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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