Graves eye disease

Graves' eye disease (Graves' obitopathy) is an autoimmune disorder associated with hyperthyroidism

What is it?

Graves' eye disease a syndrome in which the muscles and fat tissues behind the eyes begin to grow abnormally, causing bulging eyes. This is the most common non-thyroid manifestation of Graves' hyperthyroidism. It can be found in patients with no past history of hyperthyroidism or even in patients that are hypothyroid. Graves disease is a condition driven by antibodies that are not functioning properly. 

There is not a lot of data about the true incidence of this condition. An estimate from 2010 shows the incidence in the Unite States to be approximately 13.9 per 100,000 population per year. About half of patients with Graves' do not have eye disease severe enough to warrant medical intervention, but most patients with Graves' will have abnormalities detected  by use of CT or MRI imaging. Severe forms of Graves eye disease account for only about 5% of cases and disease in both eyes in up to 85%. Eye disease is present before the onset of hyperthyroidism in 20% of patients, concurrently in 40% and in the six months after diagnosis in about 20%, and after treatment for Graves hyperthyrodism in the remainder (most commonly after radioiodine therapy).  

How is it diagnosed?

Graves eye disease is diagnosed clinically by your physician. There are a number of manifestations. The eyes can be protruding out of the sockets, which is also called exophthalmos or proptosis. The eyes can have a 'stare' like quality where the whites of the eye are more visible that usual. The eyes can have a redness associated with them along with excessive tearing. This is a common classification system for Graves eye disease. 
houston graves eye disease
Class 0: No signs or symptoms

Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)

Class 2: Soft tissue involvement (edema of conjunctivae and lids, conjunctival injection, etc.)

Class 3: Proptosis (eyes pushed out of socket)

Class 4: Extraocular muscle involvement (usually with double vision)

Class 5: Corneal involvement (primarily due to lagophthalmos- the inability to close eye lids completely)

Class 6: Sight loss (due to optic nerve involvement)


How is it prevented and treated?

Primary prevention is to remove all risk factors. Although not fully understood, there is one feature of Graves' eye disease that is very clear. Several studies have shown that patients who both smoke cigarettes and have Graves' are somewhat more likely to develop eye disease.  Smoking needs to be stopped as soon as possible in patients with Graves' disease. Radioactive iodine treatment of hyperthyroidism carries a small risk of causing progression of Graves' eye disease, but only in specific patients (cigarette smokers, patients already known to have eye disease). The progression is halted in these patients who received a course of oral prednisone at the same time as the radioiodine. 
 
Secondary prevention prevention is detection of early disease when it is still asymptomatic and when early treatment can stop the disease from progressing.  Antithyroid medications do not have any substantial effect on eye disease. Selenium (100mcg twice per day) and pentoxifylline (600mg twice per day) for 6 months versus placebo seemed to have a beneficial effect of a 159 patients with mild thyroid eye disease.  Thyroid surgery does not seem to change the natural history of eye disease. 

Tertiary prevention is when medical intervention can prevent further worsening of the complications after the disease has declared itself. Eye pads to prevent corneal scratching and artificial tear drops are the main measures at this point. The options include oral prednisone, external radiation to the eye.  In severe cases, surgical correction of eye disease can be considered in select patients. 


A longitudinal cohort study of 8,404 patients, aged 18 years or older, with newly diagnosed Graves' disease. The authors examined risk factors associated with the development of thyroid-associated ophthalmopathy among patients with newly diagnosed Graves' disease.  8.8% of patients with newly diagnosed Graves' disease developed thyroid-associated ophthalmopathy. After adjustment for potential confounders, surgical thyroidectomy, alone or combined with medical therapy, was found to be associated with reduced risk for thyroid-associated ophthalmopathy (adjusted HR=0.26; 95% CI, 0.12-0.51) compared with radioactive iodine therapy alone. Use of statins for 60 days or more in the previous year, compared with less than 60 days of use or non-use, was associated with reduced risk for thyroid-associated ophthalmopathy (adjusted HR=0.60; 95% CI, 0.37-0.93).


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Updated 12-21-2014

References 
THYROID Volume 12, Number 10, 2002
Marcocci C, et al. Selenium and the Course of Mild Graves' Orbitopathy. N Engl J Med 2011;364;1920-31
Stein JD et al. JAMA Ophthalmol. 2014;doi:10.1001/jamaophthalmol.2014.5103.

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