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Guillermo Rocha
W Bruce Jackson
Marginal Ulcers orPeripheral Ulcerative Keratitis
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• 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
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
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• Crescent shaped, destructive inflammatory lesion affecting the juxtalimbal corneal tissue
• Often associated with systemic disease
• May signify “vasculitis” and thus, be potentiallylife-threatening
Peripheral Ulcerative Keratitis (PUK)
Rowe JA, Barney NP. Principles and Practice of Cornea, Ch 32; Copeland, Afshari, Eds.
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These are all PUK –How do you manage them?
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MARGINAL INFILTRATIVE / ULCERATIVE KERATITIS
Bacteria and Fungi Viruses Acanthamoeba
Systemic Autoimmune/Inflammatory
Local Toxic
InfectiousSterile
Etiology
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1 2
3 4
5 6
What would you use?
• No therapy• Antibiotics• Steroids• Antifungals• Antihistamines• Systemic drugs
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TWO CASES TO CONSIDER
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What would you do?
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• History
• The patient
• Previous therapies
KNOW MORE ABOUT…
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What would you do?
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• Enhance wound healing
• Prevent perforation
• Address the underlying condition
MANAGEMENT PRINCIPLES
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ETIOLOGIC CONSIDERATIONS
LOCALNON-INFECTIOUS
SYSTEMIC NON-INFECTIOUS
LOCALINFECTIOUS
SYSTEMIC INFECTIOUS
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Which is which?
LOCALNON-INFECTIOUS
LOCAL INFECTIOUS
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SYSTEMIC NON-INFECTIOUS
LOCAL INFECTIOUS
Which is which?
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NON INFECTIOUS PERIPHERAL INFILTRATIVE KERATITIS
Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds.
Microulcerative
Macroulcerative
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• 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.
Microulcerative
Macroulcerative
• Punctate marginal keratitis
• Peripheral keratitis associated with blepharitis
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NON INFECTIOUS PERIPHERAL INFILTRATIVE KERATITIS
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
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• 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?
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PERIPHERAL CORNEAL INFLAMMATION
Stern GA. Cornea, Ch 23; Krachmer, Mannis, Holland, Eds.
INFECTIOUS IMMUNOLOGIC
EPITHELIUM Usually epithelial defect Usually intact initially
DISCHARGE Usually Unlikely
INFILTRATES Spread centrally Spread concentrically
HYPOPYON Common Uncommon
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• Treat without testing?
• Treat, but testing required?
Which Ones Need to Be Worked Up?
LOCALNON-INFECTIOUS
SYSTEMIC NON-INFECTIOUS
LOCALINFECTIOUS
SYSTEMIC INFECTIOUS
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• Avoid treating with topical steroids
HERPETIC ULCERS (HSV)
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CONSIDER THE ROLE OF:
DRY EYETESTING
REVIEW OF SYSTEMS
CULTURES SYSTEMICTESTING
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• 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
BACK TOSLIDE 78
BACK TOSLIDE 97
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• Bacterial
• Viral
• Fungal
• Acanthamoeba
• Chalmydia
CULTURES
BACK TOSLIDE 78
BACK TOSLIDE 97
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• Rule out those conditions associated with peripheral ulcerative keratitis
REVIEW OF SYSTEMS
BACK TOSLIDE 78
BACK TOSLIDE 97
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• Complete blood count
• Erythrocyte sedimentation rate
• C reactive protein
• Urinalysis
• Chest X-ray
• Renal function tests
• Syphilis, Hepatitis C
SYSTEMIC TESTING
BACK TOSLIDE 78
BACK TOSLIDE 97
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• Rheumatoid factor
• Antinuclear antibodies
• Antineutrophil cytoplasmic antibodies (ANCA)
• Tissue biopsy
– Lung, kidney
SYSTEMIC TESTING
BACK TOSLIDE 78
BACK TOSLIDE 97
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MARGINAL INFILTRATE
When to culture?
When to use antibiotics?
When to add steroids?
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ETIOLOGIC CONSIDERATIONS
LOCALNON-INFECTIOUS
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ETIOLOGIC CONSIDERATIONS
• Catarrhal infiltrates• Phlyctenulosis• Acne rosacea• Psoriasis• Contact lenses• Topical anesthetic abuse• Toxic• Food allergies• Mooren’s ulcer (??)
LOCALNON-INFECTIOUS
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ETIOLOGIC CONSIDERATIONS
LOCALINFECTIOUS
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ETIOLOGIC CONSIDERATIONS
• Bacterial• Viral• Fungal• Acanthamoeba
LOCALINFECTIOUS
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• One infiltrate
• Larger than 2mm in diameter
• Less than 3mm from the visual axis
ALWAYS CULTURE
1-2-3 RULE
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• History of contact lens wear or trauma
• Non resolving
• Ring infiltrate
ALWAYS CULTURE
CONSIDER CORNEAL BIOPSY
ALSO…
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ETIOLOGIC CONSIDERATIONS
SYSTEMIC INFECTIOUS
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ETIOLOGIC CONSIDERATIONS
• Herpes virus• ChlamydiaSYSTEMIC
INFECTIOUS
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ETIOLOGIC CONSIDERATIONS
SYSTEMIC NON-INFECTIOUS
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ETIOLOGIC CONSIDERATIONS
• Rheumatoid arthritis
• SLE
• Discoid lupus
• Scleroderma
• Relapsing polychondritis
• Crohn’s
• Ulcerative colitis
• Polyarteritis nodosa
• Wegener’s granulomatosis
• Churg-Strauss
• Benign hypergammaglobulinemic purpura
• Temporal arteritis
SYSTEMIC NON-INFECTIOUS
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• Enhance wound healing
• Prevent perforation
• Address the underlying condition
MANAGEMENT PRINCIPLES
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ENHANCE WOUND HEALING
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• Lid Hygiene
• Antibiotic coverage
• Lubrication: Preservative-free
• Autologous serum drops
ENHANCE WOUND HEALING
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PREVENT PERFORATION
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• 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
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ADDRESS THE UNDERLYING CONDITION
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• Glucocorticoids
– IV pulse initially
– Oral
• Systemic immunomodulators
– Antimetabolites
– Alkylating agents
– T cell inhibitors
– Biologics
ADDRESS THE UNDERLYING CONDITION
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• Glucocorticoids
– IV pulse initially: 1g per day, for 3 consecutive days
– Oral: 1mg/kg/day, not to exceed 60-80 mg/day
ADDRESS THE UNDERLYING CONDITION
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• Systemic immunomodulators
– Antimetabolites:
• MTX, AZT, Mycophenolate mofetil, Leflunomide
– Alkylating agents:
• Cyclophosphamide
– T cell inhibitors:
• Cyclosporin A
– Biologics:
• Infliximab, etanercept, rituximab
ADDRESS THE UNDERLYING CONDITION
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Back to Our Two Cases to Consider
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What would you do?
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• History
• The patient
• Previous therapies
KNOW MORE ABOUT…
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• 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
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CASE HISTORY SH
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CASE HISTORY SH
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CASE HISTORY SH
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CASE HISTORY SH
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What would you do?
• 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?
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• 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
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CASE HISTORY SH: 3 WEEKS LATER
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• Worse again: 20/60
• New lesions superiorly and inferiorly
• What would you do?
ONE MONTH LATER…
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• 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
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IMPROVED AND STABLE
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IMPROVED AND STABLE
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WHAT ABOUT ANCA?
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• Antineutrophil cytoplasmic antibodies are specific and sensitive markers for different forms of vasculitides
ANCA
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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
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CASE HISTORY FW: 5MO
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CASE HISTORY FW: 5MO
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CASE HISTORY FW: 5MO
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CASE HISTORY FW: 5MO
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CASE HISTORY FW: 5MO
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CASE HISTORY FW: 8MO
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CASE HISTORY FW: 8MO
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CASE HISTORY FW: 8MO
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What would you do?
• 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?
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• 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
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CASE HISTORY FW:Follow Up –on Ciprofloxacin gtt/ung
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CASE HISTORY FW:Follow Up –on Ciprofloxacin gtt/ung
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CASE HISTORY FW:Follow Up –on Ciprofloxacin gtt/ung
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CASE HISTORY FW:Follow Up –on Ciprofloxacin gtt/ung
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• Worse again!
• Marked inflammation, PUK, discharge, corneal thinning and vascularization
• Extreme photophobia
• NO intraocular inflammation
BUT… 2 MO LATER
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What would you do?
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• 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
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LATEST FOLLOW-UP
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LATEST FOLLOW-UP
• Well controlled on oral Prednisone and Methotrexate
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ETIOLOGIC CONSIDERATIONS
DIAGNOSTIC CONSIDERATIONS
MANAGEMENT PRINCIPLES
SUMMARY
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ETIOLOGIC CONSIDERATIONS
LOCAL NON-INFECTIOUS
SYSTEMIC NON-INFECTIOUS
LOCALINFECTIOUS
SYSTEMIC INFECTIOUS
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DIAGNOSTIC CONSIDERATIONS:
DRY EYETESTING
REVIEW OF SYSTEMS
CULTURES SYSTEMICTESTING
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MANAGEMENT PRINCIPLES:
ENHANCEWOUND HEALING
PREVENT PERFORATION
ADDRESS UNDERLYING CONDITION
REFERAS NEEDED