THYROID RELATED

IMMUNE ORBITOPATHY
PRESENTER: DR MUDASIRA MOHAMMAD
MODERATOR: PROF. DR EJAZ AKBAR WANI

DEPARTMENT OF OPHTHALMOLOGY (GMC

SRINAGAR)
INTRODUCTION:
 Thyroid eye disease (TED) or thyroid-associated orbitopathy (TAO) is an
autoimmune inflammatory disorder characterized by enlargement of the orbital
fat and extraocular muscles.

 M/C cause of unilateral and bilateral proptosis in adults.

 It is mainly associated with hyperthyroidism but also with hypothyroidism and

euthyroid states.
Epidemiology
 Prevalence is more in women than men (16 per
100,000 vs. 3 per 100,000, respectively).

 Both genders demonstrate a bimodal pattern of age

of diagnosis (40-44 and 60-64 years in women; 45-49
and 65-69 years in men).

 The median age of diagnosis is 43 years for all

patients.
 RISK FACTORS
Race(Caucasians)
 Female Gender
 Expression of HLA-B8,DR3, and DQA1 may increase
susceptibility to the disease .
 Radioactive iodine (RAI) therapy
 Positive family history
Cont.
 Thyroiddysfunction and presence of TSH receptor
antibodies.

 Smoking (Stimulates hyaluronic acid production and an

increase in adipogenesis) .

 Selenium deficiency: Selenium helps in the protection of

oxidative damage of thyroid hormones.
PATHOGENESIS
 .

Autoantibodies initiate the Once stimulated, orbital fibroblasts

IGF-1R/TSHR signaling complex, and cause inflammation and the
this activates orbital fibroblasts expansion of muscle and fat tissue
behind the eye
Clinical picture

 The thyroid state of a patient presenting with TED is

quite variable:
 - 90% hyperthyroid.
 - 6% euthyroid .
 - 3% with Hashimoto’s thyroiditis.
 - 1% hypothyroid.
 80% of patients experience thyroid eye disease within 8
months prior to or following endocrine disease.
RUNDLE CURVE:
TWO STAGES:
 Active stage:
There is active inflammation, which can lead to orbital
muscle enlargement, conjunctival injection and chemosis,
ocular pain, and swelling of the periocular tissues and
eyelids.
 The quiescent phase or fibrotic phase :
in which the eyes are white although painless motility defect
may be present.
Clinical Features :
 Clinical
features can be broadly classified into:
A)Soft tissue involvement:

Symptoms include:
Grittiness,red eyes,lacrimation,photophobha and puffy
eyelids.
Signs include :
Epibulbar hyperemia
Periorbital swelling
Tear insufficiency
 B)Lid Retraction:
 Occurs in about 50%of patients.
 Overaction of Mullers muscle is postulated to occur as a

result of sympathetic overstimulation secondary to high level

of thyroid hormones.
 Fibrotic contraction of LPS and Inferior Rectus can occur.
 Symptoms:

Staring or bulging eyelid apperance, difficulty in closing

eyes,ocular surface symptoms.
 Signs :

Scleral show
C)Proptosis:
 Proptosis axial, unilateral or bilateral,symmetrical or

asymmetrical and frequently permanent.

D)Restrictive Myopathy :
 Between 30&50% ofpatients with TED develop ophthalmoplegia

which may be permenent.

Symptoms:Double vision
Signs :in approximate order of frequency:
Elevation defect : caused by fibrotic contraction of inferior
rectus.
Abduction defect:due to fibrosis of medial rectus .
Depression defect: secondary to fibrosis of superior rectus.
Addiction defect:caused by fibrosis of lateral rectus.

E)Optic Neuropathy:
Symptoms: Impairment of central vision.
Signs: Decrease in VA
Color desaturation
RAPD
Visual field defects
SIGNS:
.
COMMON SIGNS

Von graeffe’s sign Kochers sign Vigourox sign

Enroth sign
Joffroy’s sign Moebius Goldzeiher’s sign
sign
MEASUREMENT :
 EXOPHTHALMOMETER
 (HERTEL’S ,NAUGLE’S ,LUEDDE)
 The measurement , in Hertel’s exophthalmometer, is
done from the lateral orbital rim to the anterior corneal
suface.
 The patient and examiner must be at the same level.
 Locate the orbital notch with the patients eyes closed on

the temporal side of orbital rim near the lateral cathus.

 The prisms or the mirrors are slid across the bar to adjust

the footplates to fit on the orbital rim. The

exopthalmometer is opened so that the grooves are placed
in the orbital notch.
 The separation of exophthalmometer should be noted
(baseline reading)
 The patient is then asked to open the eyes and look straight

ahead.
 Look into the exophthalmometer, the red lines should

overlap to avoid parallax. Look into the mirrors located

at each end of the exophthalmometer. Note the millimeter
mark corresponding to the corneal apex and the baseline
reading
Limitations of Hertel’s:
unreliable in case of poor fixation, uncooperative patients with
convergence or head movements. It cannot be done in presence of
depressed or fractured lateral orbital rim.
 Luedde’s exophthalmometer: It is a transparent thick plastic
ruler.
It is more accurate than Hertel’s exophthalmometer in presence of
facial asymmetry.
 Naugle exophthalmomter: it uses fixation points above and below

the superior and inferior orbital rim(cheekbones and forehead). It

measures the difference in proptosis between two eyes rather than
absolute measure with the Hertel. It is preferred in case of an
orbital fracture or after lateral orbitotomy.
 Investigations:

LABS:CBC ,Thyroid function test (tri iodothyronine,T3;Free thyroid (T4),Serum

thyroid stimulating hormone (TSH);Thyrotrophic receptor antibodies (TRAB);ESR.

USG:On cross section ,there is increase in thickness of the Extraocular [Link]

also helps in visualization of tendinous intersections.
CT Scan :Typical radiological features seen on CT are :
- Muscle belly enlargement that typically spares the tendinous insertion
- Increase in retro orbital fat volume.
- Crowding of optic nerve at the orbital apex.
MRI : location and involvement of the ocular muscles generally follow the described CT
appearances.
CT SAGITTAL CT AXIAL
 MRI ORBIT

AXIAL VIEW CORONAL VIEW

DIFFERENTIAL DIAGNOSIS :

[Link] gravis –
MG patients can also present with diplopia. However, MG
tends to worsen throughout the day and improves after rest
while diplopia in TED is not typically variable.
 Diplopia associated with TED is restrictive in nature, which
can be determined by forced duction testing.
 MG patients may present with ptosis, which is not
associated with TED.
2. Orbital myositis – it causes enlargement and inflammation of the
muscle body and tendon insertion.
 Not associated with eyelid retraction.
 It is usually unilateral.
 A bilateral presentation would be unusual for OM, whereas TED

can present either way.

3. Orbital pseudotumour:
– Orbital tumors are typically unilateral in presentation and
can cause proptosis and a wide variety of motility
disturbances depending on location.
Orbital pseudotumors are unlikely to cause eyelid retraction
or lid lag. Depending on area involved maybe:
A) MYOSITIC PATTERN(M/C)
B) LACRIMAL PATTERN
C) ANTERIOR(EYE AND RETROBULBAR FAT)PATTERN
D) DIFFUSE(INTRA-CONAL) PATTERN
E) APICAL(APEX OR INTRACRANIAL )PATTERN
4. Carotid-cavernous fistula (CCF) – Patients may hear pulse-
synchronous tinnitus.
 Presentation may include proptosis, pulsatile exophthalmos,
 Dilated conjunctival and episcleral vessels,
 Elevated intraocular pressure, or enlarged EOM .
 CCF would not cause eyelid retraction or temporal flare.
4. Inflammatory orbitopathy: such as granulomatosis with
polyangitis – GPA
 Typically presents with a mix of upper airway, lower airway,

and renal pathologies.

 Patients may have conjunctivitis, episcleritis, scleritis,

and/or uveitis .
 Other than conjunctivitis, these findings are uncommon in

TED patients.
5. IgG4 disease :

 Tumefactive lesions and fibrosis commonly present in the

biliary tree, retroperitoneum, salivary glands, orbit, and
lymph nodes. It is involves both humoral and cell-mediated
immunity.
 Orbital IgG4 disease often involves painless swelling of the

extraocular muscles, lacrimal glands, and infraorbital

nerves in combination with paranasal sinus disease.
 Werners NO SPECS CLASSIFICATION

Class grades

0 No signs or symptoms
1 Only signs (upper lid retraction and stare, ± lid lag)
2 Soft tissue involvement (edema of conjunctiva and lids, conjunctival injection
3 Proptosis
4 Extraocular muscle involvement (usually with diplopia)
5 Corneal involvement (primarily lagophthalmos)
6 Sight loss (due to optic nerve involvement)
 Clinical activity score(CAS):
pain. . painful feeling behind globe within last 4
weeks
. pain on attempted gaze within last 4
weeks
Redness . Redness of eye lids
. Redness of conjunctiva
swelling . Chemosis
. Swelling of eye lids
. Swelling of caruncles
. Increase of proptosis>2mm within last 1-
3months
Impaired function . Decrease in visualacuity of >1 line on the
snellens chart within last 1-3 months
. Decrease in the eye movements of <5
degrees within the last 1-3months
 EUGOGO disease severity classification
Mild Lid retraction <2mm
Exophthalmos <3mm above normal for race and gender
Transient or no diplopia
Corneal exposure responsive to lubricants

Moderate to severe Lid retraction > 2mm

Exophthalmos >3mm above normal for race and gender
Transient or constant diplopia

Sight threatening Compressive optic neuropathy and or corneal breakdown warranting

immediate action
VISA CLASSIFICATION
 Devised by Dolman and Rootman
 Based on four disease endpoints that can be used in the

office setting to record changes and to guide and assess

therapy
 These clinical points are vision ,inflammation ,strabismus

and appearance
 This classification helps direct appropriate management in a

logical sequence depending on which aspect of the disease

are affecting them at any point in the course of their
disease.
MANAGEMENT
Management part includes :
 A)Lifestyle modifications
 B) Supportive Measures
 C)Medical Management
 D)Radiation Therapy
 E)Surgical Management
 F) Treatment of emergent conditions
 G) Newer modalities
 Lifestyle modifications
 Sodium restriction to reduce water retention and tissue edema
.
 Smoking cessation .
 Sleeping with the head of the bed elevated to decrease orbital

edema .
 Sunglasses to decrease photophobia .
Overview of Treatment Options
 Corticosteroid Therapy:
- Corticosteroids are a mainstay of treatment in TED. The
benefit derived from corticosteroid administration is due to
anti inflammatory and immunosuppressive effects.
 Oral prednisone:

- This is typically started in high doses (60-100 mg daily).

Most effective in treating soft tissue changes and optic
neuropathy
- Usually tapered slowly over a course of several months
Multiple studies show a mean effectiveness rate of ~ 60%.
Intravenous (IV) corticosteroids
 IV steroids are usually better tolerated and more effective
(mean effectiveness ~ 70%).
 DOSE:0.5 gm once weekly for 6 weeks
 0.25 gm once weekly for another 6 weeks
 Biologic Immunomodulators

 Mycophenolate mofetil
Reduces proliferation of B and T cells of the immune system
and also suppresses antibody formation by B cells.

 AZATHIOPRINE-inhibits DNA synthesis

 TOCILIZUMAB –blocks IL-6 receptor

 RITUXIMAB-targets CD-20
 Teprotumumab
 Human monoclonal antibody against the IGF-1 receptor.

 10mg/kg IV in first week, then 20mg/kg IV for 7 more

weeks) administered to patients with active, moderate to
severe TED result in significant decrease in CAS, diplopia.

 Some patients treated with teprotumumab may experience

temporary auditory impairment and infusion reactions .
Orbital Radiotherapy

 Orbital radiotherapy (ORT) has been used in the

management of TED for nearly a century and can be used
alone or in conjunction with corticosteroid.
 ORT can be used to treat the following sequelae of TED

- Compressive optic neuropathy .

- Ocular surface and periorbital tissue inflammation .

- Orbital congestion .

- Strabismus and ocular motility deficits .

o Contraindications to orbital radiotherapy

 Diabetic retinopathy
 Hypertensive retinopathy
 Theoritical concern for tumourogenesis therefore avoided in
below 35 years old patients
 Increased incidence of cataract
Treatment of Emergent Conditions

o Optic Neuropathy
 Corticosteroid therapy
◦ This is considered first-line therapy for compressive optic neuropathy.
◦ This may be primary treatment, or a temporizing measure, until surgical
decompression can be performed .
 IV methylprednisolone.
◦ High-dose IV methylprednisolone (830 mg weekly for 6 weeks, followed by 415
mg weekly for 6 weeks) in pulsatile administration is more efficacious than oral
corticosteroids
Orbital Decompression

 GOALS

 Treat compartment syndrome

 Proptosis reduction

 Prepare orbit for strabismus surgery

 Improve eye lid function

 Lateral wall decompression

 Medial wall decompression

 Risks involving orbital decompression
 Optic nerve damage
 CSF leak due to dura rupture
 Worsens strabismus
 Worsens asymmetry
 Infections
 Hypoaesthesia
Exposure keratopathy
 Patients at high risk for corneal exposure include those with a combination
of proptosis, eyelid retraction, lagophthalmos .

 Ocular surface lubrication

 Increasing tear production via immunosuppression (cyclosporine,

loteprednol , fluorometholone )

 Decreasing tear evaporation by Increasing oil content of tears (Omega-3

fatty acids )

 Decreasing surface area for exposure and evaporation with eyelid surgery
- Lid retraction repair, Orbital decompression ,Lid tarsorrhaphy
 Punctal plugs
Treatment of lid Retraction
 The most commonly used non –surgical treatment options
include :
 a) Hyaluronic Acid:It is used in for treatment of upper eyelid

retraction due to its properties of being

reversible ,repeatable and [Link] mechanism of action is
thought to be a combination of mechanical effects such as
stretching,bursa formation and biological effects involved in
wound remodeling.A reduction in MRD1 from 1.7mm to
1.2mm after injection of 0.2 to 0.4ml of HA gel in upperlid
has been seen in a study by Manicuni etal.
 b)Botulinum toxin type A (BTA):It acts by inhibiting
acetylcholine release causing a neuromuscular blockage
effect .BTA is injected via transcutaneous or
transconjuctival route into the levator muscle .Typically 2.5
to 10units are injected per eyelid and effect is thought to
last for about 3 months.A marked improvement of MRD1
has been observed after BTA.
 C)Triamcinolone acetonide :
 TA injections in the upper

eyelid have been used to manage

retraction specifically .Most
groups employ a dose of 20mg via
subconjuctival injections.
A mean reduction of 2.19 mm
Of MRD1 has been seen after 6
Months post injection.
 MANAGEMENT OF INACTIVE STAGE

 Decompression surgery can alter globe positioning

 Decrease eyelid retraction, and affect extraocular motility

 It should precede any extraocular muscle or eyelid surgery.

Strabismus
 TED affects extraocular muscles in a predictable manner.
 The inferior rectus and medial rectus are most commonly involved.

 This presents as hypotropia and/or esotropia .

 Most patients with diplopia due to strabismus will not require surgical
intervention, as most can be effectively managed with prism spectacles .

 Indications for strabismus surgery
 Patients having intractable diplopia in primary gaze or with reading.
 Abnormal head positioning may be present.
 The position of the globe is cosmetically unacceptable.
Surgical approach
 Delay
strabismus surgery until disease stability has been
demonstrated.
 Recession of the affected muscles is the most commonly used
surgical method .
 Although diplopia is frequently improved post-operatively, normal

ocular motility is infrequently achieved for the following reasons

 Restrictive nature of myopathy

 Large muscle recessions

 Ongoing chronic disease

summary
 TED is an autoimmune disease associated mainly with hyperthyroidism,
but also with hypothyroid and euthyroid states.

 Smoking is the most significant modifiable risk factor.

 Early initiation of treatment will reduce the final severity of disease.

 Currenttherapeutic options include local supportive measures,

corticosteroids, external beam radiation and steroid-sparing
immunosuppressive agents for reducing the inflammation during active
disease, and surgery for correcting the residual abnormalities
secondary to fibrosis in the inactive state of the disease .
.

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