Click here for Frequently Asked Questions on Graves' Eye Disease.
Thyroid ophthalmopathy, also known as Graves' eye disease, often coexists with autoimmune thyroid diseases such as Graves' disease or less commonly, Hashimoto's thyroiditis. Although the majority of patients with eye disease will present with both hyperthyroidism and the eye disease simultaneously, the eye involvement may precede or follow the development of hyperthyroidism, or may be present alone, without evidence for thyroid dysfunction. Although puzzling and confusing, some physicians suggest that we consider Graves' eye disease and Graves' hyperthyroidism as two separate diseases, that may run independent courses.
At present there is no accurate way of predicting whether a patient with Graves' disease of the thyroid will also develop Graves' eye disease. In some cases, particularly in subjects with involvement of only one eye, it may be useful to obtain an ultrasound or CT scan of the eye muscles to check for thickened eye muscles behind the eye, which is strongly suggestive of Grave's eye disease. Some physicians will search for the presence of circulating antibodies against eye muscle components in patients with suspected Graves' eye disease. Nevertheless, although mild eye abnormalities are common in patients with Graves' hyperthyroidism, many patients with mild thickening of the eye muscles or mild eye irritation will never develop significant clinical difficulty with Grave's eye disease. Furthermore, there is no scientifically validated intervention, diet, or medication, other than potentially toxic immunosuppressive drugs or radiation, that will reduce the chance of developing progressive Grave's eye disease.
Patients who smoke appear to be at higher risk for eye disease. Indeed, smokers seem to also respond less well to therapy. In a small study of patients treated initially with steroids and, 6 weeks after the beginning of drug therapy, with orbital irradiation, the response to treatment was delayed and considerably poorer in smokers. See Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol. 2003 Jun;87(6):773-6. Other factors associated with an increased risk of developing eye disease after radioactive iodine include a very elevated level of Free T3, elevated levels of TSH receptor antibodies, and previous detection of the existence of Graves opthalmopathy.
There is some evidence that treatment of Grave's hyperthyroidism with Radioactive iodine carries a slightly increased risk (15-20% increased risk) for exacerbation of eye disease, and patients with moderate to severe eye involvement are sometimes treated with steroids around the time of the radioactive iodine therapy.
Eye involvement may involve one or both eyes and may include excessive redness, tearing, itching, pressure, puffiness, pain and increased prominence of the eyes. The symptoms are caused in part by inflammation of the eye muscles behind the eye, causing the eyeball to be pushed forward and appear more prominent. Impairment of eye muscle function may lead to double vision if the muscles cannot move the eye coordinately in all directions. If the eyelids cannot be closed properly, excessive dryness may occur, sometimes leading to painful corneal abrasions. Local measures that are helpful may include artificial tears or lubricant to maintain appropriate degrees of moisture in the eye. Patients with severe eye involvement may need treatment with Steroid hormones, immunosuppressive agents, radiation, or surgery and such patients should see an ophthalmologist. For example, the combined use of orbital radiation and either intravenous or oral steroids does reduce symptoms and eye prominence (proptosis) in the majority of treated subjects with severe Graves' eye disease. See Comparison of the Effectiveness and Tolerability of Intravenous or Oral Glucocorticoids Associated with Orbital Radiotherapy in the Management of Severe Graves' Ophthalmopathy: Results of a Prospective, Single-Blind, Randomized Study. J Clin Endocrinol Metab. 2001 Aug 1;86(8):3562-3567.
Despite the coexistence of thyroid and eye disease and the common designation of "Graves' Disease" for both problems, the eye disease and the thyroid disease are thought to be immunologically related yet separate diseases. Many patients with eye disease have increased levels of circulating TSI (thyroid stimulating immunoglobulins) that may be measured using sensitive cell-based research assays utilizing chimeric receptors J Clin Endocrinol Metab. 2010 Mar 17. [Epub ahead of print] A Novel Thyroid Stimulating Immunoglobulin Bioassay Is a Functional Indicator of Activity and Severity of Graves' Orbitopathy
If one looks carefully with sensitive ultrasounds or CT scans, many patients with Graves' hyperthyroidism have some evidence for eye muscle thickening on these imaging studies. Surprisingly, treatment of the hyperthyroidism, which is almost always successful, may have no impact on the subsequent course of the eye disease. Indeed, the eye involvement can get better, remain the same, or deteriorate, independent of the course of the thyroid disease, which almost always does get better with treatment. The lack of therapeutic options for treatment of the eye disease is very frustrating for patients, many of whom may be quite concerned about the appearance and or function of their eyes. Furthermore, the symptoms and visual difficulties associated with some forms of Grave's eye disease may result in time off from work and inability to perform usual tasks at 100% efficiency as described Public Health Relevance of Graves' Orbitopathy J Clin Endocrinol Metab. 2012 Nov 26.
Taking steroid hormones (Glucocorticoids) such as prednisone or cortisone for the treatment of eye problems for even a few weeks or months can be associated with the development of side effects. These may include sleep disturbance, increased appetite and weight gain, acne, mood changes, increased risk of infections, worsening diabetes, and rarely, problems with joints and bones such as avascular necrosis requiring joint replacement. Although most patients taking steroid hormones for Graves eye disease for a short period of time will not develop serious side effects, the risks of the potential side effects must be balanced against the benefit of taking the medication to protect or improve the eye condition.
For an overview of the diagnosis and treatment of thyroid eye disease, see Thyroid eye disease Semin Ophthalmol 1999 Jun;14(2):52-61 or Management of Graves' ophthalmopathy: reality and perspectives Endocr Rev 2000 Apr;21(2):168-99 and Thyroid Eye Disease Curr Treat Options Neurol 2000 Sep;2(5):401-406, or Graves ophthalmopathy. Curr Opin Ophthalmol. 2001 Oct;12(5):347-51. and The pathophysiology of thyroid-associated ophthalmopathy. Ophthalmol Clin North Am. 2002 Mar;15(1):113-9 and Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres. Eur J Endocrinol. 2002 Jul;147(1):1-11. For a review of the relative merits of oral vs. intravenous glucocorticoids, and radiotherapy, alone or in combination with steroids, see Treatment modalities for Graves' ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab. 2009 Aug;94(8):2708-16. Retrospective anaylsis of treatment outcomes suggests that intravenous steroid administration may be more effective than oral administration of glucocorticoids (steroids). Graves' orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis J Clin Endocrinol Metab. 2009 Sep;94(9):3381-6
To review the use of immunosuppressive drugs for the treatment of Graves' eye disease, see Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts. Eur J Endocrinol. 2001 Apr;144(4):311-8
Radiation of the eye muscles and soft tissues behind the eye (retrobulbar radiation) is a proven effective treatment for progressive Graves' eye disease. Analysis of a one year follow-up cohort of 189 patients demonstrated sustained improvement in many objective parameters of eye disease, including the extent of proptosis, double vision, and visual acuity. The improvements can take as long as 6 months to occur after radiotherapy. See Long-term results of irradiation for patients with progressive Graves' ophthalmopathy. Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):766-74.
To review results of transnasal decompression surgery for patients with Graves' disease, see Follow-up of transnasal orbital decompression in severe Graves' ophthalmopathy. Ophthalmology. 2001 Feb;108(2):400-4.
To review the current theories on why Grave's eye disease develops, see Thyroid-associated eye disease. Heufelder AE, Joba W Strabismus 2000 Jun;8(2):101-111
Any new therapies for thyroid eye disease?
Analysis of the effectiveness of various therapies to attenuate the immune system (which contributes to the development of the eye disease) have assessed the utility of rituximab, a monoclonal antibody directed against the CD 20 antigen on B lymphocytes. A randomized double blind controlled trial compared the effects of rituximab (initially 2000 then 500 mg in 2 doses 2 weeks apart plus the weekly placebo infusions to mask treatment) with intravenous weekly infusions of methylprednisolone (Total cumulative dose of 7.5 grams) in 32 patients. Primary endpoint was the reduction in disease activity after 24 weeks. Both treatments were effective, but rituximab was more effective in suppressing disease activity at 16, 20 and 24 weeks and fewere patients 'relapsed' or needed surgery after rituximab. Follow-up out to 76 weeks also showed a sustained reduction in levels of TSH receptor stimulating antibodies with rituximab. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe graves' orbitopathy: a randomized controlled study J Clin Endocrinol Metab. 2015 Feb;100(2):422-31
Is there any way to reduce the side effects associated with steroid therapy?
Some evidence from non-randomized small trials suggests that intravenous pulse steroid therapy twice a week may be associated with fewer side effects and may be more effective than oral steroid therapy for the treatment of Graves' eye disease. See High-dose intravenous corticosteroid therapy for Graves' ophthalmopathy. J Endocrinol Invest. 2001 Mar;24(3):152-8. and Graves' orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis J Clin Endocrinol Metab. 2009 Sep;94(9):3381-6. Furthermore, weekly intravenous steroid therapy appeared to be associated with a better treatment outcome compared to daily therapy with oral steroid tablets, as described in Randomized, single blind trial of intravenous vs. oral steroid monotherap In Graves' orbitopathy. J Clin Endocrinol Metab. 2005 Jul 5; [Epub ahead of print]. In contrast, treatment with steroids does not seem to adversely impact the success of the treatment for hyperthyroidism Glucocorticoids do not influence the effect of radioiodine therapy in Graves' disease. Eur J Endocrinol. 2005 Jul;153(1):15-21.
Can I get glaucoma if I have thyroid-associated eye disease?
Glaucoma (increased pressure in the eye) may be seen in patients with Graves' ophthalmopathy, particularly if swelling of the eye muscles causes increased pressure in the orbit and eyeball. See Open-angle glaucoma associated with Graves disease. Am J Ophthalmol. 2000 May;129(5):613-7 and Prevalence and management of elevated intraocular pressure in patients with Graves' orbitopathy. Br J Ophthalmol. 1998 Jul;82(7):754-7 and The prevalence and implications of ocular hypertension and glaucoma in thyroid-associated orbitopathy. Ophthalmology. 1997 Jun;104(6):914-7. Treatment of the eye disease usually results in a decrease in intraocular pressure. See Intraocular pressure changes after treatment for Graves' orbitopathy. Ophthalmology. 2001 Jan;108(1):145-50. In contrast, hypothyroidism does not appear to be associated with a significantly increased risk of glaucoma. See Hypothyroidism and glaucoma. A study of 100 hypothyroid patients. Am J Ophthalmol. 2001 Jan;131(1):126-8.
Should I have surgery to correct my appearance?
It is generally advisable to wait some time to see if the eye abnormalities gradually correct on their own, which often happens. Patients with residual protrusion or significant lid retraction can consider corrective surgery to improve their cosmetic appearance.
How can I prevent my eyes from getting worse?
At present, there is no easy and safe validated medicine shown to prevent the deterioration of eye disease in affected patients. Radiation of the eyes (orbits and behind the eyes) does seem to be effective in the majority of patients, but it may take months for the benefits of radiation to become evident. Smoking seems to be a risk factor for Graves' eye disease, hence smoking cessation seems to be prudent in severely affected patients. There is anecdotal retrospective evidence that "destroying the thyroid" either by removing it surgically, and/or with radioactive iodine, may indirectly benefit the eye disease, but this is not yet widely accepted. See Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of graves' ophthalmopathy. Thyroid. 2003 Jul;13(7):653-8.
I have heard that "Botox injections" can make the eye disease better?
There have been a few reports, of some patients with eye disease experiencing improved vision and reduced pressure in the eyes after injection of the toxin in the eye muscles, as described in Botulinum A toxin injection for restrictive myopathy of thyroid-related orbitopathy: effects on intraocular pressure. Am J Ophthalmol. 2003 Apr;135(4):427-31.
What about selenium?
Patients with mild Graves disease of less than 18 months duration were given either selenium (100 mg twice daily) or the anti-inflammatory agent pentoxifylline (600 mg twice daily) for 6 months, then followed after discontinuation of therapy for another 6 months. The majority of patients studied had proptosis, but most did not have double vision. Patients treated with selenium had a decrease in their disease activity scores. Selenium was well tolerated with few adverse events. There were only modest changes in visual acuity or level of propotosis, however eyelid aperture was reduced and appearance and quality of life improved. Selenium and the Course of Mild Graves' Orbitopathy N Engl J Med 2011; 364:1920-1931
I have diabetes-Any interaction with the drugs I take?
Although information is still limited, a single case report describes worsening of thyroid eye disease possible due to expansion of retrorbital fat following treatment with the peroxisome proliferator-activated receptor (PPAR) agonist, Pioglitazone. See Peroxisome Proliferator-Activated Receptor-gamma in Thyroid Eye Disease: Contraindication for Thiazolidinedione Use? J Clin Endocrinol Metab. 2003 Jan;88(1):55-9.