A case of Mooren’s Ulcer

1. A case of Mooren’s Ulcer Dr Johnson Tan Medical Officer Tan Tock Seng Hospital

2. Presenting history • 50/Indian/Male h/o PTB and DM • Left prosthetic eye (trauma 28 yrs ago) • Aug 03: R eye redness x 1/52 • VA® 6/6, peripheral infiltrate with central epithelial defect associated with localized injection and early pannus, CDR of 0.8 • Imp: R marginal keratitis; glaucoma suspect • Treated with gutt Tobradex • Epithelial defect healed with an area of localised pannus that appeared inflammed

3. June 2004 • R eye irritation, redness and blurring of vision x 4/7 (minimal pain) • VA® 6/18, area of pannus with 80% peripheral thinning and localised injection, no ED • Imp: MK vs Mooren’s ulcer. • Treated with gutt FML/ciloxan responded

4. July 2004 • While steroids were being tailed down, pain and BOV worsened  Steroids stepped up with minimal improvement • Peripheral epithelial defect with 60-70% thinning a/w pseudopterygium 5-7 o’clock • Imp: R Peripheral Ulcerative Keratitis ?Mooren’s

5. Management • Gutt predforte hourly and gutt ciloxan qds • Added oral steroids • Right conjunctival resection 17/8/04 • Histology: ulcer with mixed inflammatory base /no malignancy • Oral steroids were tailed down with improved response by late Aug 04 • Subsequently defaulted FU

6. 18/8/04

7. Progression and Management Feb 05: flare: 5-8 o’clock thinning conjunctival resection (2nd) 1/3/05 Oral prednisolone restarted Defaulted FU Jun 05: recurrence 5-11 o’clock Restarted on aggressive topical & oral steroids

8. 27/6/05

9. Progression and Management • Aug 05: Minimal improvement. 3-11 o’clock thinning • Oral prednisolone stepped up to 60mg/day • Oral cyclophosphamide started • conjunctival resection (3rd) 26/8/05 • Pulsed IV cyclophosphamide commenced 2/52 after 2/52 of oral cyclophosphamide

10. 23/8/05

11. 30/8/05

12. 2/52 later, VA® 6/24, progressive thinning >95% with descematocele : high perforation risk • Oct 05 : lamellar keratoplasty complicated by wound leak  resuturing of graft on POD4 • Recovering well VA 6/24, small persistent epithelial defect. • On reducing dose of prednisolone and g tobramycin and pred forte. • Currently completed 6 doses of IV cyclophosphamide (25 Jan 06)

13. 3/10/05

14. Treatment summary • Topical steroids with antibiotic cover • Oral steroids • Oral cyclophosphamide, pulse IV • Conjunctival resection x3 • Lamellar keratoplasty

15. Peripheral ulcerative keratitis Definition: crescent shaped destructive inflammation of the juxtalimbal corneal stroma associated with an epithelial defect, presence of stromal inflammatory cells, and stromal degradation Diagnosis • Rule out CTD first

16. Ocular Infective Non infective Mooren’s ulcer Pellucid Degeneration Terrien’s Degeneration Senile Furrow Degeneration Blepharitis (MK, rosacea) Keratoconjunctivitis sicca Neurotrophic keratopathy Exposure keratopathy Contact lens use chem injury/trauma Systemic Infective (TB, Syphillis, HZV, NG, HIV) Non infective CTD (RA, SLE, RP, WG, PAN) Sarcoidosis leukemia Causes of PUK

17. Mooren’s ulcer • "chronic serpiginous ulcer of the cornea or ulcus roden " • painful, relentless, chronic ulcerative keratitis, with no associated scleritis • steep, overhanging central edge • starts in periphery and may progress centrally or circumferentially to involve the entire cornea

18. idiopathic, with no associated scleritis • M:F = 1.6:1 • Complications: irregular astigmatism, iritis, hypopyon, glaucoma, cataract, perforation (13-36%), blindness

19. Classification • Wood T, Kaufman H. Mooren's ulcer. Am J Ophthalmol 1971;71:417-422

20. Classification • Unilateral MU - painful progressive corneal ulceration in elderly patients, non-perfusion of the superficial vascular plexus of the anterior segment. • Bilateral aggressive MU - young, progresses circumferentially, then centrally in the cornea; vascular leakage and new vessel formation, extending into the base of the ulcer. • Bilateral indolent MU - middle-aged patients, progressive peripheral corneal guttering in both eyes, with little inflammatory response; no change from normal vascular architecture except an extension of new vessels into the ulcer • Watson PG. Management of Mooren’s Ulceration. Eye, 11: 349-356, 1997

21. Etiology • Unknown etiology • Pathophysiology: • Autoimmune (cell-mediated and humoral) • still unknown if cell-mediated and/or humoral immune mechanisms are involved directly in the pathogenesis of MU or may be that they just accompany the corneal destruction that is caused by another mechanism

22. Diagnosis • Typical ulcer morphology • History and physical examination

23. Investigations • FBC • ESR • RF • complement fixation, circulating immune complexes • ANA, ANCA, • VDRL, TPHA • CXR • Scrapings for culture & sensitivity

24. Treatment • Stepwise approach • Topical steroids • Oral steroids and Immunosuppressive chemotherapy • Conjunctival resection • Lamellar keratoplasty/ penetrating keratoplasty

25. Steroids • Intensive topical steroids • Oral prednisolone 60-100mg od • Indication - when topical therapy ineffective after 7-10days or topical steroids may be contraindicated because of precariously deep ulcer or infiltrate

26. Conjunctival resection • Indication: ulcer progresses despite the steroid regimen • conjunctiva adjacent to the ulcer contains inflammatory cells that may produce antibodies against the cornea and cytokines, which amplify the inflammation and recruit additional inflammatory cells - Chow C, Foster CS. Mooren’s Ulcer. Int Ophthalmol Clin, 36:1-13, 1996 - Brown SI. Mooren's ulcer. Treatment by conjunctival excision. Br J Ophthalmol. 1975 Nov;59(11):675-82

27. Immunosuppressive chemotherapy • bilateral or progressive MU that fails therapeutic steroids and conjunctival resection • combination of oral prednisolone and an immunomodulatory agent is initiated at the same time. • Oral prednisone controls the active inflammatory process until the immunomodulatory agent takes effect (abt 4-6/52). • Prednisone is subsequently tapered and the patient maintained on the systemic immunomodulatory agent.

28. Immunosuppressants • Cyclophosphamide • Oral • IV – 1g monthly IV Cy • Severe Moorens ulcer: efficacy of monthly cyclophosphamide intravenous pulse treatment]; ev Med Interne. 2003 Feb;24(2):118-22. French. • Cyclosporin A • 0.5% Topical CSA • Zhao JC, Jin XY.Immunological analysis and treatment of Mooren's ulcer with cyclosporin A applied topically.cornea. 1993 Nov;12(6):481-8 • 1% Topical CSA • Mooren's ulcer in China: a study of clinical characteristics and treatment Br J Ophthalmol 2000;84:1244-1249 ( November ) • Systemic CSA • plasma trough levels of 150-200 ng/ml is recommended as initial treatment of choice • Mooren ulcer. 4 severe bilateral disease courses with systemic cyclosporin A therapy; Klin Monatsbl Augenheilkd. 1997 Nov;211(5):306-11 • Hill J, Potter P. Treatment of Mooren’s Ulcer with cyclosporine A: Report of three cases. Br J Ophthalmol, 71:11-15, 1987.

29. Immunosuppressants • NO comparative studies on type of immunosuppressants and route of administration

30. Additional surgical procedures • Lamellar keratectomy - arrest the inflammatory process and allow healinG • Mgmt of perforation – tissue glue, BCL, patch graft • Agrawal V, Kumar A, Sangwan V, Rao GN . Cyanoacrylate adhesive with conjunctival resection and superficial keratectomy in Mooren's ulcer. Indian J Ophthalmol. 1996 Mar;44(1):23-7

31. Lamellar Keratoplasty • Principle: remove necrotic ulcerative cornea thoroughly and to reconstruct anatomical structure of the cornea • removes antigenic targets of the cornea • eliminates the risk of graft rejection • prevents perforation • improves vision • Martin NF, Stark WJ, Maumenee AE. Treatment of Mooren's and Mooren's-like ulcer by lamellar keratectomy: report of six eyes and literature review. Ophthalmic Surg. 1987 Aug;18(8):564-9. • Kinoshita S, Ohashi Y, Ohji M, Manabe R. Long-term results of keratoepithelioplasty in Mooren's ulcer.Ophthalmology. 1991 Apr;98(4):438-45.