2. Lets start..
• 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.
3. Girl you are in grave danger!!
• Per 100,000
person year
3
16
• 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.
5. Asians (7.7%)Europeans (42%)
Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol (Oxf) 1992;36:291-4.
7. 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.
8. Risk factors
• Smoking (strongest modifiable
risk factor)
• Family history
• Monozygotic twins
11. 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.
12. Clinical features
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.
Both extra-ocular muscles & adipose
tissue
Predominance of any one type
Basis of signs & symptoms in TED is expansion of......
14. Signs
• Eyelid Retraction (91%)
• Proptosis (62%)
• Restrictive Myopathy (42%)
• Soft Tissue Involvement
• Optic Neuropathy (6%)
conjunctival
hyperemia
(34%)
eyelid edema
(32%)
chemosis (23%)
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.
15. Soft Tissue Inflammation
• Often the earliest sign.
• consists of
periorbital edema
conjunctival hyperemia
chemosis
superior limbic keratoconjunctivitis
16. 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)
17. 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)
18. 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
19. • 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.
20. 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.
22. 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
23. • Thyroid ophthalmopathy
+
exotropia
• Convergence insufficiency
• Inferior rectus muscle
restriction may mimic double
elevator palsy
• Forced ductions or elevated
intraocular pressure with eye
movement for confirmation.
} Concurrent MG
24. 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 (EUGOGO) survey. Br J Ophthalmol. 2007;91:455-458.
25. Clinical signs in TED
• Facial signs
joffroy’s sign-absent creases in the forehead on
superior gaze
26. Eyelid signs
Kocher’s sign-staring appearance
Vigouroux sign-eyelid fullness
Rosenbach’s sign-tremors of eyelids
Riesman’s sign-Bruit over the eyelids
27. 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
28. Lower eye lid signs
• Enroth ’s sign-edema of lower lid
• Griffith’s sign- lower lid lag on
upgaze
30. 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
32. 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.
34. 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.
35. Limitations
• Does not necessarily show sequential
involvement
• Inability to assess disease activity
• No prognostic or clinical implication
36. 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.
37.
38. Clinical Activity Score
1. Pain on or behind the globe
2. Pain on eye movement
3. Redness of the eyelids
4. Redness of the conjunctiva
5. Swelling of the eyelids
6. Chemosis
7. Swollen caruncle
8. Increase of proptosis
9. Decreased eye movement
10. Decreased visual acuity
Pain
Redness
Swelling
Function
39. 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
40.
41. EUGOGO classification
• minor lid retraction (<2 mm)
• mild soft-tissue involvement
• exophthalmos <3 mm above normal
• no or intermittent diplopia
• corneal exposure responsive to lubricants
Mild GO
• lid retraction ≥2 mm
• moderate or severe soft-tissue involvement
• exophthalmos ≥3 mm above normal
• inconstant or constant diplopia
Moderate to
severe GO
• DON and/or
• corneal breakdown
Sight-threatening
GO
Bartalena, L. et al., 2008. Consensus statement of the European groupon Graves’ orbitopathy (EUGOGO) on management of Graves’
orbitopathy. Thyroid 18 (3), 333–346.
45. 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
46.
47. Management
Krassas GE, Heufelder AE. Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts. Eur J
Endocrinol 2001;144:311-8
T – Tobacco abstinence
E – Euthyroidism
A – Artificial tears
R – Referral
S – Self help groups
50. 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 cumulative dose 8 gm
51. Radiotherapy
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.
MOA
Non specific anti-
inflammatory
effect
Destroys the
radiosensitive
lymphocytes
Reduces
glycosaminoglyca
ns production.1,2,3
Dose
Cumulative
dose : 20 Gy
per eye
fractioned in:
10 daily doses
over a period of
: 2 wks
A/E
transient
exacerbation of
inflammation
Prevented by
concomitant
glucocorticoid
administration.3
•effective in for congestive signs, optic neuropathy and extraocular muscle involvement
•not very effective against proptosis, eyelid retraction
52. Management of DON
Start with
• IVMP 1gm
If improvement
• Continue with
pulse/oral
steroids
No improvement
after 72 hrs
• Orbital
decompression
• f/b steroids+/-
RT3 days
54. Types of surgery
• Orbital decompression
• Strabismus surgery
• Eyelid surgery
55. 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
56. 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.
57. 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
