Apical bleeding: a rare cause of blindness after orbital decompression / Sangramento apical: uma causa rara de cegueira pós descompressão orbitária

ABSTRACT Orbital decompression is widely performed for the management of proptosis for cosmetic and functional cases of Graves orbitopathy. The main side effects include dry eye, diplopia, and numbness. Blindness after orbital decompression is extremely rare. The mechanisms of vision loss after decompression are not well described in the literature. Considering the devastating effect and rarity of this complication, this study presented two cases of blindness after orbital decompression. In both cases, vision loss was provoked by slight bleeding in the orbital apex.

RESUMO A descompressão orbitária é uma cirurgia amplamente empregada para correção da proptose em casos cosméticos e funcionais da orbitopatia de Graves. Os principais efeitos colaterais induzidos pela descompressão são olho seco, diplopia e parestesias. Amaurose pós descompressão é uma complicação extremamente rara e cujos mecanismos são pouco discutidos na literatura. Considerando o efeito devastador representado pela perda visual e a escassez de relatos dessa complicação, os autores apresentam dois relatos de amaurose após descompressão orbitária. Nos dois casos a perda visual ocorreu devido a sangramento de pequena monta no ápice orbitário.

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.

Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Outcome of tocilizumab treatment in corticosteroid-resistant thyroid eye disease / Resultados del tratamiento con tocilizumab en la enfermedad ocular tiroidea resistente a glucocorticoides

Introduction: Thyroid eye disease (TED) is a complex and incompletely understood rare autoimmune disorder.ObjectivesTo analyze the experience and the outcomes obtained with the use of intravenous tocilizumab in the treatment of TED.MethodsA retrospective analysis of adult patients diagnosed with active TED resistant to intravenous corticosteroids treated in a tertiary hospital between May 2012 and May 2021.ResultsEleven patients were included with a mean age of 52±12 (range 35–67) years. Nine patients were female and two were male. Patients received a median of 5±3.2 doses. Twenty out of twenty-four eyes achieved inactivation of TED at week 16. Proptosis response was achieved in 6/8 patients and diplopia response in 3/8 patients. The GO-QOL questionnaire showed clinically significant improvement in 9/11 patients. No serious adverse effects were reported during tocilizumab treatment. One patient required decompressive surgery 15 months after tocilizumab therapy.ConclusionThe results obtained show that the use of tocilizumab in the treatment of this pathology can be a good alternative. (AU)

Introducción: La orbitopatía tiroidea (OT) es una enfermedad rara autoinmune compleja que no se conoce completamente.ObjetivosAnalizar la experiencia y los resultados obtenidos con el uso de tocilizumab intravenoso en el tratamiento de la OT.MétodosAnálisis retrospectivo de pacientes adultos diagnosticados de OT activa resistente a glucocorticoides por vía intravenosa tratados en un hospital terciario entre mayo del 2012 y mayo del 2021.ResultadosSe incluyó a 11 pacientes con una edad media de 52±12 (rango 35 a 67) años. Nueve pacientes eran mujeres y 2, hombres. Los pacientes recibieron una mediana de 5±3,2 dosis. Veinte de 24 ojos lograron la inactivación de la OT en la semana 16. Se logró respuesta a la proptosis en 6/8 pacientes y respuesta a diplopía en 3/8 pacientes. El cuestionario GO-QoL mostró una mejora clínicamente significativa en 9/11 pacientes. No se notificaron efectos adversos graves durante el tratamiento con tocilizumab. Un paciente requirió cirugía descompresiva 15 meses después del tratamiento con tocilizumab.ConclusionesLos resultados obtenidos muestran que el uso de tocilizumab en el tratamiento de esta enfermedad puede ser una buena alternativa. (AU)

Outcome of tocilizumab treatment in corticosteroid-resistant thyroid eye disease.

INTRODUCTION: Thyroid eye disease (TED) is a complex and incompletely understood rare autoimmune disorder. OBJECTIVES: To analyze the experience and the outcomes obtained with the use of intravenous tocilizumab in the treatment of TED. METHODS: A retrospective analysis of adult patients diagnosed with active TED resistant to intravenous corticosteroids treated in a tertiary hospital between May 2012 and May 2021. RESULTS: Eleven patients were included with a mean age of 52±12 (range 35-67) years. Nine patients were female and two were male. Patients received a median of 5±3.2 doses. Twenty out of twenty-four eyes achieved inactivation of TED at week 16. Proptosis response was achieved in 6/8 patients and diplopia response in 3/8 patients. The GO-QOL questionnaire showed clinically significant improvement in 9/11 patients. No serious adverse effects were reported during tocilizumab treatment. One patient required decompressive surgery 15 months after tocilizumab therapy. CONCLUSION: The results obtained show that the use of tocilizumab in the treatment of this pathology can be a good alternative.

Adverse effects associated with peribulbar injection of triamcinolone for the treatment of thyroid eye disease: a retrospective case series / Efeitos adversos de injeções peribulbares de triancinolona na doença ocular da tireoide: estudo retrospectivo de uma série de casos

ABSTRACT Purpose: Peribulbar injection of triamcinolone is an alternative treatment for thyroid eye disease; however the safety profile of this therapeutic option remains controversial. The aim of this study was to describe the occurrence of local and systemic adverse effects after peribulbar injection of triamcinolone in patients with thyroid eye disease. Methods: This was a retrospective case series. Medical records of patients with thyroid eye disease treated with peribulbar injections of triamcinolone at a single academic institution between 2007 and 2019 were analyzed. Local and systemic complications were documented. Results: A total of 123 patients were treated. Only 11 patients (8.9%) developed local complications. The most frequent complication was the presence of superficial eyelid ecchymosis (nine patients; 7.3%). Notably, systemic complications (hyperglycemic and suprarenal inhibition after stop treatment) occurred in two patients (1.6%). All complications were transient, and the patients did not have any long-term sequelae. Conclusions: Peribulbar injection of triamcinolone for the treatment of thyroid eye disease is linked to a very low rate of local or systemic complications. Prospective studies are warranted to delve into this topic.

RESUMO Objetivo: A injeção peribulbar de triancinolona é um tratamento alternativo para doenças oculares da tireoide; no entanto, a segurança desse procedimento continua controversa. O objetivo deste artigo é descrever os efeitos adversos locais e sistêmicos de injeções peribulbares de triancinolona em pacientes com doença ocular da tireoide. Métodos: Estudo retrospectivo de uma série de casos. Foram analisados os prontuários médicos dos pacientes com doença ocular da tireoide tratados com injeções de triancinolona peribulbar em uma única instituição acadêmica entre 2007 e 2019. Foram documentadas as complicações locais e sistêmicas. Resultados: Um total de 123 pacientes foram tratados. Apenas 11 (8,9%) pacientes apresentaram complicações locais, sendo a mais frequente a presença de equimoses palpebrais superficiais (7,3%), enquanto 2 (1,6%) pacientes apresentaram complicações sistêmicas (hiperglicemia e inibição da suprarrenal após a interrupção do tratamento). Todas estas complicações foram transitórias e nenhum paciente apresentou sequelas de longo prazo. Conclusões: As injeções peribulbares de triancinolona nas doenças oculares da tireoide têm uma taxa muito baixa de complicações, tanto locais quanto sistêmicas. São necessários estudos prospectivos para aprofundar este tópico.

Trends in Graves' orbitopathy research in the past two decades: a bibliometric analysis / Tendências na pesquisa da orbitopatia de Graves nas últimas duas décadas: uma análise bibliométrica

ABSTRACT Purpose: This study was conducted to identify trends in Graves' orbitopathy research in the past two decades and to elaborate on hot topics in the field. Methods: The Web of Science database was used to extract articles on Graves' orbitopathy or its synonyms. Full data and references were exported to VOSviewer software to be analyzed. Visualization maps and charts were constructed accordingly. Results: We retrieved 1067 articles on Graves' orbitopathy from the Web of Science database. The United States ranked first in terms of the article count (25), followed by Italy (141) and the People's Republic of China (120). Wiersinga's and the University of Amsterdam's articles received the highest citation count (1509 and 3052, respectively). The University of Pisa and Thyroid published the highest number of articles (65 and 93, respectively). Co-authorship analysis showed four clusters of country collaborations: red cluster, European countries; green cluster, the United States, Brazil, Canada, South Korea, and Taiwan; a yellow cluster, People's Republic of China; and blue cluster, Japan, Australia, and Poland. Keyword analysis revealed five clusters of topics: pathogenesis, management, association, quality of life, and surgery. Analysis of co-cited references also revealed five clusters: pathogenesis, management, risk factors, clinical assessment, and surgical management. Conclusion: Research on Graves' orbitopathy has grown during the past two decades. Hot research topics are pathogenesis, management, risk factors, quality of life, and complications. Research trends have changed in the past two decades. Increasing interest in exploring Graves' orbitopathy mechanisms and associations is evident. European countries are cooperating in this field of research. The United States has established more extensive international cooperation than other countries. We believe that more international collaboration involving developing countries is required.

RESUMO Objetivo: Identificar tendências no campo de pesquisa da orbitopatia de Graves nas últimas duas décadas e analisar os ramos de maior concentração de pesquisas nessa área. Métodos: O banco de dados Web of Science foi usado para extrair artigos com "orbitopatia de Graves" ou seus sinônimos no título. Dados completos e referências foram exportados para o programa VOSviewer para serem analisados. Mapas e gráficos de visualização foram construídos a partir desses dados. Resultados: Foram obtidos 1067 artigos sobre a orbitopatia de Graves a partir do banco de dados Web of Science. Os EUA ficaram em primeiro lugar em termos de número de publicações, seguidos pela Itália e pela República Popular da China. Dentre os autores, os artigos de Wiersinga WM tiveram o maior número de citações. Quanto às instituições, os artigos da Universidade de Amsterdã tiveram o maior número de citações, mas a Universidade de Pisa publicou o maior número de artigos. Dentre os periódicos, a revista Thyroid publicou o maior número de artigos. A análise de coautoria mostrou quatro agrupamentos de colaboração entre países. O primeiro agrupamento engloba países europeus; o segundo engloba os EUA, Brasil, Canadá, Coreia do Sul e Taiwan. A República Popular da China compreende um agrupamento por si só. O quarto agrupamento inclui Japão, Austrália e Polônia. A análise das palavras-chave revelou cinco agrupamentos de tópicos de palavras-chave: patogênese, gerenciamento, associação, qualidade de vida e cirurgia. A análise das referências citadas em conjunto revelou cinco agrupamentos: patogênese, manejo, fatores de risco, avaliação clínica e manejo cirúrgico. Conclusão: A pesquisa no campo da orbitopatia de Graves cresceu nos últimos vinte anos. Os tópicos com a maior concentração de pesquisas são: patogênese, gerenciamento, fatores de risco, qualidade de vida e complicações. As tendências de pesquisa mudaram nas últimas duas décadas. Ficou evidente um aumento do interesse em explorar os mecanismos e associações da orbitopatia de Graves. Observou-se uma cooperação entre países europeus neste campo de pesquisa. Os EUA estabeleceram uma cooperação internacional mais ampla que outros países. Acreditamos que mais colaboração internacional envolvendo países em desenvolvimento seria recomendável.

Comparison of choroidal thickness in patients with active and stable thyroid eye disease / Comparação da espessura da coroide em pacientes com doença ocular tireoidiana ativa e estável

ABSTRACT Purpose: To compare the choroidal thickness in active and stable phases of thyroid eye disease. Methods: Forty-seven eyes of 47 patients with thyroid eye disease were prospectively studied. Patients were evaluated on the basis of their clinical activity scores, with scores 33 defined as active disease. Subfoveal, temporal macular, nasal macular, temporal peripapillary, and nasal peripapillary choroidal thickness measurements were performed with Cirrus enhanced depth imaging spectral-domain optical coherence tomography, and the results in the two groups were compared. Results: Twenty-four patients were int he active group, whereas 23 patients were in the stable group. Choroidal thickness was significantly higher in the subfoveal and temporal macular regions in the active group. Although the nasal macular and peripapillary values were also higher in the active group, the difference was insignificant. Conclusions: Subfoveal choroidal thickness was significantly higher in patients with thyroid eye disease in the active phase than in those with stable phase disease.

RESUMO Objetivo: Comparar a espessura da coroide nas fases ativa e estável da doença ocular tireoidiana. Métodos: Quarenta e sete olhos, de 47 pacientes com doença ocular tireoidiana foram estudados prospectivamente. Os pacientes foram avaliados com base em seus escores de atividade clínica, com escore de 33 definidos como doença ativa. As medidas subfoveais, maculares temporais, maculares nasais, peripapilares temporais e da espessura da coroide peripapilar foram realizadas com tomografia de coerência óptica de domínio espectral Cirrus EDI, e os resultados nos dois grupos foram comparados. Resultados: Vinte e quarto pacientes estavam no grupo ativo, enquanto 23 pacientes estavam no grupo estável. A espessura da coroide foi significativamente maior nas regiões macular subfoveal e temporal no grupo ativo. Embora os valores maculares e peripapilares nasais também fossem maiores no grupo ativo, a diferença foi insignificante. Conclusões: A espessura da coroide subfoveal foi significativamente maior em pacientes com doença ocular tireoidiana na fase ativa do que naqueles com doença na fase estável.

Response to tocilizumab treatment in Graves' ophthalmopathy by measuring rectus muscle thickness and chemosis using optical coherence tomography. / Evaluación del grosor de los músculos extraoculares y la quemosis tras tocilizumab en oftalmopatía de Graves mediante tomografía de coherencia óptica.

PURPOSE: To assess the extraocular muscle thickness and chemosis after treatment with tocilizumab in patients with active Graves' ophthalmopathy by optical coherence tomography. METHODS: Case series of five patients with active Graves' ophthalmopathy (clinical activity score ≥4/10) treated with 4 doses of tocilizumab. These patients had been previously treated with corticosteroids with no response. Spectral-domain optical coherence tomography was employed to determine lateral and medial rectus muscle thickness and chemosis before and after 4 doses of tocilizumab given monthly. Scanning was performed at 3 and 9 o'clock (nasal and temporal). RESULTS: The study included four women and one man with a median age of 52 years (range: 38-73). Median Graves' ophthalmopathy activity duration was 17 months (12-18). Median medial rectus and determine lateral thicknesses pre-treatment were 249µm (174-366) and 337µm (142-443), respectively. Median chemosis was 409µm (290-610). After tocilizumab treatment, median muscle thicknesses reduced to 157µm (88-187) and 197µm (99-290), respectively (P=.043; Wilcoxon) and chemosis to 59µm (0-78). Median clinical activity score decreased from 5 (4-8) to 1 (0-3). CONCLUSIONS: A reduction in extraocular muscle thickness and chemosis was observed after treatment with tocilizumab in Graves' ophthalmopathy patients using an optical coherence tomography, so this technique could be a useful complementary technique to assess the therapeutic responses.

Botulinum toxin for treatment of restrictive strabismus.

PURPOSE: To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. METHODS: We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. RESULTS: We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. CONCLUSION: Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up.

Apresentação atípica da oftalmopatia de Graves / Atypical presentation of Graves’ ophthalmopathy

A oftalmopatia de Graves é a doença orbitária mais comum e acomete 25 a 50% dos pacientes portadores da Doença de Graves e é mais frequente no sexo feminino, entre a segunda e quinta décadas de vida. A doença apresenta uma fase aguda e uma crônica, evoluindo lenta e progressivamente até estabilizar, sendo raros os casos de resolução espontânea. O tratamento dependerá da fase em que a doença se encontra e está baseado principalmente na corticoterapia via oral e endovenosa e/ou radioterapia, sendo a colchicina empregada em casos isolados. No seguinte relato de caso, abordaremos uma forma atípica de manifestação clínica da Oftalmopatia de Graves em paciente eutireoideia com anticorpos negativos na sua apresentação inicial.

Graves ‘ophthalmopathyis themost commonorbital diseaseand affects25-50% of the patients withGraves’ disease. It`s morecommon in females, between the second andfifth life`s decade. The disease hasanacute andachronic stage, slowly progressing until it stabilizes, with rarecasesof spontaneous resolution.The treatment depends on thestage andthe disease ismainly treated withoralor intravenous corticosteroids with or without radiotherapy;colchicine is usedin individual cases. In the followingcase report, we discuss an atypicalmanifestation ofGraves’ ophthalmopathyin an euthyroid patientwith negative antibodiesin the inicial presentation.

Oftalmopatía de Graves y tratamiento con I131 / Graves´ Ophthalmopathy and Radioiodine Treatment

La oftalmopatía de Graves (OG) es un desorden autoinmune que representa la manifestación extratiroidea más frecuente de la Enfermedad de Graves. Se describen múltiples factores que pueden influir en el desarrollo/progresión de la enfermedad, entre ellos el tratamiento con I131. El objetivo de esta monografía es analizar la bibliografía existente sobre la relación entre OG y tratamiento con I131, teniendo en cuenta su fisiopatología así como los factores de riesgo asociados y su profilaxis.

Graves´ ophthalmopathy (GO) is an autoimmune disorder representing the most common extrathyroidal manifestation of Graves' disease. Multiple factors can influence the development / progression of the disease, including treatment with 131I. The aim of this paper is to analyze the existing literature on the relationship between OG and treatment with I131, considering the pathophysiology and associated risk factors and prophylaxis.

[Thyroid orbitopathy, an overview with special attention to the role of radiotherapy]. / Orbitopatía tiroidea, una visión global con atención especial al papel de la radioterapia.

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves' syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids.

Therapeutic use of mini-scleral lenses in a patient with Graves' ophthalmopathy.

Patients with Graves' ophthalmopathy can be very challenging to manage secondary to the complex nature of their disease presentation. Patients may present with a variety of ocular findings including: lid retraction, periorbital and lid swelling, chemosis, conjunctival hyperemia, proptosis, optic neuropathy, restrictive myopathy, exposure keratopathy and/or keratoconjunctivitis sicca. Mini-scleral and scleral lens designs have been important in the management of irregular and regular corneas, and in the therapy of ocular surface diseases. We present here the case of a 48-year-old Caucasian male who had been diagnosed with Graves' ophthalmopathy 13 years earlier. With significant ocular surface staining and over ten diopters of astigmatism, the patient had never been able to wear contact lenses comfortably. After being fit with the Mini-Scleral Design™ lenses, his vision improved to 20/25 OU, his ocular surface improved, and overall quality of vision increased.

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials / Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de ensaios clínicos randomizados e controlados

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

OBJETIVO: Avaliar a eficácia da radioterapia (RT) com dose total de 20 Gy (RT 20 Gy) no tratamento da oftalmopatia de Graves. MÉTODOS: Uma revisão sistemática e meta-análise de ensaios clínicos randomizados foram realizadas comparando RT 20 Gy, com ou sem glicocorticoides a tratamentos clinicos para a oftalmopatia de Graves. O MEDLINE, EMBASE, bases de dados da Biblioteca Cochrane e recentes de revistas relevantes foram pesquisados. Relatórios relevantes foram revisados por dois revisores. A resposta à radioterapia foi definida através do sucesso clinico de acordo a cada ensaio clínico. Nós também avaliamos a qualidade de vida e se a radioterapia produzia menos efeitos colaterais comparados a outras intervenções. RESULTADOS: Um total de 8 ensaios clínicos randomizados (439 pacientes) foram identificados. Na análise de subgrupo, a resposta global para as taxas de tratamento foi melhor para: RT 20 Gy além de glicocorticoides vs glicocorticoides sozinhos, OR=17,5 (IC95% 1,85-250, p=0,04), RT 20 Gy vs sham RT, OR=3,15 (IC95% 1,59-6,23, p=0,003) e RT 20 Gy além de glicocorticoides por via intravenosa RT 20 Gy além de glicocorticoides orais, OR=4,15 (IC95% 1,34-12,87, p=0,01). Não houve diferenças entre RT 20 Gy contra outros fracionamentos e 20 Gy RT contra glicocorticoides sozinhos. RT 20 Gy, com ou sem glicocorticoides mostraram uma melhoria no grau de diplopia, acuidade visual, neuropatia óptica, abertura palpebral, proptose e da motilidade ocular. Não foi observada diferença para os custos, a pressão intraocular e a qualidade de vida. CONCLUSÃO: Nossos dados mostraram que 20 Gy RT deve ser oferecida como uma opção terapêutica válida para pacientes com moderada a severa oftalmopatia de Graves. A eficácia da radioterapia orbital pode ser aumentada pela interação sinérgica com os glicocorticoides. Além disso, RT 20 Gy é útil para melhorar vários sintomas oculares, excluindo a pressão intraocular, sem qualquer diferença de qualidade de vida.

Surgical treatment of globe subluxation in the active phase of the myogenic type of Graves orbitopathy: case reports / Tratamento cirúrgico da subluxação do globo ocular na fase ativa do subtipo miogênico da orbitopatia de Graves: relatos de casos

The purpose of the present article is to present and discuss two cases of globe su­blu­xation in the active phase of myogenic Graves' orbitopathy and to evaluate the prevalence of this phenomenon. Two patients with the myogenic variant of Graves' orbitopathy that had being treated with oral and intravenous steroid pulses developed globe subluxation. Both had to have urgent eyelid and orbital decompression. After these observations, we reviewed the medical records of a sample of 284 patients (482 orbits) who had had orbital decompression at our Institution from 1992 to 2010, with a search for cases presenting severe proptosis or globe subluxation in the active phase of myogenic Graves' orbitopathy. No patient had to have decompression for globe subluxation in the active phase of Graves' orbitopathy. The prevalence of this event as an indication for surgery in the myogenic variant of Graves' orbitopathy was therefore 0.7% (2/284) or even less. The combination of lowering the upper eyelid and orbital decompression had a dramatic therapeutic effect on these patients des­pite the presence of intense inflammatory signs in the orbits. In conclusion, patients affected with the myogenic variant of Graves' orbitopathy may develop globe subluxation. Urgent surgical treatments should not be postponed despite the presence of active inflammation.

O objetivo do presente trabalho é apresentar e discutir dois casos de subluxação do globo ocular na fase ativa do subtipo miogênico da orbitopatia de Graves e avaliar a prevalência desse fenômeno. Dois pacientes com o subtipo miogênico da orbitopatia de Graves tratados com corticosteroide oral e pulsos intravenosos desenvolveram subluxação do globo ocular. Após estas observações, analisamos os prontuários de uma amostra de 284 pacientes (482 órbitas) que foram submetidos à descompressão orbitária em nossa Instituição no período de 1992 a 2010, buscando os casos que apresentaram proptose severa ou subluxação do globo ocular na fase ativa da orbitopatia de Graves miogênica. Nenhum paciente tinha sido descomprimido para subluxação do globo ocular na fase ativa da orbitopatia de Graves. A prevalência desse evento como uma indicação para cirurgia na variante miogênica da orbitopatia de Graves foi 0,7% (2/284) ou até menos. A combinação da correção da retração da pálpebra superior e da descompressão da órbita obteve um efeito terapêutico excelente nesses pacientes, apesar da intensa presença de sinais inflamatórios nas órbitas. Em conclusão, pacientes afetados com orbitopatia de Graves do subtipo miogênico podem desenvolver subluxação do globo. Tratamentos cirúrgicos de urgência não devem ser adiados apesar da presença de inflamação ativa.

Espessamento do tendão muscular na oftalmopatia de Graves / Muscle tendon enlargment in Graves´ophthalmopathy

OBJETIVO: Estudar a frequência do espessamento do tendão muscular em pacientes com oftalmopatia de Graves buscando estabelecer correlações com as diferentes formas clínicas da doença. A diversidade clínica e laboratorial na oftalmopatia de Graves pode levar à confusão quanto ao diagnóstico, conduta e prognóstico. Os achados radiológicos variam desde o aumento isolado do tecido adiposo até o espessamento da musculatura extraocular, caracteristicamente poupando os tendões. Em 2004,no entanto, Ben Simon descreveu o espessamento do tendão muscular na oftalmopatia de Graves. MÉTODOS: Foram avaliados 20 pacientes, de ambos os sexos, com idades entre 20 e 80 anos, com formas clínicas designadas como :forma benigna (retração palpebral),forma intermediária (diplopia na posição primária do olhar) e forma maligna ou infiltrativa (sinais de comprometimento do nervo óptico).Todos os pacientes foram submetidos à tomografias computadorizadas de órbita. Os pacientes estavam eutiroideanos, há pelo menos um ano. Os padrões tomográficos foram estudados e divididos em dois grupos: com e sem espessamento dos tendões da musculatura extraocular. RESULTADOS: Uma relação estatisticamente significativa entre espessamento do tendão e a forma clínica intermediária foi encontrada (p <0,012). CONCLUSÃO: O espessamento do tendão extraocular, encontrado em 30 por cento dos pacientes com oftalmopatia de Graves, relaciona-se positivamente com a forma intermediária da doença, caracterizada pela presença de diplopia e que constitui um achado de grande valor clínico.

PURPOSE: The aim is therefore to study the frequency of tendon enlargment in Graves' ophthalmopathy, seeking to estabilish its clinical correlations. Clinical and laboratory diversity in Graves' Ophthalmopathy sometimes may mislead its diagnosis. Radiological findings are more reliable for the diagnosis of Graves' Ophthalmopathy. Since then, a number of patterns have been described. Extraocular muscle involvement in this pathology is considered as always sparing the tendons. In 2004, Ben Simon described extraocular muscles tendon enlargment in some patients with diplopia in Graves' orbitopathy. METHODS: 20 patients, aged between 20 and 80 years, of both sexes, designated as benign (eyelid retraction), intermediate(diplopia in primary sight position) and malignant or infiltrative(signs of optic nerve compromise) forms were evaluated by orbital tomography. All patients had already been euthyroidean for at least one year. Tomographic patterns were studied and divided into two groups: with or without extraocular muscle tendons enlargment. RESULTS: Statistically significant relationship was found between tendon enlargment and intermediate form (p<0.012). CONCLUSION: Extraocular tendon involvement present in 30 percent of the patients with Graves' ophthalmopathy, and is positively correlated to intermediary form of the disease, characterized by diplopia, a very important clinical landmark.

Treatment of mild to moderate Graves' ophthalmopathy with sodium diclofenac: a pilot study / Tratamento da oftalmopatia de Graves leve a moderada com diclofenato de sódio: um estudo piloto

OBJECTIVE: To report the use of sodium diclofenac, an antagonist of PPAR-gamma and cyclooxigenase-2 (COX-2) inhibitor in the treatment of mild to moderate Graves' ophthalmopathy. SUBJECTS AND METHODS: Thirteen patients with clinical activity score (CAS) 2 to 7 were treated during a period ranging from 3 to 12 months (mean 7.8 ± 3.4) with oral sodium diclofenac, 50 mg every 12 hours. RESULTS: Extra-ocular muscle restriction and CAS improved significantly, p = 0.003 and = 0.004, respectively. Ocular pain and diplopia disappeared, except for one patient who reported improvement of these symptoms. No recurrence was found after interruption of treatment. CONCLUSIONS: Treatment of moderate Graves' ophthalmopathy with oral sodium diclofenac is a good, safe and less expensive therapeutic option. Like others new treatment trials, findings must be confirmed in a greater number of patients in a controlled study.

OBJETIVO: Relatar o uso do diclofenato de sódio, um antagonista do PPAR-gama e inibidor da ciclooxigenase-2 (COX-2) no tratamento da leve a moderada oftalmopatia de Graves. SUJEITOS E MÉTODOS: Treze pacientes com CAS (clinical activity score) 2 a 7 foram tratados durante um período de 3 a 12 meses (média 7,6 ± 3,4) com diclofenaco de sódio por via oral na dose de 50 mg a cada 12 horas. RESULTADOS: A restrição da musculatura extraocular e o índice CAS melhoraram de modo significativo, respectivamente p = 0,003 e p = 0,004. A dor ocular e a diplopia desapareceram, com exceção de um paciente que referiu melhora desses sintomas. Não houve recidiva após a interrupção do tratamento. CONCLUSÕES: O tratamento da oftalmopatia de Graves de média gravidade com diclofenaco de sódio por via oral é uma opção boa, segura e de baixo custo. Como outros novos tratamentos, ele deverá ser confirmado em um maior número de pacientes em estudos controlados.

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