Presentation layout

Introduction
Pathogenesis
Clinical manifestations of thyroid
eye disease & Treatment
Classification ( NOSPECS)
Investigations for thyroid eye
disease
Introduction
Introduction

Thyroid Disease
• Hypothyroidism
• Hyperthyroidism
• Thyroid Cancer
Introduction
Introduction
Hypothyroidism
•Low T4 & Low T3 .
•Raised TSH (unless
pituitary problem!)
Introduction

Hashimoto’s Disease
• Most common cause of
hypothyroidism (iodinated salt)
• It is an Autoimmune
lymphocytic thyroiditis
• Females > Males
• Runs in Families!
Introduction
Hyperthyroidism
• Raised T3, T4 & Low TSH
• Heat intolerance
• Weight loss (normal to
increased appetite)
• Tremor, Palpitations
• Lid retraction & Lid Lag
Introduction
Graves’ Disease
• Most common cause of
thyrotoxicosis
• Goitre, Orbitopathy,
Dermopathy
 Thyroid Eye Disease ----- Causes
TED is an eye disease associated
with disease of the thyroid gland
TED is also known as :
•endocrine exophthalmos,
•malignant exophthalmos,
•Dysthyroid ophthalmopathy,
•Ocular Graves’ disease (OGD),
•Thyroid associated orbitopathy(TAO)
•Thyroid orbitopathy (TO)
•Graves’ ophthalmopathy
• Most commonly, TED occurs with an
overactive thyroid (Thyrotoxicosis),
which itself can have different causes:
-- Grave’s disease
-- Toxic nodular goitre
• It also occurs in hypothyroidism, for
example with Hashimoto’s disease
 Grave’s disease
It is the syndrome consisting of
hyperthyroidism, goitre and eye signs

• Autoimmune (AI) origin

• Excess secretion of Thyroid Hormone
by entire gland
• usually occurs between age group of
40s and 50s
• Female:Male = 8:1
– In patients with Grave’s disease,
eye signs may precede, coincide
with or follow the hyperthyroidism

– Sometimes similar eye signs are

seen without a detectable thyroid
abnormality
 Pathophysiology

Autoantibody against TSH receptor( TSH-R) in the

Thyroid

Cross react with TSH-R in effector cells i.e. fibroblast

,adipocytes and interstitial tissue between extra
ocular muscles

Inflammatory cellular infiltration ( T lymphocyte,

plasma cells, macrophages and mast cells) in orbital
fat, lacrimal gland and ocular muscles & tissue.
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 Pathogenesis (Key Points):
• Autoimmune Disorder (IgG mediated)

• Enlargement of Extraocular Muscles

– by increase in glycosaminoglycans (GAG)

• Cellular Infiltration of Interstitial Tissues

– with lymphocytes, plasma cells, macrophages & mast cells
– Fibrosis

• Proliferation of Orbital Fat, Connective Tissue and

Lacrimal Gland
– with retention of fluid & accumulation of GAG
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 Pathology
Activated T cells, infiltrate orbital contents
and stimulate fibroblasts, leading to:

Swelling of the various tissues of the orbit

results in eyelid oedema, chemosis,
proptosis, thickening of extraocular
muscles and other signs of thyroid
ophthalmopathy.
 Enlargement of extraocular muscles
• The stimulated fibroblasts
produce glycosaminoglycans
(GAGs) which cause the
muscle to swell
• Muscle size may increase by Swollen muscles
up to 8 times
• The swollen muscles occupy
orbital space and can
compress the optic nerve Compression
• These swollen muscles can of optic nerve
cause a forward propulsion of at apex of
orbit
the globe (proptosis) so that
the eyelids do not cover well
and eyes dry out, causing Swollen muscle
(lateral rectus)
exposure keratopathy

Swollen muscle (medial rectus)

 Cellular infiltration of interstitial
tissues
• Lymphocytes, plasma
cells, macrophages
and mast cells
infiltrate extraocular
muscles, fat and
connective tissue

Lymphocyte cuff
 Pathololgy (cont’d)
• Causes degeneration
of muscle fibres
• Leads to fibrosis of
the involved muscle

Build up of fibrous
tissue
 STAGES OF THYRIOD EYE DISEASE

1. Acute, active, inflammatory ( congestive)

Mediated predominantly by lymphocytes,
fibroblasts
bilateral eyelid retraction, conjunctival
chemosis, exophthalmos, and optic nerve
compromise.
Responds to treatment

20
2 )Chronic, stable ( Fibrotic)

Hypertrophy and fibrosis of extra ocular muscles

Unresponsive to any suppressive treatment
White eyes

21
Two Stages of Development
1. Active inflammation:
Eyes red and sore
Cosmetic problem
Remission within 3 years in most
patients
10% patients develop serious long-
term ocular complications
2. Quiescent stage:
Eyes are white
Painless
motility defect maybe present
Severity may range from
discomfort to blindness
( exposure keratopathy -- optic
europathy)
 SYMPTOMS
(OCULAR)
• Ocular redness and irritation
• Decreased vision
• Proptosis
• Diplopia
• Eyelid swelling
• Eye pain
• Field loss
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 Symptoms of hyperthyroidism

Tachycardia Tremor
 Palpitations  Increased appetite
 Nervousness  Weight loss
 Diaphoresis  Hair loss
 Irritability
 Heat intolerance
 Goiter
 Skeletal muscle
weakness
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 Symptoms of hypothyroidism

Bradycardia Dry skin

Drowsiness Husky voice
Poor mentation Depression
Muscle cramps Cold intolerance
Weight gain

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 Five Main Clinical
Manifestations
1. Soft Tissue Involve
ment
2. Eyelid Retraction
3. Proptosis
4. Optic Neuropathy /
Exposure
Keratopathy
5. Fibrosed Muscles
 Ocular Signs
(PELCO)
1) Proptosis ( 60%)

2) Extra ocular motility disturbance (40%)

3) Eye-Lid signs (retraction-90%)

4) Conjuctival/corneal signs

5) Optic neuropathy ( 5%) 27

 Proptosis
Most common cause of U/L and B/L proptosis
in adults / axial and frequently permanent.
Unilateral proptosis reflects asymmetric
muscle involvement.

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29
30
 Extra ocular motility dysfunction
30-50% cases, permanent
Ballet sign (restriction of one or more extra ocular
muscles)
Initially due to edema , later fibrosis
All 4 recti are involved but mainly IR and MR

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 Restrictive myopathy

Elevation defect Abduction defect

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Depression defect Adduction defect
 Signs
• Mobius sign (poor convergence)

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 Eyelid signs
• Upper lid retraction (Dalrymple sign) -90%
with temporal flare

34
 Mechanisms for upper lid retraction

Up gaze restriction Proptosis

Fibrotic contracture of LPS

Secondary over action of LPS-SR complex
Muller muscle over action 35
 Signs of eyelid retraction

• Bilateral lid retraction • Bilateral lid retraction

• No associated proptosis • Bilateral proptosis

• Unilateral lid retraction • Lid lag in downgaze 36

• Unilateral proptosis
Lid lag on down gaze
(von Graefe’s sign)

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 Signs
Stellwag sign (incomplete and infrequent
blinking)

Goffroy sign (absent creases in the

forehead on superior gaze)
Enroth’s sign (eyelid fullness)

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 Signs
Kocher’s sign Gifford’s sign
(difficulty in upper lid
It is a staring and frightened eversion )
appearance of the eyes

39
Conjunctival signs
 Deep injection over
insertions of the
horizontal recti

 Chemosis

 Superior limbic
keratoconjunctivitis

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 Signs
Goldhziar’s sign

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 Corneal signs
Minimal staining

Ulceration

perforation

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Optic neuropathy
– optic disc oedema or
optic atrophy

– due to direct
compression of the
nerve or it’s blood
supply

– May occur in absence

of significant proptosis
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Soft Tissue Involvement -
Symptoms
• Variable grittiness
• Photophobia
• Lacrimation - watery eyes
• Retrobulbar discomfort.
 Soft Tissue
Involvement - Signs
• Periorbital and lid swelling
• Conjunctival and episcleral hyperaemia
–Sensitive sign of disease activity
• Chemosis (oedema of the conjunctiva)

• Superior limbic keratoconjunctivitis

• Keratoconjunctivitis sicca secondary to
infiltration of the lacrimal glands.
Periorbital and lid swelling is caused by
oedema and infiltration behind the orbital
septum which may be associated with
prolapse of retroseptal fat into the eyelids

Severe periorbital swelling in thyroid eye disease

Conjunctival and episcleral hyperaemia
is a sensitive sign of inflammatory
activity. Intense focal hyperaemia
may outline the insertions of the
horizontal recti.
 Soft Tissue Involvement - Rx
Frequently unsatisfactory, may be of some
benefit
• Topical Rx – lubricants (artificial tears &
ointment) reduce irritation caused by
conjunctival inflammation and mild corneal
exposure
• Elevating the head end of bed during sleep may
decrease periorbital oedema. Diuretics given at
night may also reduce the morning
accumulation
• Taping of eyelids at night may be useful for mild
exposure keratopathy
 Eyelid Retraction
• Retraction of both upper and lower eyelids occur in
50% of patients
• Normally, upper eyelid rests about 2mm below limbus,
with lower eyelid resting at the inferior limbus
• When retraction occurs, the sclera (white) can be seen
• Causes cosmetic problems
• Pathogenesis not clear
• May be due to contraction of the levator muscle by
fibrosis, or be chemically induced by high thyroid
hormone levels
• If persists when disease is inactive, can be helped by
eye lid surgery
 Eyelid Retraction – Clinical
Features
• Clinical signs:
– Lid retraction in
(front) gaze
– Lid lag i.e. delayed
descent of upper
lid in downgaze
– Staring
appearance of the
eyes
 Eyelid Retraction - Rx
• Mild eyelid retraction does not require Rx, in
50% of cases, there is spontaneous
improvement
• Rx of associated hyperthyroidism may also
improve lid retraction
• Main indications are exposure keratopathy and
poor cosmesis
• Treatment is surgical if required, when both the
eyelid retraction and thyroid are stable
•Guanethidine 5% eyedrops may decrease the lid
retraction caused by overaction. of Muller's muscle.
 Proptosis
It is defined as forward displacement of the eyeball beyond the
orbital margins.
• Proptosis is axial
• TED is the most common cause
of both bilateral and unilateral
proptosis in adults
• Proptosis is uninfluenced by
Rx of hyperthyroidism and is permanent in
70% of cases
• Severe proptosis prevents
adequate lid closure, and may lead to
severe exposure keratopathy and corneal
ulceration
 Proptosis - Rx
• Systemic steroids to reduce
inflammation
• Low dose radiotherapy
• Surgical decompression: This is
where one or more walls of the orbit
are removed causing an increase in
space and relief of the proptosis. In
extreme cases, all four walls may be
removed
 Optic Neuropathy
• Serious complication affecting about 5% of
patients
• Caused mainly through direct compression
of the optic nerve or its blood supply by
enlarged and congested rectus muscles at
the orbital apex
• May occur in the absence of proptosis
• Can cause severe but preventable visual
impairment
 Optic Neuropathy – Clinical
Features
• An early sign is decreased colour
vision
• Slow progressive impairment of visual
acuity
• Visual defects, especially central
scotomas
• Optic atrophy in chronic advanced
cases
 Optic Neuropathy - Rx
• Depends on severity
• Initial RX by systemic steroids and/or
radiotherapy
• Orbital decompression is considered
if above is ineffective or optic nerve
severely involved
 Ocular Motility Problems
• Between 30% and 50% of dysthyroid
patients develop eye movement problems
• The diplopia caused by this may be
transient, but in many, it is permanent
• Ocular motility is restricted by oedema in
the infiltrative stage and fibrosis during the
fibrotic phase
• A defect in elevation is most common due
to fibrosis of inferior rectus tethering eye
 Rx of Ocular Motility Problems
• Surgery is usually considered if there is diplopia
in primary gaze or reading position
• Diplopia must have been stable for about 6
months
• Rx is by muscle surgery, with the aim of
producing binocular vision when looking
forward, and good cosmetic result
• Botulinum toxin injection (Botox) to relax
muscles may be useful in selected cases
Clinical signs of Graves' ophthalmopathy
adopted by the
American Thyroid Association ( ATA)

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 Investigations
Lab Studies:
T3
T4
TSH

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Visual fields:
• Central scotoma or
• Inferior altitudinal defect in compressive
optic neuropathy;
• Enlarged blind spot;
• Paracentral scotoma;
Color vision:

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 Imaging Studies

• Ultrasound
– Changes in extra ocular muscles,

– Accentuation of retro bulbar fat and

– Perineural inflammation of optic nerve

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 CT/MRI
INDICATIONS-
not needed in every cases

• 1) suspected optic
neuropathy

• 2)before decompression

• 3) to exclude retro bulbar

tumor as a cause of
proptosis

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 FINDINGS
• Fusiform thickening of muscles with tendon sparing.
• Proptosis
• Thickening of optic nerve
• Anterior prolapse of the orbital septum
• Lacrimal gland enlargement without orbital erosion

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Increase in orbital fat volume without muscle
enlargement

65
 Swollen muscles
Compression
Swollen muscle Swollen muscle (medial rectus) of optic nerve
(lateral rectus) at apex of
orbit
The End