Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
Thyroid eye disease is an autoimmune disorder affecting approximately 50% of individuals with
 autoimmune thyroid diseases resulting in enlargement of ocular muscles and may lead to
 congestion of the eyelids and ocular surface, ocular movement restriction and double vision,
 and optic nerve compression and loss of vision.

 First line medical therapy is oral or intravenous corticosteroids (CS), which several studies
 have shown results in reduction of soft tissue congestion, but some studies suggesting that
 ocular restriction or visual loss may still occur in spite of CS therapy.i

 External beam radiotherapy (XRT) is second line therapy but is controversial, with some
 studies suggesting benefit in preventing onset of double vision or optic nerve compression
 while other studies suggest it has no benefit. Most proponents of XRT for TED believe that it
 is most effective early in the disease evolution. XRT has been shown to be a safe therapy
 with few side-effects, although retinopathy changes have developed in a small percentage of
 diabetics and its use is avoided for diabetics.

 Combined oral prednisone and XRT has been shown to be more effective in reducing soft tissue
 inflammation and motility complications than either monotherapy in two different studies.

 To date there have been no trials comparing combined XRT and iv CS with iv CS alone for early
 progressive TED to identify potential benefit in reducing the severity of motility disorders
 or preventing the onset of dysthyroid optic neuropathy. That is the purpose of this study.
1. Purpose: To demonstrate that combined Radiotherapy (RT) and intravenous corticosteroid
 (CS) is more effective than iv CS alone in preventing severe motility disruption
 (including strabismus and primary diplopia) and new-onset dysthyroid optic neuropathy in
 early progressive thyroid orbitopathy.

 2. Hypothesis: Combined RT and iv CS are more effective than iv CS alone in preventing
 motility problems (reduced field of single binocular vision, reduced ductions,
 strabismus and worsening diplopia) and in preventing new-onset dysthyroid optic
 neuropathy in patients with early progressive thyroid orbitopathy.

 3. Justification: Standard therapy for progressive TED is iv CS, occasionally supplemented
 with RT if complications develop in spite of appropriate iv CS therapy. A single
 retrospective study suggested that early combined treatment may prevent more serious
 visual complications; this would be the first randomized controlled prospective trial to
 see if this finding is true.

 4. Objectives: Demonstrate a statistically significant reduced rate of new onset optic
 neuropathy and double vision in patients with progressive TED with combined therapy
 versus traditional monotherapy.

 5. Research Method: Multicentre, institutional based, randomized controlled trial.

 6. Statistical Analysis:

 Subjects: 100 patients with early progressive TED randomized equally into two groups:

 1. Therapy: iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 weeks

 + XRT 100 Rads to each orbit x 10 doses

 2. Control: Same iv MP dose + no XRT
Inclusion Criteria:

 1. Active TED: Onset less than 6 months AND: Progressive with historic or measured
 worsening in one or more of VISA parameters in past 2 months: (increasing soft tissue
 inflammatory changes, development of intermittent or constant diplopia or increased
 prominence of either eye or lid retraction)

 2. Moderately severe TED (all of the following criteria must be met):

 V: No optic neuropathy I: Inflammatory score >/= 4/10 S: Intermittent or constant diplopia
 in any direction except primary gaze AND/OR restriction in ductions to < 30 degrees in any
 cardinal direction on clinical examination

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 Exclusion Criteria:

 1. Age < 35 yrs

 2. Diabetes mellitus

 3. Previous orbital surgery or radiotherapy for TED

 4. Corticosteroid or immunotherapy within previous 2 months for TED

 5. Unable or unwilling to provide informed consent-