Thyroid Eye Disease 2023 Myers PDF

Thyroid Eye Disease S A M A N T H A M Y E R S O D , FA A O ; J E S S I C A WA LT E R , O D OPT 619 ANTERIOR SEGMENT DISEASE K E N T U C K Y C O L L E G E O F O P TO M E T R Y FA L L 2 0 2 3 Outline Introduction Systemic Thyroid Disease ◦ Hyperthyroidism & Graves’ Disease ◦ Hypothyroidism & Hashimo...

Thyroid Eye Disease S A M A N T H A M Y E R S O D , FA A O ; J E S S I C A WA LT E R , O D OPT 619 ANTERIOR SEGMENT DISEASE K E N T U C K Y C O L L E G E O F O P TO M E T R Y FA L L 2 0 2 3 Outline Introduction Systemic Thyroid Disease ◦ Hyperthyroidism & Graves’ Disease ◦ Hypothyroidism & Hashimoto Thyroiditis Thyroid Eye Disease ◦ ◦ ◦ ◦ ◦ Risk Factors Pathophysiology Clinical Presentation Workup Management & Prognosis Thyroid Eye Disease AKA: TED, Graves’ ophthalmopathy, thyroid-associated orbitopathy Autoimmune inflammatory orbital disorder with characteristic clinical signs Caused by activation of orbital fibroblasts by autoantibodies directed against thyroid receptors https://upload.wikimedia.org/wikipedia /commons/8/8f/Propt osis_and_lid_re traction_from_Graves %27_D isease.j pg Thyroid Eye Disease Occurs in: ◦ Hyperthyroidism - Graves hyperthyroidism/Graves’ disease (90% of TED cases) ◦ Hypothyroidism - Hashimoto thyroiditis ◦ Euthyroid - absence of thyroid disfunction The severity/course of TED does not always correlate with activity of thyroid gland or treatment of thyroid abnormalities Systemic Thyroid Disease Review: The Thyroid Gland Structure ◦ Front of the neck; sits below the larynx (voice box) and on top of the trachea (windpipe) ◦ Small, 2-inch butterfly-like shaped gland ◦ 2 lobes, 1 on each side of the windpipe, connected by a small bridge of thyroid tissue called the isthmus ◦ Thyroid tissue has 2 types of cells ◦ Follicular cells ◦ Parafollicular cells Review: The Thyroid Gland Function ◦ Produces hormones ◦ 80% of thyroxine (T4) ◦ 20% of triiodothyronine (T3) and calcitonin ◦ T3 and T4 are produced by follicular cells ◦ T4 is an inactive thyroid hormone that circulates in the bloodstream, ready to be converted to the active form, T3 ◦ T3 and T4 increase basal metabolic rate ◦ Making the cells in the body work harder, affecting things like body temperature, heart rate, bowel function, etc. ◦ Adequate levels of iodine are required for the synthesis of T3 and T4 ◦ Calcitonin is produced by the parafollicular cells ◦ Calcitonin has a minor role in calcium regulation in the body Review: The Thyroid Gland Function ◦ The pituitary gland and the hypothalamus in the brain help regulate the thyroid and thyroid hormones through a feedback loop system (Hypothalamic-Pituitary-Thyroid Axis) ◦ The hypothalamus releases thyroid-releasing hormone (TRH) ◦ TRH stimulates the pituitary gland to produced and release thyroid-stimulating hormone (TSH) ◦ TSH then binds to TSH receptors in the thyroid gland to stimulate the production of T3 and T4 ◦ When the levels of T3 and T4 increase, they prevent the release of TRH (and thus TSH) ◦ When T3 and T4 levels drop, the feedback loop starts again ◦ This system allows your body to maintain a constant level of thyroid hormones in your body Hyperthyroidism Excessive synthesis and secretion of thyroid hormones ◦ Leads to thyrotoxicosis ◦ Hypermetabolic state where too much thyroid hormone is present in the body Causes: ◦ ◦ ◦ ◦ ◦ Graves’ disease Subacute thyroiditis Toxic multinodular goiter Toxic adenoma Others https://www.niddk.nih.gov/-/media/Ima ges/He alth-Information/Diag nostic-T ests/ThyroidA natomy _300x3 42.jpg Graves’ Disease AKA Graves’ hyperthyroidism Most common form of hyperthyroidism Autoimmune disorder ◦ Antibodies bind to thyroid stimulating hormone (TSH) receptors in the thyroid gland ◦ Stimulates thyroid activity → secretion of excess thyroid hormones (T3 and T4) → hyperthyroidism ◦ Main antibody is IgG https://healthcare.utah.edu/moran/ima ges/ted -graves -sympt oms.jpg Graves’ Disease Affects females > males (about 6:1) Presents in 4th to 5th decades of life Classic triad: https://els-jbs-prod-cdn.jbs.elsevierhealt h.com/cms/att achmen t/ec6eb d5d-e3 80-441e -8267-da28d4d7ff9b/g r1_lrg.j pg ◦ Orbital signs - up to 80% ◦ Hyperthyroidism ◦ Pretibial myxedema - Graves’ dermopathy ◦ Skin lesions found on the shins https://dermnetnz.org/assets/Uploads/dermal-i nfiltrati ve/w/pretibial -myxoe dema-0 1__ProtectWy JQcm90 ZWN0Il 0_FocusFillWzI 5NCwy MjIsInki LDEwOF0.jpg Hyperthyroidism Symptoms: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Unexplained weight loss Increased bowel frequency Sweating Heat intolerance Nervousness Irritability Palpitations Weakness and fatigue Hyperthyroidism Signs: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Enlargement of thyroid gland (goiter) Tremor Palmar erythema (red palms) Warm and sweaty skin Orbital disease →50% of patients Thyroid acropachy → nail clubbing, swelling of fingers and toes Pretibial myxedema Cardiac arrhythmias Other autoimmune conditions https://cdn.mdedge.com/files/s3fs-public/images/TH_2012_07_pp10_01.jpg Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Systemic signs in thyrotoxicosis. (A) Goitre; (B) acropachy Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Bloodwork: Thyroid Function Tests Thyroid-stimulating hormone (TSH) ◦ Most reliable screening measure of thyroid function Thyroxine (T4) ◦ 2 types- Bound and Free (unbound) ◦ Bound: attached to thyroxin-binding globulin (TBG), a carrier protein that transports T3 throughout the bloodstream ◦ Unbound/free: not attached to TBG, free to enter tissues and affect body processes ◦ 2 different lab tests ◦ Total T4 (Bound + free) ◦ Free T4 Bloodwork: Thyroid Function Tests Triiodothyronine (T3) ◦ 3 types- bound , unbound (free), reverse T3 ◦ Bound: attached to thyroxin-binding globulin (TBG), a carrier protein that transports T3 throughout the bloodstream ◦ Unbound/free: not attached to TBG, free to enter tissues and affect body processes ◦ Reverse T3: An inactive form of T3 that has no utility but can block free T3 from entering tissues ◦ 3 different lab tests ◦ Total T3 (Bound + free) ◦ Free T3 ◦ Reverse T3 Bloodwork: Thyroid Function Tests T3 Uptake ◦ The percent of TBG that is bound to thyroid hormones ◦ Indirect measure of TBG binding capacity, and thus free T3/T4 Free thyroxine index (FTI) ◦ The product of the measured T4 level and T3 uptake ◦ Takes into account the absolute hormone level and the binding capacity of thyroid-binding globulin (TBG) Bloodwork: Thyroid Function Tests 15.0 45 6.1 H H H 4.21 H 0.251 L 5.7 H Results indicating hyperthyroidism: ◦ ◦ ◦ ◦ Decreased TSH Elevated T3 and/or T4 Elevated T3 uptake Elevated FTI HypothalamicPituitary-Thyroid Axis IgG Why does hyperthyroidism result in decreased TSH levels? Graves: immunoglobulins bind to TSH-receptors in the thyroid gland Normal: ◦ TSH binds to TSH-receptors in thyroid gland ◦ Release of T3 and T4 provides inhibitory feedback to hypothalamus and pituitary ◦ Regulates production of TSH Hyperthyroid: ◦ Thyroid is stimulated to release excessive amounts of T3 and T4 ◦ Feedback causes large decrease in TSH levels Bloodwork: Autoimmune Function Tests Help identify cause of thyroid disease ◦ May identify patients at high risk for TED ◦ However, TED is mostly a diagnosis based on clinical findings Autoantibody tests: ◦ Anti-thyroid peroxidase (anti-TPO) antibody ◦ Thyroid-stimulating immunoglobulin (TSI) ◦ AKA Thyroid-stimulating antibody (TSab) or TSH-receptor antibody (TRab) Graves’ disease ◦ Elevated anti-TPO in ~70% of cases ◦ Elevated TSI/TSab/TRab in ~90-95% of cases Hyperthyroidism Systemic treatment: ◦ Symptom relief ◦ Beta blockers for cardiovascular symptoms ◦ Antithyroid pharmacotherapy ◦ Methimazole, carbimazole, propylthiouracil ◦ Radioactive iodine therapy ◦ ◦ ◦ ◦ Preferred therapy Single dose oral medication Causes fibrosis and destruction of thyroid → thyroid ablation May worsen ophthalmopathy ◦ Thyroidectomy ◦ Surgical removal of parts or all of the thyroid ◦ Reserved for severe cases that are unresponsive to other treatments or unable to use other treatments https://www.drugs.com/health-guide/i mages/2 05306.j pg Which of the following is NOT a symptom of hyperthyroidism? A. B. C. D. E. F. Unexplained weight loss Sweating Nervousness Irritability Palpitations Cold intolerance Hypothyroidism Deficiency of thyroid hormone ◦ Poor thyroid gland function ◦ Decreased stimulation of thyroid from TSH Causes: ◦ Iodine deficiency → #1 cause worldwide ◦ Hashimoto thyroiditis → #1 cause in US ◦ Autoimmune condition ◦ ◦ ◦ ◦ Pituitary issues Drug-induced Post-partum And more Hashimoto Thyroiditis AKA lymphocytic thyroiditis Autoimmune condition causing destruction of thyroid cells Body thinks thyroid antigens are foreign → production of antibodies → chronic immune reaction → lymphocytic infiltration of thyroid → destruction of thyroid tissue https://www.endocrineweb.com/sites/default/files/wy siwyg_i mageu pload/3 7373/2 020/01/ 10/RecognizingNodule _iStock -11745 72604.j pg Hypothyroidism Symptoms: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Fatigue, lethargy Weight gain Cold intolerance Dry skin Hair loss Weak extremities Depression Forgetfulness, impaired memory Specific to Hashimoto thyroiditis: ◦ Feeling of fullness in the throat ◦ Thyroid enlargement ◦ Exhaustion ◦ Neck pain or sore throat Hypothyroidism Signs: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Slowed speech and movements Jaundice Pallor Coarse hair Hair loss → outer 1/3 of eyebrows Periorbital swelling Bradycardia Myxedema – swelling of eyelids, extremities https://upload.wikimedia.org/wikipedia /commons/thumb/9/9f/Signs_ and_sy mptoms_of_hy pothyr oidism.png/300 px-Signs_and_s ymptoms_of_h ypothy roidism.png Hypothyroidism 4.2 20 1.0 L L L 0.69 L 10.1 H 2.0 Workup: ◦ TSH → elevated ◦ T4, T3 → low or normal ◦ Anti-TPO → elevated in 90% of Hashimoto thyroiditis cases ◦ *hallmark ◦ TSI/TSab/TRab → normal or elevated ◦ elevated in only ~10% of cases ◦ T3 uptake→ low ◦ FTI→ low or normal Others abnormal results you may see: ◦ Complete blood count → anemia (low RBC) ◦ Lipid profile → Hyperlipidemia ◦ Creatinine → elevated Systemic Management Levothyroxine (Synthroid) ◦ Thyroid hormone replacement ◦ Long term, daily dose Surgical treatment for: ◦ Large goiter ◦ For complications or cosmesis ◦ Malignancy Which of the following lab results would support a diagnosis of Graves’ disease? A. Low TSH, high T4, high anti-TPO, high TSI B. High TSH, high T4, high anti-TPO, low TSI C. Low TSH, low T4, low anti-TPO, low TSI D. High TSH, low T4, high anti-TPO, high TSI Thyroid Eye Disease Thyroid Eye Disease Autoimmune inflammatory orbital disorder with characteristic clinical signs Hyperthyroidism carries a higher risk for TED than other thyroid states ◦ Can still occur with euthyroidism, hypothyroidism Epidemiology ◦ Women affected 5-6x more often than men ◦ Same statistic as Graves’ disease ◦ Median age = 43 Risk Factors ◦ Smoking = the major modifiable risk factor ◦ Risk is directly correlated with number of cigarettes smoked per day ◦ Stress ◦ Hyperthyroidism ◦ Radioactive iodine treatment can worsen TED Pathophysiology Organ-specific autoimmune reaction leads to inflammation of EOMs, connective tissue, orbital fat, and lacrimal gland 1. Antibodies react against thyroid gland cells and orbital fibroblasts 2. Infiltration of T cells, cytokines, other cellular materials, glycosaminoglycans (GAGs) 3. GAGs bind water (osmosis) → swelling, congestion, connective tissue remodeling 4. Enlargement of EOMs and soft tissues of orbit Pathophysiology Enlargement of orbital tissues causes: ◦ Increased volume of orbital contents ◦ EOMs may swell up to 8x normal size ◦ Increased intraorbital pressure ◦ Compression of optic nerve ◦ Eventual degeneration of muscle fibers → fibrosis ◦ Causes a tethering effect on the involved muscle ◦ Manifests as restrictive myopathy and diplopia https://media.springernature.com/full/s pringer-static/i mage/a rt%3A 10.1038 %2Fnre ndo.20 09.61/ MediaObjects/4 1574_2 009_Ar ticle_BFnrendo200961 _Fig1_ HTML.j pg Thyroid Eye Disease Diagnosis is made when 2 of the 3 are present: 1. Concurrent or recently treated immune-related thyroid disfunction ◦ Graves hyperthyroidism ◦ Hashimoto thyroiditis ◦ Circulating thyroid antibodies without a coexisting dysthyroid state 2. Typical ocular signs ◦ ◦ ◦ ◦ ◦ ◦ Chemosis and/or caruncular edema Restrictive strabismus in typical pattern Unilateral or bilateral eyelid retraction with typical lateral flare Unilateral or bilateral proptosis Compressive optic neuropathy Fluctuating eyelid edema/erythema 3. Radiographic evidence of TED ◦ Unilateral or bilateral fusiform enlargement of any of the rectus muscles and/or the levator muscle complex Clinical Presentation Congestive/inflammatory stage ◦ Red, painful eyes ◦ Remits in 1-3 years ◦ 10% of patients develop serious long-term ocular complications Fibrotic/dormant stage ◦ White eyes ◦ Painless motility defects General involvement: ◦ ◦ ◦ ◦ ◦ Lid retraction Soft tissue involvement Proptosis Restrictive myopathy Optic neuropathy Ocular Signs of TED Lid Retraction Affects 50% of Graves disease patients Retraction of upper and/or lower lids Unilateral or bilateral Proposed mechanisms: ◦ High levels of thyroid hormones → sympathetic overstimulation → overaction of Muller muscle ◦ Fibrotic contraction of levator palpebrae, recti muscles, and adhesion to orbital tissues Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Lid signs in thyroid eye disease. (A) Mild left lid retraction; (B) moderate bilateral asymmetrical lid retraction – Dalrymple sign; (C) severe bilateral lid retraction – Kocher sign; (D) right lid lag on downgaze – von Graefe sign Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Lid Retraction Symptoms: staring or bulging appearance of eyes, difficulty closing eyes, dry eye symptoms Signs: ◦ Upper lid margin sitting at or above superior limbus ◦ Normal = 2mm below limbus ◦ Lower lid margin sitting below inferior limbus ◦ Normal = at the inferior limbus ◦ AKA “scleral show” https://www.researchgate.net/profile/Christos-Haritoglou/publication/7959 853/figure/fig4 /AS:278 591158 931458 @1443 432716 072/A-Male-pa tient-w ith-mar ked-upper-eye lid-retr action-i n-Grave s-disea se-B-Sa me-pati ent_Q3 20.jpg There are many ocular signs of TED named after their discoverers… Dalrymple’s Sign Lid retraction in primary gaze (widened palpebral fissure) Most common presenting sign of TED Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Lid signs in thyroid eye disease. (A) Mild left lid retraction; (B) moderate bilateral asymmetrical lid retraction – Dalrymple sign; (C) severe bilateral lid retraction – Kocher sign; (D) right lid lag on downgaze – von Graefe sign Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Kocher Sign Severe bilateral lid retraction ‘”stare”appearance Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Lid signs in thyroid eye disease. (A) Mild left lid retraction; (B) moderate bilateral asymmetrical lid retraction – Dalrymple sign; (C) severe bilateral lid retraction – Kocher sign; (D) right lid lag on downgaze – von Graefe sign Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Von Graefe Sign Upper lid lag on downgaze https://media.springernature.com/full/s pringer-static/i mage/a rt%3A 10.1007 %2Fs00 417-00 4-1012-x/Medi aObject s/s0041 7-004-1 012-xfhc3.jpg Mobius Sign Unable to converge or maintain convergence Caused by TED myopathy https://image.slidesharecdn.com/ep3-160307123524/95/ophthalmology-eponyms-ii-23-638.jpg?cb=1564319071 Means Sign Increased scleral show on upgaze (globe lag) A form of TED myopathy (limited upgaze) https://entokey.com/wp-content/uploads/2016 /07/DA 1-DB5-D C1-C21-FF2.gif Enroth’s Sign Eyelid edema/puffiness https://www.researchgate.net/profile/ Andrei-Cucu/publication/3045 81387/fi gure/fi g1/AS:3 784132 746813 45@14 672321 63899/ Opthamopathy -in-Gra ves-dise ase-eye lid-ede ma-Enr oth-sign -and-conjunctiv al-che mosis-Dr .png Other ocular signs… Boston’s Sign → Jerky, irregular movement of upper lid on downgaze Gifford’s sign → difficulty everting upper lid Griffith’s Sign → lower lid lag on upgaze Rosenbach’s sign → Fine tremors of the eyelids when closed Stellwag Sign → infrequent and incomplete blinking Video demonstrating multiple signs: https://www.youtube.com/watch?v=AS_UxTrdvcA Soft Tissue Involvement Symptoms: grittiness, redness, epiphora, photophobia, puffy lids, retrobulbar discomfort Signs: ◦ Bulbar injection ◦ Inflammatory ◦ Focal hyperemia at insertions of medial and lateral recti muscles ◦ Periorbital swelling ◦ Edema and infiltration behind the orbital septum ◦ Chemosis ◦ Prolapse of retroseptal fat into the eyelids Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Soft tissue involvement in thyroid eye disease. (A) Epibulbar hyperaemia overlying a horizontal rectus muscle; (B) periorbital oedema, chemosis and prolapse of fat into the eyelids; (C) superior limbic keratoconjunctivitis Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Soft Tissue Involvement ◦ Insufficient/unstable tear film ◦ Dry eye ◦ Corneal signs: ◦ ◦ ◦ ◦ ◦ Punctate epithelial erosions Superior limbic keratoconjunctivitis (SLK) Bacterial keratitis Thinning Scarring https://webeye.ophth.uiowa.edu/eyefor um/atl as/page s/Punct ate-epi thelial-erosions/Expos ure-PEE -LRG.jpg https://webeye.ophth.uiowa.edu/eyefor um/atl as/page s/Supe rior-limbic-kera toconjunctiviti s-SLK/S LK.jpg Proptosis Symptoms: same as lid retraction; suddenonset diplopia Signs: ◦ Unilateral or bilateral ◦ Symmetric or asymmetric ◦ Often permanent Complications: ◦ Exposure keratopathy (poor lid closure, lid retraction, tear disfunction) ◦ Corneal ulceration and infection https://images.medicinenet.com/images /article /main_i mage/ bulging-eyes.jpg Restrictive Myopathy Affects 30-50% of TED patients May be permanent Mechanism of muscle restrictions: ◦ Initially → inflammatory edema ◦ Later → fibrosis ◦ Because the myopathy is restrictive in nature, should not improve with ductions or forced ductions ◦ Only the belly of the EOM is inflamed, tendons are spared Symptoms: ◦ Diplopia ◦ Discomfort in some positions of gaze Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 Restrictive thyroid myopathy. (A) Defective elevation mainly of the right eye; (B) reduced depression of the right eye secondary to fibrosis of the right superior rectus; (C) defective elevation of the left eye in the same patient shown in (B) Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Restrictive Myopathy I M S L O Signs (most to least frequent muscle affected) ◦ Elevation deficit ◦ Due to fibrotic contracture of the inferior rectus ◦ Mimics superior rectus palsy ◦ Abduction deficit ◦ Fibrosis of medial rectus ◦ Simulates a CN 6 palsy ◦ Depression deficit ◦ Superior rectus ◦ Adduction deficit ◦ Lateral rectus https://www.researchgate.net/publicati on/340 572016 /figure/ fig1/AS :87901 811087 7697@ 158658 565748 5/Extra ocular-muscles-8.png ◦ Obliques Optic Neuropathy Affects up to 6% of TED patients Ocular emergency Compression of optic nerve or its blood supply occurs at the orbital apex ◦ Due to congested/enlarged recti muscles and swollen orbital tissue ◦ Orbital compartment syndrome ◦ Can occur without proptosis Can lead to severe visual impairment if left untreated https://media.springernature.com/origi nal/spri nger-st atic/ima ge/chp%3A10. 1007% 2F978-9 81-10-7 668-8_ 28/Med iaObjects/3712 38_1_E n_28_F ig1_HT ML.jpg Optic Neuropathy Symptoms: blurred vision, vision loss, reduced color vision, orbital pain ◦ May be accompanied by other TED symptoms Signs: ◦ ◦ ◦ ◦ ◦ Reduced VA Reduced color vision and brightness perception RAPD VF defects Optic nerve edema (but may appear normal) NOSPECS Classification N – No physical signs or symptoms O – Only signs, no symptoms (lid signs) S – Soft tissue involvement P – Proptosis E – EOM involvement C – Corneal involvement S – Sight loss (optic nerve involvement) A system for grading presence/severity of TED A right abduction deficit in a patient with active TED would indicate which muscle is most likely affected? A. Right lateral rectus B. Right medial rectus C. Left medial rectus D. Left lateral rectus E. Right superior rectus F. Right inferior rectus Differential Diagnoses for TED TED- tendons spared Any other cause of orbital inflammation, proptosis, muscle restrictions, or palsies Orbital pseudotumor Carotid-cavernous fistula Inflammatory orbitopathy ◦ granulomatosis with polyangiitis, idiopathic orbital inflammation, etc. Orbital myositis Idiopathic orbital inflammationtendons involved Orbital tumors Workup for TED Complete ophthalmologic exam with close attention to: ◦ ◦ ◦ ◦ VA Pupils Color vision EOMs & cover test https://ars.els-cdn.com/content/image/3 -s2.0-B978032 339316 400014 4-f14-01 -97803 233931 64.jpg ◦ If diplopic or abnormal CT/EOM finding ◦ CT in 9 POG ◦ Ductions, possibly forced ductions ◦ ◦ ◦ ◦ ◦ Visual field External observation Exophthalmometry Slit Lamp exam Dilated fundus exam https://www.opsweb.org/resource/res mgr/op_ externa l/skippy_normal_540. jpg Workup Labs for thyroid function: ◦ ◦ ◦ ◦ ◦ ◦ ◦ TSH T3, T4 (Free and total) T3 uptake FTI Anti-TPO TSI Perform if suspicious for TED with no known diagnosis of thyroid dysfunction ◦ Not particularly useful in monitoring TED treatment and progression ◦ TED and systemic thyroid disease severity often do not correlate CT/MRI of orbits ◦ EOM belly enlargement, sparing tendons ◦ Optic nerve compression Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 CT scan showing muscle enlargement in thyroid eye disease. (A) Axial view showing fusiform enlargement of the medial rectus muscle; (B) coronal view showing symmetrical involvement of the medial, superior and inferior rectus muscles as well as the... Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Treatment & Management Discontinue smoking Manage thyroid disfunction ◦ Endocrinology referral Mild disease: ◦ Dry eye, SLK, exposure keratopathy management: ◦ Topical lubricants ◦ Artificial tears, gels, and ointments ◦ Topical anti-inflammatories for exacerbation ◦ Steroids (fluorometholone, lotemax, prednisolone) ◦ NSAIDs (ketorolac, bromfenac) ◦ Cyclosporine (Restasis) – long term for dryness ◦ Eyelid taping or sleep mask at bedtime for exposure ◦ Elevate the head while sleeping for reduction of periorbital edema https://www.eyeeco.com/blog/wp-cont ent/upl oads/20 18/10/t his-one -e1539 630235 587.jpg Moderate-Severe Disease Goals: ◦ Reduce acute inflammation ◦ Prevent long-term complications Systemic steroids ◦ Oral prednisolone (60-80 mg/day, then tapered with improvement) ◦ Use for about 2-3 months ◦ May need long-term low dose Orbital steroid injection ◦ If unable to tolerate systemic side effects ◦ Less effective Low-dose radiotherapy ◦ Alone or with steroids ◦ Takes about 6 weeks to be effective ◦ Adverse effects → cataracts, retinopathy Immunosuppressants ◦ Azathioprine Moderate-Severe Disease Optic neuropathy: ◦ ◦ ◦ ◦ Pulsed IV methylprednisolone Orbital wall decompression Orbital apex decompression Orbital radiotherapy New therapies: ◦ Drugs targeting immune response in TED Orbit Salmon, John F., MD, FRCS, FRCOphth, Kanski's Clinical Ophthalmology, Chapter 4, 113-154 ◦ Monoclonal antibody treatment – rituximab, teprotumumab (Tepezza) ◦ Tepezza blocks insulin-like growth factor (IGF) receptors, reduces proptosis by reducing orbital inflammation ◦ Given as 1 IV infusion every 3 weeks, for a total of 8 infusions Axial CT following bilateral lateral and medial wall decompression (Courtesy of A Pearson) Copyright © 2020 © 2020, Elsevier Limited. All rights reserved. Managing Post-Inflammatory Complications Proptosis ◦ Surgical decompression if severe ◦ Removal of bone and orbital fat ◦ Increases volume of orbit ◦ Also for compressive optic neuropathy Restrictive myopathy - diplopia ◦ Prism or occlusion ◦ Botox ◦ Strabismus surgery – recession of affected muscle ◦ For persistent diplopia in primary gaze or when reading ◦ Must have stable deviation for 6-12 months, no active inflammation http://www.sarawakeyecare.com/Atlas ofophthalmology/Ocul oplastic/botoxt eda.jpg Lid retraction ◦ Mild cases may improve spontaneously ◦ Botox to levator and Muller muscle ◦ Recession or disinsertion of Muller muscle, levator aponeuroses, or lower lid retractors NOSPECS Classification System Grades disease severity Treatment: N – No physical signs or symptoms No treatment indicated O – Only signs, no symptoms Lubrication & lid taping S – Soft tissue involvement NSAIDs, steroids, elevation P – Proptosis Steroids, radiotherapy, decompression E – EOM involvement Surgery, botox C – Corneal involvement Management of proptosis and corneal condition S – Sight loss (optic nerve involvement) Steroids, decompression Which of the following does NOT increase risk of developing thyroid orbitopathy? A. Smoking B. Radioactive iodine therapy C. Steroid intake D. Stress Questions? References Bagheri, N. Wajda, BN. The Wills Eye Manual. 7th edition. Wolters Kluwer. 2017. Gandhi R, Durairaj VD. Thyroid Eye Disease. Amercian Academy of Ophthalmology EyeWiki. 7 July 2021. Accessed 24 Oct 2021. Kim, HJ. How to Recognize & Treat Thyroid Eye Disease. Review of Ophthalmology. 7 Nov 2013. Robert S. Feder M. 2021-2022 Basic and Clinical Science Course, Section 7: Oculofacial Plastic and Orbital Surgery. American Academy of Ophthalmology; 2021. Accessed October 10, 2021. Salmon, John F., MD, FRCS, FRCOphth. Kanski's Clinical Ophthalmology, Ninth Edition.