Severe Graves' Ophthalmopathy Research Articles

Role of Radiotherapy in Thyroid-Related Ophthalmopathy: A Case Series

Purpose To explore the role of radiotherapy (RT) in management of moderate to severe thyroid-related eye disease in terms of efficacy, treatment outcome, and response. Material and methods A case series of 5 patients with moderate to severe Graves Ophthalmopathy treated with orbital RT between July 2020 and March 2021. Patient symptoms and ophthalmic findings prior to RT and after 6 months post RT were analyzed. Computed tomography was performed before and after RT to compare orbital (muscles) volume change. Endpoints including improvement in ocular symptoms such as diplopia, proptosis, extraocular movement were compared. Acute and long-term complications were documented to assess its safety and treatment response. Results Addition of RT improved diplopia, visual acuity, proptosis, and color vision significantly. RT also decreased upper lid edema, optic nerve compression, and reduced intraocular muscle bulk. Extraocular muscles diameter reduced significantly. Patients experienced relief of symptoms and significant reduction in diplopia clinically. Conclusion External beam radiation is a safe and effective intervention in thyroid ophthalmopathy. Our study demonstrated that radiation is effective in decreasing inflammatory signs, symptoms, and muscle bulk. This treatment modality is well tolerated, and long-term complications are tolerable.

A case of severe Graves's ophthalmopathy

A case of severe Graves's ophthalmopathy

Endoscopic orbital decompression in Graves ophthalmopathy - Case report

Abstract Graves ophthalmopathy, an autoimmune disease, associated with hypermetabolism, enlargement of the thyroid gland and exophthalmia are the most frequent expressions of Graves’ disease, which often require surgical treatment. We present the case of a 41-year-old male with severe Graves ophthalmopathy for which we performed an endoscopic orbital decompression with good surgical outcome, the patient being discharged after 48 hours.

A Century of Hyperthyroidism at Mayo Clinic

From the Division of Endocrinology & Metabolism, Mayo Clinic, Jacksonville, FL (R.C.S.); and the Division of Endocrinology & Metabolism, Mayo Clinic, Rochester, MN (J.C.M.). H yperthyroidism was first described by Caleb Hillier Parry (1825), Robert Graves (1835), and Karl von Basedow (1840). At the beginning of the 20th century, the causes were poorly understood and treatment was limited to surgery because antithyroid drugs and radioactive iodine (RAI) were unavailable until the early 1940s. Because of high surgical mortality, treatment was often delayed until the condition was advanced, and a multistage procedure might be required. Initially, hot water was injected into the thyroid, then a thyroid artery was ligated, and subsequently one or both thyroid lobes were resected. Furthermore, critically ill patients who survived surgery risked postoperative death from thyroid storm. Understanding of the etiology, pathology, physiology, clinical manifestations, and management of hyperthyroidism has evolved over the past 100 years, and new insights continue to emerge. Mayo Clinic physicians and scientists, working across disciplines, have contributed importantly to understanding this illness. This review of the Mayo Clinic experience will highlight these achievements, including pathologic clarification of the most common forms of hyperthyroidism, isolation of a crystalline product of thyroid hormone, development of a basal metabolism laboratory, discovery of a method to reduce postoperative mortality, investigation of the kinetics of thyroid hormones using radioisotopes, development and/ or establishing the clinical utility of laboratory tests to diagnose and monitor therapy for hyperthyroidism, clinical characterization of extrathyroidal manifestations of Graves disease, surgical management of severe Graves ophthalmopathy, the role of orbital radiotherapy, and the pathogenesis of Graves ophthalmopathy.

Optic Neuropathy in 2 Thyroidectomized Patients with Moderate to Severe Graves Ophthalmopathy Following L-Thyroxine Withdrawal Prior to Radioiodine Treatment for Thyroid Carcinoma

ABSTRACT Objective: To report on 2 patients with moderate to severe Graves ophthalmopathy (GO) who developed dysthyroid optic neuropathy following levothyroxine (LT4) withdrawal in preparation for ...

Is radioiodine more likely than antithyroid drugs to worsen ophthalmopathy in patients with Graves disease?

This Practice Point commentary discusses the findings and limitations of a systematic review by Acharya et al. that assessed the utility of radioiodine to treat Graves hyperthyroidism. The authors examined 10 randomized controlled trials, and focused on the potential causative relationship between radioiodine and Graves ophthalmopathy. They concluded that the risk of Graves ophthalmopathy following radioiodine therapy is higher than that after treatment with antithyroid drugs (relative risk [RR] 4.23). The risk of severe Graves ophthalmopathy was also found to be increased after treatment with radioiodine (RR 4.35). Glucocorticoid prophylaxis was highly effective in preventing disease progression in patients with pre-existing Graves ophthalmopathy (RR 0.03). Here, I highlight the issues to consider when interpreting and generalizing these results, such as the limitations imposed by the inconsistency of disease classification and description in the various trials. Although this systematic review highlighted the small but real risk of Graves ophthalmopathy progression following radioiodine therapy, it could not provide insight into the extent of this progression or identify which patients are at highest risk and so might benefit most from prophylaxis.

Clinical Evaluation of the Long-Term Response to Intravenous Pulses of Methylprednisolone in Patients With Moderate to Severe Graves Ophthalmopathy

Clinical Evaluation of the Long-Term Response to Intravenous Pulses of Methylprednisolone in Patients With Moderate to Severe Graves Ophthalmopathy

Patients with severe Graves ophthalmopathy (GO) have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission

Patients with severe Graves ophthalmopathy (GO) have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission

Psychological Disturbance in Graves Ophthalmopathy

To study mood disturbance in Graves ophthalmopathy. Forty-eight patients (mean age, 55 years; 40 women and 8 men) with Graves ophthalmopathy from a university-based referral center were classified into two groups, 24 with moderate/severe disease (study group) and 24 with negligible/mild disease (control group). The groups were matched with regard to demographic and medical characteristics. All participants completed a mood survey to assess differences in degree of emotional distress. The Profile of Mood States survey, a 65-item self-reported inventory designed to assess emotional distress, was the primary outcome measure. A total mood disturbance score was assigned by summing the scores derived on the 6 subscales of the survey--tension, depression, vigor, confusion, fatigue, and anger. Analysis of variance revealed that patients with moderate/severe Graves ophthalmopathy showed significantly greater emotional distress than patients with mild/negligible Graves ophthalmopathy on the Profile of Mood States mean total score (P<.001). Additionally, patients who had disfigurement (proptosis) as the predominant clinical feature had significantly elevated emotional distress compared with the control group (P = .01), whereas no significant difference was detected between the control group and patients with diplopia as the predominant clinical feature (P = .20). Patients with moderate to severe Graves ophthalmopathy have significant mood disturbance, especially when disfiguring signs are predominant. We propose that evaluation of the psychological burden of the disease should be considered in routine follow-up and in decisions regarding treatment.

The Effect of Cigarette Smoke Constituents on the Expression of HLA-DR in Orbital Fibroblasts Derived from Patients with Graves Ophthalmopathy

Numerous studies have established a strong association between smoking and Graves disease, but the underlying mechanism of Graves ophthalmopathy has not been elucidated. Recent studies of Graves ophthalmopathy have focused on the orbital fibroblast as an integral component in the pathogenesis of this disorder. This investigation focuses on the effect of cigarette smoke constituents, nicotine and tar, to alter the expression of human leukocyte antigen (HLA-DR) in cultured orbital fibroblasts from patients with Graves disease. HLA-DR expression was quantified by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate--polyacrylamide gel electrophoresis with immunoblotting and also by direct immunofluorescence. Cultured orbital fibroblasts, obtained from patients undergoing orbital decompression for severe Graves ophthalmopathy, failed to express HLA-DR as analyzed by both immunoblotting and direct immunofluorescence when treated with nicotine alone (25-300 ng/ml). The expression of HLA-DR increased three-fold when nicotine (25 ng/ml) in combination with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). Cultured orbital fibroblasts treated with tar alone (60-600 ng/ml) failed to exhibit HLA-DR expression as assessed by direct immunofluorescence and immunoblotting. A greater than two-fold increase in HLA-DR expression occurred when tar (600 ng/ml) combined with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). The results suggest a possible molecular mechanism for the more severe ophthalmopathy observed in Graves patients who smoke cigarettes. These findings could prove useful for possible medical interventions to decrease or even inhibit the interaction between cigarette constituents, cytokines, and orbital fibroblasts.

Superior Limbic Keratoconjunctivitis: A Prognostic Sign for Severe Graves Ophthalmopathy

To study superior limbic keratoconjunctivitis in a relatively large group of patients and to determine whether a relation exists with thyroid dysfunction. The medical records of 57 patients with superior limbic keratoconjunctivitis who were examined between 1980 and 1993 were reviewed. Thirty-seven patients (64.9%; 95% confidence interval, 51.1-77.1) had objective evidence of thyroid dysfunction. Of patients with superior limbic keratoconjunctivitis and thyroid disease, 33 (89.2%) had ophthalmopathy, which in 16 patients (48.5%) was sufficiently severe to require orbital decompression. Superior limbic keratoconjunctivitis is associated with thyroid dysfunction and appears to be a prognostic marker for severe Graves ophthalmopathy.

A New Ultrasonographic Method to Detect Disease Activity and Predict Response to immunosuppressive Treatment in Graves Ophthalmopathy

To determine whether the internal reflectivity of the eye muscles on A-mode ultrasonography serves as indicator for disease activity in Graves ophthalmopathy, thereby predicting response to immunosuppressive treatment. Eye muscle reflectivity, expressed as percentage of the initial scleral spike, was measured in the superior, medial, and lateral recti, and normal values were determined in 23 healthy controls. These were compared with values in 16 consecutive patients with untreated, moderately severe Graves ophthalmopathy. The accuracy of the measurement was assessed by calculating the intra- and interobserver coefficient of repeatability. Baseline eye muscle reflectivity in the 16 patients was correlated to the therapeutic outcome 24 weeks after start of immunosuppressive therapy. The response to treatment served as indicator for pretreatment disease activity. Eye muscle reflectivity could be measured reliably, with an intraobserver coefficient of repeatability of 8.2% in controls and 10.2% in patients. Patients had lower reflectivity than controls (54.6 +/- 17.4% versus 70.7 +/- 6.6%; P < 0.001). Reflectivity in eye muscles with the lowest echogenicity was lower in responders than in nonresponders (25.8 +/- 8.4% versus 40.6 +/- 13.6%; P = 0.02). From the individual data, a cut-off value of 40% was derived, which appeared as an accurate predictor of outcome (positive predictive value 73%; 95% confidence interval 39%-94%). Measuring eye muscle reflectivity in Graves ophthalmopathy appears to be a reliable new method to determine disease activity, with a promising accuracy in predicting therapeutic outcome of immunosuppressive treatment.