Thyroid eye disease is a condition in which the eye muscles, eyelids, tear glands and fatty tissues behind the eye become inflamed. Also known as:- Graves ophthalmopathy Thyroid associated ophthalmopathy Thyrotoxic exophthalmos and several other terms.

1. Thyroid Eye Disease
Dr Rahul Mahala
DNB Ophthalmology
Bokaro General Hospital, Bokaro
Jharkhand.

2. Thyroid eye
disease
• Thyroid eye disease (TED) is a very common
orbital disorder
• Most common cause of both bilateral and
unilateral proptosis in an adult between the
ages of 25 and 50 years
• Thyroid eye disease (TED) also known as:-
1) Graves ophthalmopathy
2) Thyroid associated ophthalmopathy
3) Thyrotoxic exophthalmos and several other
terms.

3. • Thyroid eye disease (TED) is an autoimmune inflammatory disorder involving the
soft tissues of the orbit.
• It is a self-limiting process.
• Most of patients with TED are hyperthyroid at presentation (90%).
• Some cases are associated with Hashimoto’s thyroiditis (3%).
• Primary hypothyroidism (1%).

4. Epidemiology
• Female > Male
• TED occurs 5 times more frequently in women.
• incidence of 16 per 100,000 in women and 3
per 100,000 in men.
• The age of presentation is bimodal, with peak
incidence rates occurring in the age groups of
40 to 44 years and 60 to 64 years in women.

5. Risk factors
• Smoking
• Tobacco
• Genetics
• Type of treatment for hyperthyroidism:-
Eg.Radioactive iodine
• Drugs
• Advanced age
• Smoking is the most important modifiable risk
factor.

6. Pathogenesis
• Pathological changes of TAO in the orbit appear
to involve both the extraocular muscles and the
orbital fat compartments
• Proptosis is due to expansion of orbital tissue
• The consequent increase in orbital pressure can
also lead to venous outflow congestion and
chronic periorbital oedema
• extraocular muscle enlargement is due to
deposition of glycosaminoglycan (GAG),
predominantly hyaluronic acid (HA).
• Hyaluronic acid which is hydrophilic and causes
edema in extraocular muscles

7. • Histology of extraocular muscles shows diffuse and focal lymphocytic
infiltrates and fibrosis, whereas orbital fat and connective tissue contains
few infiltrating cells.
• EFFECTOR CELL IN TAO:-
• Fibroblasts are the target cells in TAO
• They are extremely sensitive to stimulation by cytokines and
immunoglobulins
• Cellular immunity
• T cell infiltrates in TAO orbital tissues are predominantly CD4+,TCELLS
• Th1-like cytokine profile predominates in TAO retrobulbar tissue.

8. • Role of cytokines:-
• Interferon (IFN)-γ, tumour necrosis factor
(TNF)-α, IL-1β and IL-6 has been detected
mainly in TAO extraocular muscle.
• IL-4 and IL-10, Th2-type cytokines were
detected predominantly in orbital fat

9. • Increased prevalence of
HLA B8, DR-3 may
increase susceptibility to
TAO
• Higher frequency of HLA-
DRB1-16 allele in TRO
patients with severe extra
ocular muscle
involvement .

10. Clinical
features
• TED typically proceeds through a congestive
(inflammatory) stage in which the eyes are red and
painful.
• 10% of patients develop serious long term ocular
problems.
• A fibrotic (quiescent) stage follows in which the eyes are
white, although a painless motility defect may be
present.

11. Clinical features broadly can be categorized into:-
(i) soft tissue involvement
(ii) lid retraction
(iii) proptosis
(iv) optic neuropathy
(v) restrictive myopathy

12. Classification
for the
severity
• Classification for the severity of TED has been issued by
the European Group on Graves Orbitopathy (EUGOGO):-
• (i) sight-threatening due to optic neuropathy or corneal
breakdown
• (ii) moderate-severe, with one of moderate–severe soft
tissue involvement, lid retraction of 2 mm or more,
diplopia and proptosis of 3 mm or more.
• (iii) mild, with only a minor impact on daily life.

13. Werner
classification
• Werner classification reflects the severity of the
ophthalmopathy.
• Each grade is further subdivided as 0–4 and a–
c.
• Grade 0—No signs or symptoms
• Grade 1—Only signs (lid retraction)
• Grade 2—Soft tissue involvement (chemosis,
grit, etc.)
• Grade 3— Proptosis (minimum <23, moderate,
marked>28)
• Grade 4—Extraocular muscle involvement
• Grade 5—Corneal involvement
• Grade 6—Loss of sight.

14. Common
Signs of
Graves
Disease
• Lid retraction
• Lid lag (upper and lower)
• Infrequent blinking
• Exophthalmos
• Diplopia
• Lid oedema and chemosis
• Conjunctival injection over insertion of the
recti
• Increased intraocular pressure with
elevation
• Superior limbic keratopathy

15. Soft tissue
involvement
• Symptoms:-
• Grittiness
• red eyes
• Lacrimation
• photophobia,
• puffy lids
• retrobulbar discomfort.

16. • Signs:-
• 1)Epibulbar hyperaemia:-This is a
sensitive sign of inflammatory activity.
• Intense focal hyperaemia may outline the
insertions of the horizontal recti.
• 2)Periorbital swelling:caused by oedema
and infiltration behind the orbital septum,
this may be associated with chemosis and
prolapse of retroseptal fat into the eyelids

17. • Tear insufficiency and instability is common
• Corneal signs are exacerbated by lid
retraction and can include punctate
epithelial erosions, superior limbic
keratoconjunctivitis.

18. Lid retraction
• Retraction of upper and lower lids occurs in
about 50% of patients with Graves disease.
• Humorally induced overaction of Müller
muscle is postulated to occur as a result of
sympathetic overstimulation secondary to
high levels of thyroid hormones
• Contracture of the levator palpebrae and
inferior rectus muscles another
• probable mechanism

19. • Symptoms:-
• Staring or bulging eyed appearance
• Difficulty closing the eyes
• Ocular surface symptom
• Signs:-
• 1)The upper lid margin normally rests 2 mm below the
limbus
• scleral show
• 2) The lower eyelid margin normally rests at the
inferior limbus

20. • The Dalrymple sign is lid retraction in primary
gaze.
• The Kocher sign describes a staring and
frightened appearance of the eyes which is
particularly marked on attentive fixation
• The von Graefe sign signifies retarded
descent of the upper lid on downgaze

21. Proptosis
• Symptoms are similar to those of lid
retraction.
• Signs:-
• Proptosis is axial, unilateral or bilateral,
symmetrical or asymmetrical, and frequently
permanent.
• Severe proptosis may compromise lid
closure.
• Along with lid retraction and tear
dysfunction can lead to exposure
keratopathy, corneal ulceration and infection

22. • symmetrical
• Asymmetrical
• Bacterial keratitis due to severe exposure

23. Restrictive
myopathy
• Between 30% and 50% of patients with TED develop
ophthalmoplegia
and this may be permanent
• Symptoms:-Double vision, and often discomfort in some positions
of gaze.
• Signs:-
• Elevation defect caused by fibrotic contracture of the inferior
rectus.

24. • Abduction defect due to fibrosis of the
medial rectus, which may simulate sixth
nerve palsy.
• Depression defect secondary to fibrosis of
the superior rectus.
• Adduction defect caused by fibrosis of the
lateral rectus.

25. Optic neuropathy
• A fairly common (up to 6%) serious complication caused by compression
of the optic nerve or its blood supply at the orbital apex by the congested
and enlarged recti and swollen orbital tissue.
• Symptoms:-Impairment of central vision
• Signs:-Visual acuity (VA) is usually reduced, but not invariably.
• Colour desaturation is a sensitive feature.
• There may be diminished light brightness appreciation.
• A relative afferent pupillary defect.
• Visual field defects can be central or paracentral and may be combined
with nerve fiber bundle defects.
• The optic disc may be normal, swollen or, rarely, atrophic.

26. Investigation
• TSH
• Free thyroxine FT4
• Free thyroxine FT3
• Thyroid auto antibodies
• Visual fields
• Ct scan
• MRI
• Thyroid uptake scan or orbital biopsy are some
time required.

27. Treatment
• Treatment can be classified into that of mild disease,
moderate to severe active disease, and treatment of
post inflammatory complications.
• Stop smoking
• Mild disease:-
• Lubricants for superior limbic keratoconjunctivitis,corneal
exposure and dryness.
• Topical anti-inflammatory agents (steroids, non-steroidal
anti-inflammatory drugs (NSAIDs), ciclosporin) are
advocated by some authorities.
• Head elevation with three pillows during sleep to reduce
periorbital oedema.
• Eyelid taping during sleep may alleviate mild exposure
keratopathy.

28. • Moderate to severe active disease:-
• Clinical activity score:-EUGOGO suggests calculating a ‘clinical activity score’
• Determining a threshold for the use of immunosuppressive
• one point for each feature:-
• 1. Spontaneous orbital pain.
• 2. Gaze-evoked orbital pain.
• 3. Eyelid swelling considered to be due to active (inflammatory phase) TED.
• 4. Eyelid erythema.
• 5. Conjunctival redness considered to be due to active (inflammatory phase) TED.
• 6. Chemosis.
• 7. Inflammation of caruncle or plica.

29. • Systemic steroids are the mainstay of treatment for moderate to severe
disease.
• Oral prednisolone 60–80 mg/day may be given initially.
• Orbital steroid injections are occasionally used in selected cases to
minimize systemic side effects.
• Low-dose fractionated radiotherapy may be used.
• Combined therapy with irradiation, azathioprine and low-dose
prednisolone may be more effective than steroids or radiotherapy alone.
• Optic neuropathy, and corneal exposure, requires aggressive treatment.

30. • Several drugs targeting specific aspects of the immune response in TED
are under investigation, notably monoclonal antibody treatment with
rituximab.
• Post-inflammatory complications:-
• Surgery should be performed in-
• Proptosis
• Restrictive myopathy
• Lid retraction.