THYROID EYE DISEASE

GRAVE’S OPHTHALMOPATHY

Md Shahid Manzoor

03/18/2023 1
 INTRODUCTION
• Also known as Graves ophthalmopathy,
dysthyroid ophthalmopathy, thyroid
associated orbitopathy, thyrotoxic
exopthalmos.
GRAVES DISEASE ( basedow’s disease)
• Seen in 25 –disorder
autoimmune 50% of graves disease.
presents in 3rd to 4th decade of life,
F> M,
characterized by a triad of features
HYPERTHYROIDISM
ORBITAL SIGNS
PRETIBIAL MYXOEDEMA
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• also occur in absence of clinical and
biochemical evidence.
• occur in pts with Hashimoto
thyroiditis(hypothyroidism) or in
euthyoid state (euthyroid or ophthalmic
graves) .

Eye disease may be the first

presenting sign of graves disease.

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 Etiology
• GENETIC FACTOR ASSOCIATION:
AUTOIMMUNE DISEASE
• -- HLA DR3, CTLA-4, PTPN22 ASSOCIATION:
-- Myasthenia gravis,
• ( a T- cell regulatory gene). --Addison disease.

RADIOACTIVE THYROID:
Thyroid ablation with orally ingested
radioactive iodine-131 may excerbate thyroid
associated orbitopathy compared with anti-
thyroid drugs and surgical ablation.

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• STRONGLY ASSOCIATED
WITH SMOKING

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 EPIDEMIOLOGY
• Associated with:
– 90% Graves hyperthyroidism
– 6% Euthyroidism
– 3% Hashimoto thyroiditis
– 1% Primary hypothyroidism
• Onset:
– 20% of TED is diagnosed same time as
hyperthyroidism
– 60% of eye disease occur 1 year after
thyroid disease
– Only 30% of hyperthyroidism  TED
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 PATHOGENESIS
• This involves an organ specific
autoimmune reaction in which a
humoral agent (IgG antibody)
produces the following changes:
1. Inflammation of extraocular
muscles
2. Inflammatory cellular
infiltration

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 INFLAMMATION OF EXTRAOCULAR
MUSCLES
Pleomorphic cellular infiltration, increased secretion of
glycosaminoglycans,osmotic retention of water

Muscles become enlarged( 8 times their normal size, may

compress optic nerve).

Subsequent degeneration of muscle fibers eventually leads to

fibrosis

Restrictive myopathy and diplopia

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HISTOLOGICAL PICTURE SHOWING ROUND CELL
INFILTRATION OF EXTRA OCULAR MUSCLES
THYROID EYE DISEASE

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INFLAMMATORY CELLULAR INFILTRATION

Infiltration with lymphocytes, plasma cells, macrophages & mast cells of

interstitial fluid, orbital fat & lacrimal glands and
Accumulation of glycosaminoglycans & retention of fluid.

Increased volume of orbital contents and

Increased IOP

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 OCULAR SYMPTOMS
• Dry eyes
• Bulging eyes
• Diplopia
• Visual loss
• pain
• Photophobia (Corneal involvement)
• Lacrimation

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 CLINICAL MANIFESTATION

… SOFT TISSUE PROPTOSIS

INVOLVEMENT (PASSIVE OR
LID RETRACTION MECHANICAL
(PERIORBITAL & LID
SWELLING, CONJUCTIVAL PROTRUSION OF EYE
HYPEREMIA BALL)

OPTIC NEUROPATHY RESTRICTIVE MYOPATHY

(SERIOUS COMPLICATION) (OCULAR MOTILTY IS
–COMPRESSION OF OPTIC REDUCED INITIALLY BY
NERVE LEADING TO INFLAMMATORY EDEMA
VISUAL IMPAIREMENT) & LATER BY FIBROSIS

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 LID RETRACTION
• 90%
• Fibrotic contracture of levator:
– Worse in downgaze
• Secondary overaction of levator-SR complex:
– hypotropia caused by fibrosis of IR
– Worse in upgaze
• Humorally induced overaction of Muller muscle:
– Sympathetic stimulation by thyroid hormones

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 Kocher Sign Von Graefe Sign
DALRYMPLE SIGN ( lid retraction in ( staring & frightened ( retarted descent of
primary gaze) appearance of eyes) upper lid at downward
gaze) lid lag sign

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 OTHER OCULAR FEATURES
• STELLWAG SIGN
incomplete & infrequent blinking
• GROVE SIGN
resistance to pulling down the retracted upper lid
• JOFFROY SIGN
– absent creases in forehead on sup. gaze
• MOBIUS SIGN
poor convergence
• BALLET SIGN
• restriction of one or more extra ocular movements
• VIGOUROUX SIGN
eyelid fullness

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 soft tissue involvement

chemosis, conjunctival injection over the

recti insertions, puffy lids.

Chemosis

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 • Superior limbic
keratoconjunctivitis (SLK)

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 Corneal involvement

exposure keratitis
• proptosis,
• upper eyelid retraction,
lower eyelid retraction,
lagophthalmos, or a
• combination of these
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 Corneal involvement
. primary lacrimal gland dysfunction may
also be present in Graves' orbitopathy.

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 RESTRICTIVE MYOPATHY
• diplopia due to restriction.
• Order of involvement-
• .
IR MR SR LR

Braley´s sign =
increased IOP on
upgaze (>6mmHg) than
primary gaze due to IR
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restriction 20
 EXOPHTHALMOS(PROPTOSIS)

• Axial
• Uni/bilateral
• Symmetrical/asymmetrical
• Grading
• Mild-21-23
• Moderate-24-27
• Severe- 28 or more

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 Optic nerve compression
• Uncommon but serious ( 5%)
• Mc –males, elderly, diabetics.
• Inflammation of EOM  cells infiltration 
GAG  fluid retention  orbital pressure 
compression
• Dysthyroid optic neuropathy-caused by
enlarged extraocular muscle at orbital apex
compressing optic nerve

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 Optic nerve compression
• +/- proptosis
• Signs:
– Reduced VA +/-, APD+/-, color desaturation
– VF defect: central or paracentral,
increased IOP (confused with POAG)
– Optic disc is normal, might swollen and
rarely atrophic

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 Axial CT scan showing enlarged extra ocular
muscles in thyroid eye disease

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• Restriction of right eye in upgaze

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SPECIFIC

1. Thyroid profile:
• serum T3 & T4 level
• serum TSHlevel.
2.CT scan orbit ( axial &
coronal view)
3. MRI

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• Orbital CT
– enlarged muscle belly, tendon normal.
– Coca-Cola bottle sign
• muscle swelling deforming ethmoidal bones.
• MRI : changing intensities between T1- and
T2-weighted images may differentiate the
active edematous from the inactive fibrotic
muscle changes.
• Radioisotope tests Octreoscan: quantitative
uptake of radio-labelled octreotide (which is
a somatostatin analogue).

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03/18/2023 28
 Assessment Protocols of Graves’
Ophthalmopathy

• NO SPECS Classification (1969 by

Werner)
• Tells severity but not rate of progression.
• EUGOGO classification (1999) and VISA
classification (2006) .
– indicators to assess the signs of activity
– degree of severity

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 Activity and severity assessments in GO by
EUGOGO

Activity Severity
refers to the
refers to the
quality of life or
inflammatory
the risk of vision
process
loss

• GO follows a biphasic course.

• Active phase (18-36 months) then stable or
inactive phase therefore activity and severity
assesement is done.
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 Clinical active score
Activity
assesement

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 Active
ophthalmopathy

• If CAS is ˃3/7 at first examination

• > 4/10 on successive examination

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 Severity measures (absent/present)

• Lid aperture
• Swelling of the eyelids (absent/equivocal,
moderate, severe)
• Redness of the eyelids
• Redness of the conjunctiva
• Conjunctival edema
• Inflammation of the caruncle or plica

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 Severity measures
• Exophthalmos
• Eye muscle involvement (ductions in degrees)
• Corneal involvement (absent/punctate
Subjective diplopia score
keratopathy/ulcer)
0 =no diplopia
• ON Inv:BCVA, color i.e.
1=intermittent, vision,
diplopiaoptic
in disc, RAPD
primary position
(absent/present), plus of gaze, whenfields
visual tired if optic
or when first awakening
nerve compression
2=inconstant, is
i.e. suspected
diplopia at
extremes of gaze
3=constant, i.e. continuous diplopia
in primary or reading position

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 European Group on Graves’
orbitopathy (EUGOGO) on management of
GO
• Criteria for referral by physicians –
• urgent
• Non urgent

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 CRITERIA FOR URGENT REFERRAL
Symptoms Signs
• .
Unexplained deterioration in vision Obvious corneal opacity

Awareness of change in intensity or Lagophthalmos

quality of color vision in one or
both eyes

History of eye(s) suddenly Disc swelling

‘popping out’ (globe
subluxation)

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Symptoms Signs
Non urgent referral
Eyes abnormally sensitive to light: troublesome Troublesome eyelid retraction
or deteriorating over the past 1–2 months
Eyes excessively gritty and not improving
after 1 week of topical lubricants

Diplopia Abnormal swelling or redness of eyelid(s) or

conjunctiva

Appearance of the eyes has changed causing Restriction of eye movements or manifest
concern to the patient strabismus

Progressive change in appearance of the eyes Tilting of the head to avoid double vision
and/or eyelids over the past 1–2 months

Pain in or behind the eyes: troublesome or

deteriorating
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 Smoking and Grave’s orbitopathy
• Promotes development of GO
• Detoriates pre-existing GO
• Decreases effectiveness of treatments
for GO
• Promotes progression of GO after
radioiodine treatment

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 Hyperthyroidism and GO
• Euthyroidism should be restored
promptly and maintained stably in all
patients with GO
• Frequent monitoring of thyroid status
(every 4–6 weeks) is imperative in the
initial phases of treatment

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 Hyperthyroidism
Pts with active GO
and GO
Pts with inactive GO

radioiodine with prophylactic radioiodine without steroid

steroid cover cover as long as hypothyroidism
is avoided .

0.3–0.5 mg of prednisone/kg particularly if other risk

bw per day orally 1–3 days after
radioiodine and tapering the factors for GO
dose until withdrawal 3 months progression, such as
later smoking, are absent
Shorter periods of
glucocorticoid therapy (1–2
months) may be equally
protective

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 Severity classifications in GO
Sight-threatening GO: Patients with dysthyroid optic
neuropathy (DON) and/or corneal
breakdown. This category
warrants immediate intervention.

Moderate-to-severe GO: Patients without usually have any one or more : lid
sight-threatening GO whose eye disease retraction ˃2 mm, moderate or severe soft
has sufficient impact on daily life to tissue involvement,
justify the risks of immunosuppression (if exophthalmos˃3 mm above normal for
active) or surgical intervention (if inactive) race and gender, inconstant or constant
diplopia.

Mild GO have only a minor impact on one or more of the following: minor lid
daily life insufficient to justify retraction (˂2 mm), mild soft tissue
immunosuppressive or involvement, exophthalmos ˂3 mm above
surgical treatment normal for race and gender, transient or no
diplopia, and corneal exposure responsive
to lubricants

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 PTS with GO

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 Management of mild GO

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 Management of mild GO

• Glucocorticoids - rarely justified in mild GO

• Watchful waiting
6-month course with is appropriate.
oral selenium(100 𝜇g
• Rehabilitative
twice daily)
surgery :if GO inactive
significantly improved
quality of life,reduced
ocular involvement,
and slowed Botulinum toxin injection
progression of the ds. To reduce upper lid retraction
and is a valuable therapeutic
option in active disease where
definitive surgery remains
contraindicated

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 Measures that may alleviate symptoms in
GO

• Lubricant e/d during the day and/or lubricant

ointments at night-time -for GO pts having sym
of corneal exposure
• symptomatic diplopia –
– given prisms if appropriate
• Botulinum toxin injection
– for upper lid retraction

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 Moderate-severe GO
• Active Inactive

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 Treatment of moderate-to-severe GO
that is ACTIVE

500mg methyl prednisolone weekly for 6 weeks followed by

250mg• weekly
CAS >3/7 pulses
for another of i.v. for
6 weeks, glucocorticoids
a cumulative dose(GCs)
of
4.5 g
• Screen pts for liver dysfxn, htn, h/o peptic
The total cumulative
dose of methyl
ulcer, diabetes, urine infection,prednisolone
and glaucoma.should
• Bisphosphonates -when long-term (˃38 g in one
not exceed
course of therapy.
months) oral GC therapy (average daily
dose>5 mg prednisone or equivalent) is used.

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Treatment of moderate-to-severe GO that is
ACTIVE
Used cautiously
• Orbital irradiation -diplopiainor
ptsrestricted
younger
motility. than 35 years
– Dose (10 Gy) is as effective as 20 Gy. in patients with
Avoided
– Doses ˃20 Gy are not recommended .
diabetic retinopathy
– 10 sessions over 2 weeks severe hypertension

.
• oral GCs + OR is more effective than either
treatment alone.

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 Other alternatives to corticosteroids
• Methotrexate
– weekly dose of 7.5mg to 10mg orally administered
– recurrence of inflammatory signs of orbitopathy
after withdrawal of corticosteroid treatment
because of onset of steroid side effects
– or intolerance.
• Cyclosporin A
– 5mg/kg/day in 2 doses plus oral glucocorticoids
• Azathioprine.
• TSH-R antagonists:
– monoclonal TSH-R-blocking antibodies
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 Mgtt of DON and exposure
Keratopathy
• Active Inactive

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Glucocorticoids and orbital decompression in
DON
• High-dose i.v. GCs - first-line treatment for DON
• Orbital decompression
– if response to i.v. GCs is absent or poor after 1–2
weeks
– side effects.
– who cannot tolerateGCs.

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 Sight-threatening corneal breakdown in GO

• For corneal healing

– Frequent topical lubricants (preservative-free )
If corneal perforation/severe ulceration
– moisture chambers
appropriate antibiotics
– blepharorrhaphy
emergency glueing
– tarsorrhaphy
amnion membrane as shield
•corneal
If above measures are ineffective
grafting
Once the corneal breakdown
– systemic is brought
GCs or surgical under control, it is
decompression.
imperative that treatment is offered to improve lid closure
•
and .
thus prevent further episodes of corneal breakdown

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 Rehabilitative surgery

• orbital decompression
• squint surgery (to restore binocular
single vision in the primary position at
distance and near).
• lid lengthening
• blepharoplasty/browplasty.

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Timing and the order of surgery for GO
• Surgical management should proceed in
the following sequence:
• orbital decompression
• squint surgery
side effects of the preceding
• lid lengthening with or followed by
step can interfere with the
blepharoplasty/browplasty,
step that follows.
• Reason-
• .

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• Rehabilitative surgery performed in pts
who have had inactive GO for at least 6
months

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 Orbital decompression
• 1-, 2-,and 3-wall decompression with
orbital fat removal depending on the
degree of exophthalmos.
• Proptosis regression after surgery
varies:
– 5.6 to 6.5mm after 3-wall decompression
– 3.2 to 4.8mm after 2-wall decompression.
• Surgically induced diplopia is the most
common complication of orbital
decompression
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 Lid retraction sx

• Surgery is recommended
– significant upper lid retraction of >1 mm
– asymmetry of palpebral apertures
– lateral (temporal) flare.

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 Lid retraction sx

through
• Surgery foran eyelid
upper lidcrease incision
retraction is
where
divided the levator aponeurosis
into
and Muller’s
• Anterior muscle
approach are
disinserted from the tarsus until
• Posterior approach through the
appropriate height of the eyelid
conjunctiva and Muller’s muscle.
is achieved.

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 Lid retraction sx
• Lower lid lengthening - lower lid
retraction.
• In lower lid retraction SPACERS repair
auricular cartilage
• the conjunctivahard and LLmucosa
palate retractors are
expanded polyethylene microplates
detached from the tarsus
autogenous edge of the tarsus
transplants
through a posterior
donor sclera,approach
or pericardium and a
porcine acellular dermal matrix

spacer is placed between the retractors

and tarsus.

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 GO in children
Glucocorticoid
• Euthyroidism should be restored
s - avoided in
children Orbital
promptly and maintained in children radiotherapas in
y is C/I in
adults. children .

• Children with GO should be managed

conservatively if vision is not threatened
.
• Simple measures to address specific
Exposure to active and
symptomspassive
cansmoking
be utilized
should be as for adults.
avoided
• .
• .
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