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Rheumatology, Thyroid Dysfunction and the Eye Rheumatology, Thyroid Dysfunction and the Eye Greg Caldwell, OD, FAAO June 4, 2016 Everything Therapeutic: Houston June 4, 2016 Disclosures $ Greg A. Caldwell, OD, FAAO will mention many products, instruments and companies during our discussion, I don’t have any financial interest in any of these products, instruments or companies. $ American Optometric Association, Trustee ¬ No industry lecturing ¬ Thank you to the members and those who join $ All of these cases have entered/referred to my practice Disclosure Statement (next slide) Learning Objectives $ Enhance clinical understanding of rheumatology and thyroid dysfunction and their ocular associations $ Enhance clinical diagnosis of ocular manifestations of rheumatologic diseases and thyroid disease $ Enhance clinical management and treatment of ocular manifestations of rheumatologic diseases and 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 Rules During this Presentation $ There are no rules $ Have fun, enjoy and relax $ Ask questions at the time of the case Can anyone here tell me the only dumb question? A question that is not asked Thyroid Thyroid Disease and Thyroid Eye Disease $ Thyroid is an endocrine gland $ Two types of glands ¬ Endocrine ¬ Exocrine $ Endocrine system is a control system of ductless endocrine glands that secrete hormones (chemical messenger) that circulate within the body via the bloodstream or lymph system to affect distant organs ¬ Hypothalamus ¬ Pituitary gland ¬ Thyroid ¬ Parathyroid glands Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell ¬ Pancreas ¬ Adrenal glands ¬ Gonads (testes and ovaries) ¬ Pineal gland 1 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Thyroid Thyroid $ Exocrine glands contain ducts. Ducts are tubes leading from a gland to its target organ ¬ Digestive glands have ducts for releasing the digestive enzymes ¬ Salivary glands, sweat glands and glands within the gastrointestinal tract $ Pancreas is both endocrine and exocrine ¬ Exocrine (ducted gland) secreting digestive enzymes into the small intestine. ¬ Endocrine (ductless gland) in that the islets of Langerhans secrete insulin and glucagon to regulate the blood sugar level. Thyroid $ Largest endocrine gland in the body $ Butterfly shaped $ Two lobes located on either side of the trachea in the lower portion of the neck $ Lies just below skin and muscle layer surface $ The thyroid is controlled by the hypothalamus and pituitary $ The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin Normal Thyroid Function $ Thyroid regulates: heart rate, ventilation rate, metabolic rate, and development of cells $ Thyroid disorder- approx 1 in 13 or 7.35% or 20 million people in USA, estimated 2 million undiagnosed $ Diabetes- approx 1 in 13 or 7.8% or 17.9 million people in USA , 5.7 million undiagnosed $ Pathophysiology: >40 postulates (thyroid) Thyroid Dysfunction Thyroid Dysfunction $ What is the most common cause of thyroid dysfunction? A. B. C. D. E. Cancer Surgically induced Medication toxicity or side effect Pregnancy Autoimmune disease $ Primary=Thyroid gland $ Secondary= Pituitary failure $ Tertiary= Hypothalamic $ In autoimmune disease the body typically produces ______ that attacks itself, this can be systemic or organ specific ¬ Antibodies, immunoglobulins Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 2 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Hyperthyroid Antibodies of Thyroid Dysfunction $ 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 Thyroid Dysfunction Hypothyroid $ TBAb attacks the thyroid $ T3 and T4 decrease $ TSH increases Hyperthyroidism Hypothyroidism (most common organ-specific autoimmune disorder) (Thyrotoxicosis) $ Primary-autoimmune ¬ Graves ¬ Chronic autoimmune thyroiditis 2 Graves-Basedow or von Basedow’s $ Secondary/Tertiary ¬ Excess thyroid medication for treatment of hypo or goiter ¬ Toxic multinodular goiter ¬ Toxic adenoma ¬ Excess iodine ¬ Thyroiditis (inflammatory induced) ¬ Excess hormone production ectopic tissue ¬ Thyroid carcinoma GRAVE’S (Hyperthyoidism) $ A multisystem disorder consisting of a triad ¬ Hyperthyroidism with diffuse hyperplasia of the thyroid gland ¬ Infiltrative dermopathy ¬ Infiltrative ophthalmopathy $ Prevalence: ¬ 20-40 year old female (F:M = 7:1) ¬ Genetic link $ Etiology: ¬ Autoimmune disease: hypersensitivity reaction with thyroid stimulation by the circulation of abnormal thyroid-stimulating immunoglobulins (TSI) Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell $ Primary-autoimmune 2 Hashimoto's thyroiditis ¬ Autoimmune atrophic thyroiditis 2 Primary myxedema 2 Opposite of Graves disease ¬ Postpartum thyroiditis $ Secondary/Tertiary ¬ Lithium medication ¬ Pregnancy ¬ Surgically induced ¬ Disorders of the pituitary gland or hypothalamus Hashimoto's Thyroiditis (Hypothyroidism) $ The most common cause of hypothyroidism in the United States $ It is named after the first doctor who described this condition, Dr. Hakaru Hashimoto, in 1912 $ Autoimmune disease $ Goiter formation $ 5-10 times more common in women than in men $ The underlying cause of the autoimmune process still is unknown ¬ Anti-TPO ab and Anti-TB recp ab present 3 Rheumatology, Thyroid Dysfunction and the Eye Autoimmune atrophic thyroiditis (Hypothyroidism) $ Atrophic thyroiditis is similar to Hashimoto's thyroiditis $ A goiter is not present Systemic Manifestations of Hyperthyroid (Primary or Secondary) $ Symptoms ¬ Nervousness ¬ Heat intolerance ¬ Sweating ¬ Fatigue ¬ Palpitation ¬ Insomnia ¬ Early waking ¬ Alopecia ¬ Vitiligo ¬ Brittle nails $ Signs ¬ Sweating ¬ Muscle Weakness ¬ Emotionally labile ¬ Tremor ¬ Tachycardia ¬ Arrhythmia ¬ Hypertension ¬ Brisk tendon reflex ¬ Diabetes ¬ ↑Triglycerides & Ca, ↓CHO ¬ Microcyticanemia ¬ Possible goiter ¬ Myxedema Thyroid Eye Disease (TED) $ Other names used ¬ Grave’s disease ¬ Grave's ophthalmopathy ¬ Grave's orbitopathy ¬ Exophthalmos in Graves Disease ¬ Thyroid Associated Orbitopathy (TAO) ¬ Thyroid Orbitopathy ¬ Ophthalmic Graves Disease ¬ Inflammatory Eye Disease ¬ Endocrine Orbitopathy Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell June 4, 2016 Postpartum Thyroiditis (Hypothyroidism) $ These women develop antibodies to their own thyroid during pregnancy, causing an inflammation of the thyroid after delivery Systemic Manifestations of Hypothyroid (Primary or Secondary) $ Symptoms ¬ Cold intolerance ¬ Weakness ¬ Reduced energy ¬ Lethargy ¬ Muscle cramps ¬ Constipation ¬ Increased sleeping ¬ Weight gain ¬ Reduced appetite ¬ Joint stiffness $ Signs ¬ Cool, scaling skin ¬ Puffy hands and face ¬ Deep voice ¬ Myotonia ¬ Delirium ¬ Bradycardia ¬ Slow reflexes ¬ Obesity ¬ Hypothermia ¬ Myxedema Why is this so confusing? $ Thyroid Eye Disease ¬ Is often seen in conjunction with Graves' Disease (hyperthyroid) ¬ Is seen in people with no other evidence of thyroid dysfunction ¬ Is seen in patients who have Hashimoto's Disease (hypothyroid) $ Most thyroid patients, however, will not develop thyroid eye disease 4 Rheumatology, Thyroid Dysfunction and the Eye Why is this so confusing? $ The eye symptoms usually occur at the same time as the thyroid disease ¬ However they may precede or follow the obvious symptoms of the thyroid abnormality $ The incidence of thyroid eye disease associated with thyroid dysfunction is higher and more severe in smokers ¬ There is no way to predict which thyroid patients will be affected Thyroid Eye Disease $ Commonly known as Graves' ophthalmopathy June 4, 2016 Why is this so confusing? $ While eye disease may be brought on by thyroid dysfunction ¬ Successful treatment of the thyroid gland does not guarantee that the eye disease will improve ¬ No particular thyroid treatment can guarantee that the eyes will not continue to deteriorate ¬ Once inflamed, the eye disease may remain active from several months to as long as three years ¬ There may be a gradual or, in some cases, a complete improvement Thyroid Eye Disease $ 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 $ Another 10% of all cases are seen in patients with autoimmune hypothyroidism, either Hashimoto's thyroiditis, atrophic thyroiditis or Hashitoxicosis $ Another 10% of all cases are seen in people with normal thyroid function $ The high and low levels of T3 and T4 $ The antibodies that are attacking the thyroid gland ¬ 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 Thyroid Eye Disease Phase secondary to abnormal thyroid hormone levels (T3/T4) (Thyroid Eye Disease) $ Hyperthyroidism eye symptoms $ Thyroid Eye Disease has 2 phases ¬ A phase secondary to abnormal thyroid hormone levels 2 Increased or decreased FT3 and FT4 levels 2 Once these levels are normalized, ocular symptoms will resolve ¬ Excess hormone acting on the nerves that supply the eye ¬ Usually spastic and include staring ¬ Dryness ¬ Eyelid retraction $ Hypothyroidism eye symptoms ¬ Deficient hormone causing venous congestion, impaired circulation and fluid stagnation ¬ Periorbital edema ¬ Congestive Autoimmune form of Thyroid Eye Disease 2 Active phase-stimulating or blocking TRAb are causing ocular activity 2 Plateau phase-reduced activity 2 Resolution phase-symptoms regress and eyes return to normal $ This form of TED resolves within a few weeks after thyroid hormone levels (FT4 and FT3) are corrected and brought back into the normal range $ The pituitary hormone TSH can stay low or suppressed for many months during the 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 Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 5 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Euthyroid Graves' disease Congestive Autoimmune form of Thyroid Eye Disease (Active phase, Plateau phase, Resolution phase) $ Caused by both stimulating and blocking TSH receptor antibodies (TRAb) and also immune system chemicals known as cytokines $ Secondary targets appear to be TSH receptor antigens (epitopes) located on orbital fibroblasts as well as dermal fibroblasts $ Active “inflammatory” phase of TED varies ¬ 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 $ If thyroid function is normal. How does one develop thyroid eye disease? $ 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 General Ocular Symptoms Similar receptors are found in the skin, fat and muscle of the orbit $ Prominent eyes, stare $ Pain $ Lacrimation $ Eyelid swelling $ Foreign-body sensation $ Double vision $ Photophobia $ Decreased vision in one or both eyes NOSPECS: Grading System $ 1969 by S.C. Werner ¬ Class 0: No signs or symptoms ¬ Class 1: Only signs, upper lid retraction ¬ Class 2: Soft Tissue involvement with symptoms ¬ Class 3: Proptosis ¬ Class 4: EOM involvement ¬ Class 5: Corneal Involvement ¬ Class 6: Sight Loss $ Class 2-6 document severity ¬ ¬ ¬ ¬ 0: absent A: minimal B: moderate C: marked $ 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/ NOSPECS: Grading System $ 0: No symptoms or signs $ 1: Only signs (upper lid retraction without lid lag or proptosis) $ 2: Soft tissue involvement with symptoms (excess lacrimation, sandy sensation, retrobulbar discomfort) ¬ ¬ ¬ ¬ Grade 0: absent Grade A: minimal (edema of lids, injection, sandy feeling) Grade B: moderate (edema of lids, injection, chemosis, FBS, pain behind eyes) Grade C: marked $ 3: Proptosis associated with classes 2-6 only ¬ Grade 0: absent ¬ Grade A: minimal: 21mm -23mm ¬ Grade B: moderate: 24mm -27mm ¬ Grade C: marked: 28mm or more ¬ Specify if inequality of >3 mm between eyes, or if progression of >3 mm under observation inflammatory or passive/congestive) Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 6 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 NOSPECS: Grading System $ 4: EOM involvement (usually with diplopia) ¬ 0: absent ¬ A: minimal (limitation of motion, patient reports diplopia but no obvious restriction ¬ B: moderate (evident restriction of motion) ¬ C: marked (position of globe is fixed) $ 5: Corneal involvement (due to proptosis, incomplete closure, lagophthalmos) ¬ 0: absent ¬ a: minimal (staining) ¬ b: moderate (ulceration) ¬ c: marked (clouding, necrosis, perforation) $ 6: Sight loss (due to optic nerve involvement) ¬ 0: absent ¬ A: minimal (disc pallor or edema, or VF defect, vision 20/20-20/60) ¬ B: moderate (same as A but VA 20/70-20/200) ¬ C: marked (blindness, VA < 20/200) LEMO Classification $ 1991-Boergen and Pickardt $ Complements NOSPECS $ 4 finding-categories ¬ Lid ¬ Exophthalmos ¬ Muscular ¬ 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 LEMO Classification Lid (L) Exophthalmos (E) Muscular (M) Optic Nerve (O) $ 0: missing $ 0: missing $ 0: missing $ 0: missing $ 1: lid edema only $ 1: eye closing not impaired $ 2: real retraction (impaired lid $ 2: conjunctival injection in the $ 1: detectable in imaging only $ 1: regarding color vision only closing) $ 3: retraction and upper lid edema $ 4: retraction and global lid edema morning $ 3: persistent conjunctival injection $ 4: corneal complications $ 2: Pseudoparesis $ 3: Pseudoparalysis or detected via VEP $ 2: peripheral scotoma $ 3: central scotoma L1E1M2O0 Endocrine ophthalmopathy with lid edema, exophthalmos , pseudoparesis of external eye muscles, and no optic nerve involvement Grading Scales $ New grading scales are trying to be developed to not only grade the severity but also help to determine if inflammatory or passive stage Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell Lid Involvement $ Lid Retraction $ Lid Lag $ Lagophthalmus 7 Rheumatology, Thyroid Dysfunction and the Eye Lid Retraction June 4, 2016 Eyelid Lag: von Graefe’s Sign $ Scleral show in primary gaze $ Occurs in ~90% of Grave’s patients ¬ Excess stimulation of Muller’s muscle ¬ Fibrotic inferior rectus ¬ Mechanical restriction or infiltration of levator ¬ Increased orbital volume causes exophthalmos $ Immobility or lagging of upper eyelid on downward gaze $ Fibrosis of the inferior rectus muscle may induce lower lid retraction $ 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 Lagophthalmos $ Inability to form a complete lid closure with a normal blink due to Exophthalmos/ Proptosis $ Often leads to corneal exposure Conjunctiva Soft Tissue Involvement $ Conjunctiva $ Chemosis $ Periorbital edema “If it is Red think TED” Dr. Andy Morgenstern 12-7-2013, OMS-Contemporary Resort $ Conjunctival and episcleral injection ¬ Especially near the horizontal recti insertions $ Chemosis ¬ Edema of the conjunctiva and caruncle $ Superior Limbic Keratoconjunctivitis ¬ 65% correlation between SLK and systemic thyroid disease ¬ Rheumatoid arthritis ¬ Sjögren’s syndrome Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 8 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Infiltrative Orbitopathy (Exophthalmos/Proptosis) Periorbital Edema $ Inflammation of the subcutaneous connective tissue $ May be first sign of thyroid eye disease $ Greatest in the morning $ 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) Infiltrative Orbitopathy (Exophthalmos/Proptosis) Exophthalmometry $ Is race dependent (Asians versus Black men is statistically significant) $ Hertel or Luedde results $ Adults ¬ Average reading 17 mm ¬ 95% of population have readings between 13-21mm $ General concerns ¬ A difference of 2 mm or more between the eyes ¬ A measurement of more than 24 mm 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 Race Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 9 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Restrictive Myopathy IOP in Thyroid Eye Disease $ Secondary to edema and fibrosis of EOM’s $ A rise in IOP has been reported with TED $ Inferior Rectus (IR) muscle is most commonly involved $ I would have higher suspicion when you see $ Occurs in 30-50% of patients $ Diplopia may be transient but in 50% it’s permanent ¬ Periorbital edema ¬ Exophthalmos, proptosis ¬ Restrictive myopathy $ Some literature reports IOP in up gaze to be part of the diagnoses of thyroid dysfunction Restrictive Myopathy Corneal Exposure $ Exposure keratopathy secondary to exophthalmos and lagophthalmos $ Significant threat to visual function Obvious restrictive myopathy but also note the periorbital edema, and conjunctival hyperemia Optic Neuropathy $ Affects 5% of patients $ Usually mild to moderate exophthalmos and shallow orbits $ Enlargement of the recti muscles compresses ONH or its blood supply at the apex of the orbit $ Compression MAY occur without significant proptosis $ Compressive and/or ischemic and/or toxic Treatment of Thyroid Eye Disease $ Depends on what phase of the disease we are in: ¬ Phase secondary to abnormal thyroid hormone levels ¬ Active “inflammatory” phase ¬ Plateau phase and Resolution “Passive” phase $ Depends on what orbital tissue or structures are involved $ Depends on the risk of vision loss $ Depends if primary, secondary or tertiary thyroid dysfunction $ Management consists of: ¬ ¬ ¬ ¬ Control of inflammation Prevention of ocular and visual damage Addressing ocular motor abnormalities Improving cosmetic disfigurement $ Patient education is essential $ Communication with an endocrinologist or internist will ensure proper patient care Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 10 Rheumatology, Thyroid Dysfunction and the Eye Treatment of Thyroid Eye Disease $ Palliative (hormone imbalance, active, passive) ¬ Lubricants ¬ Topical anti- inflammatory (Lotemax/Restasis) ¬ Prisms $ Steroids (active phase) ¬ Orals ¬ Peri-ocular injections ¬ IV with oral steroid taper $ Orbital radiotherapy (active phase) Smoking causes the thyroid eye disease to be more severe Smoking causes treatments to be less effective $ Orbital Decompression (passive phase) ¬ Fat removal orbital decompression (FROD) 2 Large orbits ¬ Bone removal orbital decompression (BROD) 2 Small orbits ¬ Both FROD and BROD Lid Retraction, Eyelid Lag, Lagophthalmos June 4, 2016 Treatment of Thyroid Eye Disease $ Paradigm shifts ¬ Decrease in orbital radiotherapy ¬ Waiting for passive stage but doing surgery ¬ Increase usage of fat removal orbital decompression as first approach ¬ Peri-orbital injection of steroids for recurrent disease after orals $ Future ¬ Looking for better or different ways to treat the active phase of this disease Lid Retractor Surgery $ Must treat underlying thyroid dysfunction $ Abnormal hormone level and Active phase ¬ Treat the exposure keratitis with lubricants ¬ Tape eyelids shut at night ¬ Lid weight ¬ Moisture chamber at night ¬ Antibiotic ointments $ Passive Phase ¬ ¬ ¬ ¬ Surgical Management Inferior rectus recession Mullerotomy Recession of lower lid retractors Conjunctiva, Periorbital edema $ Topical lubricants ¬ ¬ ¬ ¬ Artificial tears Ointments at night Topical steroids Restasis? $ Tape eyelids closed at night or use mask Infiltrative Orbitopathy (Exophthalmos/Proptosis) $ Orbital Disease Consult ¬ Systemic steroids to reduce inflammation ¬ Low dose radiotherapy ¬ Surgical orbital decompression $ 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 Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 11 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Restrictive Myopathy Corneal Exposure $ Non-surgical (while waiting for stability) ¬ Teach proper head position to alleviate diplopia ¬ Prism in spectacle correction (Fresnel or ground in) ¬ Oral steroids ¬ 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 Optic Neuropathy $ Systemic Steroids ¬ If rapidly progressive and painful in the early stage of the disease ¬ Only if no contraindications ¬ Prednisolone 80-100mg, expect results within 48hrs. Taper dose and d/c within 3 mo $ IV Methylprednisolone $ Radiotherapy: if contraindication to steroid $ Orbital decompression Orbital Decompression (Surgical/Cosmetic) $ Manage the corneal defect as first line ¬ Lubricating and antibiotic ¬ Lid taping ¬ Moisture barrier $ Orbital Disease Consult ¬ High dose oral steroids 2 120-140mg /day x 7 days ¬ Orbital decompression Orbital Decompression $ 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 Thyroid Eye Disease and Depression $ When facial disfigurement occurs, thyroid eye disease is equivalent to the diagnosis of cancer and AIDS Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 12 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Orbital Decompression IOP in Thyroid Eye Disease (Medical/Vision Threatened) $ 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 IOP in Thyroid Eye Disease $ Thyroid Hormone Levels ¬ Serum TSH concentration Serum total T4 (Thyroxine) ¬ Serum total T3 (Triiodithyronine) ¬ Estimation of the serum free T4 (or T3) concentration ¬ Thyroglobulin (Tg) level $ Anti-thyroid antibodies ¬ ¬ ¬ ¬ Thyrotropin receptor antibodies (TSI) TSH binding inhibiting immunoglobulins (TBII) Anti-TPO antibodies Thyroglobulin (Tg) Antibodies (TgAb) $ Commonly used thyroid tests ¬ ¬ ¬ ¬ Resin T3 uptake test Sensitive serum TSH test (Thyroid stimulating hormone) TRH stimulation test (Thyroid releasing hormone) Thyroid (T3) suppression test ¬ Sonography ¬ Needle Biopsy ¬ Thyroid Scan Laboratory Testing $ Hypothyroid ¬ Low FT4, High TSH, indicates primary check antibodies ¬ Low FT4, Low TSH, indicates secondary or tertiary, TRH stimulation, MRI ¬ Hashimoto’s (primary disease) 2 Most common 2 Low FT4, High TSH, High Anti-TPO Ab, High levels of Thyroglobulin (Tg) Antibodies (TgAb), Anti-TB Recp Ab (approx 10% present) ¬ Autoimmune atrophic thyroiditis 2 Low FT4, High TSH, Low Anti-TPO Ab, Low levels of Thyroglobulin (Tg) Antibodies (TgAb), Anti-TB Recp Ab (approx 60% present) ¬ Treatment: Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid) $ Hyperthyroid ¬ High FT4, Low TSH ¬ TSI present Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell Sign’s in Thyroid Eye Disease $ Dalrymple’s sign: Lid retraction $ von Graefe’s sign: Upper lid lag on downward gaze $ Griffith’s sign: Lower lid lag on downward gaze $ Boston’s sign: Jerky irregular movement of the upper lid on downward gaze $ Jellinek’s sign: Increased pigmentation of the lids $ Stellwag’s sign: Infrequent blinking $ Kocher’s sign: Increased lid retraction with visual fixation $ Enroth’s sign: Puffy swelling of the lids $ Rosenbach’s sign: Tremor of closed lids $ Mobius’ sign: Weakness of convergence $ Ballet’s sign: Palsy of one or more extraocular muscles $ Suker’s sign: Weakness of fixation on lateral gaze $ Cowen’s sign: Jerky papillary contraction to consensual light $ Knies’ sign: Unequal dilatation of the pupils $ Jeffrey’s sign: Absence of forehead wrinkling on upward gaze 13 Rheumatology, Thyroid Dysfunction and the Eye Questions June 4, 2016 Rheumatology and the Eye “Eye said Go to your Rheum” Rheumatology Where the Eye and Rheumatology Overlap $ Specializes in the diagnosis and therapy of clinical problems involving ¬ Joints ¬ Osteoporosis ¬ Musculoskeletal pain disorders ¬ Soft tissues $ Connective Tissue Disease $ Vasculitides $ Spondyloarthropathies 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 Connective Tissue Disease Connective tissue diseases secondary to gene abnormalities $ Connective tissue diseases that are strictly due to genetic $ Connective tissue disease is any disease that has the connective tissues of the body as a primary target of pathology $ The connective tissues are composed of two major structural protein 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 inheritance include ¬ Marfan syndrome 2 Gene FBN1 on chromosome 15 2 Can have tissue abnormalities in the heart, aorta, lungs, eyes, and skeleton ¬ Ehlers-Danlos syndrome 2 Many types with numerous genes 2 Typically have loose, fragile skin and hyperextensible joints depending on type diseases of the connective tissues Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 14 Rheumatology, Thyroid Dysfunction and the Eye Connective tissue diseases secondary to autoimmunity $ Cannot be regularly defined by gene abnormalities $ The spontaneous over activity of the immune system ¬ Results in the production of extra antibodies into the circulation $ Systemic Lupus Erythematosus $ Rheumatoid Arthritis $ Sjogrens Syndrome $ Systemic Sclerosis $ Polymyositis /Dermatomyositis $ Mixed Connective Tissue $ Wegner’s Granulomatous Similar Structures $ The connective tissues are composed of two major structural protein molecules ¬ Collagen ¬ Elastin $ Sclera- the opaque , white, fibrous, protective, outer layer of the eye containing collagen and elastin fibers Connective Tissue Diseases Disease Auto-antibody Systemic Lupus Erythematosus Rheumatoid Arthritis Sjogrens Syndrome Systemic Sclerosis Polymyositis/Dermatomyositis Mixed Connective Tissue Disease Wegener’s Granulomatosus Anti-dsDNA, Anti-SM RF, Anti-RA33 Anti-Ro(SS-A),Anti-La(SS-B) Anti-Scl-70, Anti-centromere Anti-Jo-1 Anti-U1-RNP c-ANCA 53 year old woman $ 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 $ Synovial membrane: A layer of connective tissue that lines the cavities of joints, tendon sheaths, and bursae and makes synovial fluid , which has a lubricating function. $ Ténon’ s Capsule –a layer of connective tissue which forms a thin membrane that envelops the eyeball from the optic nerve to the limbus , separating it from the orbital fat and forming a socket $ 5 years ago same eye was red, it resolved without treatment Review of Systems Discussion OD June 4, 2016 OS Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 15 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Knuckles Treatment $ Lotemax qid OS $ Ibuprofen 400 mg qid PO $ Artificial tears $ Educate patient on finding and possible underlying etiologies ¬ This reveals an uncle with severe arthritis, no definite diagnosis $ Blood work? if so what test? ¬ Antinuclear antibody (ANA) and rheumatoid factor (RF) 6 days later Lab Results $ Treatment ¬ Lotemax 1st Day 2 TID=1 week 2 BID=1week 2 QD=1week $ Ibuprofen 200mg QID $ Review of lab results Day 6 Final Outcome $ Diagnosed with rheumatoid arthritis ¬ Current treatment successful $ No ocular occurrence since treatment of rheumatoid arthritis Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell Referral to Rheumatologist Episcleritis $ Typically occurs in exposure zones $ Inflammation localized to episclera: ¬ Radiate posterior from limbus ¬ Vessels are moveable ¬ Vessels blanch with sympatomimetics $ Types ¬ Simple episcleritis: 80% ¬ Nodular episcleritis: localized with variable tenderness $ Clinical Evaluation: ¬ Sectoral injection 70% ¬ Diffuse injection 30% 16 Rheumatology, Thyroid Dysfunction and the Eye Episcleritis $ 70% of the cases are idiopathic ¬ 15-20% are due to allergy ¬ 5-10% are due to systemic disease $ Testing for systemic disease indicated ¬ Multiple reoccurrences ¬ Bilateral ¬ History and exam are suspicious for systemic association $ Possible systemic etiologies ¬ ¬ ¬ ¬ ¬ ¬ ¬ ¬ Rheumatoid arthritis Lupus Ankylosing spondylitis Sarcoid Tuberculosis Gout Syphilis Wegeners June 4, 2016 48 year old woman $ 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 Diagnosis and Treatment? Treatment $ Non-Necrotizing Scleritis ¬ Depending on severity, one or combination of: 2 Oral Non Steroidal Anti Inflammatory agents – Ibuprofen or indomethacin (50 mg po bid) 2 Oral steroids $ Communication/consult with rheumatologist $ Sub-Tenon’s steroid injection is contraindicated Scleritis $ Severe inflammatory condition $ An immune mediated inflammation and destruction of the sclera $ Commonly associated with underlying systemic disease $ 4th to 6th decade of life $ Rare in children $ Female > male Scleritis $ Symptoms ¬ Gradual presentation (days) ¬ Deep boring pain 2 May worsen at night ¬ Referred pain to head and jaw ¬ Eye is tender to the touch $ Greater than 50% are bilateral Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 17 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Scleritis $ Clinical Evaluation ¬ Sectoral or diffuse injection at all levels of vessels ¬ Blue hue in natural light ¬ Vessels do not blanch or move Classification of Scleritis Classified by location and appearance of inflammation Location Subtype Anterior Sclera Diffuse Anterior Scleritis 40% Nodular Anterior Scleritis 44% Necrotizing Anterior Scleritis with Inflammation 10% Necrotizing Anterior Scleritis w/out Inflammation 4% Posterior Scleritis 2% Posterior Sclera Non Necrotizing Scleritis $ Diffuse ¬ Portion involved in 60% ¬ Entire sclera involved in 40% ¬ Red/blue hue Prevalence Necrotizing Scleritis $ Most destructive form $ 60% develop ocular/systemic complications $ 40% have vision loss $ 30% mortality rate at 5 years $ Nodular ¬ Scleral nodule ¬ Deep red-purple ¬ Nodule is immobile and separate from episclera Necrotizing Scleritis $ Begin as localized patch of inflammation $ Symptoms>>>findings $ May present as avascular patch of sclera surrounded by injection $ Inflammation spreads to involve entire globe without appropriate treatment Necrotizing Scleritis Without Signs of Inflammation (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 Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 18 Rheumatology, Thyroid Dysfunction and the Eye Posterior Scleritis June 4, 2016 Posterior Scleritis $ May occur in isolation or with associated anterior involvement $ Presentation ¬ Pain (ocular/head) ¬ Proptosis ¬ Visual loss ¬ Restricted motility $ Posterior Findings ¬ Choroidal folds ¬ Exudative retinal detachment ¬ Papilledema $ Easily missed if no associated anterior scleritis $ Diagnosis confirmed with ultrasound, CT, or MRI ¬ Hallmark : thickened sclera $ Most have no identifiable related systemic disease Management $ Laboratory evaluation warranted ¬ Scleritis is often associated with systemic disease (some fatal) ¬ Common etiologies 2 Rheumatoid Arthritis 2 Systemic Lupus Erythematosus 2 Ankylosing spondylitis 2 Wegeners 2 Gout 2 Polyarteritis nodosum 2 Hansen disease Rheumatoid Arthritis Treatment $ Non-Necrotizing Scleritis ¬ Depending on severity, one or combination of: 2 Oral Non Steroidal Anti Inflammatory agents – Ibuprofen or indomethacin (50 mg po bid) 2 Oral steroids ¬ Topical steroids and NSAID’s ineffective $ Necrotizing Scleritis ¬ Oral/ IV steroids ¬ Immunosuppressive/ cytotoxic agents $ “Sub-Tenon’s steroid” injection is contraindicated Rheumatoid Arthritis $ Inflammation of the synovial tissue $ 1% of the population $ Women affected 2-3 X more than men $ Age of onset is 40-50 $ Juvenile form (lymphocytic) with synovial proliferation $ Symmetric involvement of peripheral joints, hands, feet and wrists $ Occasional systemic effects: vasculitis, visceral nodules, Sjogren syndrome, pulmonary fibrosis $ Anti-RA-33 autoantibodies $ RA associated nuclear antigen (RANA) Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 19 Rheumatology, Thyroid Dysfunction and the Eye Rheumatoid Arthritis: Diagnostic Criteria June 4, 2016 Rheumatoid Arthritis fusiform synovitis 1. Morning stiffness (>1h) 2. Swelling of three or more joints 3. Swelling of hand joints (prox interphalangeal, metacarpophalyngeal, or wrist) 4. Symmetric joint swelling 5. Subcutaneous nodules 6. Serum Rheumatoid Factor 7. Radiographic evidence of erosions or periarticular osteopenia in hand or wrists 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 Early Intermediate Rheumatoid Arthritis Vasculitis Late Courtesy of J. Cush, 2002. Rheumatoid Arthritis Vasculitis / Digital Necrosis Rheumatoid Arthritis Disease Modifying Anti-rheumatic Drugs /DMARDs § Methotrexate (MTX) § Hydroxychloroquine § Leflunomide § Sulfasalazine § Cyclosporine § Parenteral/oral gold § Azathioprine § D-penicillamine § 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. Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 20 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Rheumatoid Arthritis 45 year old woman (Biologic DMARDs) $ Reports a black line in her vision OD § Enbrel (Fusion Protein) $ “The line in my vision does not move like a floater” § 50-100mg SQ q week $ Vision 20/20 OU § Remicade (chimeric MAB) $ Externals: unremarkable § 3mg/kg -10mg/kg Q 4-8weeks $ SLE: unremarkable § Humira (humanized MAB) § 40mg SQ qow Cotton Wool Spots Fundus Photo OD $ Non-specific finding ¬ Hypertension ¬ Diabetes ¬ Connective Tissue Disease ¬ HIV Retinopathy ¬ Blood dyscrasia 2 Leukemia 2 Anemia Many Faces of CWS Laboratory Work-Up $ Sed rate $ ANA $ Rheumatoid factor $ ACE $ HLA-B27 $ Fasting blood glucose (FBG) $ Lipid profile No under lying etiology History of uncontrolled HTN and DM Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell $ Complete blood count (CBC) 21 Rheumatology, Thyroid Dysfunction and the Eye Results Referred to Rheumatologist $ Complete blood count (CBC): ¬ WBC ¬ Hemoglobin ¬ Hematocrit ¬ Platelet count 2.9 9.1 33.9% 110 $ Sed rate: $ ANA: $ Rheumatoid factor: $ ACE: $ HLA-B27: $ Fasting blood glucose (FBG): $ Lipid profile: low low low low June 4, 2016 $ Patient diagnosed with systemic lupus Anemia 48 high 1:640 speckled pattern negative normal negative normal normal Systemic Lupus Erythematosus erythematosus (SLE) and treated with an immunosuppressant $ CWS have resolved and no other occurrences Systemic Lupus Erythematosus $ General ¬ autoimmune multisystem disease ¬ prevalence 1 in 2,000 ¬ 9 to 1; female to male (1 in 700) ¬ peak age 15-25 ¬ immune complex deposition ¬ photosensitive skin eruptions, serositis, pneumonitis, myocarditis, nephritis, CNS involvement Systemic Lupus Erythematosus: Diagnostic Criteria Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell $ Anti-Nuclear Antibodies (ANA)-positive $ Specific labs ¬ dsDNA antibodies ¬ Anti-Sm antibody ¬ Anti-SSA and Anti-SSB – may also be positive Systemic lupus erythematosus 1982 classification criteria definitions $ Malar rash Fixed erythema, flat or raised, sparing the nasolabial folds $ Discoid rash $ Photosensitivity Raised patches, adherent keratotic scaling, follicular plugging; older lesions may cause scarring Skin rash from sunlight $ Oral ulcers Usually painless $ Arthritis Nonerosive, inflammatory in two or more peripheral joints $ Serositis Pleuritis or pericarditis 22 Rheumatology, Thyroid Dysfunction and the Eye Systemic lupus erythematosus 1982 classification criteria definitions $ Renal disorder Persistent proteinuria or cellular casts $ Neurologic disorder Seizures or psychosis $ Hermatologic Hemolytic anemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,00/mm3) $ Immunologic disorder Antibodies to dsDNA or SM or positive antiphospholipid antibodies (IgG or IgM antibodies, lupus anticoagulant, or falsepositive serologic test positive serologic test for syphilis) June 4, 2016 Systemic Lupus Erythematosus $ Antinuclear antibody test Positive Systemic Lupus Erythematosus Systemic lupus erythematosus butterfly rash, discoid type $ Discoid Lupus: Cutaneous manifestations $ Scar upon healing Systemic lupus erythematosus photosensitivity Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell Systemic lupus erythematosus interarticular dermatitis 23 Rheumatology, Thyroid Dysfunction and the Eye Systemic lupus erythematosus retinal vasculitis Systemic Lupus Erythematosus Disease Modifying Anti-rheumatic Drugs /DMARDs $ Methotrexate (MTX) $ Cyclosporine $ Hydroxychloroquine $ Parenteral/oral gold $ Leflunomide $ Azathioprine $ Sulfasalazine $ D-penicillamine $ Cytoxin $ Minocycline* $ Cellcept June 4, 2016 Systemic Lupus Erythematosus $ Treatment: Rheumatologist involvement $ Avoidance of sun $ Use of sunscreens $ DMARDs 37 year old woman $ Referred in for punctal plug insertion due to dry eyes, temporary plug outcome was successful ¬ Currently using 2 Systane q1-2h OU 2 Restasis bid OU 2 Systane night PRN $ She wants plugs to help decrease her usage of lubricants $ SLE: confirms almost absent tear prism and mild to moderate Lisamine green staining $ Anything suspicious here? * Not approved by the FDA for the treatment of RA. ACR guidelines for the management of rheumatoid arthritis. Arthritis Rheum. 2002;46:328-346. Results Treatment $ Permanent plugs RUL/RLL $ Labs ordered: ¬ ESR, CRP, ANA, RF, SS-A, SS-B and thyroid panel $ Excellent outcome to permanent plugs RLL/LLL $ ESR: $ CRP: $ ANA: $ RF: $ SS-A: $ SS-B : $ Thyroid panel: 33 mm/hr 1.7 1:320 positive positive positive normal $ Referral to rheumatologist for diagnosis and treatment Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 24 Rheumatology, Thyroid Dysfunction and the Eye Diagnosis $ Sjögren’s Syndrome June 4, 2016 Definition of Sjögren’s Syndrome A chronic systemic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands leading to dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca) as a consequence of progressive glandular destruction and dysfunction Sjögren’s Syndrome Sjögren’s Syndrome $ 1-2 million Americans affected ¬ 90% women $ 2nd most common autoimmune rheumatic disease $ A major women’s health problem Common features $ Primary or secondary $ Dry mouth and dry eyes $ Serum autoantibodies ¬ RF, anti-Ro/SSA, anti-La/SSB $ Glandular and extraglandular manifestations $ Overlap with other autoimmune rheumatic diseases $ Women > Men (9:1) Sjögren’s Syndrome Sjögren’s Syndrome (Ocular signs) $ Reduced tear production ¬ Measured by Schirmer test (Oral features) $ Dry mouth $ Decreased tear breakup time $ Sore or burning mouth $ Epithelial staining with diagnostic dye $ Intolerance to acidic or spicy foods $ Filamentary keratitis by biomicroscopy $ Abnormalities of taste $ Difficulty with chewing and swallowing dry foods $ Difficulty with phonation (speaking) $ Difficulty wearing dentures Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 25 Rheumatology, Thyroid Dysfunction and the Eye Dental Caries (Decay) in Sjögren’s Syndrome Patients June 4, 2016 Salivary Glands Sjögren’s Syndrome Normal Salivary Gland Why Can Muscarinic Agonists Be Used to Stimulate Saliva? $ The severity of salivary dysfunction is disproportionate to the amount of lymphocyte infiltration $ Most Sjögren’s syndrome patients have remaining acinar cells in their salivary glands $ Muscarinic receptors on these cells are still capable of responding to stimulation $ In sufficient dosages, muscarinic agonists can increase secretion of exocrine glands Salivary Gland SS Evoxac $ Mechanism of Action ¬ A cholinergic agonist that binds to muscarinic receptors and stimulates exocrine glands $ Muscarinic receptor subtypes ¬ Evoxac has high affinity for M1 and M3 subtype 2 Secretion from salivary glands and stomach ¬ Evoxac has a lower affinity for the M2 subtype 2 Slow heart rate, Reduce contractile forces of atrium, reduce conduction velocity of AV node $ Sufficient dosages, muscarinic agonists can increase secretion of exocrine glands Connective tissue diseases secondary to autoimmunity Common Ocular Involvement Potential Ocular Involvement $ Systemic Lupus Erythematosus $ Systemic Sclerosis $ Rheumatoid Arthritis $ Polymyositis /Dermatomyositis $ Sjogrens Syndrome $ Mixed Connective Tissue $ Wegner’s Granulomatous Connective tissue diseases secondary to autoimmunity $ Cannot be regularly defined by gene abnormalities $ The spontaneous over activity of the immune system ¬ Results in the production of extra antibodies into the circulation Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell $ Systemic Lupus Erythematosus $ Rheumatoid Arthritis $ Sjogrens Syndrome $ Systemic Sclerosis $ Polymyositis /Dermatomyositis $ Mixed Connective Tissue $ Wegner’s Granulomatous 26 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Vasculitides The vasculitides are a group of diseases characterized by non infectious necrotizing vasculitis and resultant ischemia Vasculitides $ Polyarteritis Nodosa $ Churg-Strauss Syndrome $ Hypersensitivity Vasculitis $ Wegener’s Granulomatosis $ Giant Cell Arteritis $ Behcet’s Disease $ Cogan’s Disease $ Kawasaki Disease 32 year old man Fundus Reveals $ “I have bleeding in my eyes”, patient requests 3rd opinion $ “I have been tested for high blood pressure and diabetes 4 times, I don’t have either one” $ Vision 20/20 OU Work Up $ CBC/diff $ ACE $ FTA ABS $ VDRL $ HLA-B27 $ PPD $ ANA $ RF Results and Fundus 3 Weeks Later normal normal negative negative negative normal negative negative Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 27 Rheumatology, Thyroid Dysfunction and the Eye Ask and You Shall Receive June 4, 2016 Refer to Rheumatologist $ Testing and examination reviews Behcet's diagnosis ¬ Vasculitis with triad of oral and genital ulcers and uveitis or iritis ¬ Ulcers, covered in pale pseudomembrane 2 Painful, on lips, gingiva, buccal mucosa, tongue, palate and oropharynx 2 Genital ulcers similar in appearance 2 Heal in days to weeks with scarring $ The treatment of Behcet's syndrome depends on the severity and the location of its manifestations in an individual patient ¬ This patient oral steroids and Remicade 80 year old man Photos OU $ Reports a sudden loss of vision OD $ Vision is count fingers at 2 feet OD and 20/25 OS $ APD OD grade 4 $ Fundus photos OU CRAO Treatment/Work-Up/Follow-Up? $ Anterior chamber paracentesis (less than 24 hours) $ STAT blood work ¬ 2-10% of all CRAOs are caused by thrombosis from Giant Cell Arteritis (GCA) ¬ Sed-rate ¬ C-reactive protein Laboratory Results What are we looking for? 2 Qualitative or quantitative? ¬ CBC with diff $ Monitor for neovascularization, every 3-6 weeks Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 28 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Immediate Treatment and Referral $ Rx given to patient to stop and get po steroids $ Immediate referral to rheumatologist for systemic management ¬ Schedule temporal artery biopsy Giant Cell Arteritis Giant cell arteritis (temporal artery biopsy) (Management) § Corticosteroids: § 0.5-1mg/kg/day in divided dosages § Taper Rx over 1-2 months to obtain oral dosing schedule between 5-7.5mg/d Multiple giant cells lining up and infiltrating the internal elastic lamina § DMARDs § Methotrexate most commonly used § Dosage: 10-20mg/wk § Remicade clinical trial unsuccessful 9 Months Later “The cherry flavor is not long lasting” 9 months earlier Giant Cell Arteritis $ Most common vasculitis $ Most common initial complaint ¬ Headache-boring and constant (47%) ¬ 90% will develop headache $ ESR >50mm/hr $ Confirmed by temporal artery biopsy of affected side ¬ 5-7cm in length, if negative, biopsy contra lateral side ¬ False negative rate of 5-40% $ Tender and erythematous temporal artery 50% $ Tender scalp $ Jaw ischemia 50% $ Lingual ischemia 25% Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 29 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Giant Cell Arteritis Giant Cell Arteritis § Clinical features § § § § § § § § § Laboratory features Headache Temporal artery abnormality Jaw claudication Visual loss diplopia Extremity claudication PMR symptoms Weight loss, fever Respiratory symptoms § § § § Elevated ESR Elevated CRP Anemia Elevated alkaline phosphatase (ACR 1990 criteria classification) § Must have at least 3 of the 5 criteria present. § § § § § Age > 50 years at disease onset New headache Temporal artery abnormality (tender or decreased pulse) Elevated Westergren ESR > 50 mm/hr Abnormal artery biopsy: mononuclear cell infiltrate, granulomatous inflammation, usually multinucleated giant cells § Sensitivity 93.5% and specificity 91.2% Giant cell arteritis: (forehead) Giant cell arteritis: scalp necrosis Giant cell arteritis: (scalp necrosis) Polymyalgia Rheumatica (Association) $ 10-15% of patients with PMR have GCA ¬ GCA can develop long after onset and treatment of PMR $ PMR is found in 50% of patients with giant cell arteritis $ Muscular pain, morning stiffness of proximal muscles, elevated ESR without inflammatory joint or muscle disease ¬ Low grade fever, wt loss, malaise $ Low dose prednisone ¬ Treatment of GCA requires larger doses of corticosteroids than does treatment of PMR Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 30 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Spondyloarthropathies $ Prevalence is similar to Rheumatoid Arthritis, 1-2% $ Share similar clinical, radiographic, and genetic features Spondyloarthropathies $ A cluster of overlapping forms of inflammatory arthritis ¬ Are distinct from rheumatoid arthritis ¬ Affect the spine ¬ Affect the entheses (insertions of tendons and ligaments) $ The syndromes include ¬ Ankylosing spondylitis ¬ Reactive arthritis (Reiter's syndrome) ¬ Psoriatic arthritis ¬ Enteropathic arthritis $ Syndromes sometimes included (controversial) ¬ Whipple's disease ¬ Behcet's syndrome Seronegative Spondyloarthropathy Spondyloarthropathy $ Seronegative refers to the absence of the specific antibodies (or substance) that were being tested for ¬ Rheumatoid factor $ Spondyloarthropathies are inflammatory joint diseases of the vertebral column associated with the major histocompatibility complex (MHC) Class I molecule ¬ HLA-B27 HLA B27 HLA-B27 & Uveitis $ Features $ The major histocompatibility complex is encoded by several genes located on human chromosome 6 $ Most (but not all) patients with spondylitis carry a gene called HLA-B27 $ People carrying the HLA B27 gene ¬ Marked or severe presentation ¬ Anterior iritis ¬ Unilateral ¬ Acute onset, <3 months $ Can occur as a HLA B27 uveitis $ Can occur with a spondyloarthropathy ¬ Are at increased risk of developing spondylitis ¬ The majority (over 75%) will never develop the disease $ HLA-B27 is not helpful in prognosis Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 31 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Ankylosing Spondylitis $ Ankylosing spondylitis is a chronic, usually progressive, disease involving the articulations of the spine and adjacent soft tissues $ HLA B27 positive 90% $ Uveitis 20-40% chance Reactive Arthritis $ A spondyloarthropathy following enteric (GI tract) or urogenital infections and occurring in individuals who are HLA-B27 positive ¬ What was once referred to as “Reiter syndrome” and is now referred to as reactive arthritis 2 Was described as a triad of arthritis, nonspecific urethritis, and conjunctivitis, often accompanied by iritis $ Can cause inflammation in the joints of the spine, legs and arms and in other parts of the body $ The syndrome usually begins with urethritis followed by conjunctivitis and rheumatological findings ¬ Arthritis begins within 1 month of infection in 80% of patients $ HLA B27 positive 40-80% $ Uveitis 20-40% chance Psoriatic Arthritis Enteropathic Arthritis $ A form of chronic, inflammatory arthritis associated with the occurrence of an inflammatory bowel disease (IBD) $ Patients with psoriasis have a 5-42% chance of developing psoriatic arthritis $ About 20% of people who develop PsA will eventually have psoriatic spondylitis ¬ The inflammation in the spine can lead to complete fusion ¬ Spondylitis associated with psoriasis 2 60-70% are HLA-B27 positive 2 Psoriatic arthritis without spondylitis 15% HLA B27 positive $ Uveitis 7% chance ¬ Ulcerative colitis ¬ Crohn's disease $ About one in five people with Crohn's or ulcerative colitis will develop enteropathic arthritis ¬ Approximately 50-60% of patients with spondylitis in association with IBD have HLA-B27 $ The most common areas affected are the peripheral (limb) joints ¬ In some cases, the entire spine can become involved as well $ Uveitis 3-11% chance Undifferentiated Spondyloarthropathy (USpA) $ To describe symptoms and signs of spondylitis in someone who does not meet the criteria for a definitive diagnosis of AS or related disease ¬ Unrecognized by many physicians ¬ Initial diagnosis of Spondyloarthropathy or Unclassified Spondyloarthropathy if certain symptoms are present but are not enough to make a specific diagnosis What Drug Do Rheumatologists Use Quite Often? 2 Over time, most people with USpA will develop a well-defined form of spondylitis such as ankylosing spondylitis Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 32 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 32 year old man Lab Work-Up? $ “Doc my eye hurts like” hell 2 Was not “hell” but rhymes with truck $ Started hurting yesterday $ SLE: diffuse G3 injection with limbal flush, A/C G4 cell and flare with light fibrin formation at pupil, multiple KP’s $ Fundus unremarkable but iris to lens synechia at 2 and 6 o’clock $ Diagnosis marked iritis, first episode Lab Work-Up? $ CBC with diff $ SED rate (ESR) $ ANA $ RF $ ACE normal normal negative negative normal $ FTA ABS $ VDRL $ HLA-B27 $ Lyme titer $ PPD $ Chest X-ray $ CBC with diff $ FTA ABS $ SED rate (ESR) $ VDRL $ ANA $ HLA-B27 $ RF $ Lyme titer $ ACE $ PPD $ Chest X-ray Refer to Rheumatologist negative negative positive negative negative normal $ After labs and images patient was diagnosed with Ankylosing Spondylitis ¬ Systemic disease is treated by rheumatologist ¬ Ocular disease managed by optometrist Patient reports lower back pain but thought it was only due to job as a brick and block layer 52 year old woman What is needed for a Plaquenil baseline ocular examination? $ Referred in by the rheumatologist for baseline ocular examination due to Plaquenil therapy for rheumatoid arthritis ¬ 200 mg bid PO (400 mg) ¬ Started 1 week ago $ VA 20/20 OU $ In 2011 the screening recommendation changed for Plaquenil retinopathy ¬ The last recommendation was 2002 $ Externals: unremarkable $ SLE: normal with adequate tear prisms $ IOP 15 OU Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 33 Rheumatology, Thyroid Dysfunction and the Eye Plaquenil (Antiprotozoals/Antimalarial Therapy) $ Classification ¬ Hydroxychloroquine ¬ Chloroquine $ Hydroxychloroquine (Plaquenil) ¬ Safe, well absorbed ¬ Avoid if there is a G6PD deficiency 2 Glucose-6-phosphate dehydrogenase deficiency 2 Metabolic enzyme involved in cell metabolism ¬ Dosage: 200-400mg/d $ Properties ¬ Rapidly absorbed in GI tract ¬ Immunomodulatory & anti-inflammatory ¬ Inhibit cell division/RNA transcription/ mononuclear cell phagocytosis/ cytokine secretion What is needed for a Plaquenil baseline ocular examination? $ History (Plaquenil history questions) ¬ Dosage (400 mg daily) ¬ Number of years on medication or cumulative dose (recent literature) ¬ Any renal or liver impairment $ Risk Factors ¬ Cumulative Dosage 2 400 mg x 365 = 146,000 mg/yr or 146 g/yr 2 146 g x 5 yrs = 730 g 2 146 g x 7 yrs = 1022 g (1000 g) ¬ Daily dose >400 mg ¬ Short stature with typical dose ¬ Age: Elderly at more risk ¬ Renal or liver function 2 Impairment places the patient at higher risk ¬ Existing retinal or macular disease What is needed for a Plaquenil baseline ocular examination? $ Slit lamp examination ¬ Plaquenil can deposit in the cornea, if found here it is suggesting drug accumulation 2 Less than 20% at 400 mg develop corneal deposits $ Fundus examination with 90 or 78/20 ¬ Look for unrelated/current pathology ¬ Consider red free to enhance RPE changes $ Fundus photos $ Visual fields ¬ Central 10-2 white on white Sita-Standard 2 Plaquenil scotomas are typically found within 10° of fixation ¬ Para-central scotomas $ SD-OCT ¬ Special attention to the inner and outer segment line $ Counseling patient on the risk of toxicity (educational sheet) ¬ Avoidance of liability ¬ The need for periodic ocular examination ¬ Screening can recognize toxicity early and minimize visual loss but can not prevent all toxicity or guarantee there will be no vision loss Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell June 4, 2016 Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy $ Last recommendations were 2002 by the American Academy of Ophthalmology $ Improved screening tools and new knowledge about prevalence of toxicity have prompt the change ¬ 1% after 5-7 years of use or a cumulative dose of 1000 grams (Plaquenil) $ There is no treatment for this condition ¬ Therefore must be caught early $ Screening for the earliest hints of functional or anatomic change $ Plaquenil toxicity is not well understood What is needed for a Plaquenil baseline ocular examination? $ Best corrected visual acuity $ Color vision? ¬ Not sensitive enough to detect retinal toxicity ¬ If color vision affected then patient will most likely have absolute scotoma and visual acuity affected ¬ In early retinal toxicity there is a relative scotoma, normal color vision and normal acuity ¬ Studies show blue-yellow occur first then red-green in plaquenil toxicity 2 Ishihara does not test for blue-yellow 2 D-15 is less sensitive than Ishihara 52 year old woman $ 200 mg bid PO (400 mg daily) $ 1 week duration $ Normal stature $ No history of renal or liver impairment $ VA 20/20 OU Just Kidding $ Color vision D-15 normal $ SLE: normal, (-) deposits and normal tear prisms $ Fundus with 90/20, normal $ Photos taken, normal $ VF 10-2 Sita-stand done OU, normal $ SD-OCT done, special attention to inner and outer segment $ Risk of toxicity education sheet given to patient $ RTC 1 year for follow up (Comprehensive dilated exam with 10-2) 34 Rheumatology, Thyroid Dysfunction and the Eye Not Recommended for Screening June 4, 2016 Plaquenil Cranium Keepers $ Annual screening for first 5 years or < 1000 g ¬ Comprehensive dilated exam and 10-2 $ Fundus photography ¬ Recommend at baseline ¬ Not sensitive for screening $ Time Domain OCT- insufficient resolution for screening $ Amsler grid- can use as adjunct if desired $ Color vision $ After 5 years, >1000 g or high risk ¬ Comprehensive dilated exam, 10-2 and SD-OCT $ Discontinue if toxicity occurs: ¬ Keratopathy is not a reason to discontinue 2 Less than 20% develop corneal deposits at 400 mg/daily ¬ Repeatable visual field defect is a reason to consider discontinuing treatment ¬ Documented change to inner/outer segment of retina $ Goal: ¬ Recognize the para-central functional change (10-2) ¬ Recognized the para-central structural change (SD-OCT) ¬ Bull’s Eye maculopathy is too late PLAQUENILZONE Plaquenil Toxicity Oh Boy! SYMMETRICAL AND NOTHING OBVIOUS Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 1-1.5MMPERIMACULARGCC THINNINGTHEFIRSTSIGNOF PLAQUENILTOXICITY WHY?THICKESTLAYER OFGANGLIONCELLSAND SMALLESTGANGLION CELLSATTHATLOCATION. VERYSENSITIVETOTOXICITY 35 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 WHATDOYOUSEEONTHESCANS? A. B. C. D. THINNINGOFTHEGCCINTHEPLAQUENILZONE MACULAREDEMA COMPROMISEDPIL NOTHINGOFIMPORT DO YOU SEE ANY PROBLEM IN THE PLAQUENIL ZONE? WHATDOYOUSEEONTHESCANS? A. B. C. D. THINNINGOFTHEGCCINTHEPLAQUENILZONE MACULAREDEMA COMPROMISEDPIL NOTHINGOFIMPORT DO YOU SEE ANY PROBLEM IN THE PLAQUENIL ZONE? AUGUST2014 Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell AUGUST2014 36 Rheumatology, Thyroid Dysfunction and the Eye WHATDOYOUSEEONTHESCANS? A. B. C. D. THEFLYINGSAUCERSIGN MACULAREDEMA INCREASEDPERIMACULARRETINALTHINNING AANDC June 4, 2016 WHATDOYOUSEEONTHESCANS? A. B. C. D. THEFLYINGSAUCERSIGN MACULAREDEMA INCREASEDPERIMACULARRETINALTHINNING AANDC A A C C THEENDGAME…ONCEYOUDISCONTINUE PLAQUENILITSTAYSAROUNDAWHILETO CREATEDAMAGE..LONG½LIFE BILATERALCOMPROMISEOFTHEPIL(WHITEARROWS) AFTERCOLLAPSEOFPERIFOVEALRETINA(REDDASHED ARROWS)WITHFLYINGSAUCERATTACK(BLUEARROWS) Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell WAYOUTTATHEBARN 37 Rheumatology, Thyroid Dysfunction and the Eye June 4, 2016 Questions? Hope You Enjoyed Thank You! Greg A Caldwell, OD, FAAO [email protected] 814-931-2030 cell 38 Glaucoma-Enough Pearls to Make a Necklace Glaucoma “Enough Pearls to Make a Necklace” Greg Caldwell, OD, FAAO June 4, 2016 Everything Therapeutic: Houston June 4, 2016 Disclosures $ Greg A. Caldwell, OD, FAAO will mention many products, instruments and companies during our discussion, I don’t have any financial interest in any of these products, instruments or companies. $ American Optometric Association, Trustee ¬ No industry lecturing ¬ Thank you to the members and those who join $ All of these cases have entered/referred to my practice Disclosure Statement (next slide) What are the Two Types of Glaucoma? Risk Factors for Developing Glaucoma? Strong associations Academic Answer $ Open Angle Glaucoma $ Closed Angle Glaucoma Clinical Answer $ Those at risk to develop glaucoma $ Those who have glaucoma but are at a higher risk of progressing $ Age ¬ The older we are the higher the risk ¬ Validity is an issue but increase risk $ IOP ¬ The higher the IOP the higher the risk $ CCT ¬ Thinner corneas increases risk $ CDR ¬ Larger CDR increases risk Development / Progression Moderate association $ Family history $ Race (6-8x’s) ¬ Black Americans are at higher risk ¬ Surrogate of thinner CCT, higher IOP and larger CDR? Weak associations $ Refractive Error ¬ Poor association ¬ High myopia increase risk $ Systemic Disease-mixed ¬ HTN, migraine, DM, thyroid, sleep apnea 55 Year Old Men 500 microns CCT and 21 mm Hg with Goldmann Case 1 $ What is the true IOP? 1. 2. 3. 4. 18 mm Hg 21 mm Hg 24 mm Hg Don’t Know 600 microns CCT and 21 mm Hg with Goldmann $ What is the true IOP? 1. 2. 3. 4. 18 mm Hg 21 mm Hg 24 mm Hg Don’t Know Corneal Curvature Corneal Thickness Corneal Rigidity Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 1 Glaucoma-Enough Pearls to Make a Necklace June 4, 2016 61 year old woman $ You saw her 4 weeks ago and her IOP’s were 24 OD and 25 OS at 3:35 PM Case 2 $ Is in today for a morning IOP check and pachymetry Results Corneal Pachymetry $ Right and left eyes minimum corneal thickness differed by $ Pachymetry results ¬ OD 525 OS 565 $ IOP’s at 8:15 AM ¬ OD 28 OS 29 an average 8 μm $ 242 eyes $ Although a wide range of values exists in simulated Any Concern Here? keratometry, minimum corneal thickness, and posterior corneal elevation, ¬ Interocular pachymetry symmetry in all these parameters was very high in this group of consecutive patients. ¬ Asymmetry of these interocular parameters may warrant repeat clinical testing for accuracy and may predict corneal abnormalities. ¬ This study points out potentially clinically important high interocular corneal symmetry data in simulated keratometry, corneal thickness, and posterior corneal elevation. MYROWITZ Elliott H, KOUZIS Anthony C, O'BRIEN Terrence P. High interocular corneal symmetry in average simulated keratometry, central corneal thickness, and posterior elevation. Optometry and vision science. 2005, vol. 82, no5, pp. 428-431 Pachymetry Anterior Segment Imaging Pachymetry Ultrasonic versus Optical CCT measurement caliper Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 2 Glaucoma-Enough Pearls to Make a Necklace Anterior Segment Imaging with OCT Pachymetry June 4, 2016 Post-LASIK Less Than 15 Degrees Get Consult Development of Glaucoma $ OHTS- found DM to be protective What are your thoughts on DM being protective? $ OHTS, EMGTS and AGIS $ OHTS- found an increase in pattern standard deviation (PSD) to increase risk Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 3 Glaucoma-Enough Pearls to Make a Necklace June 4, 2016 Effect of H1 Antagonists on Histamine Release from Human Conjunctival Mast Cells1,2 120 120 Olopatadine PATANOL® solution 80 60 Ketotifen ZADITOR* 40 20 0 Azelastine OPTIVAR* -20 -40 Epinastine ELESTAT* -60 -80 Effect at marketed concentration -100 -8 -7 -6 -5 -4 -3 -2 -1 log [Drug] (M) *Trademarks are the property of their respective owners. 1. Yanni JM et al, The in vitro and in vivo ocular pharmacology of olopatadine. J Ocul Pharmacol Ther. 1996; 12:389-400. 100 % Inhibition of Histamine Release % Inhibition of Histamine Release 100 80 60 40 20 0 -20 -40 -60 -80 -100 -8 -7 -6 -5 -4 -3 -2 -1 2. Brockman HL et al, Interactions of olopatadine and selected antihistamines with model and natural membranes. Ocul Immunol Inflamm, 2003; 11:247-268. Progression $ Many practitioners feel that the risk factors for developing glaucoma and the glaucoma to progress are essentially the same $ However, once treatment commences things change ¬ One obviously is IOP $ Furthermore, the patients will get older and comorbitities may develop Risk Factors of Progression of Glaucoma? $ Age $ Systemic Diseases $ IOP ¬ DM, Migraine, HTN $ Diurnal IOP fluctuation $ Visual field loss $ CDR ¬ The more NRR loss the higher the risk to progress $ CCT ¬ Not a risk of progressing in appropriately treated patients with glaucoma $ Disc hemorrhage $ This is where most of our evidence based medicine done ¬ EMGTS ¬ AGIS Disk Hemorrhages ¬ Associated with progression $ Family history ¬ Especially those with functional vision loss Non-Specific Finding $ Non-specific finding $ However, when associated with glaucoma it typically indicates you should: ¬ Initiate a more careful monitoring ¬ Re-evaluate the therapy you are doing ¬ Treat the patient if not being treated Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 4 Glaucoma-Enough Pearls to Make a Necklace June 4, 2016 1-7-05 Non-Specific Finding 2-20-06 11-27-06 4-23-06 Disc Hemorrhage 11-27-06 9-12-05 Adjacent to Existing Loss Pallor Patient declined treatment for 10 years Pallor Laminar Dots $ Found in many normal eyes $ 34% of myopic eyes have laminar dots $ Shape of dots may be clinically helpful in determining glaucoma damage to optic nerve head ¬ Round holes become more horizontal slits in glaucoma Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 5 Glaucoma-Enough Pearls to Make a Necklace June 4, 2016 Lamina Cribrosa Laminar Dots Confusion in Glaucoma NEI Clinical Trials Across the Spectrum of Glaucoma $ Evidence based medicine is taking reliable and unbiased research evidence and applying it to clinical expertise and patient wishes to arrive at an appropriate treatment or management $ Clinical decisions are based on valid evidence ¬ Not gut feelings, hear say or peer influences $ Occurs when we apply a piece of evidence based medicine in the wrong area of our glaucoma paradigm $ Occurs when we don’t know where to apply the piece CIGTS OHTS Early Glaucoma Ocular Hypertension of evidence based medicine in our glaucoma paradigm Advanced Glaucoma AGIS GLT FFSS EMGT ongoing trials interim results completed trials Studies and Goals CCT GDX OCT Age (Very Abbreviated) HRT VF SWAP IOP Study Disease State IOP Endpoint OHTS High IOP 20% Decrease EMGTS Early 20% CIGTS Newly Dx VF & IOP dependent (As low as 40 %) CNTGS Advanced Progressive NTG 1/3 decrease AGIS Advanced < 18 mm Hg RNFL and optic nerve change (detectable) Short wavelength automated perimetry VF changes Retinal nerve fiber layer change (undetectable) Treatment Ganglion cell death/axon loss Acceleration of apoptosis Normal VF Thres hold VF FDT Tr e Age at m IOP &Diurnal IOP CDR and Hemes en Standard automated perimetry VF change t VF change (moderate) VF change (severe) Blindness Glaucoma Continuum Weinreb et al. Am J Ophthalmol. 2004;138:458-467. Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 6 Glaucoma-Enough Pearls to Make a Necklace CCT GDX Rates of Progression OCT Age HRT VF SWAP IOP O H TS June 4, 2016 VF RNFL and optic nerve change (detectable) EMGTS Acceleration of apoptosis FDT Short wavelength automated perimetry VF changes Retinal nerve fiber layer change (undetectable) Treatment Ganglion cell death/axon loss VF Thres hold Tr e Age at m IOP &Diurnal IOP en $ OHTS $ EGPS Standard A automated GI S perimetry VF change t Treated $ EMGTS $ CNTGS Untreated 1%/yr 2%/yr 45%/yr 4%/yr $ OHTS $ EGPS $ EMGTS $ CNTGS 2%/yr 2%/yr 62%/yr 12%/yr VF change (moderate) CDR and Hemes VF change (severe) Normal Blindness Glaucoma Continuum $ It is generally accepted that in early glaucoma patients: $ Treated patients will have a rate of worsening of 4% $ Untreated patient will have a rate of worsening 8-10% Weinreb et al. Am J Ophthalmol. 2004;138:458-467. CNTGS $ If Normal Tension Glaucoma is left untreated ¬ 1/3 would progress within 3 years ¬ ½ would progress within 5-7 years $ Therefore, most cases of NTG progress slowly ¬ If you treat someone and there is no progression is it your treatment or is it because the disease is so slow? 50 year old woman Case 3 ONH Appearance $ Recently has moved to the area and needs followed for her “ocular hypertension” $ Diagnosed 18 months ago $ Currently is using Travatan qd OU (PM) $ VA 20/15 OU $ Externals: unremarkable $ SLE: slight hyperemia OU $ IOP: 13 OD and 14 OS @ 8:30 AM Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 7 Glaucoma-Enough Pearls to Make a Necklace June 4, 2016 Review of Records $ Diurnal IOP without medication ¬ OD 16-19 8:00 AM thru 5:30 PM ¬ OS 17-20 8:00 AM thru 5:30 PM $ Pachs ¬ OD 505 ¬ OS 505 $ VF results MD and PSD MD $ 54 spots on 24-2 ¬ All 54 spots reduced by 1 DB (54DB) ¬ MD 1DB $ 54 spots on 24-2 ¬ 27 spots reduced by 2 DB (54 DB) ¬ MD 1 DB $ 54 spots on 24-2 ¬ 13.5 spots reduced by 4 DB (54DB) ¬ MD 1 DB PSD $ Low PSD (Generalized loss) ¬ 1.00 DB $ Moderate PSD (More localized loss) ¬ 3.00 DB $ High PSD (Localized loss) ¬ 5.00 DB Treatment Discussion Why is this patient being treated? Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell $ Repeat visual field $ Discontinue Travatan $ Get GDX nerve fiber analysis 8 Glaucoma-Enough Pearls to Make a Necklace Repeated VF Cranium Keeper June 4, 2016 GDX Results Thoughts on Mean Deviation (MD) What is the Mean Deviation on a visual field of a blind eye? $ Do not back door patients into the ocular hypertension treatment study ¬ Via thin pach results $ A patient needs to be suffering from ocular hypertension to use the study $ Thin pachs tell us: ¬ Patients with ocular hypertension are at high, medium or low risk for development $ If you have a diagnostic instrument learn how it works and make proper interpretations Thoughts on Mean Deviation (MD) $ Turn on your VF let it run ¬ 30 DB (decibel) $ 0-5 (1/6) 30% reduction $ 5-10 (1/3) 40% reduction $ >10 (1/2) 50% reduction Surgical Update Endoscopic Cyclophotocoagulation (ECP) $ How many DB difference to reliable VF should cause a RAPD? ¬ 3 DB for a small APD, the larger the difference the greater the APD Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 9 Glaucoma-Enough Pearls to Make a Necklace What is Endoscopic Cyclophotocoagulation (ECP) $ Ciliary body processes are visualized with an endoscope and are photocoagulated with a laser $ Result is decreased aqueous production and lower IOP Endoscopic Cyclophotocoagulation (ECP) $ Gaining in popularity $ Typically done at the time of cataract surgery ¬ Increase number of surgeons are combining phaco with ECP June 4, 2016 History of Endoscopic Cyclophotocoagulation (ECP) $ Martin Uram, MD (Retinologist) ¬ Wanted another treatment for neovascular glaucoma ¬ Cyclocryotherapy 2 Painful, limited to moderate success to lower IOP and high complication rate Benefits of Endoscopic Cyclophotocoagulation (ECP) $ Performed through small incision $ Easy access to ciliary processes while the patient is aphakic $ Easy to perform $ Typically able to reduce the amount of drops the patient uses ¬ Increase in quality of life $ Possibly more sustained IOP control ¬ Studies show fluctuating IOP as risk factor Limitations of Endoscopic Cyclophotocoagulation (ECP) $ Transient iritis ¬ Treated with steroids $ Cystoid macular edema (CME) reported to be 1% $ No reports of hypotony or phthisis Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell Replacing Filters/Trabeculectomy $ Phaco/Filter ¬ Additional 25-30 minutes of surgery ¬ Numerous post op visits ¬ Failure rate ¬ Marked IOP reduction or hypotony $ Phaco/ECP ¬ Additional 5 minutes of surgery ¬ Standard cataract post op visits ¬ Minimal failure rate ¬ Gradual IOP reduction 10 Glaucoma-Enough Pearls to Make a Necklace Expectations $ Study of 707 eyes with cataracts and controlled glaucoma ¬ 626 ECP/Phaco ¬ 81 Phaco only $ ECP ¬ Pre-op IOP 19.08 $ Phaco only ¬ Pre-op IOP 18.6 Post-op IOP 15.73 Post-op IOP 18.93 $ 68% are able to reduce 1 glaucoma medication $ Approximate savings $800-1500/year for the patient Video of ECP June 4, 2016 Post Op $ Pred-Forte ¬ Every 2 hours to qid for 1 month $ Nevanac ¬ Bid or tid for 1 month $ Cycloplegia ¬ Homatropine or Scopolamine ¬ 1-12 weeks Thank-You and Hope You Enjoyed Greg Caldwell, OD, FAAO [email protected] Greg Caldwell, OD, FAAO [email protected] 814-931-2030 cell 11 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 Disclosures Oral Antibiotics in Eye Care Greg Caldwell, OD, FAAO June 4, 2016 Everything Therapeutic: Houston $ Greg A. Caldwell, OD, FAAO will mention many products, instruments and companies during our discussion, I don’t have any financial interest in any of these products, instruments or companies. $ American Optometric Association, Trustee ¬ No industry lecturing ¬ Thank you to the members and those who join $ All of these cases have entered/referred to my practice Disclosure Statement (next slide) Learning Objectives $ Review adverse/allergic reactions to oral medications $ Review the FDA Pregnancy Categories for medications ¬ Review new guidelines: Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products $ Discuss renal impairment and its impact on prescribing oral medications Patient Wants Second Opinion 42 year old woman OD red and painful Va 20 20 cc 20 Current Correction R -2.00-1.00 x 180 L -3.00-1.00 x 180 $ Identify and review the most appropriate oral antibiotics for usage in ocular infections, so one can implement a timely and effective treatment $ Furnish the clinician with pearls, therapeutic options and guidance around pitfalls Slit Lamp Evaluation $ Findings ¬ OD only red and injected ¬ Stuck shut this morning EOMS: full, unrestricted CT: ortho D/N PERRL (-)APD CF: full by FC OU New Diagnosis? $ Diagnosis ¬ Bacterial conjunctivitis $ Ocular history reveals ¬ 3rd time in past 10 months ¬ Vigamox 2 Successfully resolves in 2-3 weeks Recurrent bacterial conjunctivitis secondary to dacryocystitis Why recurrent and slow to resolve? Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 1 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients Dacryocystitis June 4, 2016 Medical History $ Before we Rx any medications we take a thorough medical history which includes: $ Treatment discussion? ¬ Topical antibiotics ¬ Oral antibiotics $ Remember to check for? $ Patient is allergic to Penicillin and Keflex ¬ Which antibiotic would you use? Adverse/Allergic Reaction to Systemic Medication • CC • HPI • ROS • Kidney disease, liver disease, dialysis • PFS History • Current Medications • Allergies…Adverse Reactions/Allergies • Pregnancy…any chance you might be pregnant? FDA Pregnancy Categories $ Category A- studies in pregnant women, no risk $ Hypersensitivity- fever, rash, photosensitivity or ANAPHYLAXIS • Hematologic- neutropenia, eosinophilia, increase in PT/PTT • GI- nausea, vomiting, diarrhea • Liver Failure • CNS- dizziness, HA, confusion, seizures • Ototoxicity • Cardiac- dysrrhymias Pregnancy and Lactation Labeling Rule-FDA December 4, 2014 Final Rule $ Effective June 30, 2015 ¬ Effective now for new medications and a 3-5 year phase in period (application) $ Labeling for human prescription drugs and biological products will include: ¬ Pregnancy ¬ Lactation ¬ Females and Males of Reproductive Potential $ Pregnancy (8.1) ¬ Pregnancy Exposure Registry – omit if not applicable ¬ Risk Summary – required subheading ¬ Clinical Considerations- omit if none of the headings are applicable $ Category B- animal studies no risk but human not adequate…or…animal toxicity but human studies no risk…safe $ Category C- animal studies show toxicity human studies inadequate but benefit of use may exceed risk…avoid $ Category D- evidence of human risk but benefits may out weigh risks…avoid $ Category X- fetal abnormalities, risk>benefits…avoid Pregnancy and Lactation Labeling Rule-FDA December 4, 2014 Final Rule $ Lactation (8.2) ¬ Risk Summary- required subheading ¬ Clinical Considerations– omit if not applicable ¬ Data– omit if not applicable $ Females and Males of Reproductive Potential (8.3) - omit if none of the headings are applicable $ Pregnancy testing– omit if not applicable $ Contraception– omit if not applicable $ Infertility – omit if not applicable 2 Disease-associated maternal and/or embryo/fetal risk- omit if not applicable 2 Dose adjustments during pregnancy and the postpartum period - omit if not applicable 2 Maternal adverse reactions - omit if not applicable 2 Fetal/Neonatal adverse reactions- omit if not applicable 2 Labor or delivery - omit if not applicable ¬ Data- omit if none of the headings are applicable 2 Human Data - omit if not applicable 2 Animal Data- omit if not applicable Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 2 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 Antibiotic Paradigm Renal Impairment $ Identify patients on hemodialysis Antibiotic Paradigm $ Adjustment made by patient’s creatinine clearance (CrCl)…ml/min ¬ Work with patient’s PCP/Internist Penicillin Macrolide Cephalosporin Quinolone Sulfonamide Augmentin Zithromax Keflex Cipro Bactrim Cross Reaction Allergies Penicillin Macrolide Cephalosporin Quinolone Sulfonamide Augmentin Zithromax Keflex Cipro Bactrim Sulfonylurea (Glyburide) (Glipizide) Sulfonamide (Celebrex) Carbonic Anhydrase Inhibitor Diamox Thiazide Diuretic Hydrochlorothiazide (HCTZ) Augmentin $ Amoxicillin and potassium clavulanate ¬ Uber amoxicillin $ Kills everything, good for everyone – 12 weeks old and older $ Safe in pregnancy…category B $ Watch for PCN allergies $ Adults: 250, 500 and 875 mg ¬ 125 mg of potassium clavulanate $ Children <100 pounds: oral suspension 25-45 mg/ kg divided into 2 doses Zithromax (azithromycin) $ Macrolide antibiotic (erythromycin) $ Drug of choice in PCN sensitive patients $ All age groups and pregnancy category B $ No renal adjustment $ Adult: ¬ 250 mg bid (day1), 250 mg qd (day 2-5), 6 pack ¬ 500 mg qd x 3 days, tri-pack $ Children<16: 10 mg/kg (day1), 5 mg/kg (day 2-5) $ Covers Staph, Strep and Haemophilus influenzae $ Better tolerated than erythromycin, little GI upset $ Chlamydia…1 g qd $ Covers Staph, Strep and Haemophilus influenzae Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 3 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 Keflex (cephalexin) Zithromax (azithromycin) $ “The Vegas Drug”- Chlamydia…1 g qd $ Cross reaction with PCN sensitive patients $ 1st generation, moderately affective against PCN-ase $ Good for Gram +, not good for Haemophilus (-) $ Available in 250 and 500 mg $ Category B $ Adult: typically, 500 mg bid x 1 week ¬ Maximum 4 g in 24 hrs $ FYI...Drug of choice for blow out fractures Ceftin (cefuroxime) PCN $ Minimal cross reaction with PCN sensitive patients $ 2nd generation Cross Reaction $ Better for Haemophilus (-) $ Children: 3 months to 12 years old, oral Keflex suspension 15 mg/kg divided into 2 doses x 10 days $ Available in 125, 250 and 500 mg ¬ FYI: adults typically 250 mg bid x 10 days Ceftin $ Category B Cipro (ciprofloxacin) Levaquin (levofloxacin) $ In my opinion, an end of the line, antibiotic to use… allergic to PCN, cephlosporins, macrolides… $ Really effective $ Would avoid if pregnant…category C $ Only use 18 years or older (oral) $ Cipro and Levaquin available in 250, 500 and 750 mg ¬ Cipro 750 mg for only severe infections $ 500 mg bid x 1 week-Cipro $ 500 mg qd x 1 week-Levoquin $ Levaquin-tendon ruptures Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell Sulfa Drugs $ Limited use…last line of defense $ Contraindicated in pregnancy and sickle cell disease ¬ Category C $ High incidence of Steven-Johnsons $ Cross reaction with: oral hypoglycemics, CAI’s, celebrex and thiazide diuretics…all sulfa based $ Bactrim SS ¬ 400 mg sulfamethoxazole/ 80 mg trimethoprim ¬ 1-2 tab PO bid $ Bactrim DS (double strength) ¬ 800 mg sulfamethoxazole/ 160 mg trimethoprim ¬ 1 tab PO bid 4 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 Summary How About $ PCN, Ampicillin and Amoxicillin Allergies Penicillin Macrolide Cephalosporin Quinolone Sulfonamide Adults Augmentin Zithromax Keflex Cipro Bactrim Children Augmentin Zithromax Ceftin Avoid Bactrim $ Dicloxacillin, 250mg qid x 1week $ Remember…patient allergic to PCN and Keflex $ Treatment ¬ Vigamox gtts TID ¬ Zithromax 2 Disp: z-pak 2 Use as directed PO $ Dilation and Irrigation ¬ Contraindication and indication What group of antibiotics are we missing? $ Confirmed nasolacrimal duct blockage ¬ DCR, dacryocystorhinostomy Clinical Pearl Treatment Failure $ If you continue to think of doxycycline and minocycline as antibiotics, treatment failure will be the result $ From this point on consider them a steroid 48 year old man OU red, gritty, sandy and dry feeling Va 20 20 20 cc 20 Current Correction R -2.00 sphere L -3.00 sphere EOMS: full, unrestricted CT: ortho D/N Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell PERRL (-)APD CF: full by FC OU 5 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 A Closer Look $ Diagnosis ¬ Rosacea $ What findings support your diagnosis? ¬ Telangiectasias ¬ Erythema of the cheeks, forehead and nose ¬ Rhinophyma 2 Indicates chronic $ Let us get a closer look Tetracycline Minocycline Analog Rosacea Blepharitis (Inflammatory Blepharitis, MGD) $ Diagnosis? $ Treatment? ¬ In my opinion, most under treated condition ¬ Warm compresses ¬ Lid hygiene ¬ Artificial tears ¬ Omega 3 fatty acid Staph Aureus Staph Epidermidis Lipase Turbid Inspissated MG Meibomian Gland Secretions (Lipid) Marginal Foam (Soap) Phospholipids Arachidonic Acid 2 EPA and DHA total 1500 mg (1000 mg minimum) ¬ Dermatological consult (Acne Rosacea) ¬ Oral antibiotics…??? Prostaglandins Thromboxines 2 Which one and why?? Leukotrienes How About Steroids? Minocycline / Doxycycline $ Drug of choice for marginal inflammatory blepharitis (posterior blepharitis) $ AB, anti-inflammatory and anti-collagenase $ Inhibits lipase enzyme $ No renal adjustment $ 50-100 mg qd-bid 2-12 weeks (pulse) My Paradigm for Minocycline / Doxycycline $ Status of MG ¬ Inspissated ¬ Turbid Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell ¬ Maximum dosage for 2-12 weeks (pulse) 2 100 mg BID, QD ¬ 50-100mg qd while turbid ¬ 20 mg longer treatments 2 Periostat (Doxycycline) ¬ Lower maintenance dose $ 20 mg Periostat (Doxycycline) ¬ Helpful in those with stomach or GI sensitivity ¬ Excellent for those requiring long maintenance dose $ Minocycline / Doxycycline Paradigm ¬ Clear ¬ 20 mg if maintenance dose needed 6 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients Customize Treatment $ 50 mg Minocycline with pill cutter (25 mg) $ Oracea- 40 mg of Doxycycline total ¬ 30 mg immediate release ¬ 10 mg sustained release $ Alodox Kit ¬ 20 mg Doxycycline ¬ Ocusoft lid scrub June 4, 2016 Precautions With Oral Tetracycline Analogs $ Enhanced photosensitivity $ Avoid in children and pregnancy (Category D) $ Can enhance Coumadin $ Can enhance the action of digoxin $ ?Long term use with increase risk of breast cancer? $ AzaSite (azithromycin opthalmic solution) 1.0% ¬ Initiate early in treatment ¬ Adjunctive when patient is already on Doxycycline ¬ Alternative in states that do not have oral therapeutic licensure Benign intracranial hypertension “It’s not rare if it’s in your chair” ¬ 1 paper/study, not regarded as highly reliable study ¬ Further investigation discredited the association $ Benign intracranial hypertension, reported cases ¬ 17 cases from 1978-2002 9-13-2010 8-19-2010 10-6-2010 8-31-2010 8-19-2010 Minocycline Successfully Treated $ Less photosensitivity $ Less GI upset $ Less bacterial resistance $ Warm Compresses $ Lid Scrubs $ Artificial Tears, Systane Balance $ Omega 3 (1500 EPA and DHA) $ Mino 100 mg PO 6 weeks, 50 mg 3 months, 20 mg maintenance (Doxy) $ Steroids, Tobradex qid (5 weeks with taper) ¬ Moderately red and thickened lid margins ¬ Marginal infiltrates Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 7 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 What is an Inspissated MG? I Can’t Believe It’s Not Butter!® Squeeze 6 Month Later 1 Year Later Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 8 Oral Antibiotics-Feel More Confident and Comfortable in One Hour Prescribing Oral Antibiotics for Your Patients June 4, 2016 Thank-You and Hope You Enjoyed Greg Caldwell, OD, FAAO [email protected] Greg A. Caldwell, OD, FAAO [email protected] 814-931-2030 cell 9