Graves ophthalmopathy: etiology, epidemiology, pathogenesis, symptoms, diagnosis, promising medical therapy

Aistė Čemerkaitė1, Justė Čemerkaitė1, Simona Liolytė1

1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine


The annual incidence of Graves ophthalmopathy (GO) in female population is 16, whereas in men 3 cases out of 100 thousand. Up to 90% of patients are diagnosed with hyperthyroidism at the onset of GO, but it may also occur 18 months prior to the initial manifestation of GO. In pathogenesis predominates autoimmune inflammation, in which the main effectors are orbital fibroblasts, autoimmune stimulation directly affecting TSH and indirectly IGF-1 receptors, which eventually results in significant remodelation of orbital tissues. Graves’ ophthalmopathy usually occurs about 40-60 years of age, is more common in women, and the risk of developing the disease is increased by genetic factors. In order to avoid the effects of modifiable risk factors, it is recommended to maintain euthyreosis, quit smoking and avoid stress. During treatment for Graves’ disease with radioiodine therapy, signs of ophthalmopathy occurs more frequently or progression is more common compared with other treatment methods. Patients generally complain of dry eyes, fear of light, watery eyes, double vision, pain or discomfort behind the eyeball, impaired vision. During the examination, edema of the eyelids and conjunctiva, erythema, retraction of the upper eyelid, proptosis are observed. The diagnosis of Graves’ disease is based on the symptoms expressed by the patient and the changes visible during the objective examination, which corresponds to the symptoms of Grefe, Miobius, Dalrymplis, Štelvag. Laboratory tests in most patients show an increase in LT3, LT4 and a decrease in TTH. Visual methods such as ultrasound, CT, MRI are important for disease progression monitoring and choice of treatment, helping to identify specific changes in GO and disease course activity, which is assessed by 7 signs of inflammation, assuming clinically active GO with a clinical activity score (CAB). ≥ 3 points and inactive when KAB < 3 points. Management of GO is often not optimal because no pathogenetic treatment is applied. According to the latest data, intravenous glucocorticoids are the drug of first order for the treatment of moderate to active GO. They are effective in reducing symptoms, inflammation, early diplopia, but has limited effect on exophthalmos. A new drug, the insulin-like growth factor receptor-1 (IGF-1) inhibitor teprotumumab, has recently been successfully applied in treatment of GO. It has been shown to have rapid and strong positive effect, with a reduction in CABG of ≥ 2 points and proptosis of ≥ 2 mm.

Keywords: Graves’ ophthalmopathy, thyroid disease, proptosis, clinical activity score, active GO, IGF-1 receptor, teprotumumab, symptomatic treatment, intravenous glucocorticoids