Guillermo Rocha W Bruce Jackson Marginal Ulcers or Peripheral Ulcerative Keratitis

In this interactive module, peripheral ulcerative keratitis will be reviewed. This will be in the context of a diagnostic classification, management algorithm and case presentations. Learning Objectives 2 To better understand the various etiologies of corneal ulcers including Infectious vs. Non-Infectious and Systemic vs Local Discuss the approach to diagnosis including dry eye testing, review of systems, cultures and systemic testing Review management principles including wound healing, prevention of perforation and addressing the underlying condition

Crescent shaped, destructive inflammatory lesion affecting the juxtalimbal corneal tissue Often associated with systemic disease May signify “vasculitis” and thus, be potentially life-threatening Peripheral Ulcerative Keratitis (PUK) 3 Rowe JA, Barney NP. Principles and Practice of Cornea, Ch 32; Copeland, Afshari, Eds.

4 These are all PUK – How do you manage them?

MARGINAL INFILTRATIVE / ULCERATIVE KERATITIS 5 Bacteria and Fungi Viruses Acanthamoeba Systemic Autoimmune/ Inflammatory Local Toxic Infectious Sterile Etiology

What would you use? No therapy Antibiotics Steroids Antifungals Antihistamines Systemic drugs

TWO CASES TO CONSIDER 7

8 What would you do?

History The patient Previous therapies KNOW MORE ABOUT… 9

10 What would you do?

Enhance wound healing Prevent perforation Address the underlying condition MANAGEMENT PRINCIPLES 11

ETIOLOGIC CONSIDERATIONS 12

13 Which is which?

14 Which is which?

NON INFECTIOUS PERIPHERAL INFILTRATIVE KERATITIS 15 Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds. Microulcerative Macroulcerative

Generally manifestation of systemic, immune- mediated disease Most common: Rheumatoid arthritis, Wegener’s granulomatosis and polyarteritis nodosa NON INFECTIOUS PERIPHERAL INFILTRATIVE KERATITIS Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds. 16 Microulcerative Macroulcerative Punctate marginal keratitis Peripheral keratitis associated with blepharitis

NON INFECTIOUS PERIPHERAL INFILTRATIVE KERATITIS 17 Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds. Microulcerative Punctate marginal keratitis –Staphylococci, Streptococci, Haemophilus, hypersensitivity to medications Peripheral keratitis associated with blepharitis –Catarrhal ulceration –Phlyctenulosis –Peripheral rosacea keratitis

Size Number Location Intervening space …not really, although: –Catarrhal may have intervening space, and be located at the 2, 4, 8 and 10 o’clock positions Are There Any Distinguishing Features? 18

PERIPHERAL CORNEAL INFLAMMATION Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds. 19

Treat without testing? Treat, but testing required? Which Ones Need to Be Worked Up? 20

Avoid treating with topical steroids HERPETIC ULCERS (HSV) 21

CONSIDER THE ROLE OF: 22

Dry Eye Questionnaire Assessment of lid margins Tear film breakup time Corneal and conjunctival staining Tear osmolarity Schirmer test Serology: SSA, SSB, Rheumatoid Factor, ANA DRY EYE TESTING 23 BACK TO SLIDE 78 BACK TO SLIDE 78 BACK TO SLIDE 97 BACK TO SLIDE 97

Bacterial Viral Fungal Acanthamoeba Chalmydia CULTURES 24 BACK TO SLIDE 78 BACK TO SLIDE 78 BACK TO SLIDE 97 BACK TO SLIDE 97

Rule out those conditions associated with peripheral ulcerative keratitis REVIEW OF SYSTEMS 25 BACK TO SLIDE 78 BACK TO SLIDE 78 BACK TO SLIDE 97 BACK TO SLIDE 97

Complete blood count Erythrocyte sedimentation rate C reactive protein Urinalysis Chest X-ray Renal function tests Syphilis, Hepatitis C SYSTEMIC TESTING 26 BACK TO SLIDE 78 BACK TO SLIDE 78 BACK TO SLIDE 97 BACK TO SLIDE 97

Rheumatoid factor Antinuclear antibodies Antineutrophil cytoplasmic antibodies (ANCA) Tissue biopsy –Lung, kidney SYSTEMIC TESTING 27 BACK TO SLIDE 78 BACK TO SLIDE 78 BACK TO SLIDE 97 BACK TO SLIDE 97

MARGINAL INFILTRATE 28 When to culture? When to use antibiotics? When to add steroids?

ETIOLOGIC CONSIDERATIONS 29

ETIOLOGIC CONSIDERATIONS 30 Catarrhal infiltrates Phlyctenulosis Acne rosacea Psoriasis Contact lenses Topical anesthetic abuse Toxic Food allergies Mooren’s ulcer (??)

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ETIOLOGIC CONSIDERATIONS 34

ETIOLOGIC CONSIDERATIONS 35 Bacterial Viral Fungal Acanthamoeba

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One infiltrate Larger than 2mm in diameter Less than 3mm from the visual axis ALWAYS CULTURE RULE 38

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History of contact lens wear or trauma Non resolving Ring infiltrate ALWAYS CULTURE CONSIDER CORNEAL BIOPSY ALSO… 40

ETIOLOGIC CONSIDERATIONS 41

ETIOLOGIC CONSIDERATIONS 42 Herpes virus Chlamydia

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ETIOLOGIC CONSIDERATIONS 45

ETIOLOGIC CONSIDERATIONS 46 Rheumatoid arthritis SLE Discoid lupus Scleroderma Relapsing polychondritis Crohn’s Ulcerative colitis Polyarteritis nodosa Wegener’s granulomatosis Churg-Strauss Benign hypergammaglobulinemic purpura Temporal arteritis

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Enhance wound healing Prevent perforation Address the underlying condition MANAGEMENT PRINCIPLES 61

62 ENHANCE WOUND HEALING

Lid Hygiene Antibiotic coverage Lubrication: Preservative-free Autologous serum drops ENHANCE WOUND HEALING 63

64 PREVENT PERFORATION

Collagenase or collagenase synthetase inhibitors –1% Medroxyprogesterone –10-20% Acetylcysteine Cyclosporine 0.05% Doxycycline Tissue adhesive, bandage CL, lamellar and tectonic grafts, amniotic membrane transplant CAUTION: topical steroids PREVENT PERFORATION 65

66 ADDRESS THE UNDERLYING CONDITION

Glucocorticoids –IV pulse initially –Oral Systemic immunomodulators –Antimetabolites –Alkylating agents –T cell inhibitors –Biologics ADDRESS THE UNDERLYING CONDITION 67

Glucocorticoids –IV pulse initially: 1g per day, for 3 consecutive days –Oral: 1mg/kg/day, not to exceed mg/day ADDRESS THE UNDERLYING CONDITION 68

Systemic immunomodulators –Antimetabolites: MTX, AZT, Mycophenolate mofetil, Leflunomide –Alkylating agents: Cyclophosphamide –T cell inhibitors: Cyclosporin A –Biologics: Infliximab, etanercept, rituximab ADDRESS THE UNDERLYING CONDITION 69

Back to Our Two Cases to Consider 70

71 What would you do?

History The patient Previous therapies KNOW MORE ABOUT… 72

62yoM Original presentation: conj cyst OD -marsupialization MGD = full Lid Hygiene, tea tree oil facewash, Doxycycline Possible history of CRVO? Amblyopia? 5 mo later: PUK CASE HISTORY SH 73

CASE HISTORY SH 74

CASE HISTORY SH 75

CASE HISTORY SH 76

CASE HISTORY SH 77

What would you do? 78 Do you think this is Dry Eye/Ocular Surface related? Do you think this is a local infection? Do you think this is related to a systemic condition? Do you think systemic testing is warranted?

62yoM Original presentation: conj cyst OD -marsupialization MGD = full Lid Hyg, TTO, Doxy Possible history of CRVO? Amblyopia? 5 mo later: PUK Prednisolone acetate 1% tid –better 3 wks later Tests: all negative, except atypical ANCA CASE HISTORY SH 79

CASE HISTORY SH: 3 WEEKS LATER 80

Worse again: 20/60 New lesions superiorly and inferiorly What would you do? ONE MONTH LATER… 81

Enhance wound healing –Lid hygiene –Fucidic acid to lids Prevent perforation –Prednisolone acetate 1% –Doxycycline 100mg PO qhs Address the underlying condition –Systemic testing: Atypical ANCA (+) –Referral to Internal Medicine MANAGEMENT HISTORY 82

IMPROVED AND STABLE 83

IMPROVED AND STABLE 84

WHAT ABOUT ANCA? 85

Antineutrophil cytoplasmic antibodies are specific and sensitive markers for different forms of vasculitides ANCA 86

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51yoF Glaucoma on multiple meds Chronic red eye OS 1-2 yrs Is this toxic? Stopped everything Some improvement, but… 4-5mo later, worse, gooey, leaky, on Pataday Now with PUK OD perfectly fine CASE HISTORY FW 88

CASE HISTORY FW: 5MO 89

CASE HISTORY FW: 5MO 90

CASE HISTORY FW: 5MO 91

CASE HISTORY FW: 5MO 92

CASE HISTORY FW: 5MO 93

CASE HISTORY FW: 8MO 94

CASE HISTORY FW: 8MO 95

CASE HISTORY FW: 8MO 96

What would you do? 97 Do you think this is Dry Eye/Ocular Surface related? Do you think this is a local infection? Do you think this is related to a systemic condition? Do you think systemic testing is warranted?

51yoF Glaucoma on multiple meds Chronic red eye OS 1-2 yrs Toxic? Stopped everything 4-5mo later, worse, gooey, leaky, on Pataday PUK Cultures: –Dx Strep Anginosus, Eikenella corrodens –Sensitive to Ciprofloxacin –Improved! CASE HISTORY FW 98

CASE HISTORY FW: Follow Up –on Ciprofloxacin gtt/ung 99

CASE HISTORY FW: Follow Up –on Ciprofloxacin gtt/ung 100

CASE HISTORY FW: Follow Up –on Ciprofloxacin gtt/ung 101

CASE HISTORY FW: Follow Up –on Ciprofloxacin gtt/ung 102

Worse again! Marked inflammation, PUK, discharge, corneal thinning and vascularization Extreme photophobia NO intraocular inflammation BUT… 2 MO LATER 103

104 What would you do?

Enhance wound healing –Lid hygiene –Continue with topical ciprofloxacin Prevent perforation –IV Methylpredisolone 1g daily for 3 days –Continue with oral Prednisone Address the underlying condition –Referral to Internal Medicine: IMT Improved at last visit MANAGEMENT HISTORY 105

LATEST FOLLOW-UP 106

LATEST FOLLOW-UP 107 Well controlled on oral Prednisone and Methotrexate

ETIOLOGIC CONSIDERATIONS DIAGNOSTIC CONSIDERATIONS MANAGEMENT PRINCIPLES SUMMARY 108

ETIOLOGIC CONSIDERATIONS 109

DIAGNOSTIC CONSIDERATIONS: 110

MANAGEMENT PRINCIPLES: 111