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Editors
Graves' Ophthalmopathy
Essentials
- Graves' ophthalmopathy is an autoimmune disorder of the orbital tissues. It affects some of the patients with Graves' disease (Basedow's disease), and it usually coincides with a hyperthyroid phase.
- It is important to recognise Graves' ophthalmopathy early in primary care; it can be mistaken for conjunctivitis.
- All patients with Graves' ophthalmopathy warrant a referral for further assessment in a specialist centre.
- Early initiation of treatment will improve treatment results.
- Also known as: thyroid eye disease (TED), Graves' orbitopathy and thyroid-associated ophthalmopathy/orbitopathy
- The disease is classified based on both the inflammatory activity (active - inactive) and the severity (mild - moderate - severe), according to which the treatment line is selected.
Aetiology and epidemiology
- The condition is associated with hyperthyroidism of Graves' disease; ophthalmopathy is the most common extrathyroidal manifestation of Graves' disease.
- The presence of TSH-receptor antibodies is an important aetiological factor.
- The patient is usually also hyperthyroid.
- In a minority of patients, ophthalmopathy can precede the onset of hyperthyroidism or begin after the hyperthyroid phase has been treated.
- Approximately 3 to 5% of patients have sight-threatening ophthalmopathy.
Symptoms and signs
- The patient is often a female who, in addition to red and bulging eyes, presents with hyperthyroidism.
- The ocular symptoms include
- gritty ocular sensation, ocular redness, watering and photophobia
- periorbital oedema and redness
- pain on eye movement, especially when looking up, limitation of motion and diplopia
- retro-orbital pain
- lagophthalmos
- in a very severe form of the disease impairment of vision.
- Graves' ophthalmopathy is often misdiagnosed as bacterial or allergic conjunctivitis.
Laboratory tests
- Serum TSH and free T4 assays are used to verify thyroid dysfunction.
- The free T3 level is measured if serum TSH is undetectable and free T4 is within the reference range.
- The concentration of serum TSH-receptor antibodies is usually markedly increased in severe Graves' ophthalmopathy.
- All patients warrant a referral for further assessment in a specialist centre.
- The primary care physician should give advice regarding symptomatic treatment.
- Lubricating eye drops.
- Protecting the eyes from the wind and sun.
- Smoking cessation; smoking worsens pre-existing ophthalmopathy.
- The treatment in specialist centres aims to promptly restore euthyroidism.
- Both severe hyperthyroidism and hypothyroidism exacerbate ocular symptoms.
- Radioactive iodine may lead to the progression of ophthalmopathy.
- Antithyroid drug therapy and thyroidectomy are neutral treatments as far as eyes are concerned.
- In most cases, the simplest approach is to continue with antithyroid drug therapy until the ophthalmopathy improves.
- TSH-receptor antibody concentration and thyroid function tests should be monitored.
- The treatment of Graves' ophthalmopathy
- The adequacy of local therapeutic measures should be checked.
- Make sure that the patient has quit smoking.
- In a mild disease with inflammatory activity, treatment with selenium (100 µg twice daily orally) may be tried for 6 months. However, local conditions regarding the prevalence of selenium deficiency vary, so there is no guarantee on the effectiveness of the therapy in regions where selenium intake is sufficient.
- Glucocorticoids administered in pulses present the mainstay of treatment in active Graves' ophthalmopathy.
- Mycophenolate treatment may be combined to the aforementioned treatment.
- Intravenous rituximab treatment is sometimes used.
- Surgical decompression of the orbit is indicated in sight-threatening compressive optic neuropathy.
- In the acute phase of the disease, retrobulbar irradiation may be used for diplopia, as well as for ocular pain and motility disturbances, occurring after pulse therapy.
- The patient may require surgical orbital decompression as well as surgery to the eye muscles and eyelids during the chronic phase of the disease.
Follow-up
- It can take long for ophthalmopathy to subside; treatment often requires both patient's and physician's patience.
- Graves' ophthalmopathy may sometimes reactivate during the follow-up period.
- The patient should be referred again to a specialist centre.
- The patient is given advice regarding local measures and smoking cessation.
References
- Bartalena L, Baldeschi L, Boboridis K et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J 2016;5(1):9-26. [PubMed]
- Kotwal A, Stan M. Current and Future Treatments for Graves' Disease and Graves' Ophthalmopathy. Horm Metab Res 2018;50(12):871-886. [PubMed]
- Bartalena L, Kahaly GJ, Baldeschi L et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol 2021;185(4):G43-G67. [PubMed]