Thyroid Ophthalmopathy
Department of Ophthalmology
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1Acknowledgement
? UptoDate: Graves' orbitopathy: Diagnosis and Treatment.
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? Cummings Otolaryngology. Girod, Douglas A.; Wemer, Richard D.;Larsen, Christopher G. Published January 1, 2015. ? 2015.
? Endocrinology : Adult and Paediatric. Burch, Henry B.; Bahn, Rebecca
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S.. Published January 1, 2016. ? 2016.
? Some of the images used were taken from eyetext.net
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2Learning Objectives
? At the end of this class the students shal be able to :
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? Understand the pathogenesis and clinical features of thyroid eye disease.? Enumerate and elicit the common eye signs of thyroid ophthalmopathy.
? Have a basic understanding of principles of management of the disease.
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3
Introduction
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? Thyroid eye disease is an autoimmune disease producing symptomsrelated to inflammation, accumulation of fluid in the orbit and also to
adipogenesis raising intra-orbital pressure.
? Synonyms
? Graves' ophthalmopathy/orbitopathy (GO)
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? Thyroid eye disease (TED)? Thyroid associated ophthalmopathy (TAO)
? Dysthyroid ophthalmopathy
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Epidemiology? Prevalence of thyroid ophthalmopathy = 0.4%
Women > Men
? But severity greater in men
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? Bimodal age distribution ? Peak incidence in fourth and sixth decadesof life
? May be exacerbated by stress and smoking
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? Most common cause of exophthalmos? >50% of cases with Graves' disease have eye involvement
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Etiology? Graves' hyperthyroidism (90%)
? Hypothyroid Hashimoto's thyroiditis
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? Euthyroid subjects with no current or past evidence of thyroid hyper
or hypofunction (so called euthyroid Graves' disease).
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? In patients with Grave's disease, eye signs may precede, coincide withor follow the hyperthyroidism
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Risk factors
? Smoking (strongest modifiable risk factor)
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? Family history
? Monozygotic twins
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7Pathogenesis
? Autoimmune process manifesting as:
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? Extraocular muscle myositis
? T-cel inflammatory infiltrate
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? Fibroblast proliferation? Glycosaminoglycan overproduction
? Increase in soft tissue mass within
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bony orbit due to extraocular muscle
enlargement, increased orbital fat and
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connective tissue? Later in disease, inflammatory
infiltrate replaced by widespread
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fibrosis
? "Inactive" phase occurs after 8months
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to 3years8
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pathogenesisPleomorphic cel ular infiltrate
Increased secretion of GAG's
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Osmotic imbibition of water
Muscular swel ing upto 8 times
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Subsequent degeneration leading tofibrosis
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Histology
Fluid and inflammatory cells separate the muscle bundles of the
extraocular muscles
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Histology
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Lymphocytes, plasma
cells, macrophages
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and mast cellsinfiltrate extraocular
muscles, fat and
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connective tissue
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HistologyDegeneration
of muscle fibres
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Leads to fibrosis
of the involved
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muscle12
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Natural History of Thyroid Eye Disease? Progressive phase lasting for up to 18 months
? Stable (inactive) phase
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13Course of disease
? Inflammatory/active phase Fibrotic/inactive phase
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Clinical course of orbital disease proceeds independently of thyroid gland
dysfunction and treatment
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14Symptoms
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? Foreign body sensation? Epiphora (tearing)
? Photophobia
? Bulging of eyes
? Puffiness of eye lids
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? Diplopia? Visual loss
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Signs? Eyelid Retraction
? Proptosis
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? Restrictive Myopathy
? Soft Tissue Involvement
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--- Conjunctival hyperaemia, lid oedema and chemosis? Optic Neuropathy
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Clinical signs in TED
? Facial signs
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? Joffroy's sign-absent creasesin the forehead on superior
gaze
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Clinical eye lid signs in TED
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? Kocher's sign- staring appearance? Rosenbach's sign- tremors of eyelids
? Von graefe's sign- lid lag on downgaze
? Dalrymple's sign- lid retraction
? Stellwag's sign- incomplete & infrequent blinking
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? Gifford's sign- difficulty in everting the upper lid? Enroth 's sign- edema of lower lid
? Griffith's sign- lower lid lag on upgaze
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Soft Tissue Inflammation
? Often the earliest sign.
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Consists of? periorbital edema
? conjunctival hyperemia
? chemosis
? superior limbic keratoconjunctivitis
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Eyelid retraction
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? Also cal ed Dalrymple's sign.? Normal y, upper eyelid- 2mm below limbus
? Lower eyelid-inferior limbus
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? When retraction occurs, the sclera (white) can
be seen
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Occurs due to :? Increased sympathetic stimulation of M?ller's
muscle by thyroid hormone
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? Overaction of the levator muscle contracting
against a tight inferior rectus
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20Proptosis
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? Usually (90%) bilateral? Thyroid eye disease is the most common
cause of unilateral
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and bilateral proptosis in adults? Axial
? Resulting from enlargement of the
extraocular muscles and adipose
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tissue, as well as orbital fat
? Deposits and the infiltration of orbital
tissues by GAGs and leukocytes
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Proptosis
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? It does not respond to hyperthyroidismtreatment
? Is permanent in 70% of cases.
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? Severe proptosis prevents adequate lidclosure
? May lead to severe exposure
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keratopathy and corneal ulceration.
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Restrictive Myopathy
? Eye movements are restricted due to oedema in extraocular muscles
during infiltrative stage and subsequent fibrosis.
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? Despite expansion of the extraocular muscles , the muscle fibresthemselves are normal.
? IR>MR>SR>LR
? Pressure exerted by a fibrotic inferior rectus muscle on the
globe may cause a spike in intraocular pressure during upgaze.
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Dysthyroid Optic Neuropathy
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(DON)Optic neuropathy as result of optic nerve compression
from enlargement of extraocular muscles
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WERNER?S CLASSIFICATION - NOSPECS
? Class 0: No signs or symptoms
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? 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
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? Class 6: Sight loss (optic nerve involvement)25
EUGOGO classification
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? Mild : eyelid swelling , lid retraction, proptosis
? Moderate-Severe : Active disease (EOM dysfunction, diplopia ,
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proptosis >25 mm)? Very severe : Compressive Optic Neuropathy , Corneal exposure
(needs emergent surgery)
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VISA classification
? V (Vision) , I (inflammation), S (Strabismus) , A (Appearance)
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? Vision/CON? Inflammation/Congestion : based on documented change of
inflammation rather than absolute value
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? Strabismus/Motility : measuring ductions and alignments? Appearance/Exposure
? Score of 5 or more --> Active disease or progression (Consider
Steroids)
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Differential Diagnosis
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? Orbital tumors (primary or metastatic)? Orbital pseudotumor
? Wegener's granulomatosis
? Orbital infection
? Carotid-cavernous sinus fistula
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Diagnosis
? Characteristic eye findings
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? Thyroid dysfunction? Imaging
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Blood investigations? Highly sensitive & specific -- T4(thyroxine) + TSH or serum TSH
? If eye findings associates with euthyroid Graves' disease ?
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? Thyroid peroxidase antibody
? Antibody to thyroglobulin
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? Others? Free T4 index
? Thyroid-stimulating immunoglobulin
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? Antithyroid antibodies
? Serum T3
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30Radiological Evaluation
? Usually employed if cause of exophthalmos is unclear (ie. normal
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thyroid lab studies, or history/physical examination inconsistent withthyroid disease)
? Also to determine optic nerve involvement if not obvious by
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fundoscopic examination.
? Distinct sparing of muscle tendons in thyroid ophthalmopathy.
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31Radiological Evaluation
? CT scan is currently the imaging study of choice.
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? MRI is sensitive for showing compression of the optic nerve.? Neuroimaging usually reveals
? Thick muscle belly with tendon sparing
? Usually IR & MR
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? Bilateral muscle enlargement is the norm? Unilateral cases usually represent asymmetric involvement rather
than normality of the less involved side
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32Axial and coronal C.T. scan in Thyroid eye disease
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33? Non-contrast enhanced coronal orbital CT scan most helpful to assess
size of extraocular muscles.
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Axial CT of orbits
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demonstrating
medial rectus
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enlargement35
Management
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? T ? Tobacco abstinence
? E ? Euthyroidism
? A ? Artificial tears
? R ? Referral
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? S ? Self help groups36
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Medical Management of Hyperthyroidism? Anti-thyroid drugs : thinoamides (PTU) , carbimazole , methimazole.
? Thionamides inhibit synthesis of thyroid hormones.
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? Need 6-8 weeks to achieve euthyroid state
? Side effects of anti-thyroid drugs
Skin rash , urticarial , arthralgia , fever
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Treatment of mild Thyroid eye disease
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38Symptomatic treatment
? Artificial tears
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? Eye shades? Raise head of bed at night
? Diplopia can be managed with prism glasses
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? Eventually may require strabismus surgery
? Conserve useful vision
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? Minimize amount of exposed cornea? May require lid surgery
? Treat optic neuropathy
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Selenium
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? 200 microgram/day for 6 months? For Mild disease
? Antioxidant effect
? Immunomodulatory effect : reduce thyroid autoantibodies
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? Reduces severity of disease and improve quality of life40
Corticosteroids
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? Intravenous , Oral? IV pulses are more effective and have less side effects
? IV dose (max 8 grams) : 500 mg weekly for 6 weeks and then 250 mg
weekly for 6 weeks
? Relapse is common (20%)
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? Steroid response is evident usually 2-4 weeks later? Moderate to severe TED : 71% respond to IV steroid vs 51% with oral
? IV steroids for compressive Optic Neuropathy
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Rituximab
? Chimeric mono-clonal antibody targets CD20
? CD20 is expressed on more than 95% of B cells and plasma cells
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? RTX removes B cells and short-lived plasma cells? RTX depletes 95% of mature B cells , blocks Ab production , and
decreases inflammatory cytokine release
? For steroid-refractory disease
? Side effects : Allergic reaction (mild) PML (severe)
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Orbital Radiation
? Mechanism : lymphocyte sterilization, destruction of tissue
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monocytes? 20 Gy in 10 divided sessions over 2 weeks
? May have a role in patients with TED who have restricted ocular
motility or active disease
? Some studies have shown benefit (controversial)
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? More suited for patients > 35 years of age? Contra-indicated in pre-existing retinopathy (diabetes , hypertensive)
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Botulinum Toxin? Neurotoxin , inhibits acetylcholine release
? For upper lid retraction (transconjunctival , transcutaneous route)
? Effect on Muller's muscle and LPS
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? Side effects of Botox : bruising , ptosis and diplopia44
Orbital Decompression for TED
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? Decompression usual y in stable phase of disease.? Indications
? compressive optic neuropathy
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? severe exposure keratopathy
? Need to discuss goals of surgery with patients.
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? Post-operative complications (diplopia, vision loss)? Outcome is variable : degree of fibrosis , fat expansion , bone
available, duration of optic neuropathy.
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? Decompression --> Muscle Surgery --> Lid surgery
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Strabismus Surgery for TED? In the stable phase with stable alignments for 6 months
? Aim is single binocular vision in primary and reading position
? Typically involves release of the restricted muscle by recession rather
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than resection
? Conjunctival dissection is challenging
? Use of adjustable sutures is strongly recommended due to the
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variability in fibrosis, resulting in unpredictable results.
? Oblique surgery can increase area of single binocular vision
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46Eye lid surgery
? The most common indication for lid surgery is upper lid retraction.
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? Graded Muller's and levator aponeurosis weakening.? Lower lid lengthening is indicated in lower lid retraction.
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Psychological Impact of TED
? Disfigurement/altered facial appearance
? Misinterpretation as hostile or angry
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? Almost 50% of TED suffer depression and/or anxiety? 90% of TED have appearance concerns (young females)
? 44% have self-confidence issues
? Quality of life measures and questionnaires
? Multidisciplinary approach (psychiatric included)
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? Support groups48
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Psychological Disturbances in TED49
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Conclusion? Activation of thyrotropin receptor on orbital fibroblast by circulating
autoantibodies plays a primary role in development of thyroid
ophthalmopathy.
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? Management is based on accurate assessment of both severity andactivity of disease.
? Immunosuppressive therapy is reserved for patients with clinically
active moderate to severe disease
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51Thank You
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