Thyroid eye disease (TED), also known as Graves' ophthalmopathy, is an autoimmune condition that affects the eyes and eyelids. It is commonly seen in patients with thyroid disease. The presentation can range from mild eyelid retraction to severe proptosis and optic neuropathy. The pathophysiology involves autoantibodies activating orbital fibroblasts and infiltrating lymphocytes, leading to inflammation and deposition of glycosaminoglycans in orbital tissues. Risk factors include smoking, female sex, and radioiodine treatment for hyperthyroidism. Clinical features depend on the stage of disease and can include dry eyes, eyelid swelling, proptosis, diplopia, and optic neuropathy. Classification systems consider soft tissue

1. THYROID EYE DISEASE
PRESENTED
BY
DR. AVURU CHUKWUNALU JAMES
9th July, 2020

2. OUTLINE
• Introduction
• Epidemiology
• Pathophysiology
• Risk factors
• Classification/clinical features
• Differential doagnosis
• Investigations
• Treatment

3. INTRODUCTION
. Its an autoimmune eye condition that is often seen
with thyroid disease,
• Also known with other names including:
1. Thyroid Eye Disease, sometimes abbreviated as TED
2. Graves' Ophthalmopathy
3. Thyroid-associated orbitopathy (TAO)
4. Grave's orbitopathy
5. Basedow's disease (in German speaking parts)
6. Parry’s disease- now outdated

5. INTRODUCTION CONTD
• TED is a part of an autoimmune process that can
affect the orbital and periorbital tissue, the thyroid
gland, and, rarely, the pretibial skin or digits
• It is the most common autoimmune disease of the
orbit
• Thyroid-associated orbitopathy is usually self-
limiting and associated with Graves disease

6. INTRODUCTION CONTD
• Ocular manifestations of thyroid disease constitute
a wide clinical spectrum, ranging from ocular
irritation, lid retraction, lid lag, and ocular injection
to infiltrative ophthalmopathy
• Graves’ disease is an autoimmune disorder that
affects the eyes, the thyroid gland, and rarely the
skin and joints.

7. INTRODUCTION CONTD
• Thyroid eye disorder is the most common
extrathyroidal manifestation of Graves’ disease,
• It is associated with hyperthyroidism in 90% of
cases and constitutes the commonest cause of
orbital and periorbital inflammation in adults.
• Up to 10% of patients may be euthyroid at the time
of onset of the eye disorder and about
• 3% may be hypothyroid

8. Introduction CONTD
• In a minority of cases, this condition complicates
Hashimoto thyroiditis
• More than 50% of patients with Graves’ disease
manifest the orbital complications characterized as
thyroid-associated orbitopathy

9. EPIDEMIOLOGY
• Women are affected up to eight times as often as
men. Sixty per cent of all patients have
hyperthyroidism. (Ten per cent of patients with
thyroid disorders develop Graves’ disease during
the course of their life)
• Graves’ disease is the most frequent cause of both
unilateral and bilateral exophthalmos
• Typically presents as Graves’ disease in the third
and fourth decade, with a four- to seven-fold
predominance in females.

10. EPIDEMIOLOGY CONTD
• Graves' disease has a prevalence of between 1 and
2.7%.
• For those with Graves' disease, there is an equal
risk between the sexes of developing ophthalmic
complications.
• Extrapolation of these figures gives an estimated
400,000 cases in the UK.

11. • IN USA; a rural Minnesota community, the annual
incidence rate was estimated at 16 cases per
100,000 women and 2.9 cases per 100,000 men.
• Sex- Various studies suggest that TAO affects
women 2.5-6 times more frequently than men.
• Severe cases of TAO occur more often in men than
in women.
• Age- TAO mostly affects patients aged 30-50 years.
Severe cases of TAO are believed to be more
frequent in patients older than 50 years.

12. EPIDEMIOLOGY IN IBADAN
;NIGERIA
• In a study "Ophthalmological Complications of Thyroid
Disease" done in Ibadan Southwestern Nigeria by
Olufunmilola A. Ogun and Jokotade O. Adeley
• A total of 75 patients with thyroid dysfunction were
evaluated, comprising 63 females and 12 males.
• There was a very low prevalence of smoking among patients
(<5%).
• Graves’ disease was the commonest thyroid disorder,
representing 70% of cases.
• Seventy-eight percent of patients were hyperthyroid, 11.8%
were euthyroid and only 9.8% of patients were hypothyroid.

13. EPIDEMIOLOGY IN
IBADAN;NIGERIA CONTD
• Two-thirds of patients reported ocular symptoms
consisting mainly of painless eye swelling (66.7%) and
ocular irritation (58%)
• Conjunctival injection, lid lag and lid retraction were
the commonest ocular signs.
• Chemosis, severe proptosis and ocular motility disorder
were very rare.
• Optic neuropathy was found in 4 patients but was
related to pre-existing glaucoma.
• Majority of patients required only ocular emollients
and tear supplements.

14. PATHOPHYSIOLOGY
• It involves an organ-specific autoimmune reaction
in which an antibody that reacts against thyroid gland
cells and orbital fibroblasts leads to inflammation of
• extraocular muscles,
• interstitial tissues,
• orbital fat and
• lacrimal glands
• characterized by pleomorphic cellular infiltration,
associated with increased secretion of
glycosaminoglycans and osmotic imbibition of water

15. Pathophysiology contd
• An IgG autoantibody called LATS (long acting thyroid
stimulant) attaches to the TSH receptors on the
thyroid gland with a more prolonged and potent
effect than TSH and without the negative feedback.
• There is a postulated exophthalmos producing factor
(EPS) but it has not been identified.
• TSH receptors have been found in the eye and
affected skin.
• Antibodies, cell mediated immunity and cytokines are
thought to be involved.

16. • The high correlation between Graves’ disease and
orbital disease suggests a shared antigen, such as TSH
receptor, thyroglobulin or thyroid peroxidase.
• Activation of orbital fibroblasts by Graves' disease-
related autoantibodies, leads to the release of T cell
chemoattractants,
• Circulating activated T lymphocytes infiltrate the
orbital tissues, where they release cytokines which, in
turn, stimulate proliferation of fibroblasts and
deposition of glycosaminoglycans (GAGs).

17. • The cytokines activate previously quiescent
fibroblasts to secrete hyaluronic acid, a
glycosaminoglycan.
• Doubling the hyaluronic acid content in the orbital
tissue causes a 5-fold increase in the tissue osmotic
load.
• In addition, preadipocyte fibroblasts are influenced
to transform into adipocytes, especially in young
patients.

18. • INFLAMMATORY CELLULAR INFILTRATES;
• infiltration with lymphocytes, plasma cells,
macrophages, and mast cells of the interstitial
tissues, orbital fat, and lacrimal glands with
accumulation of GAG and retention of fluid occurs.
• There is an increase in the volume of the orbital
contents, particularly the muscles, which can swell
to eight times their normal size.
• May lead to proptosis.

19. Pathophysiology Contd
• There may be a secondary elevation of intraorbital
pressure,
• The optic nerve may be compressed.
• Subsequent degeneration of muscle fibres
eventually leads to fibrosis(which exerts a tethering
effect on the involved muscle, resulting in
restrictive myopathy and diplopia)

20. Findings for further studies
• The insulin-like growth factor 1 receptor is an
autoantigen that may be important in TAO because
of its aberrant expression by TAO fibroblasts, the
promotion of T-cell recruitment, and the presence
of circulating activated autoantibodies.
• T helper 2 cytokines (IL-4 and IL-13) may induce the
expression of 15-lipoxygenase-1, with up-regulation
in the production of 15-hydroxyeicosatetraenoic
acid (15-HETE), causing tissue activation and
remodeling.

21. • Cyclooxygenase 2 (COX-2) is expressed at higher
levels in the orbital fibroadipose tissues of TAO.
• There is a positive correlation with increasing
severity of orbital disease, suggesting a possible
relationship with COX-2 expression and orbital
inflammation in TAO.

22. POOR PROGNOSTIC FACTORS
• The disease tends to be more severe
1. In males
2. In smokers,
3. The elongated myopic globe is at greater risk of
exposure keratopathy,
4. A tight orbit without proptosis is at greater risk of
compressive optic neuropathy
5. Age more than 50 years

23. RISK FACTORS
• Smoking - Once a patient has Graves' disease, the
major clinical risk factor for developing thyroid eye
disease is smoking. Patients with thyroid eye
disease are four times more likely to be smokers or
former smokers than never smokers. The greater
the number of cigarettes smoked per day, the
greater the risk of developing thyroid eye disease,
and giving up smoking seems to reduce this risk.
Cigarette smoking also increases the risk for
progression of ophthalmopathy after radioiodine
therapy.

24. RISK FACTORS CONTD
• GENES
• No single gene has been identified that is sufficient
and necessary for the development of thyroid eye
disease, and the genetics of thyroid eye disease has
been described as “a play in search of a cast of
characters”.
• Multiple genes are likely to be involved in the
development of thyroid eye disease, and these
interact with multiple environmental risk factors.

25. RISK FACTORS CONTD
• RADIOIODONE; Strong evidence exists that
radioiodine, which is used to treat the
hyperthyroidism, can cause a flare in thyroid eye
disease, although some controversy remains as to
what degree radioiodine worsens thyroid eye
disease
• SEX

26. CLINICAL FEATURES
• Hales and Rundle described the natural history of
dysthyroid eye disease, with the disease typically
peaking after six months and active inflammation
resolving within 18 months.
• Of 67 patients followed for an average of 15 years,
those with gross eye disease persisting for more
than six months after control of thyroid status had
a worse outcome.

27. CLINICAL FEATURES CONTD
• TAO usually has a self-limited course over 1 or more
years. Stable TAO can occasionally reactivate, but
this is uncommon.
• Signs and symptoms may vary and depend on the
stage that the patient is experiencing.
• Initially, an acute or subacute stage of active
inflammation occurs.
• Later, the patient progresses to a more quiescent
stage, which is characterized by fibrosis.

28. CLINICAL FEATURES(CF); Ocular
symptoms
• Dry eyes
• Puffy eyelids
• Angry-looking eyes
• Bulging eyes
• Diplopia
• Visual loss
• Field loss
• Dyschromatopsia
• Photopsia on upgaze
• Ocular pressure or pain

29. CF; SYSTEMIC(Symptoms of
Hyperthyroidism)
• Tachycardia/palpitations
• Nervousness
• Diaphoresis – excessive sweating
• Heat intolerance
• Skeletal muscle weakness
• Tremor
• Weight loss
• Hair loss
• Irritability
• Goiter

31. CF; SYSTEMIC(symptoms of
hypothyroidism)
• Bradycardia
• Drowsiness
• Poor mentation
• Muscle cramps
• Weight gain
• Dry skin
• Husky voice
• Depression
• Cold intolerance

32. CLASSIFICATION SYSTEM
• Numerous classification systems for TAO exist, but
they all have shortcomings.
• The simplest classification for TAO is type I and type
II.
• Type I is characterized by minimal inflammation and
restrictive myopathy.
• Type II is characterized by significant orbital
inflammation and restrictive myopathy.
• Type I and type II orbitopathy are not mutually
exclusive.

33. CLASSIFICATION CONTD
• Type I orbitopathy is characterized as
predominantly fat deposition
• Type II orbitopathy involves predominantly
extraocular muscle enlargement
• These changes are visualized on orbital imaging
performed with computerized tomography or
magnetic resonance imaging scans.

34. CLASSIFICATION CONTD(Course)
• A congestive (inflammatory) stage in which the
eyes are red and painful.
• This tends to remit within 1–3 years
• Only about 10% of patients develop serious long-
term ocular problems.
• A fibrotic (quiescent) stage follows in which the
eyes are white
• A painless motility defect may be present.

35. CLASSIFICATION; based on Clinical
features
• Soft tissue involvement
• Lid retraction
• Proptosis
• Optic neuropathy
• Restrictive myopathy

36. CLASSIFICATION; CF; Soft tissue
involvement
• Indicated by presence of Grittiness, red eyes, lacrimation,
photophobia, puffy lids and retrobulbar discomfort.
• Epibulbar hyperaemia; insertions of the horizontal recti may
be outlined in intense focal hyperaemia
• Periorbital swelling; is caused by oedema and infiltration
behind the orbital septum
• Tear insufficiency and instability
• Corneal signs such as punctate epithelial erosions, superior
limbic keratoconjunctivitis and occasionally bacterial keratitis,
thinning and scarring.

38. CF; Soft tissue; Conjunctival signs
• Deep injection especially on the temporal aspect.
Goldheizer (1900), Sattler (1909), Ohlemann (1910).
• Enlarged vessels may be visible & their appearance
suggests that they result from venous stasis
secondary to increased tissue-pressure within the
orbit.
• Chemosis may eventually occur
• Superior limbic keratoconjuntivitis
• Keratoconjunctivitis sicca

39. CLASSIFICATION; CF; Lid retraction
• Retraction of upper and lower lids occurs in about 50% of
patients with graves disease
• Occurs due to
• Overaction of Müller muscle as a result of sympathetic overstimulation
secondary to high levels of thyroid hormones
• Fibrotic contracture of the levator palpebrae and inferior rectus
muscles associated with adhesion to overlying orbital tissues
• Retraction is suspected when sclera shows below the limbus.
• Lid retraction is suspected when the margin is either level with or
above the superior limbus
• Lid retraction may occur in isolation or in association with
proptosis,

40. CF; Eyelid Signs
• Dalrymple’s sign- Lid retraction in primary gaze.
Upper eyelid is retracted with visible sclera superior
to the limbus and widened palpebral fissure
• von Graefe’s sign of lid lag (1864)- Upper eyelid
retracts when the eye depresses (overactive muscle
of Müller)
• Stellwag’s sign (1869) - Infrequency and
incompleteness of the blinking reflex. By allowing dry
eyes, may accentuate keratitis.
• Kocher’s sign- staring and Frightened gaze

42. CF; Eye lid signs Contd
• Grove sign (resistance to pulling down the retracted upper lid)
• Vigouroux sign (eyelid fullness)
• OTHER EYELID SIGNS include
• Boston’s sign: The downward movement of the upper lid is jerky and
uneven and does not correspond to that of the eye.
• Griffith’s sign (1886): lower lid lag on upgaze
• Globe lag of Means (1945): On upgaze, the upper lid tends to move
before and faster than the globe exposing the sclera above the globe
• Joffroy’s sign: on upgaze the normal creases are absent from the
forehead
• Sainton’s sign: The frontalis contracts after the levator has ceased to
act.

43. CF; Other lid signs
• Rosenbach’s sign: On gentle closure, a trembling of
the lids may be evident
• Enroth’s sign: Fullness of the lids due to puffy
oedematous swelling. Due to increased bulk of the
orbital contents, oedema & accumulation of mucin.
• Gifford’s sign (1906)- Upper eyelid is difficult to
evert (due to eyelid edema)
• Jellinek’s sign: Upper lids may show an abnormal
pigmentation.

44. CLASSIFICATION;CF; Proptosis
• Axial, unilateral or bilateral, symmetrical or
asymmetrical
• Frequently permanent
• Symptoms are similar to those of lid retraction.
• Its at first reducible on firm pressure or on
orbitonometry but recurs on release
• When marked, may compromise lid closure leading
to exposure keratopathy

46. CF; Assesment of proptosis
• Viewing the apices of the corneae from above the head
gives an accurate assessment of the relative
prominence of one eye
• Direction of the proptosis
• Severity of proptosis: Normal distance of the apex of
the cornea from the outer rim of the orbit is 10-21mm.
It should not exceed 2mm between the two eyes.
• Absolute reading of 22mm and above is considered as
proptosis while less than 10-12 mm is indicative of
enophthalmos

48. CF; Proptosis; Types of
exophthalmometry
• 3 types exist
• Absolute exophthalmometry- result is compared with a known
normal value
• Comparative exophthalmometry- results are compared from time
to time
• Relative exophthalmometry- results of the 2 eyes are compared
COMMON INSTRUMENT TYPES
• Meter rule
• Leudde exophthalmometer (1938)- thick transparent rule shaped
to rest on the lateral orbital rim
• Hertel exophthalmometer (1905)
• Naugle exophthalmometers

49. CLASSIFICATION; CF; Restrictive
myopathy
• Between 30% and 50% of patients with TED
develop ophthalmoplegia and this may be
permanent.
• Restricted initially by inflammatory oedema
• Motility restricted later by Fibrosis of EOM
• Double vision and often discomfort in some
positions of gaze may ensue

51. CLASSIFICATION; CF; Restrictive
myopathy Contd
• Order of involvement; Elevation defect(inferior
rectus) > Abduction defect( medial rectus) >
Depression defect(superior rectus) > Adduction
defect (lateral rectus)
• Graves disease may occur in association with
myasthenia gravis

52. CF; motility signs
• Moebius’s sign (1886-1891): Weakness in convergence
for near objects
• Suker’s sign (1917): Inability to maintain fixation on
extreme lateral rotation of the eyes.
• Ballet’s sign (1888): Partial or complete immobility of
one or all of the extraocular muscles without internal
ophthalmoplegia.
• Usually initial limitation of elevation followed by a
limitation of lateral movements & the eye may
eventually become fixed in depression. (Fells et al 1979)

53. CLASSIFICATION; CF; Optic
neuropathy
• Fairly common (up to 6%) serious complication
caused by compression of the optic nerve or
its blood supply
• Leads to Impairment of central vision
• To detect early involvement, advise patient to
monitor their own visual function by alternately
occluding each eye; read small print and assess
the intensity of colours, for example on a
television screen.

55. CF; Signs of Optic neuropathy
• Visual acuity (VA) is usually reduced
• Colour desaturation
• Diminished light brightness appreciation
• A relative afferent pupillary defect
• Visual field defects can be central or paracentral
and may be combined with nerve fibre bundle
defects.
• Optic disc may be normal, swollen or, rarely,
atrophic.

56. CF; Pupillary signs
• Kneis’s sign: Inequality of dilatation of the pupils
• Cowen’s sign: Jerky pupillary reaction on eliciting
the concensual light reflex
• Loewi’s sign: a ready pupillary dilatation with
adrenaline

57. “NO SPECS” classification of thyroid
eye disease, abbreviated from
Werner
• Class 0: No signs or symptoms
• Class 1: Only signs (limited to upper lid retraction
and stare, with or without lid lag)
• Class 2: Soft tissue involvement (oedema of
conjunctivae and lids, conjunctival injection, etc)
• Class 3: Proptosis
• Class 4: Extraocular muscle involvement (usually
with diplopia)

58. “NO SPECS” classification of thyroid
eye disease, abbreviated from
Werner
• Class 5: Corneal involvement (primarily due to
lagophthalmos)
• Class 6: Sight loss (due to optic nerve involvement)
• NO SPECS – is based on severity

59. Werner’s “NOSPECS”
classification
• Werner's NOSPECS classification system (and its
modifications) is one of the most commonly known
systems and is used in many endocrine studies.
• Unfortunately, patients may fall into more than one
particular class.
• Patients may not progress in an orderly fashion from
class 1 to class 6. Patients with visual loss from
compressive optic neuropathy may not show marked
proptosis or other signs of severe disease.
• As with other classification systems, it may be of
limited prognostic value.

60. classifications based upon the
degree of inflammation
• A simple “activity score” may be assigned by
awarding one point for each of retrobulbar pain,
pain on eye movement, eyelid erythema, eyelid
oedema, conjunctival injection, conjunctival
chemosis, caruncular swelling, deteriorating vision,
diplopia and worsening appearance; an activity
score of 3 or more (out of 10) indicates active
disease.
• such as that of Mourits or that of others

61. Clinical activity score
• A score of 1 is given for each feature present.
• Pain
• Painful, oppressive feeling on or behind the globe
during the last 4 weeks
• Pain on attempted up, side or down gaze during the
past 4 weeks
• Redness
• Redness of the eyelid(s)
• Diffuse redness of the conjunctiva, covering at least
one quadrant

62. • Swelling
• Swelling of the eyelid(s)
• Chemosis
• Swollen caruncle
• Increase by 2 mm or more in proptosis during a
period of one to three months

63. Impaired function
• Decrease in eye movements in any direction of 5
degrees or more during a period of one to three
months
• • Decrease in visual acuity (1 or more lines on
Snellen chart, using a pinhole) during a period of
one to three months
• The clinical activity score can be used to assess
disease progression and help guide
immunosuppressive treatment

64. • Proptosis- Exophthalmometry
(CT or MRI scan may also be used for
measurement)
• Optic nerve activity score - Visual acuity, fields and
colour vision.
• Sum one point for each of the following: spontaneous
retrobulbar pain; pain with eye movement; eyelid
erythema; eyelid oedema; conjunctival injection;
conjunctival chemosis; caruncular swelling

65. Emergency features
• An objective deterioration in visual acuity, reduced
colour perception, an acquired visual field defect,
impaired visual-evoked potentials or corneal
ulceration are signs of serious sight-threatening
disease for which urgent intervention is essential.

67. Mourits and others “activity
score”
• Eyelid- Maximal fissure width. Upper lid to limbus
distance and lower lid to limbus distance
• Cornea - Exposure keratopathy assessed by Rose Bengal
or fluorescein staining (indicate presence or absence of
staining)
• xtraocular muscles - Binocular single vision in central
30° field (indicate presence or absence, with or without
prisms) and one or more of the following measurement
techniques: Maddox rod test; alternate cover test; Hess
chart or Lancaster red–green test. Optional: intraocular
pressures, CT scan or MRI scan

68. Patient self-assessment
• Satisfaction with the following (indicate change of
each with therapy, using a scale such as “greatly
improved, improved, unchanged, worse, much
worse”):
• appearance;
• subjective visual function;
• ocular discomfort;
• diplopia

69. Management
• History
• Exam findings ;as above
• Investigations
• Treatment

70. INVESTIGATIONS-Laboratory
• BLOOD
• In screening for thyroid disease, the combination of
free T4 (thyroxine) and TSH (thyroid-stimulating
hormone) or serum TSH (thyrotropin) are highly
sensitive and specific. However, because of cost, some
recommend initially only using the TSH to screen for
thyroid disease.
• Serum TSH (thyrotropin) is useful to establish a
diagnosis of hyperthyroidism or hypothyroidism.
Usually, the TSH is low in hyperthyroidism and high in
hypothyroidism.

71. INVESTIGATION; Laboratory; Assay
• Assays that measure the binding of TSH to a
solubilized receptor are often referred to as TRAb
(thyroid receptor antibody), TBII (TSH-binding
inhibitor immunoglobulin), and LATS (long-acting
thyroid stimulator) assays.
• Assays that measure the ability of immunoglobulin
G (IgG) to bind to the TSH receptor on cells and to
stimulate adenylate cyclase production have
generally been referred to as the TSI (thyroid-
stimulating immunoglobulin

72. INVESTOGATIONS; Laboratory;
Others
• calculated free T4 (thyroxine) index, thyroid-
stimulating immunoglobulin, antithyroid
antibodies, and serum T3 (triiodothyronine). The
introduction of direct assays for TSH, free T4, and
free T3 has superseded the usefulness of total T4
and T3 resin uptake testing.
• Thyroid peroxidase antibodies and antibodies to
thyroglobulin may be useful when trying to
associate eye findings with a thyroid abnormality,
such as euthyroid Graves disease.

73. • The thyroid peroxidase test is also called the
antimicrosomal antibody test and the antithyroid
microsomal antibody test.
• The antithyroglobulin test is also called the
antithyroid antibody test.
• The serum level of hyaluronase is not a sensitive
indicator of its presence within the extraocular
muscles.

74. INVESTIGATIONS; Imaging studies
• Ultrasound
• Orbital ultrasound can quickly confirm if the patient has
thickened muscles or an enlarged superior ophthalmic
vein.
• CT scan and MRI
• If the diagnosis of TAO can be established clinically, then it
is not necessary to routinely order a CT scan or an MRI.
• If the above studies are required, obtain axial and coronal
views.

75. Neuroimaging
• Thick muscle with tendon sparing; The inferior rectus
muscle and the medial rectus muscle usually are involved.
• Isolated rectus muscle involvement may occur in up to 6%
of patients.
• Isolated lateral rectus muscle enlargement without other
evidence of muscle enlargement is uncommon in TAO but
suggests another disease process (eg, orbital myositis).
• Bilateral muscle enlargement is the norm; unilateral cases
usually represent asymmetric involvement rather than
normality of the less involved side.

77. INVESTIGATIONS-Imaging contd
• Neuroimaging may show a dilated superior
ophthalmic vein.
• Apical crowding of the optic nerve is well visualized
on neuroimaging.
• MRI is more sensitive for showing optic nerve
compression.
• CT scan is performed prior to bony decompression
because it shows better bony architecture.
• Occasionally, the proptosis of TAO results in
straightening of the optic nerve.

78. Histologic Findings
• Lymphocytic cell infiltration
• Enlargement of fibroblasts
• Accumulation of mucopolysaccharides
• Interstitial edema
• Increased collagen production
• Fibrosis with degenerative changes in the eye muscles

79. DIFFERENTIAL DIAGNOSIS
• Thyroid Eye Disease (most common cause in adults)
• Orbital Tumor
• Orbital Inflammatory Pseudotumor
• Carotid-Cavernous Sinus Fistula
• Retrobulbar Hemorrhage
• Trauma with Orbital Fracture
• Orbital Cellulitis
• Sarcoidosis
• Myaesthenia gravis

80. TREATMENT- Multidisciplinary
• Due to the complexity of the condition, the need for
careful management of any underlying thyroid
dysfunction, the potential threat to vision and the toxic
side effects of many of the therapies, close cooperation
between an
• ophthalmologist and an endocrinologist is
required. Ideally both should have a special interest in
thyroid eye disease and there is a
• strong case for seeing these patients in a joint clinic
so that medical and surgical management can be
carefully coordinated

81. Treatment
• General measures
• Medical
• Surgical

82. European Group on Graves
Orbitopathy (EUGOGO)
1. Sight-threatening; due to optic neuropathy or
corneal breakdown
2. Moderate–severe, with one of moderate–
severe
• soft tissue involvement,
• lid retraction of 2 mm or more,
• Diplopia(8 degree or more of restriction in motility)
• proptosis of 3 mm or more;
3. Mild; with only a minor impact on daily life.

83. • Inform patients that TAO usually runs a self-limited but
prolonged course over 1 or more years. Patients also
should realize that no immediate cure is available.
• Most patients with TAO can be observed; the follow-up
interval depends on disease activity.
• Monitor for visual loss from corneal exposure and optic
neuropathy and for strabismus development.
• Visual field and color vision testing may help in early
detection of visual loss.
GENERAL TREATMENT

84. GENERAL TRATMENT CONTD
• If a patient has dry eye symptoms, consider using
artificial tears during the day, lubricating ointment
at night, and punctal plugs.
• Sleeping with the head of the bed elevated may
decrease morning lid edema.
• Encourage patients to stop smoking to decrease the
risk of congestive orbitopathy.
• In patients with diplopia, prisms may be beneficial
to those with small-angle and relatively comitant
deviations.

85. Treatment; Mild disease
• Lubricants; superior limbic keratoconjunctivitis,
corneal exposure and dryness.
• Topical anti-inflammatory agents(NSAIDs, Steroids,
ciclosporin)
• Head elevation with three pillows during sleep;
reduces periorbital oedema.
• Eyelid taping during sleep; alleviates mild exposure
keratopathy.

86. TREATMENT; Moderate–severe
active disease
• Clinical activity score of 3 or more out of 7 ( i.e after
proptosis, diplopia, decrease in vision has been
ruled out...sight threatening)
• Systemic steroids are the mainstay of treatment
for moderate–severe disease.
• Oral prednisolone 60–80 mg/day may be given initially
and tapered depending on response.
• Intravenous methylprednisolone is often reserved for
acute compressive optic neuropathy
• Orbital steroid injections (less effective than systemic)

87. TREATMENT; Moderate–severe
active disease contd
• Low-dose fractionated radiotherapy
• Used in addition to steroids or when steroids are
contraindicated or ineffective
• Has delayed effect and so not used alone as sole
treatment
• positive response is evident within 6 weeks
• Maximal improvement by 4 months;
• About 40% of patients will not respond
• Combined therapy with irradiation, azathioprine
and lowdose prednisolone may be more effective
than steroids or radiotherapy alone.

88. • such as etanercept, infliximab, and daclizumab, have
been used in patients with TAO, but more studies are
required to determine their adverse effect profile as
compared to steroids. Octreotide, pentoxifylline,
nicotinamide, plasmapheresis, and intravenous
immunoglobulin are not mainstream medical
treatments of TAO.
• Octreotide, a potent synthetic somatostatin analogue,
has a beneficial effect in TAO, especially in patients with
a positive Octreoscan-111. Lanreotide is a longer-acting
somatostatin analogue, which is administered only
once every 2 weeks; it may provide some benefit.
Antitumor necrosis factor drugs

89. • Pentoxifylline and nicotinamide may be useful. Both
agents are believed to inhibit cytokine-induced
glycosaminoglycan synthesis by the retroorbital
fibroblasts.
• The role of plasmapheresis and intravenous
immunoglobulin (IV Ig) is not well delineated. One
randomized trial of IV Ig (1 g /kg body weight for 2
consecutive d q3wk) versus oral prednisolone (for 20
wk with initial dose of 100 mg/d) showed both
treatments to be equally effective in patients with
active TAO. Fewer adverse effects were observed in the
IV Ig treatment group.

90. Orbital radiation
• This procedure sometimes is prescribed for moderate-
to-severe inflammatory symptoms, diplopia, and visual
loss in patients with TAO.
• The radiation (1500-2000 cGy fractionated over 10 d)
usually is administered via lateral fields with posterior
angulation. Radiation is believed to damage orbital
fibroblasts or perhaps lymphocytes.
• Radiation requires several weeks to take effect, and it
may transiently cause increased inflammation. Thus,
most patients are maintained on steroids during the
first few weeks of treatment.

91. Orbital radiation contd
• Better response to radiation is observed in patients
with active inflammation who are treated within 7
months of TAO onset. Radiation may be more
effective if combined with steroid treatment.
• Cataract, radiation retinopathy, and radiation optic
neuropathy are possible risks. They are not
common if treatment is appropriately fractionated
and the eyes are shielded.

92. TREATMENT-sight-threatening
• Aggressive treatment for Optic neuropathy and
corneal exposure
• Pulsed intravenous methylprednisolone (commonly
used).
• Regimens including 0.5–1 g on 3 successive days
with conversion to oral treatment such as 40 mg/day
prednisolone.
• Monitor Patients including their liver function tests, give
gastric protective treatment and osteoporosis
prophylaxis.

93. TREATMENT-optic nerve
compression
• Orbital wall decompression and/or orbital apex
decompression may be considered if steroids are
ineffective
• Orbital radiotherapy may be administered(used as
an adjunct to other modalities)

94. TREATMENT; optic nerve
compression; immunotherapy
• Drugs under investigation, notably
• monoclonal antibody treatment with
1. Rituximab and
2. Teprotumumab.
• Teprotumumab is an inhibitor of insulin-like growth
factor 1 receptor (IGF-1R) and is effective in reducing
proptosis and the Clinical Activity Score in patients
with TED.

95. TREATMENT; Proptosis.
• Residual proptosis after active inflammation has
remitted can have cosmetic and functional
problems.
• For significant proptosis, the treatment of is
surgical.
• Surgical decompression increases the volume of
the orbit by removing the bony walls and may
be combined with removal of orbital fat

96. TREATMENT; Restrictive myopathy
• Surgery(recti muscle recession) is required in most
cases when pt experiences
• persistent diplopia in the Primary and reading positions
of gaze
• provided the inflammatory stage has subsided
• Angle of deviation has been stable for at least 6–12
months.
• Diplopia may be alleviated, with prisms or
sometimes botulinum toxin if above criteria not
met

97. TREATMENT; Lid retraction
• Mild lid retraction frequently improves
spontaneously(does not require treatment)
• Control of hyperthyroidism may be beneficial.
• Botulinum toxin injection to the levator
aponeurosis and Müller muscle (temporary
measure)
• Lid surgery

98. Surgical Care
• Approximately 5% of patients may require surgical
intervention.
• The patient should know that multiple-staged
procedures may be required.
• In elective cases, listen carefully to what the patient
desires; the patient's expectations may not be realistic.
• The timing of surgery is important.
• Unless compressive optic neuropathy or severe corneal
exposure is present, surgery generally is delayed during
the active inflammatory phase of TAO.

99. Surgical care contd
• Surgery usually is performed during the quiescent
cicatricial phase of the disease.
• Taking preoperative photographs is advised.
• With strabismus surgery, document prism
measurements or fields of binocular single vision.
• Recording baseline-automated perimetry also is useful.
• The sequence of surgery is important.
• If the patient has marked proptosis, strabismus, and lid
deformity, perform surgery in the following order

100. ORDER OF SURGERY
• Orbital decompression
• Strabismus surgery
• Lid-lengthening surgery
• Blepharoplasty

101. Surgical care; Orbital
decompression
• Thoroughly explain the potential complications of
orbital decompression (eg, blindness, hemorrhage,
diplopia, periorbital numbness, globe malposition,
sinusitis, lid malposition) to the patient before surgery.
• Orbital decompression may be performed as the initial
treatment of compressive optic neuropathy or used if
medical treatment is ineffective. A combination of
medical and surgical treatment may be required in
compressive optic neuropathy.

102. SURGICAL CARE; orbital
decompression; procedure
• To decompress the optic nerve, at least 2 orbital walls
usually are decompressed
• Medial decompression for compressive neuropathy
must be taken posteriorly all the way to the apex of the
optic canal.
• Surgery can be approached from a transorbital or trans-
sinus route. Transorbital routes include subciliary
incisions, lid crease incisions, medial incisions
(cutaneous, transcaruncular), and coronal incisions.
Trans-sinus routes include transantral approaches and
endoscopy.

103. Orbital decompression contd
• One-wall (deep lateral) decompression is effective
(approximately 4–5 mm reduction in proptosis)
• Two-wall (balanced medial and lateral
decompression(3-6mm)
• Three-wall decompression includes the floor with
a reduction in proptosis of 6–10mm
• Four- wall decompression removal of part of the
orbital roof in addition(10-16mm of globe
retropulsion)

105. TREATMENT; Surgical care;
Strabismus surgery
• generally is delayed until TAO is inactive and the
prism measurements have been stable for at least 6
months.
• Patients should realize that the goal of surgery is to
minimize diplopia in primary and reading positions.
Expecting binocular single vision in all positions of
gaze may not be realistic. Patients also should
realize that multiple strabismus surgeries and
prisms may be required

106. Surgical Care; Strabismus surgery;
Inferior rectus muscle recession
• Surgery of the inferior rectus muscle deserves special
mention.
• It may decrease upper lid retraction, but it often results
in lower lid retraction despite dissection of the lower
lid retractors.
• Because the inferior rectus muscle has subsidiary
actions (excyclotorsion and adduction), inferior rectus
muscle recessions may lead to a component of
intorsion and A-pattern strabismus.

107. Botulinum toxin injections
• Botulinum toxin injections are used by some
clinicians during the acute phase of TAO as a
temporizing measure until orbital decompression
can be completed.
• Optic neuropathy following a botulinum
toxin injection for strabismus in a patient with TAO
has been reported.

108. Lid-lengthening surgery
• If restoration of the euthyroid state does not improve
lid retraction, consider lid-lengthening surgery. This
surgery decreases corneal exposure and can be used to
camouflage mild-to-moderate proptosis.
• Lateral tarsorrhaphies can decrease upper and lower lid
retraction
• Two to three millimeters of upper lid retraction can be
ameliorated with a Müller muscle excision. Lateral
levator tenotomy is often helpful to decrease the
temporal flare. If further amounts of lid recession are
required, levator recession can be considered

109. Blepharoplasty
• This is the last phase of restorative surgery in TAO.
Lower lid blepharoplasty can be approached
transconjunctivally if no excess lower lid skin is
present.
• Upper lid blepharoplasty is performed
transcutaneously with conservative skin excision.
Brow fat resection may be considered. Dacryopexy
may be required if lacrimal gland prolapse occurs.

110. CONCLUSION
• Thyroid eye disease is an important endocrine
condition that manifests in the orbits
• Presentation might be first to the ophthalmologist
• Adequate skills to ensure accurate dagnosis and
follow up with intervention when appropriate is
essential
• Co-management with other specialist such as the
endocrinologist is the rule

111. References
• Kanski’s Clinical opthalmology; A systmatic approach,
9th Ed, thyroid eye disease,P. 119-125
• Thyroid associated orbitopathy;Edsel B ln, MD, Mph,
FRSC;
https://emedicine.medscape.com/article/1218444-
overview#:~:text=Thyroid-associated%20orbitopathy
• Thyroid Eye disease- Eyewiki;
https://eyewiki.aao.org/Thyroid_Eye_Disease
• Severe Ophthalmological Complications of Thyroid
Disease are Rare in Ibadan, Southwestern Nigeria:
Results of a Pilot Study, Olufunmilola A. Ogun and
Jokotade O. Adeleye;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481
1264/

112. REFERENCES contd
• Bartley, G. B. (1994). The epidemiologic
characteristics and clinical course of
ophthalmopathy associated with autoimmune
thyroid disease in Olmsted County,
Minnesota. Transactions of the American
Ophthalmological Society, 92, 477.
• Menconi, F., Marcocci, C., & Marinò, M. (2014).
Diagnosis and classification of Graves'
disease. Autoimmunity reviews, 13(4-5), 398-
402.

113. References Contd
• Thornton, J., Kelly, S. P., Harrison, R. A., &
Edwards, R. (2007). Cigarette smoking and
thyroid eye disease: a systematic
review. Eye, 21(9), 1135-1145.
• Mizokami, T., Wu Li, A., El-Kaissi, S., & Wall, J.
R. (2004). Stress and thyroid
autoimmunity. Thyroid, 14(12), 1047-1055.
• Phelps PO, Williams K. Thyroid Eye Disease for
the Primary Care Practitioner. Disease-a-Month
60(2014)292–298. [PMID 24906675]

114. THANK YOU