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Thyroid eye disease ( Graves Ophthalmopathy )

Overview of the clinical diagnostic and treatment options in thyroid eye disease (Graves Ophthalmopathy).

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Thyroid eye disease ( Graves Ophthalmopathy )

  1. 1. Thyroid Eye Disease Raed Behbehani , MD FRCSC
  2. 2. Thyroid Eye Disease • 1-2% of women , 0.5% of men • Female : Male ratio , 5:1 • Infiltration of immune effector cells and thyroid-antigen-specific T cells into thyroid and TSH receptors carrying tissues • TSHR is found on thyroid epithelial cells , adipocytes and bone cells. • Fibroblast activation is caused by inflammatory cytokines released by T-cells and macrophages.
  3. 3. Pathology • Infiltration of connective tissue with mononuclear cells (lymphocytes, macrophages , plasma cells) • Activation of CD4+ and CD8+ T-cells and integration with B cells, plasmas cells and macrophages. • Release of pro-inflammatory cytokines. • Accumulation of GAG in the EOM and fat. • CD34 + fibrocytes key in the pathogenesis , • Antigen in orbit : Thyroglobulin • TSHR is found on thyroid follicles and orbital fibroblasts
  4. 4. Systemic Signs and Symptoms • Symptoms : Hyperactivity , hear intolerance , palpitations , weight loss and gain (increased appetite) , Diarrhea . • Signs : Tachycardia , atrial fibrillations , tremor , goiter , warm moist skin, lid retraction and lag , exophthalmos. • Eye signs usually start within a year of hyperthyroidism (75%) • Occasionally eye signs start years later.
  5. 5. Laboratory investigations • Endocrine : low or borderline TSH ,normal or elevated T4 , elevated T3, TSHR autoantibodies • T3 toxicosis . • T4 toxicosis (excess iodine intake) • Eleveated bilirubin , liver enzymes , ferritin (diagnostic confusion) • Microcystic anemia and thrombocytopenia.
  6. 6. TSHR Auto-antibodies • Antibodies that bind to TSH receptors. • Binding assay : measures both Thyroid stimulating and thyroid blocking antibodies • Cell-based assay : can distinguish thyroid stimulating and thyroid blocking antibodies by their effect on cyclic AMP production in cell lines. (more useful to measure activity and prognosis)
  7. 7. Imaging in TED • Enlargement of EOM, orbital fat expansion , increase lacrimal gland size. • CT is the study of choice (Bone and soft tissues)
  8. 8. CT in TED • For initial diagnosis and for planing for decompression surgery • Bone remodeling (medial wall) • Enlargement of EOM , lacrimal glands, anterior soft tissue swelling , prominent SOV maybe seen
  9. 9. MRI in TED • Quantitative and qualitative • Assess disease activity • Increased T2 in EOM - good response to XRT and steroids • Increased T2 in EOM - active stage ( high water content) • Low T2 in EOM- inactive fibrotic stage
  10. 10. Ultrasound in TED • A and B-scan • operator dependent • Normal muscle - low internal reflectivity • Active phase - lower internal reflectivity (swelling) • Fibrotic phase- irregular high reflectivity (scar)
  11. 11. Medical Management of Hyperthyroidism • Anti-thyroid drugs : thinoamides (PTU) , carbimazole , methimazole. • Thionamides inhibit synthesis of thyroid hormones. • Need 6-8 weeks to achieve euthyroid state • Side effects of anti-thyroid drugs : Skin rash , urticarial , arthralgia , Fever
  12. 12. Natural History of Thyroid Eye Disease • Rundle’s curve • Progressive phase lasting for up to 18 months • Stable (inactive) phase
  13. 13. Clinical Features – Lid retraction Pathogenesis : sympathetic stimulation , overaction of LPS alone with SR compensating for IR restriction , inflammation and fibrosis of LPS.
  14. 14. Clinical Features-Proptosis • Due to expansion of orbital fat and muscles. • Complete subluxation of the globe (sometimes) • Prolapse of the lacrimal glands • Corneal exposure/ epithelial defects • Absence of Bell’s phenomenon (tight IR)
  15. 15. Strabismus • 30% of patients with TED • Diplopia can be intermittent or constant • During the active phase : enhancement of fat surrounding affected muscles • Inferior Recti , Medial Recti (most common) • Any type of Strabismus ( ET and HopT most common) • Oblique muscle involvement more common.
  16. 16. Compressive Optic Neuropathy • 5%-7% of TED • Direct compression of the optic nerve at the orbital apex • Dyschromatopsia , RAPD ( absent if bilateral) • Disc edema in 40% • Visual fields • Often in the active phase of the disease • Proptosis may be minimal (tight lids)
  17. 17. Thyroid CON
  18. 18. Clinical Activity • NOSPECS – not very useful • EUGOGO classification : Mild : eyelid swelling , lid retraction, proptosis Moderate-Severe : Active disease (EOM dysfunction, diplopia , proptosis >25 mm) Very severe : CON , Corneal exposure (needs emergent surgery)
  19. 19. Clinical Activity • Clinical Activity Score (CAS) : -Binary scale -1 point for each periocular soft tissue inflammatory sign -Points for proptosis ( 2 mm or more) , decreased motility (8 degrees or more) or decreased visual acuity over last 3 months. -CAS > 4 means 80% PPV for response to steroids
  20. 20. CAS Limitations • Score does not correlate with significant complications (CON) , each sign has equal point weight • Patients with low CAS may develop severe complications (like CON) • Cannot measure response to therapy
  21. 21. VISA classification • V (Vision) , I (inflammation), S (Strabismus) , A (Appearance) • Vision/CON • Inflammation/Congestion : based on documented change of inflammation rather than absolute value • Strabismus/Motility : measuring ductions and alignments • Appearance/Exposure • Score of 5 or more —> Active disease or progression (Consider Steroids)
  22. 22. VISA Classification
  23. 23. VISA Classification
  24. 24. Risk Factors for Progression • Smoking • Life stressors • Hypothyroidism following radio-iodine treatment • Positive family history of auto-immune disease • Increasing age
  25. 25. Medical Management of TED • Assessment of clinical severity of disease. • CAS : 4 of 10 points (80% PPV to steroids) • VISA classification : popular in N America (>5 of 10) • GO-QOL : to assess effects of disease on personal and professional life. • Simple measures for mild TED ( lubricants , cold compressors)
  26. 26. Selenium • 200 ug/day for 6 months • For Mild disease • Antioxidant effect • Immunomodulatory effect : reduce thyroid autoantibodies • Reduce severity of disease and improve QOL
  27. 27. Corticosteroids • Intravenous , Oral • IV pulses are more effective and has 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%) • Steroid response is evident usually 2-4 weeks later • Moderate to severe TED : 71% respond to IV steroid vs 51% oral with SS improvement of VA , chemosis and QOL. • IV steroids for compressive ON
  28. 28. Orbital Radiation • Mechanism : lymphocyte sterilization, destruction of tissue 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) • More suited for patients > 35 years of age • Contra-indicated in pre-existing retinopathy (diabetes , hypertensive)
  29. 29. Rituximab • Chimeric mono-clonal antibody targets CD20 • CD20 is expressed on more than 95% of B cells and plasma cells • RTX removes B cells and short-lived plasma cells • RTX depletes 95% of mature B cells , blocks Ab production , and decrease inflammatory cytokine release • For steroid-refractory disease • Side effects : Allergic reaction (mild) PML (severe)
  30. 30. Botulinum Toxin • Neurotoxin , inhibits acetylcholine release • For upper lid retraction (transconjunctival , transcutaneous route) • Effect on Muller’s muscle and LPS • Side effects of Botox : bruising , ptosis and diplopia
  31. 31. Orbital Decompression for TED • In TED , expansion of fat and muscles. • Decompression usually in stable phase of disease. • Cosmetic for rehabilitation and or for severe TED. • Need to discuss goals of surgery with patients. • Post-operative complications (diplopia, vision loss) • Outcome is variable : degree of fibrosis , fat expansion , bone available , duration of optic neuropathy etc • Decompression —> Muscle Surgery —> Lid surgery
  32. 32. Orbital Decompression Fat only (First Wall) 2-3 mm Lateral Wall 3-6 mm Medial Wall 4-7 Orbital Roof 5-9 mm
  33. 33. Strabismus Surgery for TED • In the stable phase with stable alignments for 6 months • Press-on Fresnel/Botox as temporizing measure • Single binocular vision in primary and reading position • “More is less and less is More” • Conjunctival dissection is challenging • Adjustable vs Fixed sutures • Relaxed EOM positioning • Oblique surgery can increase area of single binocular vision
  34. 34. Complications of Strabismus Surgery in TED • Scleral perforation • Anterior segment ischemia (>2 muscles , old age , Atherosclerosis) — preoperative Iris FA • Slipped/lost muscles (IR) • Under-/overcorrections • Re-operation rate around 50% in TED • Intraoperative assessment of oblique muscle involvement (to increase area of binocularity)
  35. 35. Crowing of Eyebrows /Lid Complex Fat expansion/prolapse of the lacrimal glands
  36. 36. Lower Lid retraction • Can improve with decompression and removal of the floor basin. • Lower lid recession with decompression. • Spacer (ear cartillage or hard palate/allogenic material • Lower retraction repair can be combined with inferior rectus recession
  37. 37. Upper Lid Retraction • Levator recession / Mullerectomy • Full-thickness blepharotomy • Botox injections into Muller’s muscle • Filler (Hyaloronic acid) in subcinjunctival space (0.1-0.2 ml)
  38. 38. Psychological Impact of TED • 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 • Quality of life measures and questionnaires • Multidisciplinary approach (psychiatric included) • Support groups
  39. 39. Psychological Disturbances in TED
  40. 40. GO-QOL Questionnaire
  41. 41. Graves disease Mimickers • Inflammatory (IOIS , CCF , Orbital Vascular lesions, Sarcoidosis) • Neoplastic (Lymphoma , lacrimal gland tumors , meningioma) • Motility (Myasthenia , cranial nerve palsy , Orbital Myositis , orbital apex and cavernous sinus lesions) • Lid retraction (Parinaud's syndrome)
  42. 42. Graves Ophthalmopathy Mimickers
  43. 43. Graves Ophthalmopathy
  44. 44. Graves Ophthalmopathy Mimickers
  45. 45. Graves Ophthalmopathy Mimickers

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