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CONTI SymposiumOphthalmology 2021

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Animal Ophthalmology ClinicDallas and Grapevine, TX

Robert J. Munger, DVM, DACVO

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Truth or Dare

A conclusion is the place you got tired of thinking.

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Corneal Ulcers:When Corneal Ulcers Won’t

Heal or

Understanding Mistakes Before They Happen

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Problem CorneasThis #*@! cornea just wont heal!

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Problem Corneas

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Problem CorneasTrue or False?

In this case from the preceding slide the problem has been present for 5 weeks.

Multiple punctate or grid keratotomy would be a good treatment for this ulcer?

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Problem Corneas

This is a cat that has ongoing keratitis of 3 weeks duration and is developing corneal erosions. True or False. MPK would be a good treatment for this ulcer?

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Problem CorneasThis corneal ulcer has been present for 48 hours. True or false?MPK would be a good treatment for this ulcer.

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Problem Corneas

This is the eye of a 14 year old dog with recurrent corneal erosions/ulcers.True or False? MPK would be a good treatment for this ulcer?

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Problem CorneasThis is the eye of a 14year-old shepherd cross with a corneal ulcer of 1 week duration. True or False? MPK would be a good treatment for this ulcer?

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Problem Corneas

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Problem Corneas

True or False?In the cases from the preceding slide

multiple punctate or grid keratotomy would be a good treatment for those ulcers?

FALSE!!!

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What’s the Point?! Multiple punctate keratotomy (MPK) or grid

keratectomy (GK) has become one of the most overused and misused treatments of corneal ulcers; lately this includes Alger Brush Debridement (ABD)

! Often detrimental when not used appropriately! Use confined only to true recurrent corneal

erosions ! Should NEVER be used in any

other types of corneal ulcers

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Most Common Mistakes

! Trial and error antibiotic therapy! Failure to recognize the type/origin of an ulcer! Failure to recheck promptly! Inappropriate debridement and treatments– Failure to recognize underlying cause (eg. repeated

debridement of eye with KCS, exposure keratitis, etc.)

– Herpetic disease in cats– Rare fungal infetions

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What Prevents Healing?! Infection! Foreign bodies and other irritants! Conformation! Physiologic interference– Recurrent erosions– Corneal degeneration– Host factors – MMPs, proteolytic enzymes

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Target Identification

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Problem Corneas: Goals

!Understand common and potential pathogens!Understand pathophysiology (disease process)!Understand species and breed variations!Develop rational therapeutic measures!Evaluate response to your plan

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Problem Corneas: Mode of Infection

!Primary infections rare – except viral disease

!Bacteria and fungi require pre-existing damage to cornea

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Problem Corneas: Pathogens

! Viral – Rare with dendritic or geographic erosions

! Bacteria – Pseudomonas, E. coli, Proteus, Streptococcal Staphylococci

! Fungi - Rare

! Viral – Common! Dendritic and geographic erosions

! Mycoplasma; Chlamydophila

! Bacteria – similar to dogs

! Fungi - Rare

Canine Feline

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Secondary Refractory Erosions

! Trichiasis, distichiasis, ectopic cilia, foreign body

! Entropion, lagophthalmos, exposure keratitis! Tear film abnormalities! Neurotrophic or neuroparalytic keratitis! Corneal sequestrum! Herpetic keratitis! Corneal edema/bullous keratopathy

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What’s In A Name?Recurrent Erosions

! a.k.a. recurrent epithelial erosions, Boxer ulcers, spontaneous chronic corneal epithelial defects (SCCED)

! Middle-aged dogs! Loose epithelial edges! Stroma not involved! Usually present >1-2 weeks

Indolent Ulcers! Slow to develop, heal or

progress ± pain; persistent! For this lecture: Any slow-

healing ulcers that are not recurrent epithelial erosions

! No loose edges; stroma may be affected

! Any age may be affected

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Recurrent Corneal Erosions: Classical Features

! Erosions may be quite large when loose epithelium is debrided.

! Fluorescein spreads under loose epithelium.! Corneal vascularization may be mild to severe.! When final healing occurs it is rare for the same

eye to be involved twice.! Fellow eye within a year.

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Recurrent Corneal Erosions

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Recurrent Erosions

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Recurrent Erosions

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Pathogenesis of Recurrent Erosions

! Incompletely defined! Disorganized epithelial architecture

(dysmaturation)! Absent or poorly organized basement

membrane and adhesion complexes! Acellular adjacent stromal ! Variable stromal fibroplasia, cellular infiltrates,

& vascularization

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True or False – If a recurrent erosion is not healing, a different antibiotic should be initiated.

FALSE! They are not infected!!!

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Recurrent Erosions - Histopathology

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EM – Basement Membrane DZ

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MPK & Grid Keratotomy

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MPK & Grid Keratotomy

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Alger Brush with Diamond Burr

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True or False - When a recurrent erosion has not healed within 5 days after performing a multiple punctate keratotomy the procedure should then be repeated.

False!Allow at least 2 weeks to pass before

repeating.

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Refractory Erosions – Herpetic

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True or False – Multiple punctate keratotomy or grid keratotomy should be

performed when a cat has a chronic recurrent erosion.

FALSE!!! Put down the needle and step away from

the cat!

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Which of the following is the best topical antibiotics for cats?

A. Neomycin, polymyxin B, bacitracin

A. Erythromycin

B. Terramycin

C. Neomycin, polymyxin B, 0.1% dexamethasone

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Secondary Refractory Erosions

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Secondary Refractory Ulcers

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Senile Corneal Degeneration

"Calcium &/or lipid depositions.

"Initial superficial ulcers

"Deep slough ±corneal perforation

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Rx: Senile Corneal Degeneration

" Topical 1% EDTA

" Topical antibiotics

" Keratectomy +/-

corneal graft or

conjunctival flap

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Problem CorneasCorneal Endothelial Decompensation

(Degeneration/Dystrophy or Secondary to Damage to Endothelium

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Corneal Endothelial Dystrophy! Boston terriers (5-9 years)! Chihuahuas (6-13 years) ! Dachshunds (8-11 years) ! Possibly in Basset hounds ! Familial - unknown mode of inheritance

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Corneal Endothelial Dystrophy

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Corneal Endothelial Dystrophy/Degeneration

! Hypertonic saline (5%) - Muro 128â

! Topical/systemic steroids in immune mediated disease and inflammation

! Systemic doxycycline

Medical Therapy Disappointing

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Corneal Endothelial Dystrophy/Degeneration

Past! Thermal keratoplasty in refractory cases! Homologous penetrating keratoplasty (high risk of

graft rejection)Present

! Keratoleptynsis (Gundersen Flaps)Future

! Corneal Endothelial Transplant EK – DSEK vs. DMEK)

Surgical Therapy

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Thermal Keratoplasy

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Keratoleptynsis

! 15 year old FS G. Ret.

! 6 weeks postop.! Treated initially for REE! Painful bullous

keratopathy resolved

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Keratoleptynsis

Mandy – 9 year-old FS Boston terrier 5 months postop.

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Gundersen flaps deteriorate over time !!!

! Superficial Keratectomy and Conjunctival Advancement Hood Flap (SKCAHF) for the

Management of Bullous Keratopathy: Validation in Dogs With Spontaneous Disease! Horikawa, T; Thomasy, S; et al. Cornea:

2016:35(10); 1295-1304Conclusions: ”…The increase in corneal thickness

over time, after performing SKCAHF, is likely because of progressive endothelial

decompensation.…”

WE AREN’T CURING ANYTHING !!!

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DSEK vs. DMEK! Advantages – Replaces defective endothelium.

Lower graft rejection than full-thickness corneal transplant

! DSEK (Descemet’s Stripping Endothelial Keratoplasty) – Implants the back 20-30% of donor cornea

! DMEK (Descemet’s Membrane Endothelial Keratoplasty) – Implants Descemet’s membrane and endothelium.

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DMEK in Human

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“Lucky” Stroup10y old Boston Terrier

After3/26/19

790Microns

1-day post graft7/26/17

Courtesy of Dr. Micki Armour

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“Tebah” Stineman1y old Tibetan Terrier

Before 8/21/18

After4/12/19

1,670 microns

660microns

Courtesy of Dr. Micki Armour

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Graft Rejections - All is Not Roses! Poor patient and client selection– Ability to perform follow up appointments

effectively– Compliance with eye drops and medical protocol– Excessive keratitis

! Inability to visualize ! Other causes

Courtesy of Dr. Micki Armour

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Luna Mosser: July 2018Courtesy of Dr. Micki Armour

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Luna Mosser: August 2018Courtesy of Dr. Micki Armour

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Corneal Infection! Preceded by epithelial damage! Bacterial production of proteolytic &

collagenolytic enzymes and toxins - progression of the ulcer

! Neutrophils, degenerate epithelial cells & fibroblasts produce proteolytic enzymes which can contribute to keratomalacia

! Fungi can penetrate into healthy stroma

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Deep Corneal Ulcers

Progression of ulcers due to degeneration of the cornea

and/or infection with production of enzymes & toxins which destroy the

corneal stroma

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Deep Progressive Ulcers!Always assume infection but remember host

defense factors as well!No room for half measures!Aggressive therapy and timely rechecks

#Anti-collagenolytic/anti-proteolytic therapy#Antibiotics – Topical and systemic#Recheck in 24 hours#Anti-inflammatory and pain therapy#Surgery preferably when infection controlled

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Potentiation of Infection! Corticosteroids and NSAID’s inhibit immune

response and potentiate activity of proteolytic and collagenolytic enzymes

! Cyclosporine inhibits cell mediated immunity but not acute inflammatory response > contraindicated in fungal and viral keratitis but not in bacterial infections

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Bacterial Ulcers - Diagnosis

! Clinical signs: pain, exudates and infiltrates, hypopyon, blepharospasm, photophobia, miosis

! Gram stains of corneal scrapings of ulcer edge! Culture and sensitivity early whenever you

suspect infections!!!! There can be some wicked bacteria involved!MRSA and MRSP!Stenotrophomonas maltophilia (Gm -)!Capnocytophaga sp. (Say whaaaatttt???)

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Antibiotic Rx of Bacterial Ulcers! Initial intense topical broad spectrum antibiotic

altered as indicated by culture sensitivity! Staphylococci - Cephalothins, quinolones,

bacitracin, gentamicin! Streptococci - CHPC, erythromycin, penicillins,

quinolones! Pseudomonas & E. coli - gentamicin,

tobramycin, quinolones, amikacin

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Adjunctive Rx of Bacterial Ulcers

! Systemic antibiotics! Topical atropine! Inhibit proteolytic and collagenolytic

enzymes: autologous serum, 5-10% acetylcysteine, 1% EDTA

! Remove necrotic debris! 360-degree conjunctival flaps,

conjunctival pedicle flaps, and other grafts

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Mycotic Keratitis

!Most common in horses!History of topical inhibitors of cell-

mediated immunity (steroids, CSA)!Injury with vegetative matter or other

source of fungal spores - especially deep penetrating wounds

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Mycotic Keratitis - Diagnosis

! Clinical signs - insidious onset, slow healing erosion, typical appearance of fungal colony -interlacing branches or fuzzy appearance, stromal abscess or yellow-white plaque, severe corneal vascularization, keratouveitis, hypopyon

! Corneal scrapings: center and edges of ulcer, cultures and cytology

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Diagnostics!Viral – Problematic; false negatives and false

positives with PCR, IFA, etc.; !Bacterial – Gram stains, cytology, culture and

sensitivity on corneal scrapings!Fungal – Cytology; culture on Saborauds-

dextrose slants; sensitivities expensive

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Superficial Ulcers

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Bacterial Ulcers

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Bacterial Ulcers

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Canine Mycotic Keratitis

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Equine Mycotic Keratitis

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Topical Support Therapy! I-drop™Vet Gel! Optixcare Eye Health;

Lubricant Gels! EyeQ™ Amniotic

Eyedrops! Artificial Tears! Vizoovet™! Remend™ Corneal

Repair Gel

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Optixcare For Cleaning Lids

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Surgical Options for Ulcers! Conjunctival flaps – pedicle flap/graft, 360-degree flaps! Autologous (transpositional – CCT, etc.) and homologous (free)

corneal grafts ! Amnion and other extracellular matrix (ECM) technology

xenografts– Vetrix® BioSIS - small intestinal mucosa– Acell® - acellular porcine bladder submucosa – Vetrix® EyeQ Ocular Discs and grafts are decellularized

amniotic membrane discs, carefully processed to remove cells and other immunogens.

! Alternatives to surgery?

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Amnion Allografts in Humans“Amniotic membrane-based allografts are classified as a naturally derived biomaterial and are currently being used in wound and soft tissue repair applications. Characterization of this tissue has revealed many growth factors, cytokines, and protease inhibitors that can play a role in wound repair. Amnion has been shown to stimulate cellular activity including proliferation, migration, and secretion of soluble paracrine factors in vitro, and has also demonstrated the ability to recruit reparative adult stem cells to the site of implantation in vivo. In addition, these allografts have been shown in randomized clinical trials to be effective in healing various dermal and soft tissue wounds.”

(Lei, "Dehydrated Human Amnion/Chorion Membrane (dHACM) Allografts as a Therapy for Orthopedic Tissue Repair", 2017)

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Amnionic Membrane Grafts! The clinical efficacy has been attributed to its anti-

inflammatory, anti-scarring, and immuno-privileged components that promote rapid corneal re-epithelialization.

! Can be used as either a tissue to be sutured, as an inlay, or as a temporary patch graft as an onlay to cover the damaged ocular surface.

! Vetrix® EyeQ Ocular Discs and grafts are decellularized amniotic membrane discs, carefully processed to remove cells and other immunogens.

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Vetrix® EyeQ Amniotic Eye Drops! Store at room temperature until reconstituted

them refrigerate; discard after 1 month; do not lay on side

! Cost to client ~ $130.00 / vial! “Provides scaffolding for healing”! As an alternative to or an adjunct to surgery

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Corneal Ulcers - The Bottom Line! Ulcers may progress rapidly (24 hours) to

perforation given the right circumstances! Aggressive early therapy is imperative! Follow up within 24-48 hours ! Use of 3rd ELF’s for progressing ulcers is

poorly conceived.

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Questions?

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Questions?

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