Help! A Corneal Ulcer Just Walked In!

What Do I Do Next?
Senior Instructor: Sonal S Tuli MD
Course: 247
Sunday, October 13, 2019
2:00 PM - 4:15 PM
Room: SOUTH 314
Published: 8-25-19 10:41 PM

Join the conversation: #aao2019

® 2019 American Academy of Ophthalmology. All rights reserved.
 Help! A Corneal Ulcer Just
Walked In. What Do I Do
Next?
Sonal Tuli, M.D.
Director, Cornea and External Diseases
University of Florida

Disclosures
• I have no financial interests or relationships
to disclose

Outline
• Classification and classic features of types of corneal
ulcers
– Management in the office
– Which ones need tertiary care referral?
• Medical management
• Surgical management

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 Introduction
• Medical and/or surgical emergency
• Annual incidence – 11 per 100,000 to 11 per 10,000
depending on the geographic location
• Primarily divided into infectious and non-infectious
• Infectious more common but non-infectious harder to
recognize and treat
• Treatment may be diametrically different for infectious vs.
non-infectious

Bacterial

Fungal
Infectious
Parasitic

Viral

Ulcers Neurotrophic

Chemical burns
Non- Immune
infectious
Toxic or factitious

Other

Infectious

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 Bacterial
• Contact lenses > trauma
• History of 1-2 days
• Foreign body sensation
• Mucopurulent discharge
• Gram negative typically but MRSA ing

Bacterial Keratitis
• Gram Negative • Gram Positive
– Copious discharge – Minimal discharge
– Hypopyon frequent – Mild A/C reaction
– Significant tissue – Minimal tissue
destruction destruction
– Edges ill-defined – Edges well defined
– May have ring – May have abscess

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 Crystalline Keratopathy
• Strep. Viridans or enterococci
• Patients on chronic steroids – usually corneal
transplant patients
• No inflammation
• Glycocalyx protects organism
• Most need transplant as do not respond medically

Treatment
• Scrape and culture + smear
• Frequent fortified antibiotics – q ½ hour
– Tobramycin or Gentamicin 1.4%
– Vancomycin or Cefazolin 2%
• Modify based on Gram stain and culture
• Steroids within 48 hours if accurate diagnosis and
antibiotics
• Cyclopentolate for pain and pupil
• Supplement with oral/subconjunctival

• Vancomycin
• Cefazolin
• Tobramycin/Gentamicin
• Tobramycin/Gentamicin
• Fluoroquinolones
• Ceftazidime/Ceftriaxone

• Ceftriaxone/Ceftazidime
• Fluoroquinolones

• Vancomycin
• Clindamycin
• Amikacin
• Amikacin
• Clarithromycin
• Azithromycin
• Amikacin
• Sulfacetamide
• Bactrim

5
 SCUT
• Overall no benefit or harm using steroids in
bacterial keratitis
• Larger, central, deep ulcers did benefit
• Nocardia did much worse with steroids
• Epithelial healing was a little slower
• Starting early may be better than later

Fungal Keratitis
• 8-16% of culture-positive infectious keratitis
• Trauma and contact lenses
• Slow progression over about a week
• Minimal discharge
• More photophobia and deep pain

6
 Fungal Keratitis
• Feathery borders
• Ring infiltrates
• Satellite lesions
• Endothelial plaque
• Formed hypopyon
• May penetrate A/C without perforation

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 Treatment
• Therapy with any 2 - Natamycin 5%, Amphotericin B
0.15%, Voriconazole 1%
• Modify based on organism
• Duration 2-4 weeks
• Frequent scraping not advocated
• NO steroids
• Oral Fluconazole or Ketoconazole

8
 Treatment

Filamentous
Fungi

Aspergillus Candida

MUTT
• Voriconazole vs Natamycin for filamentous fungi
• Natamycin significantly better
• Fusarium did not respond to Voriconazole
• Suggested not using Voriconazole as
monotherapy in fungal keratitis
• MUTT 2 – oral voriconazole addition helped only
in Fusarium

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 Acanthamoeba
• Incidence may be increasing
• Contact lens wearers – rarely trauma
• Masquerader – average time to diagnosis 4
weeks
• HSV misdiagnosis almost universal
• Severe pain out of proportion to findings

Acanthamoeba
• Raised epithelial lines early
• Pseudodendrites
• Perineuritis pathognomonic
• Patchy or confluent stromal infiltrates
• Rings with clear or granular center
• Late – scleritis, thinning, perforation
• Cataracts and glaucoma in advanced

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 Treatment
• Triple therapy with
– PHMB / Chlorhexidine - 0.02%
– Brolene / pentamidine / hexamidine – 0.1%
– Clotrimazole 1% / Neomycin
• Treat for at least 6 months decreasing
medications and frequency

Herpes
• Frequently misdiagnosed
• Reactivation of latent herpes in TG
• Epithelial infectious, stromal immune
• Hypoesthesia sensitive sign
• Dichotomous branching, terminal bulbs
• Keratic precipitates in stromal
• Necrotizing may resemble bacterial

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13
 Treatment
• Epithelial
– Gentle debridement
– Topical antivirals – Trifluridine, ganciclovir
– Oral antivirals – Acyclovir, Valcyclovir
• Stromal
– Steroids with oral antiviral prophylaxis
• Necrotizing
– Topical and oral antivirals, topical steroids

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 Drug Treatment Prophylaxis Adverse Effects

Follicular
Trifluridine 9 times a day Not indicated conjunctivitis
Topical

Epithelial toxicity

Ganciclovir 5 times a day Not indicated Epithelial toxicity

HA, nausea
Acyclovir 400 mg 5x/d 400 mg bid
Nephrotoxicity
Systemic

TTP & hemolytic

Valcyclovir 500 mg tid 500 mg qday
uremic syndrome

Famvir 250 mg tid 250 mg qday Same as ACV

Non-infectious

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 Neurotrophic
• Minimal inflammation though may have hypopyon
• Smooth, thick, gray edges
• Reverse staining*
• Loss of sensation
• Decreased tearing

Reverse Staining - Neurotrophic

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 Treatment
• Surface support
• Lubrication
• Bandage contact lens
• Steroids
– Yes if inflammation
– No if quiet
• Protease inhibitors
• Growth factors

17
 Chemical Burns
• Alkali worse than acid or heat
• Prognosis depends of amount of ischemia and loss of
limbal stem cells
• Immediate copious irrigation
• Surface support, amniotic membrane
• Steroids
• Anti-proteolytics

Autoimmune
• Peripheral ulcerative keratitis (PAN) or central
keratolysis (Sjögren’s)
• Proteolytic substances from limbal vessels or tears
• Can rapidly perforate
• 10-year mortality may be up to 50%
• May have severe pain (Mooren’s)

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 Management
• PUK
– Systemic steroids immediately
– Immunosuppression long-term
– Conjunctival resection
• CK
– Surface support
• Usually avoid topical steroids in both

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20
 Toxic or Factitious
• Anesthetic abuse prototypical
• Ring ulcer
• Total epithelial defect
• Hypoesthesia but severe pain
• Most will deny
• Health care workers

Management
• Stop abuse
• Surface support
• Steroids cautiously
• Bandage contact lens
• ?Psych referral

21
 Vernal
• Young males in tropics
• Severe itching, giant papillae
• Limbal form – usually AA males
• Horner-Trantas dots
• Shield ulcers
– Inflammation vs mechanical damage
– Smooth edges with amorphous deposits

Treatment

• Very hard to treat

–Steroids
–Anti-histamines
–Cyclosporine
–Bandage contact lens
–Resection of papillae?

22
 Management

Underlying Causes

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 Culture

Medical Management

27
 Lubrication
• Remove toxic substances from eye
• Reduce abrasive action of lids
• Spread available growth factors
• Decrease osmolality - abrades surface
• If tears required ≥ 4 times daily, or any other
topical medications used, use preservative free

Doxycycline
• Inflammation = proteases (MMPs) = melting
• Doxycycline/minocyline/tetracycline - inhibit MMPs
• All ulcers but especially
– Alkali burns and blepharitis related
• Doxy 100 mg bid for 1, then qday
• Topical erythromycin or azithromycin in intolerant
• Oral Erythromycin/Azithromycin in children

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 Ascorbate and Citrate
• Adjuvant to collagenase inhibitors
• Especially useful in alkali burns where low levels
are seen
• May modulate neutrophil effects
• 1 gm vitamin C qday
• 10% topical drops

Steroids
• Decrease rate of epithelial healing, production of
collagen and keratocyte proliferation
• However, in inflamed eyes WBC actively produce
collagenases
• I’m confused…
– Inflammation but no infection = use
– No inflammation = do not use
– Infection = use cautiously + antimicrobials

Systemic steroids
• Always start immediately in PUK as other drugs
will take time to be effective
• Start 1 mg/kg if possible
• Taper based on response
• Caution in DM, GI ulcers, etc.
• Short-term solution though may need long-term

29
 Immunomodulators
• 10 year mortality decreased from 50% to 0%
and ulcer progression decreased from 75% to
0% on systemic cyclophosphamide
• TNF-a inhibitors (Embrel) may be more targeted
and reduce adverse effects
• Manage in conjunction with rheumatologist

Autologous Serum
• Initially used as a preservative free tear
• Tsubota recognized that it had various growth
factors (EGF, TGF, NGF, IGF-1)
• AS has been found to be beneficial in
neurotrophic ulcers, epithelial defects, keratitis
sicca, recurrent erosions
• Risk of infection as non-preserved

Autologous Serum
• Draw 10 cc blood in red/orange top tube
• Allow to clot for 30 minute to 2 hours
• Centrifuge for 15 minutes
• Draw out supernatant serum
• Dilute 1:4 with BSS
• Divide into 1 cc aliquots and freeze
• Thaw and use each vial for 2-3 days

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 Other Medical Therapy
• Restasis - may inhibit IL and lymphocytes – help with
PUK, vernal
• Neutraceuticals – flax seed, canola, soybean and fish oil –
omega-3 FA - surface inflammation – rTG better
• Acetylcysteine 5-10% – MMP inhibitor – especially useful
in alkali burns or filamentary keratitis
• 5% NaCl ointment – decreases edema, lubricates,
prevents exposure

Surgical Management

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 Punctal Occlusion
• Increase natural tear film that contains growth factors,
lubricates and protects
• Collagen plugs to test if needed
• Silicone plugs or thermal cautery
• Plugs colonize – limit to 6 months
• Not in inflamed eyes

Bandage Contact Lens

• Rationale – protect the corneal surface from
abrasive action of the lids
• Decrease pain by covering exposed nerves
• Allow vision as well as view of ulcer
• High risk of infection
• High DK lenses theoretically better

32
 Amniotic membrane
• Thick basement membrane and avascular stroma
• BM contains type IV & VII collagen, laminins, and
fibronectin
• Stroma contains growth factors, protease inhibitors,
anti-angiogenic and anti-inflammatory factors

Procedure
• Put on stromal (sticky) side down
• Tissue glue vs. suture vs. self-retaining
• Will melt in 10 days so if needed longer, use
multilayer or thicker
• Can use multilayer to build corneal thickness

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 Glue
Cyanoacrylate Fibrin Glue
Synthetic Biologic

Polymerize rapidly
Polymerize very slowly
especially with fluid

Rigid and uncomfortable Soft

Toxic Non-toxic

Bacteriostatic or Theoretic risk of disease

bacteriocidal transmission
Long-term – epithelium
growing under dislodges Rapidly degraded
the glue

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 Corneal Transplants
• Full thickness vs. Lamellar
• Studies have found lamellar much worse visual
outcomes than PKP
• Tectonic grafts much worse outcomes than optical
after ulcer healed
• Herpes worst outcome after PKP

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 Tarsorrhaphy
• Decreasing the exposed corneal area
• Tear evaporation decreased
• Tear spread more effectively
• Allow eye to be viewed
• BCL synergistic with tarsorrhaphy
• Patient resistance is issue
• Superglue or Botox® options

Gundersen Flap
• First described for neurotrophic ulcers
• Fallen into disfavor
• Useful in cases where vascularized tissue can heal
diseased stroma
• Also provide serum based growth factors
• Partial pedicle grafts in scarred eyes

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 Investigational Therapies
• Ilomastat – very powerful MMP inhibitor – decreased
ulceration in alkali burns as well as pseudomonas
ulcers
• Growth factors – EGF, FGF and NGF are being
evaluated in clinical trials
• Gene therapy – ribozymes, SiRNAs
• Organ cultured corneas

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 Conclusions
• Determine the cause of the ulcer
• Remove aggravating factors
• Treat the direct cause – antibiotics,
immunosuppression, etc.
• Eliminate toxic medications, surface support,
collagenase inhibitors
• More aggressive – BCL, AMT, AS
• Finally surgical – PKP, Conj flaps

Please Evaluate The Course

Two ways to evaluate:
1. Get scanned coming into the room (you’ll get a daily digest
tonight with links to all of the evaluations)
= OR =
2. Go to the Mobile Meeting Guide (www.aao.org/mobile),
where handouts are also located, and click on the
“Evaluate” button.

Your evaluation is critical and very much appreciated!

Thank You!

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