OCULAR INFLAMMATORY DISEASE

1. OCULAR INFLAMMATORY DISEASE C. Stephen Foster, MD, FACS, FACR Harvard Medical School Massachusetts Eye Research and Surgery Institution

2. Ocular Inflammatory Disease • By far, the number one cause of blindness, worldwide • Infection • Trauma • Cancer • Autoimmunity

6. UVEITIS • What is it? • What is its importance? • What is the history of its therapy? • What does the future hold?

7. UVEITIS • What is it?

8. Etymology • Uvea, from uva (Latin = grape) • itis, (Greek = inflammation) Therefore, inflammation of the uvea Ophthalmia and flegmoni, general terms

9. Anatomy The uvea or uveal tract is the middle, highly vascular layer of the eyeball • Iris • Ciliary body • Choroid

14. UVEITIS • What is it? • What is its importance?

15. The Problem Uveitis continues to blind people, even 60 years after the introduction of steroid therapy. 12.3 million cases in the USA 45,000 new cases/year in the USA alone 10% of all cases of blindness Annual costs in the USA: $242.6 million

16. The Problem Uveitis is the third leading cause of preventable blindness in developed countries

17. How Does Uveitis Blind? • Glaucoma

19. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema

20. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema • Cysts/holes

21. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema • Cysts/holes • Membrane

22. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema • Cysts/holes • Membrane • Optic neuropathy

23. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema • Cysts/holes • Membrane • Optic neuropathy • Retinopathy

24. How Does Uveitis Blind? • Glaucoma • Hypotony • Maculopathy • Edema • Cysts/holes • Membrane • Optic neuropathy • Retinopathy • Neovascularization

25. What Is the Evidence? • Smith RE. 1989. Pars Planitis. In: Medical Retina, chapter 96 • Laaksonen AL. 1966. A prognostic study of JRA. Analysis of 544 cases. Acta Paediatr Scand. 1966;Suppl:166 • Kanski JJ. JRA and uveitis. Surv Ophthalmol. 1990;34:253-67 • Rothova A, et al. 1996. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 80 • 35% of uveitic eyes: blind

26. UVEITIS • What is it? • What is its importance? • What is the history of its therapy?

27. Uveitis Therapy Through the Ages • The Ebers Papyrus (1500 BC) - Egypt • Hippocratic Corpus (4th century BC) - Greece • Galen (AD 131-201) – Rome • Aetius of Amida (AD 502-575) – Byzantium • Yves (1772) – Paris • Schmidt (1800) – Vienna • Waldrop, Saunders, Travers, MacKenzia, Middlemore, Dalrymple (1808-1852) - England

28. Uveitis Therapy Through the Ages • The Edwin Smith Surgical Papyrus New York Academy of Medicine 1700 BC The oldest known existing ophthalmic document Based upon, among other things, writings from the time of Imhotep (2640 BC)

29. Uveitis Therapy Through the Ages The Edwin Smith Surgical Papyrus contains references to inflammatory conditions of the eye. Physicians with special interest in the eye were identifiable as early as the 6th Egyptian Dynasty (2400 BC).

30. Uveitis Therapy Through the Ages Pepi-Ankh-Or-Iri, physician to the Pharaoh The most ancient identifiable ophthalmologist Royal Oculist Palace Eye Physician and Guardian of the Anus

31. Uveitis Therapy Through the Ages Pepi-Ankh-Or-Iri embraced the concept of whdw (ukedhu), “the rotten stuff par excellence” He subscribed to the practice of expurgation therapy for uveitis. This practice continued through the next 3900 years for a variety of ailments.

32. Uveitis Therapy Through the Ages Additional therapies evolving through time included employment of poltices and solutions 100 of the 237 medication recipes in the Ebers papyrus are for eye disease Zinc, antimony, copper, aloe, yellow ochre, red ochre, myrrh, malachite, ink powder, galena and djaret were predominant.

33. Uveitis Therapy Through the Ages Roman period : 2ndC BC – 4thC AD • Cannabis, opium, plant extracts • Cathartics and enemas

34. Uveitis Therapy Through the Ages Byzantine period : 4thC AD – 15thC AD • Opium, barley, milk, honey, oil, breast milk, egg white, iron, copper, pepper drops and poltices • Blood letting • Oral and rectal administration of antidotes

35. Uveitis Therapy Through the Ages Modern period (15thC AD to present) Scarpa, 1806 : “A strong countrywoman, 35 years old, was brought into the hospital in April 1796, on account of violent, acute ophthalmia in both her eyes, with great tumefaction of the eyelids, redness of the conjunctiva, pain, and fever”

37. Uveitis Therapy Through the Ages Scarpa, 1806 : “I took away blood abundantly from the arm, foot, and also locally by means of leeches applied near both the angles of the eyes, and I also purged her” These remedies helped to abate the inflammatory stage of the violent ophthalmia. Emollient herbs boiled in milk; quince seed mucilage; bags of tepid mallows; blistering

39. Louis Braille – 1809-1852 It was during this era that a very young French boy was blinded in one eye by an accidental puncture of that eye with an awl in his father’s saddle shop. Sympathetic ophthalmia uveitis blinded the other eye by the time the child was 9 years old

40. Uveitis Therapy Through the Ages MacKenzie, 1830. Dilation of the pupil with tincture of belladonna, bloodletting, purging, blister therapy 1900 – Fever therapy: fever induced by intramuscular injections of milk and subsequently with typhoid protein. Sometimes fatal; persisted into the early 1950’s

41. Uveitis Therapy Through the Ages 1949 – Hensch – Corticosteroid therapy 1950 – Dan Gordon – Cornell University, New York City

43. The History of Immunosuppressive Therapy for Uveitis E. Roda-Perez. El tratamiento de las uveitis de etiologia ignota con mostaza nitrogenada. Arch Soc Oftal Hisp Am. 1952; 12: 131-151

44. Wong – 1965 Newell – 1966 Moore – 1968 Gills – 1970 Mamo – 1970 Godfrey – 1974 Andrash - 1978 Martinez - 1978 The History of Immunosuppressive Therapy for Uveitis

45. Prevalence of Visual Disability and Blindness Despite Corticosteroid Therapy:It’s a Disgrace! Evidence-based analysis of peer-reviewed literature indicates that the prevalence of visual disability and blindness secondary to uveitis has not measurably changed in the past 40 years. Why is that? How can that possibly be?

46. Steroid MonotherapyStuck in second gear • Few departments of Ophthalmology have an Ocular Immunologist on their faculty • Therefore,

47. Steroid MonotherapyStuck in second gear Most ophthalmologists completing their residency training have never been exposed to uveitis patient management with anything other than with steroids

48. Lessons from Rheumatology • Rheumatologists learned the lesson the hard way too: steroid and NSAID therapy first, reserving immunomodulatory therapy for patients with advanced disease, resulted in progressive joint damage and great disability.

49. Lessons from Rheumatology • Early employment of steroid-sparing immunomodulatory, disease-modifying agents results in vastly superior outcomes • The toxicity of medication side effects is less with this approach too

50. Lessons from Rheumatology • The battle-cry throughout the world of rheumatology has, therefore, become: “The Mission is Remission” • Ophthalmologists can and should learn from them