• assessment
• history
• examination
• purpose of assessment
• Hydraulic disease
• interpretation of blood tests etc
• subclinical hypothyroidism
• other factors
• treatment of thyroid condition itself
• treatment of TED
• severity of TED...is treatment needed?
• IV methylprednisolone in the active phase
• after the active phase
• source/abbreviations   another site   seminar
  

• 50% of Graves disease patients have clinical TED, (40% more shown with CT scan),
  • ~10% have severe eye problems.
  • Worse with age
  • worse after radioactive iodine
  • 20 x worse in smokers
  • worse if thyroid control poor.
  • worse if hypothyroidism or hyperthyroidism occurs
  • worse if anti-thyroid antibodies present
• It is an organ specific autoimmune disease leading to inflammation in the orbit, glycoaminoglycans deposition in cells, and such cells swell up with water.
• 10% male;  2% of all females develop TED, age 20-50y
• in 20% TED precedes the thyroid problem itself...patients are euthyroid at presentation
• is is also called AIHT (autoimmune hyperthyroidism)
• TED occurs most often 2 years after AIHT, sometimes 20 years later
• 40% of patients are thyrotoxic with weight/appetite changes
• if only the eyes are affected (TED), 78% will have been thyrotoxic, 2% hypothyroid
• hypothyroidism..easy diagnosis   TSH high, T4 low
• subclinical  hypothyroidism..easy diagnosis   TSH high, T4 normal
• when looking up, eye pressure elevates >4mm in TED
• blood levels of thryoid antibodies will be high in nearly all TED patients
• antibody tests 2011

• typically starts 1-2 years after thyroid disease starts, but could precede thyroid disease. May occur 20y after the thyroid disease starts.
• need past ocular history
• any history of myasthenia?
• excellent review NEJM Bahn 2010
• dry, gritty, photophobia, watering, double vision, pressure behind eyes.

Vision etc

• VA
• pinhole VA
• colour vision
• APD
• optic nerve can be damaged...stretched by proptosis or compressed by swollen muscles.

Soft tissue

• periorbital oedema
• periorbital erythema
• conjunctival injection
• chemosis
• inflammation of caruncle/plica
• plica visible when eye closed? (severe)
• prolapse of conjunctiva
• keratinisation of conjunctiva
• upper lid retraction
• lid lag
• lagophthalmos
• Bells..reduced = inferior rectus involved
• photos
• severe chemosis

Slit-lamp

• cornea...epitheliopathy
• precorneal tear film, ulcer, scar
• IOP
• IOP up gaze

dilate

• optic disc swelling/atrophy
• choroidal folds

EOM

• squint

Orthoptics

• HESS, BSV

Investigate

• visual fields
• CT..thickened muscles 
• MRI/USG
• blood thyroid antibody level

Proptosis

• exophthalmos
• record with same instrument, and record name of instrument
• record and use the same intercanthal distance...in primary position
• retropulsion..present...vision is normal, reduced, vision reduces (that is can press the eyes back in socket)

Summary

• upper eyelid retraction, oedema, erythema of lids/conjunctiva, proptosis
• 3% severe: severe pain, inflammation, corneal ulceration, optic neuropathy.
• 13% pretibial (or elsewhere) skin changes..small % of these thyroid acropachy (clubbing)

Occasionally there may be no response to steroids...the actual disease is inactive

• steroids are not efffective, the eye remains exophthalmic despite treatment
• there is no actual inflammation or autoimmmune reaction taking place
• the eye is not red
• there is mechanical obstruction to venous drainage...this is termed 'hydraulic' disease
• vision may be affected; there may be considerable exophthalmos or optic nerve compression.
• surgical orbital decompression may be very helpful and very effective
• muscles enlarge in older patients, fat swells in younger Anderson 89

• hypothyroidism..easy diagnosis   TSH high, T4 low
• subclinical  hypothyroidism..TSH high, T4 normal (and no clinical features)
• measure TRH-receptor antibodies:  thyrotrophin receptor antibody (TRH receptor) levels are related to diseae activity Gerding 2000.

• treat if symptoms, family history, antibodies present, dyslipidaemia, patient's preference, osteoporosis
• low TSH is bad for the heart...TSH level directly related to heart disease

environmental

• stress
• smoking
• drugs (eg amiodarone)
• infection
• low iodine in diet

modulating factors

• pregnancy
• E2 contraception

genes

• eg DR3 CTAL4

• subtotal thyroidectomy is generally best
• radioactive iodine...15% get TED
• use steroid cover to protect eyes...30mg day 4 weeks, then 20 mg/day for 4 weeks
• as above avoid hypo and hyperthyroidism by adjusting thyroxine levels

• IV methylprednisolone in the acute stage if condition is severe enough to treat see see .
• 1g day for 3 days each week for 2 weeks
• if this works...oral prednisolone and gradually reduce dose
• if it does not work, decompression surgery.
• radiotherapy is losing popularity...not as effective as steroids
• radiotherapy is dangerous and must not be given in diabetes as it increases retinopathy
• surgical decompression can be very helpful if there is a poor response to steroids
• if oral steroids are used, they should not be used long term
• Azothiaprim, cyclosporin, and somatostatin alone are not effective
• very rare deaths with methyprednisolone (liver failure), but only if total dose >8g
• new treatments are being tried...rituximab, TSH receptor antagonists
• clinic organisation is important
• Selenium can help NEJM 2011

Patients with severe disease will have many signs and many of these (eg exophthalmos, diplopia, optic atrophy) will remain even after the disease becomes inactive.

Patients will mild disease will have few if any residual signs when the condition settles.

Patients with moderate disease will have some signs after the active phase finishes.

The active period generally does not last longer than 2 years.

Doctors need to determine which patient is in which group, when the disease is active, and if the activity is enough to lead to significant problems when the activity settles.

Treatment is given in the active phase (red block opposite) in all of the severe cases, and most of the moderate cases, and few of the mild cases.

Treatment (IV methylprednisolone) is given as early as possible in the active phase, and repeated if the activity does not settle. Severe cases may still need surgical decompression in addition, even in the active phase.

Patients with mild disease may prefer no treatment...as the steroids themselves have side effects. But those with severe disease should nearly always be offered treatment, as well as stopping smoking and having their thyroid disease itself stabilised.

enlarge

After the active phase, residual signs can only be treated with surgery.

• orbital decompression for exophthalmos
• lid surgery
• squint surgery for double vision (this needs to be stable for 6 months before surgery)

• Notes from 2007 MOS meeting & 2008 College meeting
  TED = thyroid eye disease
• There is a genetic contribution to the inflammation
• Mourits score
• there are reports of 'Triamcinolone administered as a periocular injection is effective in reducing diplopia and the sizes of extraocular muscles in TAO ophthalmopathy of recent onset. ..not associated with systemic or ocular side effects', see.
• how to predict dysthyroid optic neuropathy Arch11