● TED is an autoimmune disease caused by the activation of orbital fibroblasts by
autoantibodies directed against thyroid receptors.
● Rare disease: Incidence 19 in 100,000 people per year
● Characterized by: enlargement of the extraocular muscles, fatty and connective tissue
● Graves' disease (GD): autoimmune disorder involving the thyroid gland
○ Presence of circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR), resulting in hyperthyroidism and goiter.
○ Organs other than the thyroid can also be affected, leading to the extrathyroidal manifestations.
● TED is observed in ~ 50% of patients with GD
● Previously known as thyroid-associated ophthalmopathy (TAO), Graves orbitopathy
(GO) and other variations.
(Euthyroid) or under-
10% of patients
The course and severity of
ocular manifestation does
not always correlate with
thyroid hormone levels.
Treatment of thyroid
dysfunction does not
necessarily affect course
TED is most
90% of patients
Both men and
of the age of
The median age is 43 years for
all patients, with a range
from 8 to 88 years old.
times more than
men. Linked to a higher incidence
of Grave's disease in
Activation of orbital fibroblasts by
Graves' disease-related autoantibodies
Release of T cell chemoattractants
Fibroblasts expressing extracellular matrix molecules,
biologic materials proliferating and differentiating into
myofibroblasts or lipofibroblasts and deposition of
Bind water that lead to swelling,
congestion in addition to connective
Extraocular muscle enlargement
and orbital fat expansion.
Eyelid retraction (Dalrymple's sign) is the most common presenting
sign of TED, present in upto 90% of patients
Eyelid retraction in patient with TED. Upper lid retraction measured
with margin to reflex distance 1 (MRD1) and lower lid retraction
measured with margin to reflex distance 2 (MRD2).
TED is the most common cause for both unilateral and bilateral axial proptosis
Increased resistance to retropulsion.
Hertel’s exophthalmometer is used for the measurement of proptosis.
Extraocular muscles frequently involved in TAO.
Extraocular muscles affected results in ocular
misalignment, diplopia. Inability to look up when the
eye is adducted i.e. double elevator palsy.
Stellwag sign- Incomplete and infrequent blinking (staring look)
Grove sign- Resistance in pulling the retracted upper eyelid
Boston sign- Jerky movements of eyelids in downgaze
Gifford sign- Difficulty while everting the upper eyelid
Gellineck sign- abnormal pigmentation of upper eyelid
Upper Lid Signs
Mobius sign- Not able to converge eyes
Ballet's sign- One or more extraocular muscle restriction
Suker sign- Poor fixation in abduction
Jendrassik's sign- paralysis of all EOM = Total ophthalmoplegia
Extraocular movements signs
Knies sign- Uneven pupillary dilatation in dim light
Cowen sign- Jerky contraction of the pupil to light
Vigouroux sign- eyelid fullness
Von Graefe sign- retarded descent of upper lid in downgaze
Jofforoy sign- absent crease of the forehead in superior gaze
Kocher's sign- Staring and frightened appearance of eyes
The diagnosis can be done clinically with the characteristic clinical picture, restrictive
nature of the disease and associated systemic thyroid disease.
Though not diagnostic, thyroid hormone levels, thyroid-stimulating
immunoglobulins (TSI), anti thyroid antibodies can be suggestive of diagnosis.
Ultrasonography: Both A-scan and B-scan transocular echograms can be used to
visualize the orbital structures and determining recti muscle enlargement.
Advantage is its low cost, lack of ionizing radiation and relatively short examination
Computed tomography (CT) scan: It demonstrates enlargement of the bellies and
sparing of the tendons. It helps in assessing the relationship between the optic
nerve and muscles at the apex, which helps in planning for the surgical intervention
Magnetic resonance imaging (MRI): Fusiform rectus enlargement and orbital fat
expansion may be identified. MRI may also aide in assessing water content in the
muscles and other soft tissues. This may correlate with active inflammation.
Exophthalmos noted in axial view of
CT-scan. Patient with TED also
demonstrates enlargement of extra
ocular muscles (asterisk).
The most current grading systems of TED are the VISA classification and the European
Group of Graves' Orbitopathy (EUGOGO) classification.
The utility of these grading systems is that both assess severity and activity.
V (vision, optic neuropathy)
I (inflammation, congestion)
S (strabismus, motility restriction)
A (appearance, exposure).
The 4 severity parameters can be found in the name, and a maximum score of 20 is used
to grade the severity of disease.
Each of the four parameters has further divisions in order to better asses the activity of
EUGOGO classification attempts to assess both disease activity and disease severity.
Activity is based on four measures of inflammation, pain, redness, swelling, and impaired function, and function is
graded with decreasing monocular motion and diminishing visual acuity.
The classification system also has developed an image atlas which can be used to accurately grade the patient in front
Additionally, the EUGOGO grading system does well in differentiating management categories
For corneal exposure, lubricants,
taping and protective shields can
be tried and if necessary
tarsorrhapphy can be done.
Sleeping with the head of the
bed elevated to decrease
Both smoking cessation and
euthyroid status help preventing
further exacerbation and
decrease the duration of active
For diplopia, Fresnel
prisms or occlusion
therapy may be
Oral NSAIDs may be used for
periocular pain. Selenium has shown
significant benefit in patients with
mild, non‐inflammatory orbitopathy
Lifestyle modifications e.g.
sodium restriction to reduce
water retention and tissue
This biologic infusion therapy has been shown
in clinical studies to reduce signs and
symptoms of TED.
Teprotumumab binds to IGF-1R and blocks its
activation and signaling.
Tepezza (Teprotumumab-trbw) is the first and
only FDA-approved prescription treatment for
To decrease orbital inflammation oral prednisone in a dose of 1- 1.5-
mg/ kg can be given for a suggested maximum period of 2 months.
Intravenous (IV) corticosteroids pulse methyl prednisolone can be
considered as an alternative.
Can be used alone or in conjunction with corticosteroids.
The radiation therapy works on the similar mechanism of decreasing inflammation.
Typical dose of 2000 cGy for each orbit 200 cGy / day given over a period 10 days. It
generally improves vertical motility.
Radiation retinopathy may occur as a side effect.
In cases of significant strabismus, strabismus surgery may be required and should be
done with adjustable sutures since the muscles typically do not respond as normal
muscles would to strabismus surgery.
Strabismus surgery should be considered only after orbital decompression is
complete and muscle alignment has stabilized.
These reconstructive surgical procedures may be preformed to address
eyelid retraction or exposure keratitis.
Eyelid Retraction Repair and
Rituximab is a monoclonal antibody that targets CD‐20 on B‐cells
An ocular emergency, and occurs in <5% of patients with typical TED resulting in
slowly progressive fulminant visual loss.
It occurs due to compression from the oversized recti and orbital fat causing
compartment syndrome at the apex of orbit.
It is characterized by decrease in vision, color vision, contrast sensitivity and relative
afferent papillary defect.
The characteristic visual fields commonly show central, cecocentral, paracentral, and
nerve fiber layer bundle defects.
Optic nerve head examination can be normal, optic disc edema, or pallor
Compressive optic neuropathy
This surgical procedure enlarges
the existing space of the orbit by
partial removal of bony walls.
Orbital decompression commonly
involves the orbital floor, medial
wall, and lateral wall. In rare cases
the roof of the orbit may also be
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Reference: EyeWiki, Thyroid