Department of Ophthalmology
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Acknowledgement
? UptoDate: Graves' orbitopathy: Diagnosis and Treatment.
? Cummings Otolaryngology. Girod, Douglas A.; Wemer, Richard D.;
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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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Learning Objectives? At the end of this class the students shal be able to :
? Enumerate the common causes of proptosis
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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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Question
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? A 44-year-old female patient presents with bilateral protrusion of theeyeball along with retraction of the eyelids and lid lag on downgaze.
What is her most likely diagnosis?
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? a. Grave's disease
? b. Orbital pseudotumor
? c. Orbital cellulitis
? d. Orbital varices
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Proptosis
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? Forward displacement or protrusion of
eyebal .
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? Protrusion of globe >21mm or atleast 2mmasymmmetry between the two eyes is
abnormal.
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? Measured by Hertel's Exophthalmometer
? Differentiate from pseudoproptosis or
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apparent eyebal protrusionHigh myopia
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Lid retraction5
Proptosis
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? Axial and non-axial(Abaxial)
? Unilateral and Bilateral proptosis
Inflammation: Thyroid
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Congenital: Dermoid Cyst
orbitopathy
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Traumatic: Orbital hemorrhageSarcoidosis
Inflammatory: Orbital cellulitis
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Neoplasia: Lymphoma
Orbital psudotumour
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LeukaemiaVascular: Orbital varix
Vascular malformation:
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Cystic: Orbital cysticercosis
Arterio-venous shunts
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Tumours of the orbitLacrimal lesions: Sjogren's
syndrome
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Introduction of Thyroid eye disease
? Thyroid eye disease is an autoimmune disease producing symptoms
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related to inflammation, accumulation of fluid in the orbit and also toadipogenesis raising intra-orbital pressure.
? Synonyms
? Graves' ophthalmopathy/orbitopathy (GO)
? Thyroid eye disease (TED)
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? 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
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? Graves' hyperthyroidism (90%)
? Hypothyroid Hashimoto's thyroiditis
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? Euthyroid subjects with no current or past evidence of thyroidhyper or hypofunction (so called euthyroid Graves' disease).
? In patients with Grave's disease, eye signs may precede, coincide with
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or follow the hyperthyroidism
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Risk factors? Smoking (strongest modifiable risk factor)
? Family history
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? Monozygotic twins
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Pathogenesis
? Autoimmune process manifesting as:
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? Extraocular muscle myositis? T-cel inflammatory infiltrate
? Fibroblast proliferation
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? Glycosaminoglycan overproduction
? Increase in soft tissue mass within
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bony orbit due to extraocular muscleenlargement, increased orbital fat and
connective tissue
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? Later in disease, inflammatory
infiltrate replaced by widespread
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fibrosis? "Inactive" phase occurs after 8months
to 3years
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Pathogenesis
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Pleomorphic cel ular infiltrateIncreased secretion of GAG's
Osmotic imbibition of water
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Muscular swel ing upto 8 times
Subsequent degeneration leading to
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fibrosis12
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HistologyFluid and inflammatory cells separate the muscle bundles of the
extraocular muscles
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13Histology
Lymphocytes, plasma
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cells, macrophages
and mast cells
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infiltrate extraocularmuscles, fat and
connective tissue
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Histology
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Degeneration
of muscle fibres
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Leads to fibrosisof the involved
muscle
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Natural History of Thyroid Eye Disease
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? Progressive phase lasting for up to 18 months? Stable (inactive) phase
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Course of disease
? Inflammatory/active phase Fibrotic/inactive phase
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Clinical course of orbital disease proceeds independently of thyroid glanddysfunction and treatment
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Symptoms
? Foreign body sensation
? Epiphora (tearing)
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? Photophobia? Bulging of eyes
? Puffiness of eye lids
? Diplopia
? Visual loss
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Signs
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? Eyelid Retraction
? Proptosis
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? Restrictive Myopathy? Soft Tissue Involvement
--- Conjunctival hyperaemia, lid oedema and chemosis
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? Optic Neuropathy
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Clinical signs in TED? Facial signs
? Joffroy's sign-absent creases
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in the forehead on superiorgaze
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Clinical eye lid signs in TED
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? Kocher's sign- staring appearance
? Von Graefe's sign- lid lag on downgaze
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? Dalrymple's sign- lid retraction? Stel wag's sign- incomplete & infrequent blinking
? Enroth 's sign- edema of lower lid
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? Griffith's sign- lower lid lag on upgaze
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Soft Tissue Inflammation? Often the earliest sign.
Consists of
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? periorbital edema? conjunctival hyperemia
? chemosis
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Eyelid retraction
? Also cal ed Dalrymple's sign.
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? Normal y, upper eyelid- 2mm below limbus
? Lower eyelid-inferior limbus
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? When retraction occurs, the sclera (white) canbe seen
Occurs due to :
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? Increased sympathetic stimulation of M?ller's
muscle by thyroid hormone
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? Overaction of the levator muscle contractingagainst a tight inferior rectus
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Proptosis
? Usually (90%) bilateral
? Thyroid eye disease is the most common
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cause of unilateral and bilateral
proptosis in adults
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? Axial? Resulting from enlargement of the
extraocular muscles and adipose
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tissue, as well as orbital fat? Infiltration of orbital tissues by GAGs and
leukocytes
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24Proptosis
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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.
? Despite expansion of the extraocular muscles , the muscle fibres
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themselves 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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26Dysthyroid 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
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? 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
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? Class 5: Corneal involvement? Class 6: Sight loss (optic nerve involvement)
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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
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? V (Vision) , I (inflammation), S (Strabismus) , A (Appearance)? 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
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Steroids)30
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
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? Characteristic eye findings? 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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33Radiological Evaluation
? Usually employed if cause of exophthalmos is unclear (ie. normal
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thyroid lab studies, or history/physical examination inconsistent with
thyroid disease)
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? Also to determine optic nerve involvement if not obvious byfundoscopic examination.
? Distinct sparing of muscle tendons in thyroid ophthalmopathy.
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Radiological Evaluation
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? CT scan is currently the imaging study of choice.
? MRI is sensitive for showing compression of the optic nerve.
? Neuroimaging usually reveals
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? Thick muscle belly with tendon sparing? Usually IR & MR
? Bilateral muscle enlargement is the norm
? Unilateral cases usually represent asymmetric involvement rather
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than normality of the less involved side35
Axial and coronal C.T. scan in Thyroid eye disease
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? Non-contrast enhanced coronal orbital CT scan most helpful to assess
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size of extraocular muscles.
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Axial CT of orbitsdemonstrating
medial rectus
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enlargement
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Management
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? T ? Tobacco abstinence
? E ? Euthyroidism
? A ? Artificial tears
? R ? Referral
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? S ? Self help groups39
Medical Management of Hyperthyroidism
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? 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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40Treatment of mild Thyroid eye disease
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41Symptomatic treatment
? Artificial tears
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? Eye shades
? Raise head of bed at night
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? Diplopia can be managed with prism glasses? Eventually may require strabismus surgery
? Conserve useful vision
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? Minimize amount of exposed cornea
? May require lid surgery
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? Treat optic neuropathy42
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 life43
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
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? Relapse is common (20%)? 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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44Rituximab
? Chimeric mono-clonal antibody targets CD20
? CD20 is expressed on more than 95% of B cells and plasma cells
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? RTX depletes 95% of mature B cells , blocks Ab production , and
decreases inflammatory cytokine release
? For steroid-refractory disease
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? Side effects : Allergic reaction (mild) PML (severe)
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Orbital Radiation? Mechanism : lymphocyte sterilization, destruction of tissue
monocytes
? 20 Gy in 10 divided sessions over 2 weeks
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? May have a role in patients with TED who have restricted ocularmotility or active disease
? Some studies have shown benefit (controversial)
? 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
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? For upper lid retraction (transconjunctival , transcutaneous route)? Effect on Muller's muscle and LPS
? Side effects of Botox : bruising , ptosis and diplopia
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Orbital Decompression for TED
? Decompression usually in stable phase of disease.
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? Indications? compressive optic neuropathy
? severe exposure keratopathy
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? Post-operative complications (diplopia, vision loss)
? Outcome is variable : degree of fibrosis , fat expansion , bone
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available, duration of optic neuropathy.? 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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49Eye 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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50Psychological Impact of TED
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? Disfigurement/altered facial appearance? Misinterpretation as hostile or angry
? Almost 50% of TED suffer depression and/or anxiety
? 90% of TED have appearance concerns (young females)
? 44% have self-confidence issues
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? Multidisciplinary approach (psychiatric included)? Support groups
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52Conclusion
? Activation of thyrotropin receptor on orbital fibroblast by circulating
autoantibodies plays a primary role in development of thyroid
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ophthalmopathy.? Management is based on accurate assessment of both severity and
activity of disease.
? Immunosuppressive therapy is reserved for patients with clinically
active moderate to severe disease
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Question
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? Which of the following statement is correct regarding Thyroid eyedisease?
? a. It cannot be present in the euthyroid patient.
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? b. The earliest sign is loss of sight due to optic neuropathy? c. The lateral rectus muscle is least commonly involved.
? d. There is only unilateral involvement in the disease.
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Thank You55