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Corneal melts,
perforations and worse:
autoimmune diseases of
the cornea
Presented by
Chameen Samarawickrama- Westmead Hospital
- Liverpool Hospital
- University of Sydney
- University of New South Wales
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Financial disclosures
– Early Career Research Fellowship (Westmead Charitable Trust)
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How do you manage this?
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Aims
– Differential diagnosis
– Pathogenesis
– Work-up
– Management
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1. Systematic categorization of corneal melts
– Easiest way to think about it is to construct a 2x2 grid:
Infective Non-infective
Local
Systemic
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Local/Infective
– Microbial keratitis
– Contact lenses
– HSV/VZV
– Neurotrophic cornea
– Chlamydia
– Gonorrhoea
Microbial
HSV
Gonococcal
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Local/Non-Infective
– Terrien’s
– Pellucid
– Mooren’s
– Rosacea
– Marginal keratitis
– VKC
– Exposure
– Drugs
– NSAIDS, steroids, LA
– Trauma
Terrien’s degeneration
Pellucid marginal degeneration
Mooren’s
Rosacea
Marginal keratitis
VKC
Exposure
Trauma
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Systemic/Infective
– TB
– Syphilis
– Leprosy
– HCV
– Lyme
– Onchocerciasis
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Systemic/Non-Infective
– Connective Tissue Diseases
– Rheumatoid arthritis
– GPA/WG
– SLE
– Sjogrens
– PAN
– Relapsing polychondritis
– Scleroderma
– Sarcoid
– Bechet’s
– IBD
Rheumatoid
With PED (use PED treatment algorithms)
Rheumatoid keratolysis – no ED
GPA/WG
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Infective Non-Infective
Local Microbial keratitis Terrien’s
HSV/VZV (neurotrophic) Pellucid
Chlamydia/gonorrhoea Mooren’s
Rosacea
Marginal keratitis
VKC
Exposure
Drugs (NSAIDS, steroids, LA)
Trauma
Systemic TB Connective tissue diseases
(Rheumatoid, GPA/WG, SLE,
Sjogren’s, PAN, Relapsing
polychondritis, Scleroderma)
Syphilis Sarcoid
Leprosy Behcet
HCV IBD
Lyme disease
Onchocerciasis
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2. Pathogenesis of corneal melts
Infection
Ocular
surface
disease
Disordered
immunity
Release of
collagenases,
proteases, MMP1
Circulating immune
complexes trapped
in limbal vessels
Complexes in
peripheral cornea
Activation of
complement
Chemotaxis of
inflammatory cells
(neutrophils/macroph
ages)
Auto-antibodies
Antibodies to
corneal
stroma
Immune
complexes in
vasculitis
Toxicity
Dry eye
Antibodies to
bacteria
Peripheral HSV
& bacterial
infection
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3. Clinical and laboratory work-up
– AIM: decide if systemic or local, infective or non-infective.
– History:
– CL wear, trauma (infection); previous HSV/VZV; known CTD/IBD; previous ocular surgery
– Examination:
– Scars of HSV/VZV; rosacea/SLE/GPA facial features; RA arthropathies; lid closure (exposure)
– Slit lamp:
• Ulcer (measure), infiltrate, AC inflammation, scleritis (how bad is it)
• Dry eye (tear lake, PEEs), HSV scars, blepharitis (what caused it)
• Dilated fundus exam (CWS, vitritis, SRF etc. c/w posterior scleritis)
– Examine both eyes!
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Clinical and laboratory work-up
– Laboratory investigations:
– Corneal scrape, incl HSV swab for PCR
– Systemic vasculitis screen
– FBC, EUC, LFT, ESR, CRP
– RF, anti-CCP Abs, ANCA, ANA, ENA, ACE
– VDRL, TB-QG
– CXR
– Urine for blood and casts
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4. Immediate management
– Depends on suspected aetiology
– Local/Infective:
– Ofloxacin q1h d/n
– Valtrex 500g tds (if suspect HSV)
– Local/Non-infective:
– Ocular surface disease:
• Ensure full lid closure
• Reduce toxicity
• Lubricate
• Consider punctal occlusion (I wait until inflammation settles)
– Local inflammatory disease (Marginal, mild Mooren’s or Terrien’s)
• Topical steroids/cyclosporin
– Systemic/Infective:
– treat underlying disease
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Systemic/Non-infective (Vasculitis) - everyone
– Admit and tackle all three arms of pathogenesis
– Control of acute exacerbation:– Prednisolone 1mg/kg/day (can often get away with just 50mg/day)
– Cyclosporin 5-7.5mg/kg (under 60 yrs)
– Cyclophosphamide 1-2mg/kg (over 60 yrs; cumulative dose <20g safe)
– +/- pulsed methylprednisolone
– +/- rituximab
– No role for topical steroids
– Optimise ocular surface (lubricants, lid closure etc.)
– Decrease collagenase activity– Doxycycline 100mg/d
– Treat/prevent bacterial superinfection– Ofloxacin QID to q1h depending on clinical suspicion
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Albert et al, Arch Soc Esp Oftalmol 2011;86:118 / Huerva et al, Cornea 2010; 708-10 / Friedlin et al Br J Ophthalmol2007;1414 / Cheung et al Br J Ophthalmol 2005;89:1542 / Onal et al, Ocul Immunol Inflamm 2008;16:230-2 / Ahmadi-Simab et al Ann Rheum Dis 2005;64:1087
Study No. of pts Ophth Disease Systemic
Disease
Previous Rx
(+ Pred)
Number
Rituximab
Infusions
Albert et al 2 PUK
PUK
RA
RA
CSA/Inflix
Inflix/ Adalim
2
1 (but recurred at
8/12)
Huerva et al 1 PUK Wegeners MTX 2
Friedlin et al 1 PUK & Scleritis Wegeners Cyclop 2
Cheung et al 1 Scleritis Wegeners MMF/Cyclop 2
Onal et al 1 Nec. Scleritis Wegeners Aza/Cyclop 2
Ahmadi-Simab
et al
1 Scleritis Sjogrens MTX/CSA/Cyclo
p/Inflix
2
Rituximab for PUK
Courtesy R Stewert
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Systemic/Non-infective (Vasculitis) – special cases
– Topical protease inhibitors:
– Acetylcysteine
– Aprotinin (Trasylol; no longer available for systemic use – increased risk of death when used for control of bleeding during heart surgery)
– Therapeutic contact lenses:
– Occasionally useful
– Maintenance therapy:
– Low dose prednisolone
– Cyclosporin 1-5mg/kg (under 60 yrs)
– Methotrexate (once finished cycloposphamide) in older patients
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Acute perforation - small
– Cyanoacrylate glue – buys time in small perforations
– Corneal Glue Kit:– Sterile dressing pack
– Sterile plastic drape
– Speculum
– Cyanoacrylate glue
– Chlorsig ointment
– Bandage contact lens
– Sterile eye spears
– Skin biopsy punches (2, 3 and 4mm)
– 2% fluorescein
– Tetracaine
– Sterile gloves/mask
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Acute perforation – not small
– Lamellar corneal patch grafts
– Almost eliminates the risk of rejection
– Reduces the risk of leak in the even of re-melt or dehiscence
– ? Replacement of conjunctiva post tectonic group
– Yes
• Re-establish epithelium
– No
• Not to re-establish blood supply (with immune complexes, cells, cytokines)
• Conjunctiva = major reservoir of inflammatory cells, cytokines
Galor et al, Rheum Dis Clin North Am 2007;33:835-54
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Corneal patch technique – “copy and fix”
Samarawickrama et al. Cornea. 2015;34:1519-22
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Special case – Mooren’s ulcers
– Conjunctival resection
– Superficial keratectomy
– May be effective in some
cases by removing
antigen from the
superficial cornea
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Summary
– Peripheral melts occur in a
heterogenous group of
ocular and systemic
disorders
– Important to differentiate
what the mechanism is
– Successful management
often requires
immunosuppression and is
multi-disciplinary