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.
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.
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]