Thyroid eye disease (TED) is a chronic inflammatory disease of the eye that can occur in patients with systemic thyroid disorder. It is the most common cause of bilateral and unilateral proptosis with a female preponderance and peak incidence in the 5th decade of life.¹⁾ Although thyroid ophthalmopathy is not uncommon, its pathogenesis has not been thoroughly studied and remains unclear. A consistent pathogenic link between Graves' disease and ophthalmopathy has yet to be identified.²⁾ The pathogenesis involves immunoglobulin G antibody and an organ-specific autoimmune reaction. T-cell lymphocytes and thyroid follicular cells with shared antigenic epitopes are thought to react in the retro-orbital space. Sight-threatening compressive optic neuropathy is one of the most feared complications of thyroid ophthalmopathy. However, the occurrence of optic neuropathy is rare and constitutes about 4% to 8% of all complications.^3,4) Management of thyroid eye disease is based on the consensus statement produced by the European Group on Graves' Orbitopathy. Thyroid eye disease is usually self-limiting; its frequency is declining; and 3% to 5% cases are sight threatening.⁵⁾ Treatment for Graves' disease is directed towards alleviating symptoms, managing hyperthyroidism, and addressing issues such as smoking and other aggravating factors. The following cases illustrate the atypical and subtle presentations of sight-threatening thyroid eye disease that can be missed during an initial visit. They also illustrate the worsening of thyroid eye disease and its relationship to radioactive iodine (RAI) therapy.

Treatment of hyperthyroidism is associated with the development or progression of ophthalmopathy. Therefore, detection of this condition during clinical examination is highly important so that it can be efficiently managed.

Progression of ophthalmopathy was more common in patients treated with RAI than in those who received anti-thyroid drugs or surgery.^1,6) One study proposed that the development or progression of ophthalmopathy after RAI therapy may be related to the release of thyroid antigens as a result of radiation injury and to the subsequent enhancement of autoimmune responses directed toward antigens shared by the thyroid and orbit.⁷⁾ RAI for Graves' hyperthyroidism was followed by the development, or more often, the progression of ophthalmopathy in patients treated with RAI alone, but not in those treated with RAI and prednisolone.⁸⁾ In these two cases, both patients were not administered oral steroids prior to or during RAI therapy.

In case 1, the patient's eyes appeared not proptosed, but ptotic. Nevertheless, he had active and sight-threatening thyroid eye disease. There was evidence of optic neuropathy confirmed by constriction of the visual field, and MRI of the orbit showed crowding of the orbital apex due to enlargement of the extraocular muscles. This pathogenesis is due to the accumulation of glycosaminoglycans, which leads to a retention of water, increasing the intraorbital soft tissue volume and pushing the eye forward, resulting in proptosis. Therefore, the absence of proptosis in active TED increases the risk of optic nerve compression, because the swollen soft tissue within the confined space of the orbit prevents forward decompression of the optic nerve. Diagnosis of optic nerve dysfunction might be missed if there is no obvious proptosis as highlighted in case 1.⁹⁾ It also stated that an increase in orbital pressure will precipitate dysthyroid optic neuropathy when there is lack of proptosis. The lack of RAPD detection may suggest that there was equal and bilateral involvement of the optic nerves by compression. In case 2, both eyes appeared proptosed and there was grade 1 RAPD over the left eye with secondary high IOP in both eyes. These cases illustrate the importance of good clinical skills. The subtle signs of optic neuropathy must be detected quickly, so that a treatment plan can be initiated to prevent further vision loss.

Both patients were treated with 500 mg pulse intravenous methylprednisolone for 6 weeks and then 250 mg once weekly for another 6 weeks (total period of 12 weeks with total dose of 4,500 mg). This treatment regime was adapted according to the recommendation by Kahaly et al.¹⁰⁾ In patients receiving radiotherapy for TED, modifying the treatment can slow the development of ophthalmopathy.²⁾ The administration of glucocorticoids prior to RAI is generally expected to limit the progression of ophthalmopathy.¹¹⁾

In conclusion, active thyroid eye disease often presents as pseudoptosis instead of the classical lid retraction with 'starry' gaze (Kocher sign). Physicians need to be aware of this atypical presentation. Although RAI therapy is one of the primary treatment modalities for TED, it can also have a disastrous effect on the vision. Therefore, it is imperative for the patient to be administered glucocorticoids prior to treatment with RAI for hyperthyroidism. Family medicine practitioners and physicians need to anticipate the possibility for the development or worsening of thyroid eye disease post-RAI treatment, as timely intervention can prevent the vision loss that results from compressive optic neuropathy in active thyroid eye disease.