THYROID EYE DISEASE

THYROID EYE DISEASE

1. THYROID EYE THYROID EYE
DISEASEDISEASE
DR K HARIPRIYA
SSSIHMS

2. Also known as TRO / Graves’ orbitopathy
Self-limiting auto-immune process
Mild to severe irreversible sight threatening disease
Graves' disease is the most common thyroid
abnormality
Other associations include Hashimoto's thyroiditis,
thyroid carcinoma, primary hyperthyroidism, and
neck irradiation

3. EPIDEMIOLOGY EPIDEMIOLOGY
Most common disease affecting the orbit
Female to Male ratio 9.3:1 (mild cases)
 1.4:1 (severe cases)
Severe cases more frequent in >50 yr age group
Cigarette smoking is the strongest modifiable risk
factor
Myasthenia gravis is 50 times more common in
patients with TAO

4. ETIOLOGYETIOLOGY
80% are clinically hyperthyroid and 10% are clinically
euthyroid
◦Associated with normal to abnormal thyroid function
In patients who are hyperthyroid, eye signs of TAO
usually develop within 18 months

5. Smokers have a 5 time higher risk of developing
TAO
Cawood and colleagues have established that orbital
fibroblasts when exposed to cigarette extract
showed an increased production of
Glycosaminoglycans
There is evidence that cessation of smoking reduces
the risk of progression of orbitopathy

6. A 6.4 times risk for development of orbitopathy in
Europeans compared to Asians *
Genetic predisposition
20-60% - positive family history of thyroid disease
Concordance level is 50% in identical twins
* Tellez et al.Clin Endocrinol 1992

7. • 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 **
**Akaishi et al. Thyroid 2008

8. PATHOGENESISPATHOGENESIS

10. PATHOGENESIS PATHOGENESIS
Immune mediated inflammatory reaction
 Circulating auto antibodies like TRAb, TSI are thought
to be mediators of orbitopathy also
IGF-IR ( Insulin like growth factor I receptor ) is an
auto antigen expressed by fibroblasts
COX-2 ( Cyclo oxygenase -2 )Expressed at higher
levels in fibro adipose tissue of TRO patients

11. PATHOPHYSIOLOGYPATHOPHYSIOLOGY
Fibroblasts are the target cells in TAO
They are extremely sensitive to stimulation by
cytokines and immunoglobulins
Stimulated fibroblasts secrete Hyaluronic acid which
is hydrophilic and causes edema in extraocular
muscles
Doubling of Hyaluronic acid content causes a 5 fold
increase in tissue osmotic load

12. COURSE OF THE DISEASECOURSE OF THE DISEASE
TRO has an active inflammatory phase and a stable
post inflammatory phase
Duration of active phase 6-18 months
Management of active phase is aimed at modulating
the immune response and reducing the inflammation
Reactivation of disease occurs in less than 5 percent of
individuals

13. STAGINGSTAGING
WERNER´S CLASSIFICATION - NOSPECS
0 Nil (no symptoms or signs)
1 Only signs of: a) stare
b) lid lag
2 Soft tissue involvement: 0) absent
a) minimal
b) moderate
c) marked

14. 3 Proptosis of 3mm or more: 0) absent
a) 3-4 mm
b) 5-7 mm
c) 8 or more mm
4 Extra ocular muscle involvement: 0) absent
a) limitation at extremes of gaze
b) evident restriction of motion
c) fixation of globe

15. 5 Corneal involvement: 0) absent
a) SPE
b) corneal ulceration,
c) necrosis or perforation
6 Sight loss (due to optic neuropathy): 0) absent
a) 20/20-20/60
b) 20/70-20/200
c)Worse than 20/200.

16. MOURITS CLASSIFICATION
Clinical Activity Score ( CAS ) to grade the
inflammatory phase of the disease
The CAS consists of two conjunctival, eyelid and
two orbital signs
A score of 4 /> - active disease
Subjective in nature with very large interobserver
variation

17. Clinical Activity Score
For initial CAS, only score items 1-7
1. Spontaneous orbital pain.
2. Gaze evoked orbital pain.
3. Eyelid swelling that is considered to be due to
active inflammatory phase.
4. Eyelid erythema.
5. Conjunctival redness that is considered to be
due to active inflammatory phase.

18. 6. Chemosis.
7. Inflammation of caruncle OR plica.
Patients assessed after follow-up can be scored out
of 10 by including items 8-10.
8. Increase of > 2mm in proptosis.
9. Decrease in uniocular ocular excursion in any
one direction of > 8º.
10. Decrease of acuity equivalent to 1 Snellen
line.

19. THE VISA CLASSIFICATIONTHE VISA CLASSIFICATION
Devised by Peter Dolman and Jack Rootman
Based on four disease points
Basic form consists of 4 sections recording symptoms
on the left and signs on the right
Each disease activity is graded
Objective and reproducible
Appropriate management for patients in a logical
sequence

21. VISA INFLAMMATORY SCOREVISA INFLAMMATORY SCORE

22. Clinical signs in TEDClinical signs in TED
Facial signs
joffroy’s sign-absent creases in the
forehead on superior gaze.
Eyelid signs
Kocher’s sign-staring appearance
Vigouroux sign-eyelid fullness
Rosenbach’s sign-tremors of eyelids
Riesman’s sign-Bruit over the eyelids

23. Upper eye lid signs
Von graefe’s sign-lid lag on downgaze
Dalrymple’s sign-lid retraction
Stellwag’s sign-incomplete & infrequent
blinking
Grove sign-resistance to pulling the retracted
upper lid
Boston sign-jerky movements of lid on down
gaze
Gellineck’s sign-abnormal pigmentation of
upper lid
Gifford’s sign-difficulty in everting the upper
lid
Means sign-increase superior scleral show on
upgaze

24. Lower eye lid signs
Enroth ’s sign-edema of lower lid
Griffith’s sign-lid lag on upgaze
Conjunctival signs
Goldzeiher’s sign-conjunctival injection

25. Extraocular movement signs
Moebius sign-unable to converge eyes
Ballet’s sign-restriction of one or more EOM
Suker’s sign-poor fixation on abduction
Jendrassik’s sign-paralysis of all EOM
Pupillary signs
Knies sign-uneven pupillary dilatation in dim light
Cowen’s sign-jerky contraction of pupil to light

26. CLINICAL FEATURESCLINICAL FEATURES
1.Eyelid Retraction
2.Soft Tissue Involvement
3.Proptosis
4.Optic Neuropathy / Exposure Keratopathy
5.Strabismus

27. LID LID
RETRACTIONRETRACTION

28. Eyelid RetractionEyelid 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 problem
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

29. Eyelid Retraction – Clinical FeaturesEyelid Retraction – Clinical Features
Clinical signs:
◦Lid retraction in 1º
(front) gaze
◦Lid lag i.e. delayed
descent of upper lid
in downgaze
◦Staring appearance of
the eyes

30. SOFT TISSUE INVOLVEMENTSOFT TISSUE INVOLVEMENT

31. Soft Tissue Involvement - SymptomsSoft Tissue Involvement - Symptoms
Variable grittiness
Photophobia
Lacrimation - watery eyes

32. Soft Tissue Involvement - SignsSoft Tissue Involvement - Signs
Periorbital and lid swelling
Conjunctival hyperaemia
Sensitive sign of disease activity
Chemosis (edema of the conjunctiva)
Severe cases: conjunctiva prolapses over lower eyelid

33. PROPTOSISPROPTOSIS

34. Proptosis(exophthalmos)Proptosis(exophthalmos)
Proptosis is axial
TED is the most common
cause of both bilateral and
unilateral proptosis in adults
Proptosis is uninfluenced by R
x

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

35. OPTIC NEUROPATHYOPTIC 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

36. An early sign is decreased colour vision
Slow progressive impairment of visual acuity 6/6 to
6/9 Va in 18% of cases
Relative afferent pupillary defect -35%
Visual defects, especially central scotomas – 66%
 Swollen or pale disc - 52%

37. CORNEAL INVOLVEMENTCORNEAL INVOLVEMENT
Exposure keratitis may result from proptosis, upper
eyelid retraction, lower eyelid retraction,
lagophthalmos, or a combination of these

38. OCULAR MOTILITY OCULAR MOTILITY
PROBLEMSPROBLEMS
 30% - 50%
A defect in elevation is
most common due to
fibrosis of inferior
rectus muscle
IR>MR>SR>LR

39. CT SCAN

40. MRI SCAN

41. VISUAL FIELDVISUAL FIELD
Characteristically a central scotoma / an inferior
altitudinal defect is seen in cases of compressive
optic neuropathy
Other visual field defects include an enlarged blind
spot, para central scotoma, nerve fibre bundle
defect, or generalized constriction

42. TREATMENTTREATMENT
Compressive optic neuropathy
Inflammation
Motility disorders
Eyelid abnormalities

43. COMPRESSIVE OPTIC NEUROPATHYCOMPRESSIVE OPTIC NEUROPATHY
The treatment possibilities include high doses of
corticosteroids, irradiation,immunosupressants and
orbital decompression.
 Some patients require only one of these modalities,
while other patients need combined therapies.

44. CORTICOSTEROIDSCORTICOSTEROIDS
Intra-venous Methyl Prednisolone 1 gm alternate days
for 3-6 cycles
Cumulative dose not to exceed 6-8 gm
Effective in 63-77% *
No response in 48 hours - Steroids probably will not
work
* Rajendran et. al, CIRTED trial

45. RADIATION THERAPYRADIATION THERAPY
Lymphocytes infiltrating the orbit are highly sensitive
to Radiation. The glycosaminoglycan production by
fibroblasts is reduced
Dose =1500- 2000 cGy per eye fractioned over a
period of 2 weeks
 Co coverage with steroids
A relative contraindication in diabetics

46. Although congestive findings improve most
consistently, significant improvement in proptosis
and extra ocular muscle function has been reported.
Radiation therapy is most effective within the first
year, when significant fibrotic changes have not yet
occurred.

47. ORBITAL DECOMPRESSIONORBITAL DECOMPRESSION
 Indicated for compressive optic neuropathy when
there has been failure of or contraindication for
corticosteroids or radiation therapy
Gross proptosis with exposure keratitis and corneal
ulceration
Cosmesis for disfiguring exophthalmos.

48. ORBITAL DECOMPRESSIONORBITAL DECOMPRESSION
The swinging lower lid approach to inferior and
medial wall decompression is the most common
approach used by ophthalmologists.
Medial wall decompression to extend posteriorly
for compressive optic neuropathy

49. Medial wall removal not to extend above
the fronto ethmoidal suture
Preservation of a strut of bone between ethmoid and
maxillary bones
Lateral wall removal has little effect on apical compression
Four wall decompression requires a neurosurgical approach
Orbital fat decompression for reducing proptosis

50. AFTER 3-WALL DECOMPRESSION & FAT AFTER 3-WALL DECOMPRESSION & FAT
EXCISIONEXCISION

52. ACTIVE INFLAMMATIONACTIVE INFLAMMATION
Treatment depends on inflammatory score
Score <4 - conservative management
Score > 5 – more aggressive therapy
Oral/IV steroids
Radiotherapy
Immunosuppressive agents

53. Soft Tissue Involvement - RSoft Tissue Involvement - R
xx
Frequently unsatisfactory, may be of some benefit
Topical R
x
– 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

54. MOTILITY DISORDERSMOTILITY DISORDERS
 A major source of morbidity in thyroid orbitopathy, and
the most frequent problem associated with orbital
decompression surgery
Minimal degrees of ocular misalignment - compensatory
head posture, Fresnel plastic press-on prisms, or
temporary occlusion
If there is marked asymmetry in ocular deviation in
different fields of gaze, prisms are less effective

55. Surgery is usually considered if there is diplopia in
primary gaze or reading position
Diplopia must have been stable for about 6 months
R
x
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

56. EYELID ABNORMALITIESEYELID ABNORMALITIES
Mild eyelid retraction does not require R
x
, in 50% of
cases, there is spontaneous improvement
R
x
of associated hyperthyroidism may also improve lid
retraction
Main indications are exposure keratopathy and poor
cosmesis

57. A graded Muller’s and levator aponeurosis
weakening abnormalities(recession of lower lid
retractors,mullertomy)
Blepharoplasty is the final surgical procedure in the
rehabilitation of TRO patient
Orbital decompression is performed initially
followed by strabismus surgery and then eyelid
surgery

59. No effective means of preventing the disease or
reliably altering it’s course
Current therapeutic options aimed at reducing the
inflammation during active stage and correction of
residual abnormalities secondary to fibrosis in the
inactive stage
Intervention not targeting the cause because the
precise pathogenesis is still elusive
TO CONCLUDE...

60. TRO is a self limiting disease
Patient education
Stopping smoking
Newer medical therapies like anti CD 20 (Rituximab) to
deplete B- cell lymphocytes, anti TNF drugs,
Pentoxyfylline and nicotinamide which inhibit cytokine
induced glycosaminoglycan synthesis ,intravenous
immunoglobulin are being tried

61. More studies are required to determine the risk
benefit ratio of these new modalities
Recent advances in molecular biology,
identification of multiple genes and auto antigens
with a possible role in thyroid orbitopathy may
pave a way in preventing this common yet
poorly understood disease