PROTRACTED HYPOFRACTIONATED RADIOTHERAPY for GRAVES' OPHTHALMOPATHY: A PILOT STUDY of CLINICAL and RADIOLOGIC RESPONSE

Purpose: To evaluate the clinical and radiologic response of patients with Graves' ophthalmopathy given low-dose orbital radiotherapy (RT) with a protracted fractionation.Methods and Materials: Eighteen patients (36 orbits) received orbital RT with a total dose of 10 Gy, fractionated in 1 Gy once a week over 10 weeks. of these, 9 patients received steroid therapy as well. Patients were evaluated clinically and radiologically at 6 months after treatment. Clinical response assessment was carried out using three criteria: by physical examination, by a modified clinical activity score, and by a verbal questionnaire considering the 10 most common signs and symptoms of the disease. Radiologic response was assessed by magnetic resonance imaging.Results: Improvement in ocular pain, palpebral edema, visual acuity, and ocular motility was observed in all patients. Significant decrease in symptoms such as tearing (p < 0.001) diplopia (p = 0.008), conjunctival hyperemia (p = 0.002), and ocular grittiness (p = 0.031) also occurred. Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients. Treatments were well tolerated, and to date no complications from treatment have been observed. There was no statistical difference in clinical and radiologic response between patients receiving RT alone and those receiving RT plus steroid therapy.Conclusion: RT delivered in at a low dose and in a protracted scheme should be considered as a useful therapeutic option for patients with Graves' ophthalmopathy. (C) 2012 Elsevier Inc.

COMPARATIVE EVALUATION of OCULOMETRIC VARIABLES IN GRAVES' OPHTHALMOPATHY

OBJECTIVES: To estimate oculometric parameters of Graves' ophthalmopathy in comparison to healthy eyes using digital photography and digital image analysis.INTRODUCTION: Graves' ophthalmopathy is the main cause of eye proptosis. Because these protrusions cause clinically perceived distortions in orbital architecture, digital photographs can be used to detect and quantify these changes.METHODS: We carried out a cross-sectional study comprising 12 healthy volunteers and 15 Graves' ophthalmopathy patients with the purpose of evaluating the use of simple, non-invasive digital photography to estimate oculometric parameters of Graves' ophthalmopathy and compare them with the parameters of unaffected eyes. Facial photographs of cases and controls were taken in a standardized manner. Oculometric parameters were compared between the groups and then correlated to proptometer measures.RESULTS: All estimated oculometric variables showed significant differences between the groups, in particular with regard to mediopupilar aperture, lateral height, distance from the iris edge to the lateral boundary of the palpebral fissure, and distance from the higher point of the iris to the lateral limit of the palpebral fissure. The product of medial aperture and horizontal palpebral fissure also revealed greater discrepancy between the groups. Proptometer measures showed significant linear correlation between the distance from the iris edge to the lateral boundary of the palpebral fissure and between the distance from the higher point of the iris to the lateral limit of palpebral fissure (p<0.05).CONCLUSIONS: Comparative analysis of oculometric parameters in Graves' ophthalmopathy suggests that eye proptosis is related to an asymmetric increase in lateral oculometric measures. Standardized digital photographs can be used in clinical practice to objectively estimate oculometric parameters of Graves' ophthalmopathy patients.

Graves ophthalmopathy: low-dose glucocorticoid increases peroxisome proliferator-activated receptor-gamma gene expression

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gene expression of estrogen receptor-alpha in orbital fibroblasts in Graves’ ophthalmopathy

Graves’ ophthalmopathy (GO) is one of the most severe clinical manifestations of Graves’ disease (GD), and its treatment might involve high-dose glucocorticoid therapy. The higher incidence of GO among females, and the reported association between polymorphisms of estrogen receptor (ER) and GD susceptibility have led us to question the role of estrogen and its receptor in GO pathogenesis. We, thus, assessed estrogen receptor-alpha (ERA) gene expression in cultures of orbital fibroblasts from a patient with GO before (controls) and after treatment with 10 nM and 100 nM dexamethasone (DEX). Orbital fibroblasts showed ERA gene expression. In the cells treated with 10 nM and 100 nM DEX, ERA gene expression was, respectively, 85% higher and 74% lower, than in the control group. We concluded that ERA gene expression is found in the orbital fibroblasts of patient with GO, which may be affected by glucocorticoids in a dose-related manner. Arch Endocrinol Metab. 2015;59(3):273-6

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials

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.

Graves' ophthalmopathy: natural history and treatment outcomes

The pathogenesis of Graves' ophthalmopathy has not been yet clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an enigma. The natural course and effects of different treatment regimens are poorly documented.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Consenso brasileiro para o diagnóstico e tratamento do hipertireoidismo: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

INTRODUÇÃO: O hipertireoidismo é caracterizado pelo aumento da síntese e liberação dos hormônios tireoidianos pela glândula tireoide. A tireotoxicose refere-se à síndrome clínica decorrente do excesso de hormônios tireoidianos circulantes, secundário ao hipertireoidismo ou não. Este artigo descreve diretrizes baseadas em evidências clínicas para o manejo da tireotoxicose. OBJETIVO: O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o manejo, diagnóstico e tratamento dos pacientes com tireotoxicose, de acordo com as evidências mais recentes da literatura e adequadas para a realidade clínica do país. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. RESULTADOS: Foram definidas 13 questões sobre a abordagem clínica inicial visando ao diagnóstico e ao tratamento que resultaram em 53 recomendações, incluindo investigação etiológica, tratamento com drogas antitireoidianas, iodo radioativo e cirurgia. Foram abordados ainda o hipertireoidismo em crianças, adolescentes ou pacientes grávidas e o manejo do hipertireoidismo em pacientes com oftalmopatia de Graves e com outras causas diversas de tireotoxicose. CONCLUSÕES: O diagnóstico clínico do hipertireoidismo, geralmente, não oferece dificuldade e a confirmação diagnóstica deverá ser feita com as dosagens das concentrações séricas de TSH e hormônios tireoidianos. O tratamento pode ser realizado com drogas antitireoidianas, administração de radioiodoterapia ou cirurgia de acordo com a etiologia da tireotoxicose, as características clínicas, disponibilidade local de métodos e preferências do médico-assistente e paciente.

Estimation of spontaneous blinking main sequence in normal subjects and patients with Graves' upper eyelid retraction

Purpose. We quantified the main sequence of spontaneous blinks in normal subjects and Graves' disease patients with upper eyelid retraction using a nonlinear and two linear models, and examined the variability of the main sequence estimated with standard linear regression for 10-minute periods of time. Methods. A total of 20 normal subjects and 12 patients had their spontaneous blinking measured with the magnetic search coil technique when watching a video during one hour. The main sequence was estimated with a power-law function, and with standard and trough the origin linear regressions. Repeated measurements ANOVA was used to test the mean sequence stability of 10-minute bins measured with standard linear regression. Results. In 95% of the sample the correlation coefficients of the main sequence ranged from 0.60 to 0.94. Homoscedasticity of the peak velocity was not verified in 20% of the subjects and 25% of the patients. The power-law function provided the best main sequence fitting for subjects and patients. The mean sequence of 10-minute bins measured with standard linear regression did not differ from the one-hour period value. For the entire period of observation and the slope obtained by standard linear regression, the main sequence of the patients was reduced significantly compared to the normal subjects. Conclusions. Standard linear regression is a valid and stable approximation for estimating the main sequence of spontaneous blinking. However, the basic assumptions of the linear regression model should be examined on an individual basis. The maximum velocity of large blinks is slower in Graves' disease patients than in normal subjects. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Eficácia das terapias convencionais (Pentoxifilina e Nicotinamida/Alopurinol) comparadas a metilprednisolona intravenosa no tratamento da oftalmopatia de Graves

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Parâmetros oftálmicos em espécimes de Cuniculus paca criadas em cativeiro

Pós-graduação em Cirurgia Veterinária - FCAV

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.

Pre- and Postoperative Quantitative Analysis of Contour Abnormalities in Graves Upper Eyelid Retraction

Purpose: One of the most common problems of the surgical management of Graves upper eyelid retraction is the occurrence of eyelid contour abnormalities. In the present study, the postoperative contour of a large sample of eyelids of patients with Graves orbitopathy was measured. Methods: The postoperative upper eyelid contour of 62 eyes of 43 patients with Graves orbitopathy was subjectively classified by 3 experienced surgeons in 3 categories: poor, fair, and good. The shape of the eyelid contours in each category was then measured with a recently developed custom-made software by measuring multiple midpupil eyelid distances each 15 degrees along the palpebral fissure. The upper eyelid contour of 60 normal subjects was also quantified as a control group. Results: The mean ratio between the sum of the lateral and medial midpupil eyelid distances (lateral/medial ratio) was 1.10 +/- 0.11 standard deviation in controls and 1.15 +/- 0.13 standard deviation in patients. Postoperatively, the mean midpupil eyelid distance at 90 degrees was 4.16 +/- 1.13 mm standard deviation. The distribution lateral/medial ratios of the eyelids judged as having good contours was similar to the distribution of the controls with a modal value centered on the interval between 1.0 and 1.10. The distribution of lateral/medial ratios of the eyelids judged as having poor contour was bimodal, with eyelids with low and high lateral/medial ratios. Low lateral/medial ratios occurred when there was a lateral overcorrection, giving the eyelid a flat or a medial ptosis appearance. High lateral/medial ratios were due to a central or medial overcorrection or a lateral peak maintenance. Conclusions: Postoperative upper eyelid contour abnormalities can be quantified by comparing the sum of multiple midpupil eyelid distances of the lateral and medial sectors of the eyelid. Low and high lateral/medial ratios are anomalous and judged as unpleasant. (Ophthal Plast Reconstr Surg 2012;28:429-433)

Quantification of Orbital Apex Crowding for Screening of Dysthyroid Optic Neuropathy Using Multidetector CT

BACKGROUND AND PURPOSE: DON, a serious complication of GO, is frequently difficult to diagnose clinically in its early stages because of confounding signs and symptoms of congestive orbitopathy. We evaluated the ability of square area measurements of orbital apex crowding, calculated with MDCT, to detect DON. MATERIALS AND METHODS: Fifty-six patients with GO were studied prospectively with complete neuro-ophthalmologic examination and MDCT scanning. Square measurements were taken from coronal sections 12 mm, 18 mm, and 24 mm from the interzygomatic line. The ratio between the extraocular muscle area and the orbital bone area was used as a Cl. Intracranial fat prolapse through the superior orbital fissure was recorded as present or absent. Severity of optic nerve crowding was also subjectively graded on corona! images. Orbits were divided into 2 groups (with or without clinical evidence of DON) and compared. RESULTS: Ninety-five orbits (36 with and 59 without DON) were studied. The CIs at all 3 levels and the subjective crowding score were significantly greater in orbits with DON (P<.001). No significant difference was observed regarding intracranial fat prolapse (P=.105). The area under the ROC curves was 0.91, 0.93, and 0.87 for CIs at 12, 18, and 24 mm, respectively. The best performance was at 18 mm, where a cutoff value of 57.5% corresponded to 91.7% sensitivity, 89.8% specificity, and an odds ratio of 97.2 for detecting DON. A significant correlation (P<.001) between the CIs and VF defects was observed. CONCLUSIONS: Orbital Cls based on area measurements were found to predict DON more reliably than subjective grading of orbital crowding or intracranial fat prolapse.

Cosmetic Orbital Inferomedial Decompression: Quantifying the Risk of Diplopia Associated With Extraocular Muscle Dimensions

Purpose: To quantify the risk of new diplopia in inferomedial orbital decompression performed for cosmetic reasons. Methods: Retrospective analysis of 114 patients with Graves orbitopathy who underwent an inferomedial orbital decompression. No patient had diplopia in any of the gaze positions or optic neuropathy. A single coronal slice 9 mm posterior to the lateral orbital rim was employed to quantify the muscular index of the extraocular recti and of the superior complex. A control group of 56 patients imaged for other reasons were also measured. After surgery the oculomotor status of all patients who complained of diplopia and of 51 patients free of diplopia was measured with the prism and cover test in the primary and secondary gaze positions. Results: The rate of new-onset diplopia was 14.0% (16 patients). Eye deviations were confirmed in 14 patients. Of these, 10 had significant strabismus that warranted surgical or prism treatment. Most patients had esotropia associated with small vertical deviations. The size of the medial and inferior recti was significantly associated with the development of diplopia. The estimated odds for the appearance of diplopia in patients with muscle enlargement was 12.76 (medial rectus) and 5.21 (inferior rectus). Small-angle deviations were also detected in 27.4% of patients who did not experience diplopia. Conclusions: Medial and inferior recti enlargement is a strong predictor of new-onset diplopia. A large number of patients who do not report diplopia also present with small-angle deviations. (Ophthal Plast Reconstr Surg 2012;28:204-207)