Thyroid eye disease - (TED)

Signs of eye disease are apparent in 25-40% of Graves’ patients (Sridama & DeGroot). But actually 100% of patients with active thyrotoxicosis have some degree of eye involvement, when carefully examined with ultrasound, CT (computed tomography) or MRI scanning, despite no eye-signs are apparent (Werner).

Amino and co-workers have reported in 1980 that rather all patients have it to some extent and that only those with most severe symptoms are clinically recognized.

Graves’ disease is 7/8 times more frequent in women than in men, however TED is relatively more frequent and more severe in men, increasing with age. It is rare in children.

Eye disease usually improves with treatment of thyrotoxicosis. Reaching normal hormone levels as soon as possible, and keeping them normal, is crucial. It’s specially important not to become hypothyroid, as hypothyroidism contributes to water retention in the tissues, and elevated TSH has proved to worsen orbitopathy.

Two types of manifestations may occur in TED, i.e. two types of eye disease:

a) non infiltrative abnormalities
b) infiltrative abnormalities

a) - Non infiltrative ophthalmopathy.

It is due to thyroid hormone excess, which cause hyperactivity of the sympathetic nervous system. Usually the change is simply an elevation of the upper eyelids that makes the eyes appear more prominent. Also, eye-ball lags on upward gaze, or lid lags on downward gaze. It gives a pop-eyed appearance but measurement may show that there is no protrusion of the eyes (proptosis or exophthalmos).

These abnormalities do not imply any hazard to ocular function, and reverse once thyrotoxicosis is under control.

b) Infiltrative Ophthalmopathy.

This type has a much more serious prognosis. It may occur simultaneously with the non-infiltrative eye disease quoted above, but it is a separate disorder, and is considered a characteristic of Graves' as it mostly occurs in the type of hyperthyroidism caused by Graves’ disease. Only occasionally can it be seen in some Hashimoto’s sufferers.

So, infiltrative eye disease consists of infiltrative lesions involving the contents of the orbit. The muscles surrounding the eyeballs are enlarged and, under the microscope, an intense infiltration is seen by inflammatory cells, like lymphocytes and others. You can see a CT scan here.

Studies show that autoimmune processes lead to accumulation of lymphocytes in the muscles surrounding the eyes. The lymphocytes stimulate fibroblasts to produce glycosaminoglycans, which are highly hygroscopic (attract water), hence edema. In end stage fibrosis is present. There is controversy with regard to changes in fat volume in TED.

The cause of infiltrative eye disease (aka thyroid orbitopathy) is still unknown, but there is no doubt it is an autoimmune disorder.

It is unrelated to the blood level of thyroid hormone.

The responsible for triggering ocular autoimmune reactions is not known but some studies point out to TSH-R as being the primary antigen.

There are two main classifications for eye signs. One is called NOSPECS, taking its name from the first initial of each class of involvement. It comprises six classes and every class counts a grading of types o, a, b, c, according to severity. It can be summarized as follows:

N - no signs
O - only upper lid retraction and stare, with or without lid-lag and protrusion of the eyeball
S - soft tissue involvement
P - proptosis
E - extra-ocular muscle involvement, usually with double vision.
C - corneal involvement
S - sight loss

CAS, Clinical Activity Score is yet another different classification which is helpful to predict outcome and to select patients for surgery or other type of treatment.

This progression runs independently from the course of thyrotoxicosis.

Infiltrative ophthalmopathy often becomes stationary and symptoms either progress no further, but an unacceptable cosmetic problem or double vision may continue to harass the patient.

Eye disease can affect one eye or both eyes, being in this case more severe in one than in the other.

No more than 2 - 5% of patients with Graves' disease develop progressive severe orbitopathy. Some of these patients go blind despite all therapeutic measures, decompression surgery included.

Factors known to affect the development of eye disease:

1) - RAI, I-131, radioiodine therapy: Up to 33%

2) - Smoking: Increases risk about 7 times, though number of cigarettes per day seems not to affect neither does period of smoking. Decreases the efficacy of glucocorticoids.

3) - High T3 readings prior RAI: This could be easily corrected with antithyroid drugs, having moreover the added benefit of their immunosuppressive properties.

4) - High TSH after RAI: Hypothyroidism as a result of damage to thyroid by radiation is present soon after having RAI, and normally fine tune of T4 supplementation takes years to be reached. Thus TSH values are high after RAI more often than not, and may be above normal values for many years.

5) - High TSH-RAbs after therapy: It’s meant after RAI theraphy, which raises them, contrary to surgery and antithyroid drugs which do not raise them. Radioiodine also causes an increase in anti-TG or PO antibodies