AUTOIMMUNITY & THE EYE

1. AUTOIMMUNITY & THE EYE THE SEQUEL

2. For Your Consideration • 30 year-old Caucasian male • 12 month history of “progressive restlessness and wild eyes” • coworkers accused him of cocaine abuse! • referred for drug counseling!

3. For Your Consideration • Clinical Evaluation • violent palpitations • unbounded energy • prominent stare • proptosis with 3mm lag • tachycardia • tremor • warm moist hands • 40-g goiter

4. For Your Consideration • Diagnosis • Graves’ Disease • Thyrotropin (TSH) < 0.1 ulU/mL • T4 = 21 ug/dL • resin T3 uptake (RT3U) = 48%

5. For Your Consideration • Treatment To Achieve Euthyroid State • Propranolol • Propylthiouracil • radioactive iodine therapy • thyroidectomy

6. Rheumatoid Arthritis • General Considerations • It’s chronic, systemic, autoimmune and _______! • Onset: insidious, synovial membranes of small joints • females aged 20-40 years • most common cause of physical disability in U.S.

7. Rheumatoid Arthritis • General Considerations • Genetic and environmental factors • 2.1 million Americans

8. Rheumatoid Arthritis • General Considerations • Vs Osteoarthritis (degenerative joint disease) • constitutional signs and symptoms • morning stiffness (not helped with rest) • symmetrical

9. Rheumatoid Arthritis • Criteria For Diagnosis (4/7) • morning stiffness • swelling of joints (2) • symmetrical swelling • subcutaneous nodules • +rheumatoid factor • radiologic evidence • ocular criteria?

10. Rheumatoid Arthritis • Laboratory Findings • Rheumatoid Factor: IgM against Fc of IgG, more than 75% of patients, non-specific, titers correlate to disease severity • X-rays

11. Rheumatoid Arthritis • Course and Prognosis • majority in remission within several years • if joint symptoms persist beyond two years: bone deformities, extra-articular manifestations

12. Rheumatoid Arthritis • Treatment • nonpharmacologic: education, physical therapy, exercise, heat and cold • pharmacologic: NSAID’s, immunosuppressants, antimalarials, gold salts, steroids • DMARD’s = disease modifying anti-rheumatic drugs: methotrexate, hydroxychloroquine, sulfasalizine, leflunomide, prednisone

13. Rheumatoid Arthritis • Ocular Complications • 25% of patients • anterior > posterior segment • #1 again: KCS • furrowing of peripheral cornea, episleritis / scleritis, peripheral ulcerative keratitis, uveitis in Juvenile Rheumatoid Arthritis

14. Rheumatoid Arthritis • Ocular Complications • Management • standard • for severe corneal and scleral disease: often > 2 systemic agents

15. Sjogren’s Syndrome • Basically: • Autoimmune disorder • Causes decreased functioning • Progressive destruction • Salivary & lacrimal glands • Main ocular association: KCS

16. Sjogren’s Syndrome • General Considerations • 3% of women over age 55 • 1-4 million in US • grossly underdiagnosed autoimmune disease • involves diffuse exocrine gland secretion • sicca complex, arthralgia, fatigue, extraglandular manifestations

17. Sjogren’s Syndrome • General Considerations • Sicca Complex: dry mouth, nose, vagina • Arthralgia: intermittent and migratory, joints of hands, feet, wrists, ankles, elbows, knees • Pronounced fatigue • Extraglandular problems: skin, nervous system, kidneys, heart, stomach, pancreas • Non-Hodgkin’s Lymphoma: Primary Sjogren’s

18. Sjogren’s Syndrome • General Considerations • Primary: no collagen vascular disease, 50% • Secondary: rheumatoid arthritis, SLE, scleroderma, dermatomyositis, polymyositis, primary biliary cirrhosis

19. Sjogren’s Syndrome • Onset • insidious • diagnosis 10 years behind symptoms • instead: psychiatric referral due to lack of knowledge, isolated signs and nature of disease • Many women eventually diagnose themselves!

20. Sjogren’s Syndrome • Cause • autoimmune lymphocyte / plasma cell infiltration of lacrimal and salivary glands • viral trigger, loss of testosterone

21. Sjogren’s Syndrome • Diagnosis: what can the O.D. do? • thorough case history on dry eye patients (my patient with Lupus) • water at bedside? • fatigue, arthralgia, dryness of mucosal areas? • Schirmer < 5mm • conjunctival impression cytology

22. Sjogren’s Syndrome • Diagnosis: Revised International Classification (2002) 4/6 • Ocular symptoms • Oral symptoms • Ocular signs • Histopathology • Salivary gland involvement • serology: anti-Ro (SS-A), anti-La (SS-B), elevated ANA, high RF

23. Sjorgren’s Syndrome • Differential • Head and neck radiation tx • Hepatitis C • AIDS • Pre-existing lymphoma • Sarcoidosis • Graft vs host disease • Anticholinergic use

24. Sjogren’s Syndrome • Treatment • older women: humidity, artificial tears and saliva • younger women: NSAID’s, antimalarials, steroids, salagen (stimulates salivary gland production)

25. Sjogren’s Syndrome • Treatment • Make a difference in a patient’s life! • Support group # 1-800-4-SJOGRENS

26. Sjogren’s Syndrome • Treatment of “Mackdaddy of Dry Eye” • standard: tears, ointments, plugs, cautery • Filamentary Keratitis:topical steroids, acetylcysteine, NaCl 5%, bandage SCL’s, physical removal

27. Sjogren’s Syndrome • Treatment of Dry Eye • Cyclosporin A (Restasis, Allergan) • Has met with some success • MOA: cytokine related, anti-ocular surface inflammatory • good safety and tolerability • BID

28. My Experience With Dry Eye Treatment • What I should consider: severity, instillation, cost, preservatives, viscosity, level of meibomian gland dysfunction, inflammation • Ideally: Refresh  Systane  Restasis • MGD: Refresh Endura

29. Alcon & Optometry

30. My Experience With Dry Eye Treatment • Other options: plugs, topical steroids, tetracyclines, omega-3 fatty acids and nutritional supplements, oral secretogogues (Exovac, Salogen) • In Memphis at SCO…COST and SAMPLES, ANTI-INFLAMMATORY RX’s • “Dry eye put off and put on the sidelines”

31. Graves’ Disease • Introduction • first described by sir Robert James Graves 1835 • treated 3 female patients with goiter, violent palpitations, enlarged eyeballs • at that time, disease thought to be caused by emotional problems

32. Graves’ Disease • General Considerations • hyperthyroidism, infiltrative ophthalmopathy, infiltrative dermopathy • only cause of hyperthyroidism: significant ophthalmopathy • young to middle-aged female smokers

33. Graves’ Disease • Etiology and Pathogenesis • IgG autoantibody stimulation of TSH receptors • ophthalmopathy is also autoimmune • shared autoantigen: eye muscle membrane

34. Graves’ Disease • Diagnosis • clinical presentation • blood thyroid tests: thyrotropin, T3, T4, Free T4, TSIg(thyroid stimulating immunoglobulin), AMA(anti-microsomal antibody), anti-TPO(thyroid peroxidase) antibody • radioactive thyroid uptake: RT3U

35. Graves’ Disease • Clinical Manifestations • goiter • signs and symptoms consistent with increased metabolic rate: nervousness, insomnia, hyperactivity, emotional liability • “paper shaker” & hot handshake • ophthalmopathy: dry eye, upper lid lag on down gaze, lid retraction, proptosis, diplopia, optic neuropathy

36. Graves’ Disease • Ophthalmopathy • Keep In Mind…. • severity may not correlate with control • Onset may occur after treatment

37. Graves’ Disease • Treatment • goals: ease symptoms, make patient euthyroid. hypothyroid • alleviate symptoms: Propranolol (Inderal) • thyroid hormone synthesis blockers: propylthiouracil (PTU), tapazole (methiamazole) • radioactive iodine (several courses)

38. Graves’ Disease • Treatment • thyroidectomy • may worsen ophthalmopathy without prednisone • cigarette smoking associated with worsening ophthalmopathy

39. Myasthenia Gravis • General Considerations • autoantibodies against acetylocholine receptors • abnormal fatigueability of muscles under voluntary control • usually orbital and facial muscles

40. Myasthenia Gravis • General Considerations • prevalence: 1:20,000 • females under 50 / 7:3 • males peak in late 50’s • associated conditions: thymoma and thyroid disease, diabetes, lupus, rheumatoid

41. Myasthenia Gravis • Signs / Symptoms • majority present with ocular symptoms • ptosis and diplopia, then “spread” • vast majority develop ocular symptoms • variability of ocular fatigue • small percent ocular myasthenia only

42. Myasthenia Gravis • Recall of Residency Patient • Ptosis OD • Visit several months earlier, ptosis OS • The other resident just made a mistake

43. Myasthenia Gravis • Signs / Symptoms • Non-Ocular • limb fatigue • facial muscle weakness: difficulty breathing, chewing, talking, swallowing

44. Myasthenia Gravis • Signs / Symptoms • Ocular • worse at end of day • ptosis, orbicularis weakness, virtually any motility defect with diplopia • Cogan’s lid twitch, exposure keratitis • pupil is never involved

45. Mysathenia Gravis • Diagnosis • Optometric • history • measure palpebral apertures • pupils • sustained up gaze • squeezing closed of eyelids • diplopia without ptosis

46. Myasthenia Gravis • Diagnosis • Optometric • Ice Pack Test: > 5 minutes, improves neuromuscular transmission, complete ptosis?, safe speedy and easy with relatively high sensitivity and specificity • Sleep Test: eyes closed for 30 minutes • Family Album Topography (FAT) Scan

47. Myasthenia Gravis • Diagnosis • Referral: Neurologist / Neuroophthalmologist • Endrophonium HCL (Tensilon): IV 10 mg of Tensilon, monitor heart rate, BP, eyelid or motility defect, anti-cholinesterase, rate of complications very low but life threatening

48. Myasthenia Gravis • Diagnosis • Referral • Tensilon Complications: severe hypotension, bradycardia, cardiac arrest, respiratory arrest, seizures, vomiting • Appropriate resuscitation equipment • EMG (electromyography) • Acetylcholine antibody receptor test

49. Myasthenia Gravis • Management • lid crutches and tape • occlusion • rarely prism, ptosis or strabismus therapy • Lab testing for associated conditions • CT scan of chest / mediastinum: thymoma

50. Myasthenia Gravis • Management • anticholinesterases, steroids, immunosuppressants, thymectomy • plasmapharesis, IV gammaglobulin