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CamillaSchalin-Jäntti

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.

TreatmentSurgical Orbital Decompression for Thyroid Eye Disease, Antithyroid Drug Regimen for Treating Graves' Hyperthyroidism

  • 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]