THYROID

OPHTHALMOPATH
Y
• Thyroid eye disease is an autoimmune disease
producing symptoms related to
inflammation, accumulation of fluid in the
orbit and also to adipogenesis raising intra-
orbital pressure.
 F>M

• Per 100,000
person year

16
3

•Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, et al. The incidence of Graves’ ophthalmopathy in Olmsted
County, Minnesota. Am J Ophthalmol 1995;120:511-7.
 9

3 2 Severe
Mild

4
Moderate
1

• Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid 2002;12:855-60
 Europeans (42%) Asians (7.7%)

Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol (Oxf) 1992;36:291-4.
 different names!!
 Graves’ ophthalmopathy/orbitopathy (GO)

 Thyroid eye disease (TED)

 Thyroid associated ophthalmopathy (TAO)

 Dysthyroid ophthalmopathy

 Thyrotoxic exophthalmos

 Endocrine exophthalmos
 Etiology

• Graves’ hyperthyroidism (90%)

• Hypothyroid Hashimoto’s thyroiditis

• Euthyroid subjects with no current or past

evidence of thyroid hyper or hypofunction (so-
called euthyroid Graves’ disease).1

1.Burch HB, Wartofsky L. Graves’ ophthalmopathy: current concepts regarding pathogenesis and management. Endocr Rev.1993;14(6):747–793 .
 Risk factors
•Smoking (strongest modifiable
risk factor)

• Family history

• Monozygotic twins
Pathogenesis
 Course of disease
Inflammatory/active phase

• red and painful

•
• one to two years (range 6
months to 5 years).

• Active inflammation recurs

in about 1% of patients
after months to years of
inactivity
Fibrotic/inactive phase
 Permanent Structural
changes.
 no reliable test or sign.
 Stable clinical findings
for 6 months suggest
that the patient has
passed from the active
to the inactive phase.
 Clinical features

 Basis of signs & symptoms in TED is expansion of......

Both extra-ocular muscles & adipose

tissue

Predominance of any one type

Forbes, G. et al., 1986. Ophthalmopathy of Graves’ disease: computerized volume measurements of the orbital fat and muscle. AJNRAm. J.
.
Neuroradiol. 7 (4), 651–656
 Diplopia

Visual loss

Field loss

Ocular
pressure or
pain
Bulging eyes
symptoms
Puffy eyelids Photophobia

Lacrimation

Dyschromatopsia

Photopsia
 Signs
• Eyelid Retraction (91%)

• Proptosis (62%)
conjunctival
hyperemia
• Restrictive Myopathy (42%) (34%)

eyelid edema
(32%)
• Soft Tissue Involvement

chemosis (23%)

• Optic Neuropathy (6%)

Bartley GB, Fatourechi V, Kadrmas EF, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol.
1996;121(3):284–290.
 Soft Tissue Inflammation

• Often the earliest sign.

• consists of
 periorbital edema

 conjunctival hyperemia

 chemosis

 superior limbic keratoconjunctivitis

 Eyelid retraction

• Also called Dalrymple’s sign.

 Normally, upper eyelid- 2mm below limbus

lower eyelid-inferior limbus

 When retraction occurs, the sclera (white) can

be seen

• Lateral flare (almost pathognomic)

 Causes

increased sympathetic stimulation

of Müller’s muscle by thyroid
hormone
overaction of the levator muscle
contracting against a tight inferior
rectus
muscle scarring between the
lacrimal gland fascia and
levator(lateral flare)
 Proptosis
• Usually (90%) bilateral

• TAO is the most common cause of unilateral and

bilateral proptosis in adults

• Axial

• Resulting from enlargement of the extraocular

muscles and adipose tissue, as well as orbital fat
deposits and the infiltration of orbital tissues by
GAGs and leukocytes
• It does not respond to
hyperthyroidism treatment,
and is permanent in 70% of
cases.

• Severe proptosis prevents

adequate lid closure, and
may lead to severe exposure
keratopathy and corneal
ulceration.
 Proptosis measurement
• Hertel exophthalmometer
• Distance between the lateral
orbital rim and the anterior
surface of the cornea.
• The upper limit of normal
whites -18 mm
blacks -21 mm
Asians -12-18 mm.
• A difference in reading of more
than 2 mm between the two
eyes is suggestive of proptosis.
 Pseudoproptosis
• High myopia

• Congenital glaucoma (buphthalmos)

• Ipsilateral eyelid retraction

• contralateral enophthalmos

• Shallow orbit
 Restrictive Myopathy
• Eye movements are restricted due to edema in the
extraocular muscles during the infiltrative stage and the
subsequent fibrosis.
• Despite expansion of the extraocular muscles in TAO, the
muscle fibers themselves are normal.
• IR>MR>SR>LR1

• Pressure exerted by a fibrotic inferior rectus muscle on the

globe may cause a spike in intraocular pressure during
upgaze.2

1.Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, Gorman CA. Clinical features of Graves’ ophthalmopathy in an
incidence cohort. Am J Ophthalmol. 1996;121:284-290.
2.Konuk O, Onaran Z, Ozhan Oktar S, Yucel C, Unal M. Intraocular pressure and superior ophthalmic vein blood flow velocity in Graves’
orbitopathy: relation with the clinical features. Graefes Arch Clin Exp Ophthalmol. 2009;247:1555-1559
• Thyroid ophthalmopathy
+
exotropia } Concurrent MG

• Convergence insufficiency
• Inferior rectus muscle
restriction may mimic double
elevator palsy
• Forced ductions or elevated
intraocular pressure with eye
movement for confirmation.
 Dysthyroid Optic
Neuropathy (DON)
• Pressure from enlarged muscles on the optic nerve or
the vessels that supply it.
• This occurs when the enlarged EOM expand to
compress the optic nerve instead of producing
exophthalmos.
• Gradual decline in visual acuity, color vision
disturbance, development of an afferent pupillary
defect and central or paracentral scotomas
• Bilateral, simultaneous optic neuropathy can occur
which would eliminate a relative afferent pupillary
defect
McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, Hullo AI, Kahaly G, Krassas G, Marcocci C, Marinò M,
Mourits MP, Nardi M, Neoh C, Orgiazzi J, Perros P, Pinchera A, Pitz S, Prummel MF, Sartini MS, Wiersinga WM; European Group
on Graves’ Orbitopathy (EUGOGO). Clinical features of dysthyroid optic neuropathy: a European Group on Graves’Orbitopathy
 Clinical 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

 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

 Lower eye lid signs

• Enroth ’s sign-edema of lower lid

• Griffith’s sign- lower lid lag on

upgaze
 Conjunctival signs

• Goldzeiher’s sign-conjunctival injection

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
 Disease activity vs severity
• activity -presence of inflammation
• severity - degree of functional or cosmetic deficit at
any stage.

Dickinson AJ, Perros P. Controversies in the clinical evaluation of active thyroid-associated orbitopathy: Use of a detailed protocol with
comparative photographs for objective assessment. Clin Endocrinol (Oxf) 2001;55:283-303.
Classifications for Thyroid
Ophthalmopathy
 WERNER´S CLASSIFICATION -
NOSPECS

• Class 0: No signs or symptoms

• Class 1: Only signs (lid retraction, stare ± lid
lag)
• Class 2: Soft tissue involvement
• Class 3: Proptosis
• Class 4: Extraocular muscle involvement
• Class 5: Corneal involvement
• Class 6: Sight loss (optic nerve involvement)
Werner SC. Classification of the eye changes of Graves’ disease. Am J Ophthalmol 1969;68:646-8.
 Limitations

• Does not necessarily show sequential

involvement

• Inability to assess disease activity

• No prognostic or clinical implication

 Clinical activity score

• In 1989, Mourits et al.developed the Clinical

Activity Score (CAS) for evaluating
ophthalmopathy activity.
• Found to be of value in predicting the outcome
of immunosuppressive treatment and
immunotherapy because of its high specificity
and high positive predictive value.
• CAS ≥4 were more responsive to treatment as
compared to patients with CAS<4

Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves’
ophthalmopathy: A novel approach. Br J Ophthalmol 1989;73:639-44 .
Clinical Activity Score
1. Pain on or behind the globe
Pain
2. Pain on eye movement
3. Redness of the eyelids Redness
4. Redness of the conjunctiva
5. Swelling of the eyelids
6. Chemosis Swelling
7. Swollen caruncle
8. Increase of proptosis
9. Decreased eye movement Function
10. Decreased visual acuity
 The 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

Dolman PJ, Rootman J. VISA Classification for Graves orbitopathy. Ophthal Plast Reconstr Surg 2006;22:319-24
Bartalena, L. et al., 2008. Consensus statement of the European groupon Graves’ orbitopathy (EUGOGO) on management of Graves’
orbitopathy. Thyroid 18 (3), 333–346.

EUGOGO classification
• minor lid retraction (<2 mm)
• mild soft-tissue involvement
Mild GO • exophthalmos <3 mm above normal
• no or intermittent diplopia
• corneal exposure responsive to lubricants

• lid retraction ≥2 mm
Moderate to • moderate or severe soft-tissue involvement
severe GO • exophthalmos ≥3 mm above normal
• inconstant or constant diplopia

Sight-threatening • DON and/or

GO • corneal breakdown
Diagnosis

Characteristic
eye findings

Thyroid Imaging
dysfunction
Blood
T4(thyroxine)
highly +
sensitive & TSH or
specific serum TSH
(thyrotropin)

If eye findings
associates with Thyroid peroxidase ab
euthyroid Ab to thyroglobulin
Graves’ disease

Free T4 index
Thyroid-stimulating
Others immunoglobulin
Antithyroid antibodies
Serum T3
Imaging
 CT Scan and MRI
• CT scan is currently the imaging study of choice.
• MRI is sensitive for showing compression of the optic
nerve.
• Axial and coronal views.
• Neuroimaging usually reveals

 Thick muscle belly with tendon sparing

 Usually IR & MR
 Isolated rectus muscle involvement (SR)- upto 6%
 Bilateral muscle enlargement is the norm
 Unilateral cases usually represent asymmetric
involvement rather than normality of the less
involved side
 Management

T – Tobacco abstinence
E – Euthyroidism
A – Artificial tears
R – Referral
S – Self help
groups

Krassas GE, Heufelder AE. Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts. Eur
J Endocrinol 2001;144:311-8
Mild TED(EUGOGO)/ VISA<4

Add selenium supplements 3-6 months

Non severe TAO
 Mod to sev TED/VISA >4
IVMP pulse therapy
500mg/wk for 6 wks f/b 250mg/wk for 6 wks

Alternatively oral prednisolone 1mg/kg/day

in wkly tapering doses

Re assess after 6 wks

If non responsive change

treatment Maximum
 Radiotherapy
Non specific anti- Cumulative transient

Dose
MOA

A/E
inflammatory dose : 20 Gy exacerbation of
effect per eye inflammation
Destroys the
radiosensitive
fractioned in: Prevented by
lymphocytes 10 daily concomitant
doses glucocorticoid
Reduces administration.3
glycosaminoglyca over a period
ns production.1,2,3 of
: 2 wks

• effective in for congestive signs, optic neuropathy and extraocular muscle involvement
• not very effective against proptosis, eyelid retraction

1.Kung AVC, Michon J, Tai KS, et al. the effect of somatostatin versus corticosteroids in the treatment of Graves’ ophthalmopathy. Thyroid 1996;6:381-4.
2. Bartalena L, Tanda L. Immunotherapy for Graves’ orbitopathy: easy enthusiasm but let’s keep trying. J Endocrinol Invest 2006;29:1012-6.
3.Nielsen Ch, El Fassi D, Hasselbalch HC, et al. B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves’ ophthalmopathy the latest addition to an
expanding family. Expert Opin Biol Ther 2007;7:1061-78.
 Management of DON

Start with If improvement No improvement

after 72 hrs
• IVMP 1gm • Continue with • Orbital
pulse/oral decompression
• f/b steroids+/-
steroids
3 days RT
Surgical care
 Types of surgery

• Orbital decompression
• Strabismus surgery
• Eyelid surgery
 Orbital decompression

• Indications
compressive optic neuropathy
severe exposure keratopathy

• Transantral approach is the most

preferred

• A/E are vision loss, diplopia ,periorbital

numbness, sinusitis, oroantral fistula, facial
neuralgia,, globe malposition
 Strabismus surgery
• Patient should not have active thyroid disease for at
least 6 months

• As it is incomitant type, aim is resolution of diplopia

in primary position and downgaze.

• Typically involves release of the restricted muscle by

recession rather than resection

• Use of adjustable sutures is strongly recommended

due to the variability in fibrosis, resulting in
unpredictable results.
 Eye lid surgery

• The most common indication for lid surgery is

upper lid retraction.

• Graded Muller’s and levator aponeurosis

weakening.

• Lower lid lengthening is indicated in lower lid

retraction