Graves' Ophthalmopathy is a benign condition characterised by inflammation and fibrosis of the posterior orbit. It usually occurs in conjunction with Graves' hyperthyroidism. The goal of therapy is local control, preferably with minimally complicating therapy.
Graves' disease is an autoimmune disorder characterised by an inappropriate immune response against the TSH receptor. Antibodies directed against the TSH receptor are thought to be responsible for the increased thyroid activity in Graves' hyperthyroidism. Orbital fibroblasts are thought to express TSH receptor which may explain why the diseases occur in unison.
Increased production of glycoaminoglycans by orbital fibroblasts leads to increased tissue in the posterior orbit. This process is thought to be triggered by activated T cells or circulating autoantibodies (or both).
The severity of eye disease can be graded, using the helpful mnemonic NOSPECS:
- Grade 0 - No eye disease
- Grade 1 - Observer noted asymptomatic eye disease (eg. lid retraction noted by doctor)
- Grade II - Soft tissue involvement
- Grade III - Proptosis
- Grade IV - Extraocular muscle involvement (eg. reduced eye movements)
- Grade V - Corneal ulceration
- Grade VI - Sight loss
The initial development of Graves' ophthalmopathy is usually inflammation and oedema; fibrosis occurs after several years which makes early treatment essential.
Treatment of Hyperthyroidism
Often, the underlying hyperthyroidism presents more acute issues than the eye disease. Treatment of hyperthyroidism is either thyroidectomy, antithyroid medication (carbimazole, which prevents conversion of T3 to T4), or radioactive iodine which ablates the thyroid tissue. It is thought that radioiodine may increase the development of Graves' ophthalmopathy.
Treatment of Symptoms
Patients often complain of dry eyes, and lubricating eye drops can be useful.
Treatment of Ophthalmopathy
There are medical, surgical and radiotherapeutic approaches to managing ophthalmopathy.
Medical approaches are preferred as other options run the risk of losing sight. Steroid therapy (usually prednisolone 50 mg/day and weaned once improvement is seen … ha ha see what I did there :p). Rituximab is being explored as a potential second line therapy. For patients who do not respond well to prednisolone, orbital radiotherapy is a useful option (below).
Loss of colour vision is a sign of imminent complete vision loss and is treated as an emergency. High dose steroid therapy is commenced (prednisolone 100 mg) and orbital decompression (below) follows.
Radiotherapy is typically delivered as opposed, or slightly oblique, lateral fields that aim to treat the posterior part of the orbit (ie. posterior to equator of the eyeball). There is some controversy, given the potential for late radiation effects on vision and second malignancies, however it is usually considered as second line therapy for symptomatic eye disease that does not respond to medical therapy.
Patients are simulated supine in a thermoplastic mask. Immobilisation with kneefix is also done. A CT scan is performed through the head.
The CTV is the soft tissues of orbit, posterior to the eyeball. Treatment of this is typically opposed lateral fields whose anterior field edge runs through the equator of the eyeball. The eyeball itself is blocked using custom shielding (usually MLCs). The fields may be angled slightly posteriorly (eg. 5%) to limit the dose received by the anterior eye structures.
Patients should receive concurrent steroid therapy (eg. dexamethasone 4 mg) to prevent swelling and temporary worsening of symptoms.
Most patients develop a complete response. A number of patients will require surgery for decompression regardless (10-30%) or for diplopia.
Long term effects can occur. Cataract rates of 10% are reported. Retinopathy can also be seen more frequently, particularly when patients have other risk factors such as diabetes. Second malignancies are only documented as single case reports.
Surgical decompression is usually considered the 'last resort' but it is essential when patients have impending loss of vision, fibrosis or for cosmetic reasons. Surgery typically involves removal of one of the bony walls of the orbit; the inferior or medial walls are typically the easiest to perform.
Surgery on the extraocular muscles can assist with diplopia if it persists after the completion of other therapies.
- P: Non Malignant Disease
A good summary article is found here (you will need Red Journal access):
International Journal of Radiation Oncology*Biology*Physics Volume 82, Issue 1, Pages 117-123, January 1, 2012