Update on Graves Disease

Advances in Treatment of Mild, Moderate and Severe Thyroid Eye Disease

Diego Strianese


Curr Opin Ophthalmol. 2017;28(5):505-513. 

In This Article

New Therapeutic Advances for Mild Disease

Traditional recommendations for mild TED include relief of the ocular surface symptoms, such as dryness, foreign body sensation and tearing, with ocular lubricants. It is important to avoid risk factors that can exacerbate TED, particularly smoking and uncontrolled thyroid hormone levels.[5] In a study of 106 patients with mild TED treated with high doses of radioiodine (800 MBq) and steroid prophylaxis (starting dose of oral prednisone: 0.3–0.5 mg/kg body weight, gradually tapered and withdrawn after 6 weeks), cigarette smoking was associated with progression of TED at 6-month follow-up, despite steroid prophylaxis, with exophthalmos as one of the features most affected[6]

Lid retraction may be the only sign of mild TED. The efficacy of transconjunctival botulinum toxin type A (BTX-A) in the treatment of upper eyelid retraction has been recently evaluated in a comparative prospective study based on the dose (group 1: 5 mg–group 2: 10 mg). The mean result for group 1 was 1.75 mm reduction of retraction and 2 mm in group 2. Statistically significant differences were seen between pretreatment and week 4 in both groups, but no differences between doses. Complete improvement of keratitis and lagophthalmos was observed. One patient (group 1) exhibited complete ptosis and vertical diplopia, which resolved spontaneously at week 6. The authors concluded that transconjunctival BTX-A application is safe and effective for the treatment of eyelid retraction in dysthyroid orbitopathy with no difference between doses[7]

Studies on the natural history of mild TED have reported a spontaneous improvement in about 50% of the patients, stability in 34% and worsening in 16%.[8] However, a substantial proportion of patients with mild TED suffer from a significant decrease in their quality of life (QoL).[9] Hence, an intervention may be justified in patients with mild TED in order to improve QoL and reduce ocular signs and symptoms.

Oxidative stress has been described in TED: an increase in reactive oxygen species or reduced elimination of radicals by antioxidative enzymes results in oxidative damage to cell membranes with lipid peroxidation and oxidative DNA damage, resulting in inflammation and loss of function.[10] Selenium, a trace mineral incorporated into several selenium proteins, functions as an antioxidant, reducing thyroperoxidase antibodies in autoimmune thyroiditis. A double-blind, randomized controlled trial (RCT) of selenium supplemented for 6 months in TED was associated with improved QoL, reduced soft tissue inflammation, improved appearance and reduced progression of TED compared with placebo.[11] Excessive supplementation may increase the risk of type 2 diabetes and certain malignancies.[12] It is therefore important to test selenium plasma concentrations in order to avoid selenium supplementation in patients whose plasma selenium concentration is greater than 122 μg/l[13]