Rheumatology, Thyroid Dysfunction and August 31, 2018 the Eye
Disclosures- Greg Caldwell, OD, FAAO
$ Will mention many products, instruments and companies during our discussion Rheumatology, Thyroid Dysfunction ¬ I don t have any financial interest in any of these products, instruments or companies and the Eye $Pennsylvania Optometric Association –President 2010 2 POA Board of Directors 2006-2011 $American Optometric Association, Trustee 2013-2016 Greg Caldwell OD, FAAO ¬ Thank you to the members and those who join $I never used or will use my volunteer positions to further my lecturing Optometric Education Consultants career Northern Escape $Lectured for: Shire, BioTissue, Optovue, Alcon, Aerie August 31, 2018 $Advisory Board: Allergan $Envolve: PA Medical Director, Credential Committee Disclosure Statement $ (next slide) Optometric Education Consultants- Scottsdale and Quebec City, Owner
Learning Objectives
$Enhance clinical understanding of rheumatology and thyroid dysfunction and their ocular associations $Enhance clinical diagnosis of ocular manifestations of Thyroid Disease rheumatologic diseases and thyroid disease and $Enhance clinical management and treatment of ocular manifestations of rheumatologic diseases and thyroid eye disease Thyroid Eye Disease $Increase comfort level when ordering or interpreting laboratory tests in rheumatologic and thyroid diseases $Gain confidence in working closer with rheumatology and endocrinology
Thyroid Thyroid
$Thyroid is an endocrine gland $Exocrine glands contain ducts. Ducts are tubes leading $Two types of glands from a gland to its target organ ¬ Endocrine ¬ Digestive glands have ducts for releasing the digestive enzymes ¬ Exocrine ¬ Salivary glands, sweat glands and glands within the $Endocrine system is a control system of ductless endocrine gastrointestinal tract glands that secrete hormones (chemical messenger) that $Pancreas is both endocrine and exocrine circulate within the body via the bloodstream or lymph ¬ Exocrine (ducted gland) secreting digestive enzymes into the small system to affect distant organs intestine. ¬ Hypothalamus ¬ Pancreas ¬ Endocrine (ductless gland) in that the islets of Langerhans secrete ¬ Pituitary gland ¬ Adrenal glands insulin and glucagon to regulate the blood sugar level. ¬ Thyroid ¬ Gonads (testes and ovaries) ¬ Parathyroid glands ¬ Pineal gland
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Thyroid Thyroid
$Largest endocrine gland in the body $Butterfly shaped $Thyroid regulates: heart rate, ventilation rate, metabolic $Two lobes located on either side of the trachea in the rate, and development of cells lower portion of the neck $Thyroid disorder- approx 1 in 13 or 7.35% or 20 million $Lies just below skin and muscle layer surface people in USA, estimated 2 million undiagnosed $The thyroid is controlled by the hypothalamus and $Diabetes- approx 1 in 13 or 7.8% or 17.9 million people pituitary in USA , 5.7 million undiagnosed $The primary function of the thyroid is production of the $Pathophysiology: >40 postulates (thyroid) hormones thyroxine (T4), triiodothyronine (T3), and calcitonin
Normal Thyroid Function Discussion
Thyroid Dysfunction Thyroid Dysfunction
$What is the most common cause of thyroid dysfunction? A. Cancer $Primary=Thyroid gland B. Surgically induced C. Medication toxicity or side effect $Secondary= Pituitary failure D. Pregnancy $Tertiary= Hypothalamic E. Autoimmune disease
$In autoimmune disease the body typically produces ______that attacks itself, this can be systemic or organ specific ¬ Antibodies, immunoglobulins
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Antibodies of Thyroid Dysfunction Hyperthyroid
$TSH Receptor Antibodies $TSI attacks the thyroid ¬ Stimulating TSH receptor antibody 2 Thyroid Stimulating Immunoglobulin (TSI) $T3 and T4 increase ¬ Thyroid blocking antibody (TBAb) $TSH decreases $Thyroid Peroxidase Antibodies (TPOAb) ¬ TPO is found in thyroid follicle cells where it converts the thyroid hormone T4 to T3 ¬ TPOAb contributes to thyroid cellular destruction
$Most autoimmune thyroid dysfunctions have a combination of thyroid antibodies, however depending on which AB is more abundant results in the outcome of the disease
Hypothyroid Thyroid Dysfunction Hyperthyroidism Hypothyroidism $TBAb attacks the thyroid (Thyrotoxicosis) (most common organ-specific autoimmune disorder) $Primary-autoimmune $Primary-autoimmune $T3 and T4 decrease ¬ Graves ¬ Chronic autoimmune thyroiditis $TSH increases 2 Graves-Basedow or von 2 Hashimoto's thyroiditis Basedow s ¬ Autoimmune atrophic thyroiditis $Secondary/Tertiary 2 Primary myxedema ¬ Excess thyroid medication for treatment 2 Opposite of Graves disease of hypo or goiter ¬ Postpartum thyroiditis ¬ Toxic multinodular goiter ¬ Toxic adenoma $Secondary/Tertiary ¬ Excess iodine ¬ Lithium medication ¬ Thyroiditis (inflammatory induced) ¬ Excess hormone production ectopic ¬ Pregnancy tissue ¬ Surgically induced ¬ Thyroid carcinoma ¬ Disorders of the pituitary gland or hypothalamus
GRAVE S Hashimoto's Thyroiditis (Hyperthyoidism) (Hypothyroidism)
$A multisystem disorder consisting of a triad $The most common cause of hypothyroidism in the ¬ Hyperthyroidism with diffuse hyperplasia of the thyroid gland United States ¬ Infiltrative dermopathy $It is named after the first doctor who described this ¬ Infiltrative ophthalmopathy condition, Dr. Hakaru Hashimoto, in 1912 $Prevalence: $Autoimmune disease ¬ 20-40 year old female (F:M = 7:1) $Goiter formation ¬ Genetic link $5-10 times more common in women than in men $Etiology: $The underlying cause of the autoimmune process still is ¬ Autoimmune disease: hypersensitivity reaction with thyroid stimulation by the circulation of abnormal thyroid-stimulating unknown immunoglobulins (TSI) ¬ Anti-TPO ab and Anti-TB recp ab present
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Autoimmune atrophic thyroiditis Postpartum Thyroiditis (Hypothyroidism) (Hypothyroidism) $Atrophic thyroiditis is similar to Hashimoto's thyroiditis $These women develop antibodies to their own thyroid $A goiter is not present during pregnancy, causing an inflammation of the thyroid after delivery
Systemic Manifestations of Hyperthyroid Systemic Manifestations of Hypothyroid (Primary or Secondary) (Primary or Secondary)
$Signs $Symptoms $Signs $Symptoms ¬ Sweating ¬ ¬ ¬ Nervousness Cold intolerance Cool, scaling skin ¬ Muscle Weakness ¬ Heat intolerance ¬ Weakness ¬ Puffy hands and face ¬ Emotionally labile ¬ Sweating ¬ Reduced energy ¬ Deep voice ¬ Tremor ¬ Fatigue ¬ Lethargy ¬ Myotonia ¬ Tachycardia ¬ Palpitation ¬ Muscle cramps ¬ Delirium ¬ Arrhythmia ¬ Insomnia ¬ Constipation ¬ Bradycardia ¬ Hypertension ¬ Early waking ¬ Brisk tendon reflex ¬ Increased sleeping ¬ Slow reflexes ¬ Alopecia ¬ Diabetes ¬ Weight gain ¬ Obesity ¬ Vitiligo ¬ ↑Triglycerides & Ca, ↓CHO ¬ Reduced appetite ¬ Hypothermia ¬ Brittle nails ¬ Microcyticanemia ¬ Joint stiffness ¬ Myxedema ¬ Possible goiter ¬ Myxedema
Thyroid Eye Disease (TED) Why is this so confusing?
$Other names used $Thyroid Eye Disease ¬ Grave s disease ¬ Is often seen in conjunction with Graves' Disease (hyperthyroid) ¬ Grave's ophthalmopathy ¬ Is seen in people with no other evidence of thyroid dysfunction ¬ Grave's orbitopathy ¬ Is seen in patients who have Hashimoto's Disease (hypothyroid) ¬ Exophthalmos in Graves Disease ¬ Thyroid Associated Orbitopathy (TAO) $Most thyroid patients, however, will not develop thyroid ¬ Thyroid Orbitopathy eye disease ¬ Ophthalmic Graves Disease ¬ Inflammatory Eye Disease ¬ Endocrine Orbitopathy
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Why is this so confusing? Why is this so confusing?
$The eye symptoms usually occur at the same time as the thyroid $While eye disease may be brought on by thyroid dysfunction disease ¬ Successful treatment of the thyroid gland does not guarantee that the eye disease ¬ However they may precede or follow the obvious symptoms of the thyroid will improve abnormality ¬ No particular thyroid treatment can guarantee that the eyes will not continue to deteriorate $The incidence of thyroid eye disease associated with thyroid dysfunction is higher and more severe in smokers ¬ Once inflamed, the eye disease may remain active from several months to as long as three years ¬ There is no way to predict which thyroid patients will be affected ¬ There may be a gradual or, in some cases, a complete improvement
Thyroid Eye Disease Thyroid Eye Disease
$ Commonly known as Graves' ophthalmopathy $What causes the Thyroid Eye Disease signs and symptoms? $ About 80% of all patients with TED have the autoimmune hyperthyroid disorder known as Graves' disease $The high and low levels of T3 and T4 $ Another 10% of all cases are seen in patients with autoimmune hypothyroidism, either Hashimoto's thyroiditis, atrophic thyroiditis or $The antibodies that are attacking the thyroid gland Hashitoxicosis $ Another 10% of all cases are seen in people with normal thyroid function ¬ When thyroid function is normal, the eye condition is referred to as euthyroid Graves' disease ¬ Euthyroid is a term meaning that thyroid function tests are normal. Most people with euthyroid Graves' disease develop a thyroid disorder within eighteen months of the emergence of the eye disorder ¬ But some people with euthyroid Graves' disease never develop thyroid dysfunction
Phase secondary to abnormal thyroid hormone levels (T3/T4) Thyroid Eye Disease (Thyroid Eye Disease)
$Hyperthyroidism eye symptoms $Hypothyroidism eye symptoms ¬ Excess hormone acting on the nerves ¬ Deficient hormone causing venous $Thyroid Eye Disease has 2 phases that supply the eye congestion, impaired circulation ¬ A phase secondary to abnormal thyroid hormone levels ¬ Usually spastic and include staring and fluid stagnation 2 Increased or decreased FT3 and FT4 levels ¬ Dryness ¬ Periorbital edema ¬ Eyelid retraction 2 Once these levels are normalized, ocular symptoms will resolve ¬ Congestive Autoimmune form of Thyroid Eye Disease 2 Active phase-stimulating or blocking TRAb are causing ocular activity $ This form of TED resolves within a few weeks after thyroid hormone levels (FT4 and 2 Plateau phase-reduced activity FT3) are corrected and brought back into the normal range $ The pituitary hormone TSH can stay low or suppressed for many months during the 2 Resolution phase-symptoms regress and eyes return to normal course of treatment for hyperthyroidism and doesn't mean that the patient is still hyperthyroid $ TSH also lags at least 6 weeks behind thyroid hormone levels and often remains elevated longer in people who have been hypothyroid $ Relying on the TSH level can be misleading and in treating TED
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Congestive Autoimmune form of Thyroid Eye Disease (Active phase, Plateau phase, Resolution phase) Euthyroid Graves' disease
$Caused by both stimulating and blocking TSH receptor antibodies $If thyroid function is (TRAb) and also immune system chemicals known as cytokines normal. How does $Secondary targets appear to be TSH receptor antigens (epitopes) located on orbital fibroblasts as well as dermal fibroblasts one develop thyroid $Active inflammatory phase of TED varies eye disease? ¬ Symptoms resolve quickly although on average the active phase lasts about 12-18 months ¬ TRAb levels are high, patients are smokers, nutrient deficiencies are present, or the patient continues to be exposed to environmental triggers such as excess dietary iodine, the active phase can last as long as 5 years ¬ Avoid any lid, muscle or orbital surgery $Plateau phase and Resolution Passive phase ¬ An individual may be left with structural changes, such as eye protrusion, eyelid retraction, and in some cases, double vision ¬ There are corrective procedures that can be performed to address these problems
Similar receptors are found in the skin, fat and muscle of the orbit
You re in the Know
Normal Values Thyroglobulin 20 IU/ml Peroidase <35 IU/ml TSI 1.75 IU/ml
It does work!
General Ocular Symptoms NOSPECS: Grading System
$Prominent eyes, stare $1969 by S.C. Werner $ Class 2-6 document severity ¬ 0: absent $Pain ¬ Class 0: No signs or symptoms ¬ A: minimal ¬ Class 1: Only signs, upper lid retraction $Lacrimation ¬ B: moderate ¬ Class 2: Soft Tissue involvement with symptoms ¬ C: marked $Eyelid swelling ¬ Class 3: Proptosis $Foreign-body sensation ¬ Class 4: EOM involvement ¬ $Double vision Class 5: Corneal Involvement ¬ Class 6: Sight Loss $Photophobia
$Decreased vision in one or both eyes $Within classes 2 to 6 the investigator has to differentiate the severity grades 0, A, B, C $NOSPECS, classifies severity but not the activity or stage (active/inflammatory or passive/congestive)
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NOSPECS: Grading System NOSPECS: Grading System
$ 0: No symptoms or signs $ 4: EOM involvement (usually with diplopia) $ 1: Only signs (upper lid retraction without lid lag or proptosis) ¬ 0: absent $ 2: Soft tissue involvement with symptoms (excess lacrimation, sandy sensation, ¬ A: minimal (limitation of motion, patient reports diplopia but no obvious restriction retrobulbar discomfort) ¬ B: moderate (evident restriction of motion) ¬ Grade 0: absent ¬ C: marked (position of globe is fixed) ¬ Grade A: minimal (edema of lids, injection, sandy feeling) $ 5: Corneal involvement (due to proptosis, incomplete closure, lagophthalmos) ¬ Grade B: moderate (edema of lids, injection, chemosis, FBS, pain behind eyes) ¬ 0: absent ¬ Grade C: marked ¬ a: minimal (staining) $ 3: Proptosis associated with classes 2-6 only ¬ b: moderate (ulceration) ¬ Grade 0: absent ¬ c: marked (clouding, necrosis, perforation) ¬ Grade A: minimal: 21mm -23mm $ 6: Sight loss (due to optic nerve involvement) ¬ Grade B: moderate: 24mm -27mm ¬ 0: absent ¬ Grade C: marked: 28mm or more ¬ A: minimal (disc pallor or edema, or VF defect, vision 20/20-20/60) ¬ Specify if inequality of >3 mm between eyes, or if progression of >3 mm under observation ¬ B: moderate (same as A but VA 20/70-20/200) ¬ C: marked (blindness, VA < 20/200)
LEMO Classification LEMO Classification
$1991-Boergen and Pickardt Lid (L) Exophthalmos (E) $Complements NOSPECS $ 0: missing $ 0: missing $4 finding-categories $ 1: lid edema only $ 1: eye closing not impaired $ 2: real retraction (impaired lid $ 2: conjunctival injection in the ¬ Lid closing) morning ¬ Exophthalmos $ 3: retraction and upper lid edema $ 3: persistent conjunctival injection ¬ Muscular $ 4: retraction and global lid edema $ 4: corneal complications ¬ Optic nerve $Grade between 0 and 4 depending on severity $LEMO, classifies severity but not the activity or stage (active/inflammatory or passive/congestive)
LEMO Classification Grading Scales
Muscular (M) Optic Nerve (O) $New grading scales are trying to be developed to not $0: missing $0: missing only grade the severity but also help to determine if $1: detectable in imaging only $1: regarding color vision only inflammatory or passive stage $2: Pseudoparesis or detected via VEP $3: Pseudoparalysis $2: peripheral scotoma $3: central scotoma
L1E1M2O0 Endocrine ophthalmopathy with lid edema, exophthalmos , pseudoparesis of external eye muscles, and no optic nerve involvement
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Lid Involvement Lid Retraction
$ Scleral show in primary gaze $ Lid Retraction $ Occurs in ~90% of Grave s patients $Lid Lag ¬ Excess stimulation of Muller s muscle $ ¬ Fibrotic inferior rectus Lagophthalmus ¬ Mechanical restriction or infiltration of levator ¬ Increased orbital volume causes exophthalmos
$ Normal Lid Position ¬ Upper lid intersects cornea at the 2 and 10 o clock positions 2 ~2 mm below the limbus ¬ Lower lid coincident or 1-2mm below the limbus
Eyelid Lag: von Graefe s Sign Lagophthalmos
$Immobility or lagging of upper $Inability to form a complete lid closure with a eyelid on downward gaze normal blink due to Exophthalmos/ Proptosis $Fibrosis of the inferior rectus $Often leads to corneal exposure muscle may induce lower lid retraction
Soft Tissue Involvement Conjunctiva
$Conjunctiva $Conjunctival and episcleral injection $ Chemosis ¬ Especially near the horizontal recti $Periorbital edema insertions $Chemosis ¬ Edema of the conjunctiva and caruncle $ Superior Limbic Keratoconjunctivitis ¬ 65% correlation between SLK and systemic thyroid disease ¬ Rheumatoid arthritis ¬ Sjögren s syndrome
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“If it is Red think TED” Dr. Andy Morgenstern 12-7-2013, OMS-Contemporary Resort Periorbital Edema
$Inflammation of the subcutaneous connective tissue $May be first sign of thyroid eye disease $Greatest in the morning
Infiltrative Orbitopathy Infiltrative Orbitopathy (Exophthalmos/Proptosis) (Exophthalmos/Proptosis) $Thyroid Eye Disease is most common cause of unilateral and bilateral exophthalmos $The term exophthalmos is reserved for prominence of the eye secondary to thyroid disease $May need MRI to determine or obvious exophthalmos may be present $It is permanent in 70% of cases $Caused by increased volume of the extra ocular muscles ¬ Lymphocytic infiltration ¬ Proliferation of fibroblasts ¬ Edema within the interstitial tissue of the muscle
Infiltrative Orbitopathy (Exophthalmos/Proptosis)
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Exophthalmometry Restrictive Myopathy $ Is race dependent (Asians versus Black men is statistically significant) $ Hertel or Luedde results $ Adults $Secondary to edema and fibrosis of EOM s ¬ Average reading 17 mm $Inferior Rectus (IR) muscle is most commonly involved ¬ 95% of population have readings between 13-21mm $Occurs in 30-50% of patients $General concerns ¬ A difference of 2 mm or more between the eyes $Diplopia may be transient but in 50% it s permanent ¬ A measurement of more than 24 mm
Race Mean Normal Value Upper Limits
mm mm White women 15.4 20.1 White men 16.5 21.7 Black women 17.8 23.1 Black men 18.5 24.7 Asians ---- 18.0
IOP in Thyroid Eye Disease Restrictive Myopathy
$A rise in IOP has been reported with TED $I would have higher suspicion when you see ¬ Periorbital edema ¬ Exophthalmos, proptosis ¬ Restrictive myopathy $Some literature reports IOP in up gaze to be part of the diagnoses of thyroid dysfunction
Obvious restrictive myopathy but also note the periorbital edema, and conjunctival hyperemia
Corneal Exposure Optic Neuropathy
$Affects 5% of patients $Exposure keratopathy $Usually mild to moderate secondary to exophthalmos exophthalmos and shallow orbits and lagophthalmos $Enlargement of the recti muscles $Significant threat to visual compresses ONH or its blood function supply at the apex of the orbit $Compression MAY occur without significant proptosis $Compressive and/or ischemic and/or toxic
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Treatment of Thyroid Eye Disease Treatment of Thyroid Eye Disease
$Depends on what phase of the disease we are in: $Palliative (hormone imbalance, active, passive) ¬ Phase secondary to abnormal thyroid hormone levels ¬ Lubricants ¬ Active inflammatory phase ¬ Topical anti- inflammatory (Lotemax/Restasis) ¬ Plateau phase and Resolution Passive phase ¬ Prisms $ Depends on what orbital tissue or structures are involved $Steroids (active phase) $ Depends on the risk of vision loss ¬ Orals $ Depends if primary, secondary or tertiary thyroid dysfunction ¬ Peri-ocular injections ¬ IV with oral steroid taper Smoking causes the thyroid eye $Management consists of: disease to be more severe ¬ Control of inflammation $Orbital radiotherapy (active phase) Smoking causes treatments to be ¬ Prevention of ocular and visual damage $Orbital Decompression (passive phase) less effective ¬ Addressing ocular motor abnormalities ¬ Fat removal orbital decompression (FROD) ¬ Improving cosmetic disfigurement 2 Large orbits $Patient education is essential ¬ Bone removal orbital decompression (BROD) $Communication with an endocrinologist or internist will ensure 2 Small orbits proper patient care ¬ Both FROD and BROD
Treatment of Thyroid Eye Disease Lid Retraction, Eyelid Lag, Lagophthalmos
$ Must treat underlying thyroid dysfunction $Paradigm shifts $ Abnormal hormone level and Active phase ¬ Decrease in orbital radiotherapy ¬ Treat the exposure keratitis with lubricants ¬ Waiting for passive stage but doing surgery ¬ Tape eyelids shut at night ¬ Increase usage of fat removal orbital decompression as first ¬ Lid weight ¬ Moisture chamber at night approach ¬ Antibiotic ointments ¬ Peri-orbital injection of steroids for recurrent disease after orals $Passive Phase ¬ Surgical Management $Future ¬ Inferior rectus recession ¬ Mullerotomy ¬ Looking for better or different ways to treat the active phase of ¬ Recession of lower lid retractors this disease
Lid Retractor Surgery Conjunctiva, Periorbital edema
$Topical lubricants ¬ Artificial tears ¬ Ointments at night ¬ Topical steroids ¬ Restasis? $Tape eyelids closed at night or use mask $Elevate head at night to decrease lid edema $Oral diuretics Acetazolamide $Oral steroids ¬ 60-80mg/day for 3 months $IV steroids $Periorbital steroids ¬ Kenalog last 1 month
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Infiltrative Orbitopathy Restrictive Myopathy (Exophthalmos/Proptosis) $Non-surgical (while waiting for stability) ¬ Teach proper head position to alleviate $Orbital Disease Consult diplopia ¬ Systemic steroids to reduce ¬ Prism in spectacle correction (Fresnel or inflammation ground in) ¬ Low dose radiotherapy ¬ Oral steroids ¬ Surgical orbital decompression ¬ Botulinum toxin injection $Surgical Consult ¬ Recession of the rectus muscle/s involved ¬ Diplopia in primary gaze, reading gaze or both ¬ Stable angle of deviation for at least 6 months ¬ No evidence of active disease ¬ Binocular vision in at least primary and reading positions
Corneal Exposure Optic Neuropathy
$Systemic Steroids $Manage the corneal defect as first line ¬ If rapidly progressive and painful ¬ Lubricating and antibiotic in the early stage of the disease ¬ Lid taping ¬ Only if no contraindications ¬ Moisture barrier ¬ Prednisolone 80-100mg, expect results within 48hrs. Taper dose $Orbital Disease Consult and d/c within 3 mo ¬ High dose oral steroids $IV Methylprednisolone 2 120-140mg /day x 7 days $Radiotherapy: if contraindication ¬ Orbital decompression to steroid $Orbital decompression
Orbital Decompression Orbital Decompression (Surgical/Cosmetic)
$Not effective if no medical treatment ¬ Two-wall decompression 2 3-6 mm retro-placement of the globe ¬ Three-wall decompression 2 6-10mm retro-placement ¬ Four-wall decompression 2 10-16mm retro-placement
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Thyroid Eye Disease and Depression Orbital Decompression (Medical/Vision Threatened)
$When facial disfigurement occurs, thyroid eye disease is equivalent to the diagnosis of cancer and AIDS
IOP in Thyroid Eye Disease IOP in Thyroid Eye Disease
$A rise in IOP has been reported with TED $I would have higher suspicion when you see ¬ Periorbital edema ¬ Exophthalmos, proptosis ¬ Restrictive myopathy $Some literature reports IOP in up gaze to be part of the diagnoses of thyroid dysfunction….let s discuss
Laboratory Testing Laboratory Testing $ Thyroid Hormone Levels ¬ Serum TSH concentration Serum total T4 (Thyroxine) $Hypothyroid ¬ Serum total T3 (Triiodithyronine) ¬ Low FT4, High TSH, indicates primary check antibodies ¬ Estimation of the serum free T4 (or T3) concentration ¬ Low FT4, Low TSH, indicates secondary or tertiary, TRH stimulation, ¬ Thyroglobulin (Tg) level MRI $Anti-thyroid antibodies ¬ Hashimoto s (primary disease) ¬ Thyrotropin receptor antibodies (TSI) 2 Most common ¬ TSH binding inhibiting immunoglobulins (TBII) 2 Low FT4, High TSH, High Anti-TPO Ab, High levels of Thyroglobulin (Tg) ¬ Anti-TPO antibodies Antibodies (TgAb), Anti-TB Recp Ab (approx 10% present) ¬ Thyroglobulin (Tg) Antibodies (TgAb) ¬ Autoimmune atrophic thyroiditis $Commonly used thyroid tests 2 Low FT4, High TSH, Low Anti-TPO Ab, Low levels of Thyroglobulin (Tg) ¬ Resin T3 uptake test Antibodies (TgAb), Anti-TB Recp Ab (approx 60% present) ¬ Sensitive serum TSH test (Thyroid stimulating hormone) ¬ Treatment: Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid) ¬ TRH stimulation test (Thyroid releasing hormone) $ ¬ Thyroid (T3) suppression test Hyperthyroid ¬ Sonography ¬ High FT4, Low TSH ¬ Needle Biopsy ¬ TSI present ¬ Thyroid Scan
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Sign s in Thyroid Eye Disease
$ Enroth s sign: Puffy swelling of the $ Dalrymple s sign: Lid retraction lids $ von Graefe s sign: Upper lid lag $ Rosenbach s sign: Tremor of closed on downward gaze lids $ Griffith s sign: Lower lid lag on $ Mobius sign: Weakness of downward gaze convergence Questions $ Boston s sign: Jerky irregular $ Ballet s sign: Palsy of one or more movement of the upper lid on extraocular muscles downward gaze $ Suker s sign: Weakness of fixation on $ Jellinek s sign: Increased lateral gaze pigmentation of the lids $ Cowen s sign: Jerky papillary $ Stellwag s sign: Infrequent blinking contraction to consensual light $ Kocher s sign: Increased lid $ Knies sign: Unequal dilatation of the retraction with visual fixation pupils $ Jeffrey s sign: Absence of forehead wrinkling on upward gaze
Rheumatology $Specializes in the diagnosis and therapy of clinical problems involving ¬ Joints Rheumatology and the Eye ¬ Osteoporosis ¬ Musculoskeletal pain disorders ¬ Soft tissues 2 Not connective tissue – Muscle, nerve, and blood vessels 2 Connective tissue – Tendons, ligaments, fascia, fibrous tissues, fat, and synovial membranes
$There are more than 200 types of these diseases, including rheumatoid arthritis, osteoarthritis, gout, lupus, back pain, osteoporosis, fibromyalgia, and tendinitis
Where the Eye and Rheumatology Overlap Connective Tissue Disease
$Connective Tissue Disease $Connective tissue disease is any disease that has the connective tissues of the body as a primary target of pathology $ Vasculitides $The connective tissues are composed of two major structural protein $Spondyloarthropathies molecules ¬ Collagen ¬ Elastin $The collagen and elastin become injured by inflammation ¬ Typically due to autoimmune $“Collagen vascular disease” is an antiquated term used to describe diseases of the connective tissues
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Connective tissue diseases secondary Connective tissue diseases to gene abnormalities secondary to autoimmunity $Connective tissue diseases that are strictly due to genetic inheritance include $Cannot be regularly $Systemic Lupus Erythematosus ¬ Marfan syndrome defined by gene $Rheumatoid Arthritis 2 Gene FBN1 on chromosome 15 abnormalities $Sjogrens Syndrome 2 Can have tissue abnormalities in the heart, aorta, lungs, eyes, and $The spontaneous over $ skeleton Systemic Sclerosis activity of the immune $ ¬ Ehlers-Danlos syndrome Polymyositis /Dermatomyositis 2 Many types with numerous genes system $Mixed Connective Tissue 2 Typically have loose, fragile skin and hyperextensible joints ¬ Results in the production of $Wegner s Granulomatous depending on type extra antibodies into the circulation
Connective Tissue Diseases Similar Structures
$The connective tissues are $Sclera- the opaque , white, Disease Auto-antibody composed of two major fibrous, protective, outer layer Systemic Lupus Erythematosus Anti-dsDNA, Anti-SM structural protein molecules of the eye containing collagen Rheumatoid Arthritis RF, Anti-RA33 ¬ Collagen and elastin fibers Sjogrens Syndrome Anti-Ro(SS-A),Anti-La(SS-B) ¬ Elastin Systemic Sclerosis Anti-Scl-70, Anti-centromere $ Polymyositis/Dermatomyositis Anti-Jo-1 $Synovial membrane: A layer of Ténon s Capsule –a layer of connective tissue which forms a Mixed Connective Tissue Disease Anti-U1-RNP connective tissue that lines the cavities of joints, tendon thin membrane that envelops Wegener s Granulomatosus c-ANCA the eyeball from the optic nerve sheaths, and bursae and makes to the limbus , separating it synovial fluid , which has a from the orbital fat and forming lubricating function. a socket
53 year old woman Discussion $Referred for treatment for a red OS $3 weeks ago sudden onset of red eye $No pain, just feels like eyestrain $At times it s worse at times it s better $5 years ago same eye was red, it resolved without treatment
OD OS
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Review of Systems Knuckles
6 days later Treatment $Treatment ¬Lotemax 2 TID=1 week 1st Day $Lotemax qid OS 2 BID=1week $Ibuprofen 400 mg qid PO 2 QD=1week $Artificial tears $Educate patient on finding and possible underlying etiologies $Ibuprofen 200mg QID ¬ This reveals an uncle with severe arthritis, no definite diagnosis ¬D/C $Blood work? if so what test? $Review of lab results ¬ Antinuclear antibody (ANA) and rheumatoid factor (RF)
Day 6
Lab Results Final Outcome
$Diagnosed with rheumatoid arthritis ¬Current treatment successful $No ocular occurrence since treatment of rheumatoid arthritis
Referral to Rheumatologist
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Episcleritis Episcleritis $ 70% of the cases are idiopathic $Typically occurs in exposure zones ¬ 15-20% are due to allergy $Inflammation localized to episclera: ¬ 5-10% are due to systemic disease $ Systemic medications ¬ Radiate posterior from limbus ¬ Osteoporosis Medications- Bisphosphonates: ¬ Vessels are moveable 2 Fosamax (Alendronate), Actonel (Risedronate) – Episcleritis, uveitis, iritis ¬ Vessels blanch with sympatomimetics $ Testing for systemic disease indicated $Types ¬ Multiple reoccurrences ¬ Bilateral ¬ Simple episcleritis: 80% ¬ History and exam are suspicious for systemic association ¬ Nodular episcleritis: localized with variable tenderness $ Possible systemic etiologies ¬ Rheumatoid arthritis $Clinical Evaluation: ¬ Lupus ¬ Ankylosing spondylitis ¬ Sectoral injection 70% ¬ Sarcoid ¬ Diffuse injection 30% ¬ Tuberculosis ¬ Gout ¬ Syphilis ¬ Wegeners
48 year old woman Diagnosis and Treatment?
$My OD eye has severe pain, it started as an ache about 1 week ago, but now is a throbbing pain $It hurts to move my eye or touch my eye $The pain is radiating to my cheek $Patient does suffer from rheumatoid arthritis $VA 20/20 OU $EOMs full, but pain on movement OD $PERRL (-)APD $Confrontation fields: full OU $Let s take a look
Treatment Scleritis
$Non-Necrotizing Scleritis $Severe inflammatory condition ¬Depending on severity, one or combination of: $An immune mediated inflammation and destruction of 2Oral Non Steroidal Anti Inflammatory agents the sclera – Ibuprofen or indomethacin (50 mg po bid) $Commonly associated with underlying systemic disease 2Oral steroids $4th to 6th decade of life $Communication/consult with rheumatologist $Rare in children $Sub-Tenon s steroid injection is contraindicated $Female > male $Greater than 50% are bilateral
Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 17 Rheumatology, Thyroid Dysfunction and August 31, 2018 the Eye
Scleritis Scleritis $Clinical Evaluation $Symptoms ¬Sectoral or diffuse injection at all levels of vessels ¬Gradual presentation (days) ¬Blue hue in natural light ¬Deep boring pain ¬Vessels do not blanch or move 2May worsen at night ¬Referred pain to head and jaw ¬Eye is tender to the touch
Classification of Scleritis Non Necrotizing Scleritis
Classified by location and appearance of inflammation $Diffuse ¬Portion involved in 60% Location Subtype Prevalence ¬Entire sclera involved in 40% Anterior Sclera Diffuse Anterior Scleritis 40% ¬Red/blue hue Nodular Anterior Scleritis 44%
Necrotizing Anterior Scleritis 10% $Nodular with Inflammation ¬Scleral nodule Necrotizing Anterior Scleritis 4% w/out Inflammation ¬Deep red-purple ¬Nodule is immobile and separate from episclera Posterior Sclera Posterior Scleritis 2%
Necrotizing Scleritis Necrotizing Scleritis
$Begin as localized patch of inflammation $Most destructive form $Symptoms>>>findings $60% develop ocular/systemic complications $May present as avascular patch of sclera surrounded by $40% have vision loss injection $30% mortality rate at 5 years $Inflammation spreads to involve entire globe without appropriate treatment
Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 18 Rheumatology, Thyroid Dysfunction and August 31, 2018 the Eye
Necrotizing Scleritis Without Signs of Inflammation Posterior Scleritis (Scleromalacia Perforans)
$Predominantly seen in patients with rheumatoid arthritis (55%) $Signs of inflammation are minimal $No pain $Progressive scleral thinning $Uvea becomes visible $Eye may rupture
Posterior Scleritis Management
$ May occur in isolation or with associated anterior involvement $Laboratory evaluation warranted $Presentation ¬ Scleritis is often associated with systemic disease (some fatal) ¬ Pain (ocular/head) ¬ Proptosis ¬ Common etiologies ¬ Visual loss 2 Rheumatoid Arthritis ¬ Restricted motility 2 Systemic Lupus Erythematosus $ Posterior Findings 2 Ankylosing spondylitis ¬ Choroidal folds 2 Wegeners ¬ Exudative retinal detachment ¬ Papilledema 2 Gout $Easily missed if no associated anterior scleritis 2 Polyarteritis nodosum $Diagnosis confirmed with ultrasound, CT, or MRI 2 Hansen disease ¬ Hallmark : thickened sclera $Most have no identifiable related systemic disease
Treatment Rheumatoid Arthritis
$Non-Necrotizing Scleritis ¬Depending on severity, one or combination of: 2Oral Non Steroidal Anti Inflammatory agents $1% of the population – Ibuprofen or indomethacin (50 mg po bid) $Women affected 2-3 X more than men 2Oral steroids $Age of onset is 40-50 ¬ Topical steroids and NSAID s ineffective $Juvenile form $Necrotizing Scleritis ¬Oral/ IV steroids ¬Immunosuppressive/ cytotoxic agents $“Sub-Tenon s steroid” injection is contraindicated
Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 19 Rheumatology, Thyroid Dysfunction and August 31, 2018 the Eye
Rheumatoid Arthritis Rheumatoid Arthritis: Diagnostic Criteria
1. Morning stiffness (>1h) $Inflammation of the synovial tissue 2. Swelling of three or more joints (lymphocytic) with synovial proliferation 3. Swelling of hand joints (prox interphalangeal, $Symmetric involvement of peripheral joints, metacarpophalyngeal, or wrist) hands, feet and wrists 4. Symmetric joint swelling 5. Subcutaneous nodules $Occasional systemic effects: vasculitis, visceral 6. Serum Rheumatoid Factor nodules, Sjogren syndrome, pulmonary fibrosis 7. Radiographic evidence of erosions or periarticular $Anti-RA-33 autoantibodies osteopenia in hand or wrists $ RA associated nuclear antigen (RANA) Criteria 1-4 must have been present continuously for 6 weeks or longer and must be observed by a physician. A diagnosis of rheumatoid arthritis requires that 4 of the 7 criteria are fulfilled.
Rheumatoid Arthritis fusiform synovitis Rheumatoid Arthritis Early Intermediate Late
Courtesy of J. Cush, 2002.
Rheumatoid Arthritis Rheumatoid Arthritis Vasculitis Vasculitis / Digital Necrosis
Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 20 Rheumatology, Thyroid Dysfunction and August 31, 2018 the Eye
Rheumatoid Arthritis Rheumatoid Arthritis Disease Modifying Anti-rheumatic Drugs /DMARDs (Biologic DMARDs)
§ Enbrel (Fusion Protein) § Cyclosporine § Methotrexate (MTX) § 50-100mg SQ q week § Parenteral/oral gold § Hydroxychloroquine § Remicade (chimeric MAB) § Leflunomide § Azathioprine § 3mg/kg -10mg/kg Q 4-8weeks § Humira (humanized MAB) § D-penicillamine § Sulfasalazine § 40mg SQ qow § Minocycline*
* Not approved by the FDA for the treatment of RA. ACR guidelines for the management of rheumatoid arthritis. Arthritis Rheum. 2002;46:328-346.
45 year old woman Fundus Photo OD
$Reports a black line in her vision OD $ The line in my vision does not move like a floater