The association of carotid cavernous fistula with Graves’ ophthalmopathy

Graves’ ophthalmopathy (GO) is one of the frequent manifestations of the disorder which is an inflammatory process due to fibroblast infiltration, fibroblast proliferation and accumulation of glycosaminoglycans. Eye irritation, dryness, excessive tearing, visual blurring, diplopia, pain, visual loss, retroorbital discomfort are the symptoms and they can mimic carotid cavernous fistulas. Carotid cavernous fistulas are abnormal communications between the carotid arterial system and the cavernous sinus. The clinical manifestations of GO can mimic the signs of carotid cavernous fistulas. Carotid cavernous fistulas should be considered in the differential diagnosis of the GO patients especially who are not responding to the standard treatment and when there is a unilateral or asymmetric eye involvement. Here we report the second case report with concurrent occurrence of GO and carotid cavernous fistula in the literature.     

The clinicopathologic basis of Graves' ophthalmopathy: a review

PURPOSE: Graves' ophthalmopathy (GO) is a controversial disease, with disagreement within the medical community regarding its pathogenesis, diagnosis, and treatment. METHODS: We reviewed recent literature on clinical and pathological aspects of GO from both the endocrinologist's and ophthalmologist's perspective. RESULTS: Investigations into the pathogenesis of GO have included possible antigenic targets, orbital cell types, and development of animal models. Diagnosis has been improved recently with new tools and grading systems, but can be complicated by conditions that may simulate one or more of the findings of GO. The new findings of clinical studies also compel practitioners to reassess commonly used GO treatments such as orbital irradiation. CONCLUSIONS: Improved understanding of the pathogenic mechanisms of GO should hopefully lead to new diagnostic and therapeutic approaches to this problematic condition.     

2019甲状腺相关性眼病管理实用指南解读

甲状腺相关性眼病(Graves ophthalmopathy, GO)是一种自身免疫性疾病,常伴有眼眶组织炎症。本实用指南由一组不同学科领域成员组成的研究小组负责编写。本文将对该指南进行全面解读,希望能为GO的日常临床实践的诊断提供指导,从而改善患者的治疗效果,提高医疗服务质量。     

Increased serum interleukin-17 in Graves’ ophthalmopathy

Background

Interleukin (IL)-17 and T helper 17 (Th17) cells are reported to be involved in many autoimmune diseases. The aim of this study is to investigate the involvement of IL-17 in the pathogenesis and disease activity of Graves’ ophthalmopathy (GO).

Methods

Sixty-two GO patients and 19 healthy controls were recruited. Serum concentrations of cytokines, IL-17, IL-6, IL-23, and IL-16, were measured using multiplexed microsphere-based flow cytometric immunoassays. GO hormonal parameters, clinical activity score (CAS), exophthalmometry, and extraocular muscle involvement were evaluated, and relationships with cytokine concentrations were analyzed.

Results

The concentration and positive detection rates of serum IL-17 were significantly higher in patients with GO than in controls. The serum levels of IL-17 in active GO patients were higher than that of inactive GO patients. Serum IL-17 concentration had significant correlation with CAS (p?<?0.001).

Conclusion

The increased serum level of IL-17 and related cytokines in GO patients and the correlation of IL-17 concentration with the clinical activity scores suggest that IL-17 may play a pathophysiological role in GO.     

Graves眼病的糖皮质激素治疗

Graves眼病是指自身免疫性甲状腺疾病引起的眼眶炎症,主要累及眼外肌和球后脂肪产生突眼或眼外肌功能障碍.糖皮质激素通过免疫抑制和抗炎作用可使Graves眼病得到不同程度的缓解.本综述比较了口服、局部注射和静脉注射糖皮质激素三种治疗方法的疗效、副作用及用药指征,显示口服用药效果优于局部用药,静脉给药似乎优于口服,但副作用较大.发现Graves眼病需及早治疗,尤其是活动性眼病更需要治疗,防止眼病恶化,治疗时需权衡糖皮质激素的风险与获益.     

Endokrine Orbitopathie aus internistischer Sicht

Graves' orbitopathy (GO) is the most frequently observed extrathyroidal manifestation of Graves' disease occurring in up to 40% of patients. Most patients with Graves' orbitopathy are tested positive for TSH receptor autoantibodies (TRAb), which are pathognomonic for Graves' disease and also play a central pathogenetic role in the development of GO. For the diagnosis of Graves' disease, symptoms of hyperthyroidism, low TSH and high fT3 and/or fT4 levels and positive TRAbs are typical. All patients with Graves' disease must be regularly examined for extrathyroidal manifestations, especially for Graves' orbitopathy. For hyperthyroidism, treatment with antithyroidal drugs, such as thiamazole or propylthiouracil is initiated to quickly restore euthyroidism, which also frequently leads to improvement of Graves' orbitopathy. Smoking cessation is also heavily mandated. In cases of relapse or ineffective antithyroidal treatment, radioiodine therapy or thyroid surgery is a further definitive therapeutic option to treat hyperthyroidism. The management of Graves' orbitopathy remains clinically challenging and demands involvement of a multidisciplinary team including endocrinologists, ophthalmologists, surgeons, radiotherapists and nuclear medicine specialists.     

Relevance of TSH-receptor antibody levels in predicting disease course in Graves' orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay

Aims

To investigate if TSH-receptor antibody (TRAb) levels measured in early Graves'' orbitopathy (GO) stages are predictive of clinical disease course beyond 1 year after initial GO diagnosis and to compare performance of two newly developed TRAb assays (third-generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay vs Mc4-thyroid-stimulating immunoglobulin (TSI) bioassay) in predicting disease course.

Methods

Newly diagnosed, untreated GO patients whose duration of ocular symptoms was less than 6 months were included. One year after initial diagnosis, all patients were classified as presenting either a mild (Group 1) or severe course (Group 2) according to their clinical manifestations. The measurements of two TRAb assays at initial GO diagnosis were used for analysis.

Results

Data from 112 patients were available for analysis. Seventy-three patients (65.2%) were designated as Group 1, and 39 patients (34.8%) as Group 2. Patients with higher initial TRAb levels demonstrated a higher risk of severe disease course upon multiple regression analysis (P<0.01). The cutoff values for the prediction of severe course of the third-generation TBII and Mc4-TSI assays were 10.67 IU/l and 555.10%, respectively, with assay specificities of 84.9 and 89.0%. The TBII assay predictive power (area under the curve (AUC)=0.817; 95% confidence interval (CI) =0.732–0.902) was equivalent to the TSI bioassay (AUC=0.868, 95% CI=0.803–0.934) (P=0.203).

Conclusions

The predictive power of the third-generation TBII assay and Mc4-TSI bioassay are similarly strong. Measurement of TRAb using either third-generation TBII or Mc4-TSI in early GO periods would provide important prognostic information on future GO course.     

Graves' ophthalmopathy through the eyes of the patient: A state of the art on health-related quality of life assessment

The negative impact of the visual limitations and disfigurement associated with Graves' ophthalmopathy (GO) for a patient's daily life has always been acknowledged in clinical practice. However, only recently have the effects of GO on health-related quality of life (HRQL) been quantified using validated questionnaires. In this article, a state of the art is presented on the aims, methodology and application of HRQL assessment in GO research. HRQL assessment is important in cross-sectional studies aimed at describing the severity of GO on multiple outcome levels, including the impact of GO on patients' daily functioning and perception of health in general, and in longitudinal studies aimed at the evaluation of treatment efficacy or comparison of the effects of different treatments on HRQL. Only a few studies have measured the effects of GO on HRQL directly. Patients with GO have a relatively low HRQL, not only in the period that they are diagnosed and treated for the disease, but their low HRQL persists even many years after the final treatment. Because the current therapies for GO are primarily directed at improving (visual) functioning and appearance, these treatments should be evaluated for their effectiveness on HRQL outcomes. At the moment, the recently developed GO-QOL questionnaire is the only validated disease-specific instrument available to measure HRQL in patients with GO. The GO-QOL is recommended as an instrument to measure GO treatment effects on HRQL.     

Medikament?se Therapie und Strahlentherapie bei endokriner Orbitopathie

Drug therapy and radiotherapy in Graves' orbitopathy (GO) aim mainly at the inherent soft tissue inflammation. A timely and sustained anti-inflammatory therapy not only alleviates the current symptoms but particularly intends to limit the degree of permanent alterations. It is indicated in active GO of moderate or higher severity. Pharmacologically, glucocorticoids and if appropriate other immunosuppressive agents, such as cyclosporine are given. Adverse effects can complicate the treatment. Retrobulbar irradiation is applied against diplopia due to eye muscle involvement during the active phase.     

Co-existence of intraocular and orbital lymphoma

BACKGROUND: The concomitant occurrence of both intraocular and periocular lymphomas is extremely rare. Periocular involvement by lymphoproliferative disease ranges from benign lymphoid hyperplasia to malignant lymphoma. Intraocular lymphomas usually appear in conjunction with primary central nervous system lymphoma. CASE REPORTS: We describe clinical characteristics, standardized A- and B-scan ultrasonography, colour Doppler, computerized tomographic and magnetic resonance imaging, and immunohistological findings in three cases of concurrent choroidal and periocular involvement of lymphoma. DISCUSSION: The clinical presentation of diffuse choroidal tumours may be variable, making diagnosis of intraocular lymphoma troublesome on clinical grounds alone. The high accuracy of colour Doppler imaging is known to be effective in differentiating the benign from the malignant and adds valuable information in the differential diagnosis of a low reflective lesion. We suggest the use of auxiliary examinations such as ultrasonography and colour Doppler imaging to help in the differential diagnosis of choroidal and orbital tumours.     

B-scan ultrasonography in Graves' Orbitopathy

Diagnosing and monitoring of Graves' Orbitopathy (GO) can be supported by use of Ultrasonography (USG) and Computerized Tomography (CT); they provide supplementary information. In this retrospective study we describe 107 clinical GO patients evaluated by B-scan USG and 27 clinical GO patients evaluated by CT scan. Analysis of 236 B-scan USG included measurements of medial, inferior and lateral rectus muscles. The presence of muscle enlargement and increased orbital fat were noted by the radiologist on 27 CT scans. Sensitivity of both B-scan USG and CT scan were calculated. We suggest that B-scan USG has a high sensitivity, which is equal or better than CT scan sensitivity in diagnosing GO. Furthermore USG A and B scan combination is an effective, accurate tool in diagnosing GO, and optic neuropathy, but it also provides essential information about the GO disease activity.     

Pulsatile ocular blood flow change after treatment with systemic steroid in patients with Graves' ophthalmopathy

PURPOSE: Our previous study has demonstrated an impairment of pulsatile ocular blood flow (POBF) in patients with Graves'ophthalmopathy (GO). Here we further evaluate the haemodynamic change in GO patients after systemic steroid. METHODS: In a prospective, interventional, consecutive clinical case series, all patients with active and moderately severe GO who underwent systemic steroid treatment were evaluated. The change of POBF and the clinical activity and severity of the disease were assessed. RESULTS: In total, 11 patients underwent intravenous methylprednisolone pulse therapy followed by 2-month oral prednisolone therapy. POBF improved from a mean value of 476.5 to 614.7 microl/min (P<0.001) after treatment. Likewise, the mean clinical activity score reduced from 4.8 to 1.6. However, systemic steroid had less effect on the severity of GO. It also revealed that there is a greater improvement of POBF in those with more clinical activity score (>4) at the onset. CONCLUSIONS: Following treatment with systemic steroid we have demonstrated a significant improvement in POBF in patients with GO.     

Tocilizumab as first treatment option in optic neuropathy secondary to Graves’ orbitopathy

Dysthyroid optic neuropathy (DON) is one of the complications that can affect Graves’ orbitopathy (GO) patients. Its prevalence is estimated at less than 5%. It is usually treated with intravenous steroids, radiotherapy or orbital decompression.

Tocilizumab has been proposed as a treatment option in cases of GO refractory to steroid treatment, with good clinical results. Our aim is to report the case of a patient with optic neuropathy secondary to GO treated with tocilizumab as primary treatment option.     

Orbital involvement in chronic lymphocytic leukemia

In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults.     

Assessing Graves' ophthalmopathy-specific quality of life in Korean patients

Aim

To investigate the clinical significance of Grave''s ophthalmopathy-specific quality of life (GO-QOL) in Korean patients.

Methods

A cross-sectional study was conducted at the Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea, on 98 consecutive Grave''s ophthalmopathy (GO) patients. The GO-QOL survey provided by Terwee and colleagues and suggested by the European group on Graves'' orbitopathy (EUGOGO) was translated into Korean language and distributed to study participants. Clinical severity was judged by scores of the modified NOSPECS classification, and inflammatory activity was measured by a seven-point scale of clinical activity score (CAS).

Results

The mean GO-QOL scores were 73.7 (standard deviation (SD), 26) for visual functioning, 61.9 (SD 26) for appearance, and 67.8 for total quality of life (QOL; SD 22). The worse QOL scores for each part were significantly associated with the higher modified NOSPECS score and CAS after adjusting for confounders such as age and sex (P<0.05, respectively). In particular, decreased QOL scores for visual function were significantly correlated with a higher grade of extraocular muscle involvement (P<0.05). Lower QOL scores for appearance were associated with more severe soft-tissue involvement and proptosis (P<0.05, respectively).

Conclusions

GO-QOL suggested by EUGOGO showed correlation with objective clinical parameters. GO-QOL can be a simple and effective tool in the evaluation of the clinical and psychological illness of GO patients.     

Infectious uveitis in infancy: borreliosis, tuberculosis, lues

Infectious uveitis caused by Borrelia, tuberculosis or syphilis is a rare condition, even in childhood. Because these diseases can be treated successfully, knowledge of their diagnosis and therapy is highly important. The clinical aspects vary from simple conjunctivitis to endophthalmitis or neuro-ophthalmological diseases. The diagnosis of and therapy for borreliosis depend on the stage of the disease. The involvement of different organ systems or positive indirect tests (tuberculin skin test, interferon gamma assays) are important factors in the diagnosis of tuberculosis as the cause of a uveitis. Serology is essential for the diagnosis and monitoring of syphilis.     

Unusual Orbital Involvement in Erdheim Chester Disease: A Radiological Diagnosis

Erdheim–Chester disease (ECD) is an exceedingly rare, disseminated non-Langerhan cell histiocytosis with multisystem involvement, having characteristic sclerotic skeletal lesions. We present an unusual case primarily manifesting as an extensive orbital disease, with low-grade systemic involvement. Owing to its rarity and therefore lack of general awareness it remains a difficult clinical and pathologic diagnosis. Immuno-histochemistry of the biopsy specimen is diagnostic.     

Unusual orbital involvement in erdheim chester disease: a radiological diagnosis

Erdheim-Chester disease (ECD) is an exceedingly rare, disseminated non-Langerhan cell histiocytosis with multisystem involvement, having characteristic sclerotic skeletal lesions. We present an unusual case primarily manifesting as an extensive orbital disease, with low-grade systemic involvement. Owing to its rarity and therefore lack of general awareness it remains a difficult clinical and pathologic diagnosis. Immuno-histochemistry of the biopsy specimen is diagnostic.     

Intraocular extension of conjunctival squamous cell carcinoma

Conjunctival squamous carcinoma, which is regarded as a low-grade malignancy, usually originates at the limbus. Most cases remain superficial to the sclera. Intraocular invasion is rarely reported. We describe a woman misdiagnosed as conjunctivitis and pterygium before a clinical diagnosis of conjunctival squamous cell carcinoma. The diagnosis was made by histopathological examination of the biopsy specimen. Examination revealed an elevated mass on the nasal limbus extending intraocularly. White flaky mass occupied approximately 3/7 space of the anterior chamber. Exenteration was performed for control of local lesion. Histopathologic analysis confirmed that intraocular involvement occurs through the emissary vessels near the area of limbus. The case highlights the need for accurate diagnosis and prompt intervention. A brief review of the clinical and histopathologic features of conjunctival squamous cell carcinoma is also presented.     

Post-radioiodine De Novo Onset Graves’ Ophthalmopathy: Case Reports and a Review of the Literature

ABSTRACT

New-onset Graves’ ophthalmopathy (GO) following radioiodine treatment (RAI) and worsening of existing GO are well-described in the endocrinology literature. These phenomena are recognized by ophthalmologists, yet poorly documented in the ophthalmology literature. Two male patients, aged 43 and 62 years, respectively, with Graves’ disease without GO, received RAI. Four months later, one patient developed acute GO with unilateral reduction in visual acuity, conjunctival chemosis, lagophthalmos, bilateral severely restricted ocular motility, and lid retraction. High-dose intravenous steroids, followed by oral steroids, led to a dramatic clinical improvement. The second patient received a second dose of RAI for persistent hyperthyroidism and subsequently developed acute GO-comprising restricted ocular motility, peri-orbital swelling, and conjunctival chemosis. Symptoms gradually resolved on continued carbimazole treatment. Neither patient received pre-RAI prophylactic glucocorticoids, as currently they are only recommended for patients with pre-existing GO or multiple risk factors. We discuss the limitations of using this risk-based approach in preventing new-onset GO following RAI therapy.