisciplinary management.

Inhibitory effect of phloretin on inflammation and oxidative stress in IL-1β induced orbital fibroblasts in Graves orbitopathy and its mechanism / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of phloretin on inflammation and oxidative stress in interleukin (IL)-1β induced orbital fibroblasts (OFs) from Graves orbitopathy (GO) patients and its mechanism.Methods:The orbital fat and connective tissue from 6 eyes of 6 patients diagnosed as inactive GO who underwent orbital decompression in Henan Eye Hospital from January 2019 to December 2020 were collected.Primary OFs were isolated and passaged by explant culture and were identified by cell immunofluorescence assay.OFs were divided into control group, IL-1β induced group, and groups of various phloretin concentrations (25, 50, 75, 100 and 200 μmol/L). The viability of OFs after 24- and 48-hour treatment of the various phloretin concentrations was determined by cell counting kit-8 (CCK-8). OFs were induced by IL-1β to simulate an inflammatory environment of GO in vitro.Intracellular reactive oxygen species (ROS) levels of the normal control group, IL-1β induced group, 50 μmol/L phloretin group and 100 μmol/L phloretin group were detected by fluorescent probe (H 2DCF-DA). The concentrations of pro-inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatant of the normal control group, IL-1β induced group and phloretin treated groups (25, 50, 75, and 100 μmol/L) were examined by enzyme-linked immunosorbent assay (ELISA). The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2) proteins, as well as P38, extracelluar regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) proteins as well as their phosphorylated proteins in the MAPK signal pathway of the normal control group, IL-1β induced group and 100 μmol/L phloretin group, were detected by Western blot.The purpose and methods of the study were explained to the patients and their family members.Written informed consent was obtained.The study protocol was approved by the Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2020[07]). Results:For cultured OFs, the mesenchymal origin was confirmed by positive expression of vimentin and fibroblasts were identified by negative expression of desmin, S-100 and cytokeratin-18.CCK-8 showed that there was no significant difference in absorbance value after 24- and 48-hour treatment between 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups and control group (all at P>0.05). The ROS levels of 50 μmol/L and 100 μmol/L phloretin groups were 21.95±1.71 and 10.01±1.03, respectively, which were significantly lower than 39.27±4.01 of IL-1β induced group (both at P<0.01). ELISA showed that IL-6 concentrations in 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (4 544.25±572.98), (1 000.25±133.96), (724.25±98.63), (519.50±118.02)pg/ml, respectively, which were all significantly lower than (7 581.75±565.93)pg/ml in IL-1β induced group (all at P<0.01). IL-8 concentrations in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 679.50±676.76), (2 143.75±616.20), (1 174.75±284.18)pg/ml, respectively, which were all significantly lower than (8 411.00±939.67)pg/ml in IL-1β induced group (all at P<0.01). The concentrations of MCP-1 in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 783.25±610.24), (1 565.75±457.89), (745.75±227.01)pg/ml, respectively, which were all significantly lower than (5 533.00±602.87)pg/ml in IL-1β induced group (all at P<0.01). The relative expression levels of HO-1 and Nrf2 were significantly higher and the relative expression levels of p-P38, p-ERK, and p-JNK were significantly lower in 100 μmol/L phloretin group than IL-1β induced group (all at P<0.01). Conclusions:Phloretin reduces the oxidative stress level of IL-1β induced OFs from GO patients and inhibits the production of pro-inflammatory cytokines.The mechanism is related to the activation of Nrf2/HO-1 and the inhibition of the MAPK signal pathway.

Guideline interpretation: the 2021 European Group on Graves′ Orbitopathy Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy / 中华内分泌代谢杂志

The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification.

The change in the clinical presentation of Graves disease: a 30 years retrospective survey in an academic Brazilian tertiary center

ABSTRACT Objective Graves' disease (GD) is the main cause of hyperthyroidism among adults. It is an autoimmune condition classically marked by the Merserburg Triad (goiter, thyrotoxicosis, and orbitopathy), but the change in presentation of GD over time has rarely been studied. To determine changes in the clinical presentation of patients with GD in the last 30 years. Subjects and methods The study evaluated 475 patients diagnosed with GD between 1986 and 2016 in a single center. Patients were evaluated regarding epidemiological aspects, thyroid function, inflammatory activity of the eyes evaluated by the Clinical Activity Score; CAS, severity evaluated by NOSPECS classification and thyroid volume estimated by ultrasonography. Results Patients assessment identified an increase in the mean age of diagnosis of GD (p < 0.02), a reduction in thyroid volume (p < 0.001) and less intense orbital involvement from 2007-2016 compared to 1986-2006 (p = 0.04). The number of smoking patients was smaller from 2007 to 2016 (28.7%) than 1986 to 2006 (42.8% p = 0.001). The TSH and TRAb values did not had significant changes. Conclusion GD presentation appears to be changed in the last years compared to the typical initial presentation. There is a less frequent inflammatory involvement of orbital tissue, smaller goiters, a lower number of smokers and diagnosis at older age.

Evaluation of quality of life in patients with Graves orbitopathy and its influencing factors / 中华内科杂志

Objective To evaluate life quality of Graves orbitopathy (GO) patients using Graves orbitopathy quality-of-life questionnaire (GO-QOL) and explore the influence factors of the quality of life of GO patients.Methods This was a cross-sectional study conducted at The Third Affiliated Hospital of Southern Medical University including 145 newly diagnosed GO patients.All the patient answered the GO-QOL and underwent ophthalmic and endocrine assessments.The main outcome measures were the scores on GO-QOL 2 subscales:visual functioning and appearance.Based on the classification in the guideline of European Group on Graves Orbitopathy (EUGOGO),the patients were divided into two groups:mild and moderate to severe groups.Then the scales between these two groups were compared and influencing factors were analyzed.Finally,the floor and ceiling effects were assessed.Results The GO-QOL scores for the subscales of visual functioning and appearance were 70.91±27.83 and 61.29±26.37 respectively in 145 GO patients.Visual functioning and appearance were lower in moderate to severe group (62.71 ±28.77 and 57.52 ± 26.49,respectively) than in mild group (85.58 ± 18.77 and 68.02 ±24.99,respectively).The GO-QOL scores for the visual functioning subscale were significantly correlated with age (P =0.002),clinical active score (P =0.011) and the degree of diplopia (P =0.00,R2=0.373).The GO-QOL scores for the appearance were significantly correlated with sex (P =0.05) and thyroid-stimulating hormone levels (P =0.001,R2 =0.231).No significant ceiling or floor effects were observed for either subscale of the GO-QOL.Conclusions With the aggravation of the disease,the quality of life of GO patients is getting worse and worse.The main influencing factors of the quality of life of GO patients include age,gender,diplopia,clinical active score and thyroid-stimulating hormone levels.Close attention needs to be paid to the quality of life of GO patients.

Changes of immunoglobulins and CD series in patients with Graves' orbitopathy treated with high-dose methylprednisolone / 中华内分泌代谢杂志

Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves' orbitopathy. Methods Twenty-seven patients with active moderate-to-severe Graves' orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves'Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody ( TRAb) , anti-thyroperoxidase antibody ( TPOAb) , and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point. Results TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+/CD8+ ratio were gradually decreased after treatment. However, change of CD8+T cells was not significant (P>0.05). Conclusion High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.

Changes of immunoglobulins and CD series in patients with Graves′ orbitopathy treated with high-dose methylprednisolone / 中华内分泌代谢杂志

Objective@#To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves′ orbitopathy.@*Methods@#Twenty-seven patients with active moderate-to-severe Graves′ orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves′Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody (TRAb), anti-thyroperoxidase antibody (TPOAb), and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+ T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point.@*Results@#TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+ /CD8+ ratio were gradually decreased after treatment. However, change of CD8+ T cells was not significant (P>0.05).@*Conclusion@#High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.

A Demographic Profile And Awareness Study Of Hyperthyroidism Among Patients In A Tertiary Hospital In Western India

Background and objectives- To study the demographic profiling and awareness of hyperthyroidism among patients reporting to our hospital. Methods- A randomized retrospective study was done consisiting of 50 patients who were diagnosed with hyperthyroidism in the Out patient department of our hospital during two year period after approval by ethical committee. The data obtained were tabulated, analysed, assessed and formulated. Results- Females were more commonly affected, with age group of 60-69 being more commonly affected in the male and female category, with majority of patients belonging to the class III of kuppusamy socio-economic classification. On laterality males had more bilateral involvement with women having predominantly unilateral involvement. On treatment study, males were on a strict treatment regime as compared to their counterparts. In the socio-economic classification majority of class V category were not on any treatment. On awareness majority of male & female patients were equally unaware of the fact that they were suffering from hyperthyroidism. Conclusions- Our study showed that majority of female patients were affected, off treatment and unaware of the disease. Patients of lower socio-economic class were off treatment and unaware of the disease. As we found the group of 60-69 years were more commonly involved a thorough survey and screening of this age group is essential. With proper awareness, screening, check-ups, camps and education among we can make a remarkable difference in treatment in restoring visual function, appearance and help a reclusive patient to become socially reintegrated.

TSH-receptor antibodies may prevent bone loss in pre- and postmenopausal women with Graves' disease and Graves' orbitopathy

ABSTRACT Objective Thyrotoxicosis is established risk factor for osteoporosis due to increased bone turnover. Glucocorticoids often administered for Graves' orbitopathy (GO) have additional negative effect on bone mineral density (BMD). Our aim was to examine the influence of thyroid hormones, TSH, TSH-receptor antibodies (TRAb) and glucocorticoid treatment on bone in women with Graves' thyrotoxicosis and Graves' orbitopathy (GO). Subjects and methods Forty seven women with Graves' disease, mean age 55.6 ± 12.8 (23 women with thyrotoxicosis and 24 hyperthyroid with concomitant GO and glucocorticoid therapy) and 40 age-matched healthy female controls were enrolled in the study. We analyzed clinical features, TSH, FT4, FT3, TRAb, TPO antibodies. BMD of lumbar spine and hip was measured by DEXA and 10-year fracture risk was calculated with FRAX tool. Results The study showed significantly lower spine and femoral BMD (g/cm2) in patients with and without GO compared to controls, as well as significantly higher fracture risk. Comparison between hyperthyroid patients without and with orbitopathy found out significantly lower spine BMD in the first group (p = 0.0049). Negative correlations between FT3 and femoral neck BMD (p = 0.0001), between FT4 and BMD (p = 0.049) and positive between TSH and BMD (p = 0.0001), TRAb and BMD (p = 0.026) were observed. Fracture risk for major fractures and TRAb were negatively associated (p = 0.05). We found negative correlation of BMD to duration of thyrotoxicosis and cumulative steroid dose. Conclusions Our results confirm the negative effect of hyperthyroid status on BMD. TRAb, often in high titers in patients with GO, may have protective role for the bone, but further research is needed.

Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy

PURPOSE: To investigate associations between serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and Graves' orbitopathy (GO) activity/severity in chronic-stage GO and compare the performance of two newly-developed TRAb assays (third-generation TSH-binding inhibition immunoglobulin [TBII] assay versus Mc4 thyroid-stimulating immunoglobulin [TSI] bioassay). METHODS: This study is a retrospective review of medical charts and blood tests from Korean GO patients who first visited the departments of ophthalmology and endocrinology, Yonsei University College of Medicine from January 2008 to December 2011, were diagnosed with GO and Graves' hyperthyroidism, and were followed up for > or =18 months. Third-generation M22-TBII and Mc4-TSI assays were performed in the chronic-inactive GO patients in whom euthyroidism status was restored. Patients' GO activity/severity clinical activity scores (CAS), and modified NOSPECS scores were examined for a correlation with TRAb assays. RESULTS: Fifty patients (mean age, 41.3 years; 41 females) were analyzed. The mean duration of Graves' hyperthyroidism symptom was 63 months (range, 18 to 401 months) and that of GO was 46 months (range, 18 to 240 months). All patients had been treated previously with anti-thyroid drugs for a median period of 52.3 months, and two patients underwent either radioiodine therapy or total thyroidectomy. Mean CAS and NOSPECS scores were 0.5 +/- 0.9 (standard deviation) and 4.8 +/- 3.1, respectively. Mean M22-TBII and Mc4-TSI values were 7.5 +/- 10.2 IL/L and 325.9 +/- 210.1 specimen-to-reference control ratio. TSI was significantly correlated with NOSPECS score (R = 0.479, p 0.05), because GO inflammatory activity subsided in the chronic stages of GO. CONCLUSIONS: In chronic-inactive GO after euthyroid restoration, GO activity score did not associate with serum levels of TRAb or TBII. However, levels of the functional antibody Mc4-TSI did correlate with GO severity. Therefore, the TSI bioassay is a clinically relevant measure of disease severity even in chronic inactive GO.

Correlation between TSH Receptor Antibody Assays and Clinical Manifestations of Graves' Orbitopathy

PURPOSE: To investigate an association between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and Graves' orbitopathy (GO) activity/severity scores, and compare the performance of three different TRAb assays in assessing the clinical manifestations of GO. MATERIALS AND METHODS: Cross-sectional study. Medical records of 155 patients diagnosed with GO between January 2008 and December 2010 were reviewed. GO activity was assessed by clinical activity score (CAS) and severity graded with the modified NOSPECS score by a single observer. Serum TRAb was measured by three different methods: 1st generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay (TRAb1st); 3rd generation TBII assay (TRAb3rd); and biological quantitative assay of thyroid-stimulating immunoglobulin (TSI) using Mc4-CHO cells (Mc4-CHO TSI assay). Results were correlated with scores of activity/severity of thyroid eye disease. RESULTS: All three assays (TRAb1st, TRAb3rd, and Mc4-CHO TSI) yielded results that were significantly positively correlated with CAS (beta=0.21, 0.21, and 0.46, respectively; p<0.05) and proptosis (beta=0.38, 0.34, and 0.33, respectively; p<0.05). Mc4-CHO TSI bioassay results were significantly positively correlated with all GO severity indices (soft tissue involvement, proptosis, extraocular muscle involvement, and total eye score; beta=0.31, 0.33, 0.25, and 0.39, respectively; p<0.05). CONCLUSION: Mc4-CHO TSI bioassay was superior over the two TBIIs in assessing active inflammation and muscle restriction due to GO, whereas TBII assay would be sufficient for evaluation of patients with proptosis.

A questionnaire survey on the management of Graves' orbitopathy in China / 中华内分泌代谢杂志

[Summary] To determine how endocrinologists in China access and treat patients with Graves' orbitopathy (GO) and gain insight on how to make the management of this disease more uniform and standardized in the context that management of GO continues to be challenging.Based on the questionnaire used in the European survey on GO,a questionnaire in Chinese was drafted and circulated to the members of Chinese Society of Endocrinology (CSE).There were a total of 124 valid responders.The majority (94.4％) of the responders believe that a muhidisciplinary approaches for GO management is valuable.Over 80％ of the participants advocated the evaluation of exophthalmometry,vision,visual fields by perimetry,eye movements,fundoscopy,TSH receptor antibodies,thyroid function,and ultrasound.Steroids were preferred as the first-line therapy by 92.7％ of responders,among them,59.7％ choose intravenous route.The treatment strategy for GO with intravenous glucocorticoids therapy still remains debated.Antithyroid drugs were the most common choice (72.6％) for first-line therapy of thyrotoxicosis.Treatment options for GO were very similar among Chinese,Latin-American,and European responders,though radioactive iodine and surgical treatment were more often indicated in China.The appropriate treatment of the patient with GO is controversial even amongst thyroid specialists.Further training of clinicians,easier access of patients to specialist multidisciplinary centres,and the publication of practice guidelines may help improving the management of this condition in China.

Predicting dysthyroid optic neuropathy using computed tomography volumetric analyses of orbital structures

OBJECTIVE: To evaluate the ability of orbital apex crowding volume measurements calculated with multidetector-computed tomography to detect dysthyroid optic neuropathy. METHODS: Ninety-three patients with Graves' orbitopathy were studied prospectively. All of the patients underwent a complete neuro-ophthalmic examination and computed tomography scanning. Volumetric measurements were calculated from axial and coronal contiguous sections using a dedicated workstation. Orbital fat and muscle volume were estimated on the basis of their attenuation values (in Hounsfield units) using measurements from the anterior orbital rim to the optic foramen. Two indexes of orbital muscle crowding were calculated: i) the volumetric crowding index, which is the ratio between soft tissue (mainly extraocular muscles) and orbital fat volume and is based on axial scans of the entire orbit; and ii) the volumetric orbital apex crowding index, which is the ratio between the extraocular muscles and orbital fat volume and is based on coronal scans of the orbital apex. Two groups of orbits (with and without dysthyroid optic neuropathy) were compared. RESULTS: One hundred and two orbits of 61 patients with Graves' orbitopathy met the inclusion criteria and were analyzed. Forty-one orbits were diagnosed with Graves' orbitopathy, and 61 orbits did not have optic neuropathy. The two groups of orbits differed significantly with regard to both of the volumetric indexes (p<0.001). Although both indexes had good discrimination ability, the volumetric orbital apex crowding index yielded the best results with 92% sensitivity, 86% specificity, 81%/94% positive/negative predictive value and 88% accuracy at a cutoff of 4.14. CONCLUSION: This study found that the orbital volumetric crowding index was a more effective predictor of dysthyroid optic neuropathy than previously described computed tomography indexes were.

Color Doppler imaging of the superior ophthalmic vein in patients with Graves' orbitopathy before and after treatment of congestive disease

OBJECTIVE: To compare superior ophthalmic vein blood flow parameters measured with color Doppler imaging in patients with congestive Graves' orbitopathy before and after treatment and in normal controls. METHODS: Twenty-two orbits from 12 patients with Graves' orbitopathy in the congestive stage and 32 orbits from 16 normal controls underwent color Doppler imaging studies. Color Doppler imaging was repeated after treatment in the group of patients with Graves' orbitopathy, which included orbital decompression in 16 orbits and corticosteroids in six orbits. The findings for each group were compared. RESULTS: In the group of orbits with congestive disease, superior ophthalmic vein flow was detected in 17 orbits (anteroposteriorally in 13 and in the opposite direction in four) and was undetectable in five. After treatment, superior ophthalmic vein flow was detected and anteroposterior in 21 and undetected in one orbit. In normals, superior ophthalmic vein flow was detected anteroposterior in 29 orbits and undetectable in three orbits, indicating a significant difference between groups. There was also a significant difference between controls and congestive Graves' orbits and between congestive orbits before and after treatment, but not between controls and patients after treatment. A comparison of superior ophthalmic vein flow parameters revealed a significant difference between the groups. The superior ophthalmic vein flow was significantly reduced in the congestive stage compared with the flow parameters following treatment and in the untreated controls. CONCLUSIONS: Superior ophthalmic vein flow was significantly reduced in the orbits affected with congestive Graves' orbitopathy and returned to normal following treatment. Congestion appears to be a contributing pathogenic factor in the active inflammatory stage of Graves' orbitopathy.

Patogenia y tratamiento médico de la orbitopatía de graves / Pathogenesis and medical treatment of graves' orbitopathy

La Orbitopatía de Graves se presenta clínicamente en aproximadamente 50 por ciento de los casos de Enfermedad de Graves. La mayoría de las veces es leve y sólo en menos del 5 por ciento pone en riesgo la visión, pese a lo cual deteriora significativamente la calidad de vida de los pacientes. Hasta el momento no se conoce totalmente la patogenia, siendo posiblemente el receptor de TSH el blanco de la autoinmunidad. En cuanto al tratamiento, las medidas preventivas como lograr el eutiroidismo y la suspensión del tabaco son útiles en los distintos grados de la enfermedad. Para los casos más severos se han investigado diferentes medicamentos pero ninguno ha demostrado ser superior a los Glucocorticoides. Actualmente los consensos concuerdan en que es imprescindible clasificar al paciente según grado de actividad y severidad para orientar la terapia con mayor eficacia. Las investigaciones en curso pretenden encontrar una droga que supere el rendimiento existente

Graves' orbitopathy occurs clinically in approximately 50 percent of Graves' Disease. Most often it is mild and only less than 5 percent can threaten vision, despite which it significantly impairs the quality of life of this patients. So far its pathogenesis is not completely understood, but possibly TSH receptor is the target of autoimmunity. In relation to treatment, preventive measures such as achieving euthyroidism and the suspension of tobacco are useful in varying degrees of the disease. For more severe cases, different drugs have been investigated but none has shown superior efficacy to that of Glucocorticoids. Currently, different consensus agrees that it is essential to classify the patient according to levels of activity and severity to guide therapy more effectively. Ongoing investigations aim to find a drug that exceeds the existing performance

Neuropatía óptica distiroidea como manifestación de orbitopatía de Graves / Dysthyroid optic neuropathy: report of one case

Dysthyroid optic neuropathy is an uncommon and severe form of presentation of Graves ophtalmopathy, caused by compression and elongation of the optic nerve. Use of high dose steroids is the treatment of choice. Decompressive surgery is reserved for refractory cases. We report a 41 years old female with a dysthyroid optic neuropathy that appeared 18 years after the diagnosis of Graves disease, manifested by a marked reduction in visual acuity. Orbit CAT scan did not show compression or elongation of optic nerve. She was treated with prednisone 60 mg per day, obtaining a complete remission after 19 days of treatment. After 90 days of follow up with low doses of steroids, the patient remains asymptomatic.

Diagnostic ability of barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (± SD) were 64.47 percent ± 6.06 percent and 49.44 percent ± 10.94 percentin the groups with and without dysthyroid optic neuropathy, respectively (p<0.001). Barrett's index sensitivity ranged from 32 percent to 100 percent, and Barrett's index specificity ranged from 24 percent to 100 percent. The best combination of sensitivity and specificity was 79 percent/72 percent for BI=60 percent (odds ratio: 9.2). CONCLUSIONS: Barrett's Index is a useful indicator of dysthyroid optic neuropathy and may contribute to early diagnosis and treatment. Patients with a Barrett's index >60 percent should be carefully examined and followed for the development of dysthyroid optic neuropathy.

Radiation Therapy for Thyroid Orbitopathy

PURPOSE: The aim of this study is to evaluate the effect of radiotherapy for the patients with Graves' orbitopathy who were intolerable to corticosteroid therapy. METHODS: From December 1995 to June 2000, We reviewed medical records of thirteen patients who had received orbital radiation delivering 2000 cGy in 10 fractions over 2 weeks. RESULTS: Compressive optic neuropathy was improved in 3 of 4 patients (75%), and soft tissue swelling was improved in eight of 9 patients (88%). Proptosis was reduced in 3 of 13 (30%) patients. However, diplopia and ocular motility responded poorly and was improved only in 2 of 10 (20%) patients. No adverse effects of radiotherapy occurred in any patient. Specifically there was no sign of radiation-induced injury to optic nerve, retina, or lens. CONCLUSIONS: Radiotherapy was successful in patients with acute Graves' orbitopathy especially who had compressive optic neuropathy or soft tissue swelling. This modality was useful for those who showed intolerable side effects from the use of corticosteroid or the recurrence with corticosteroid treatment.