CORNEAL WARS: A NEW HOPE, CORNEAL WARS: OPACITY STRIKES BACK,

CORNEAL WARS: RETURN OF THE TRANSPARENCY – GUY CLARE

CORNEAL WARS – GUY CLARE MA BVSc CertVOPhthal (COPYRIGHT)

THE ‘GROSS’ CORNEA

THE CLEAR CORNEA TOTAL THICKNESS AROUND 0.8mm: -

Anterior ¼ of the globe

Has a smaller radius of curvature compared to the sclera and therefore ‘bulges’ forwards

The most anterior component (vertex) is designated the anterior pole and the position directly

opposite this on the outer sclera is the posterior pole

N.B. the equator is the maximum circumference located midway between the poles

I REMEMBER THE ANATOMICAL ARRANGEMENT OF THE CORNEA BY RELATING IT TO 5 LAYERS OF A

SANDWICH:-

2 PIECES OF BREAD REPRESENT THE: -

EPITHELIUM

ENDOTHELIUM

MAYONNAISE (or BUTTER) ON THE BREAD REPRESENTS THE: -

BASEMENT MEMBRANE OF THE EPITHELIUM

DESCEMET’S MEMBRANE (THE ‘BASEMENT MEMBRANE’ OF THE ENDOTHELIUM)

SANDWICH FILLING - STROMA

CORNEAL EPITHELIUM

THE CORNEAL EPITHELIAL CYCLE Q 7-14D

1. EXFOLIATING SURFACE SQUAMES ARE REPLACED BY UNDERLYING WING CELLS

2. IT USED TO BE THOUGHT THAT EPITHELIAL BASAL CELLS WERE THE GERMINITIVE FORCE OF

THE EPITHELIUM, BUT IT IS NOW RECOGNIZED THAT LIMBAL EPITHELIAL STEM CELLS (LESC)

MIGRATE CENTRALLY TO REPLACE BASAL CELLS

3. THE GERMINITIVE LAYER OF THE EPITHELIUM THEREFORE LIES AT THE LIMBUS

THE CORNEAL EPITHELIAL SURFACE CELLS

Are: flattened; polygonal; non-keratinized squamous cells

These squamous cells at the surface have tight junctions (zona occludens) around each cell

that prevents the penetration of tears into the inner corneal structures.

The most superficial squamous epithelial layer has microplicae and microvillae that project

anteriorly and increase the surface area thus allowing the mucin layer of the precorneal tear

film to adhere firmly to the anterior epithelium

I REMEMBER THAT THE SURFACE OF BREAD IS ‘ROUGH’ AND THIS REPRESENTS THE INCREASED

SURFACE AREA OF THE MICROPLICAE AND MIRCROVILLI

THE CORNEAL BASEMENT MEMBRANES

N.B. ALL EPITHELIA ‘SIT’ ON A BASEMENT MEMBRANE

Layer 2 - the basement membrane of the corneal epithelium isn’t given a specific name in the

dog!

In the human and Ox layer 2 is termed Bowman’s membrane

Layer 4 - the basement membrane of the ENDOTHELIUM is given a specific name: DESCEMET’S

MEMBRANE

N.B. When there is an air / Descemet’s membrane interface there is a strange phenomenon in

which the normally transparent Descemet’s membrane appears black.

THE ROLES OF THE BASEMENT MEMBRANES

SEPARATION - The B.M associated with the corneal epithelia separate their ‘epithelia’ from

the middle bulkiest layer – the stroma

The basement membranes have 2 primary

functions: -

1. 1.To ANCHOR their associated

‘epithelia’ to the middle stroma

2. 2.To isolate the stroma from growth factors so the layers can function independently

The basement membrane is an extracellular supporting layer of mucopolysaccharides and

proteins

CORNEAL EPITHELIUM BASAL CELL ‘ANCHORING’ (LAYER 1 ANCHORED TO LAYER 2)

BASAL COLUMNAR CELLS ARE TIGHTLY ANCHORED TO THEIR BASEMENT MEMBRANE BY: -

1. HEMI-DESMOSOME ‘SPOT WELDS’

2. ADHESIVE GLYCOPROTEINS – LAMININ & FIBRONECTIN

3. COLLAGEN FIBRILS

4. ADHESIVE GLYCOPROTEINS e.g. HYALURAN

‘Boxer’, ‘indolent’, SCCED or superficial non-healing ulcers happen because the basal columnar

epithelial cells do not form the necessary adhesion complexes to their basement membrane.

As a result there is non-adherence between the basal columnar layer and the epithelial

basement membrane. This results in delayed and problematic healing.

ADDITIONAL CELLS ASSOCIATED WITH THE EPITHELIUM IN A PROTECTIVE ROLE

1. MACROPHAGES – involved in phagocytosis

2. HISTIOCYTES (tissue monocyte)

3. LYMPHOCYTES

4. ANTIGEN PRESENTING LANGERHANS CELLS

EMBRYOLOGICAL SOURCES FOR THE CORNEA

STROMA COMPONENTS

CORNEAL STROMAL CELLS – THE KERATOCYTE

OCCUPY AROUND 2- 5% BY VOLUME OF THE STROMA, THEREFORE MAKING THE STROMA

RELATIVELY ACELLULAR

KERATOCYTES ARE RESPONSIBLE FOR THE SYNTHESIS OF THE EXTRA-CELLULAR MATRIX &

MATRIX METALLOPROTEASES (MMP’s)

CORNEAL EXTRA-CELLULAR MATRIX

IS COMPOSED OF ORDERED COLLAGEN FIBRES, (70% BY WEIGHT) WHOSE DIAMETER IS

AROUND 21nm

THE SPACE BETWEEN THE COLLAGEN FIBRES IS OCCUPIED BY ‘GROUND SUBSTANCE’ . THE

SPACE BETWEEN

THE FIBRES IS REGULAR AND SIMILAR TO COLLAGEN FIBRE DIAMETER

‘GROUND SUBSTANCE’ IS COMPOSED OF WATER (90%) AND GLYCOSAMINOGLYCAN (GAG’s)

THAT ARE MOSTLY BOUND TO A ‘CORE PROTEIN’ FORMING ‘PROTEOGLYCAN’

‘GROUND SUBSTANCE’ IS ‘RELATIVELY DEHYDRATED’, GELATINOUS, AMORPHOUS,

TRANSPARENT & COLOURLESS

CORNEAL STROMA ANALOGOUS TO REINFORCED CONCRETE

1. The ‘reinforced concrete’ is analogous to the stromal repeating ‘functional unit’ known as a

‘lamella’. ALL FIBRES IN A LAMELLA RUN PARALLEL TO EACH OTHER

2. the lamellae are arranged at different angles to each other

3. keratocytes occupy the space between the lamellae

4. the collagen fibrES (steel rods) are uniform in diameter and their arrangement HAS ORDER

GROUND SUBSTANCE

Proteoglycans are very good at absorbing water (like a porous, sponge), therefore 90% of the

extracellular matrix is water and therefore very good at resisting compressive forces

IT CAN ABSORB WATER, BUT IS RELATIVELY DEHYDRATED i.e. IT HAS THE CAPACITY TO

ABSORB EVEN MORE

WATER THAN IT NATURALLY HOLDS

The curved shape and water content of the cornea make it the most powerful refractive

structure of the eye

The refractive index of air is 1.00

The refractive index of cornea is 1.37

CORNEAL OXYGEN DELIVERY

1. TEAR FILM

2. LIMBAL CAPILLARY LOOPS

3. AQUEOUS HUMOUR

TEAR FILM DISTRIBUTION

1. PRE-CORNEAL TEAR FILM i.e. the part of tears in contact with the cornea

2. The ‘LACRIMAL LAKE’ i.e. the non-corneal part of the tear film residing between the lids and the

globe down to the fornices. This acts as a reservoir of tears that is distributed over the cornea

during blinking

IMPORTANCE OF THE PRE-CORNEAL TEAR FILM

OXYGEN DELIVERY TO THE CORNEA: 90% O2 FROM THE TEAR FILM, 10% AQUEOUS

MAINTENANCE OF AN OPTICALLY ‘SMOOTH’ AND UNIFORM CORNEAL SURFACE

REMOVAL OF FOREIGN MATERIAL AND DEBRIS FROM THE CORNEA AND THE CONJUNCTIVAL

SAC

ANTI-MICROBIAL ACTION (lysozyme)

CORNEAL VULNERABILITY IS RELATE DO IT BEING A ‘SPECIALISED EPITHELIUM’

N.B. blood vessels never penetrate the basement membrane of epithelia. This is true at both

the corneal epithelium and endothelium. Therefore epithelial tissues rely on the diffusion of

both oxygen and nutritional substrates from their immediate environment. This can make

them VERY vulnerable to diseases that affect their oxygen and nutritional supply

NUTRITIONAL SUPPLY TO THE CORNEA: 1/3 via the tear film and 2/3 via the aqueous humour

PRE-CORNEAL TEAR FILM – ‘SQUOSHED FROG COCKTAIL’

Is traditionally thought of as a TRI-LAMINAR structure: -

1. Inner MUCUS PHASE ‘glued’ to the squamous epithelium. The mucus is produced from

conjunctival goblet cells and is the ‘GLUE’ ANCHOR TO CORNEA

2. Middle AQUEOUS PHASE released from the lacrimal gland (2/3) and gland of the third eyelid

(1/3), responsible for OXYGEN DELIVERY

3. Outer LIPID PHASE whose origin are the meibomian glands of the eyelids, SERVES TO LESSEN

EVAPORATIVE LOSS

THE SCHIRMER TEAR TEST

MEASUREMENT OF THE AQUEOUS PHASE OF THE TEAR FILM: -

Fold the strip, whilst still in its plastic package, at the ‘notch’

Open the packet from the non-notched end and handle the strip at this ‘distal’ aspect to avoid

touching the proximal part

1mm graded strips are placed into either the dorsal or ventral conjunctival fornices

The strip is left in place for 60sec, I CLOSE THE LIDS

Record in mm the distance the aqueous phase of the tear film has been soaked into the paper

strip

DO THIS FOR BOTH EYES

SCHIRMER TEAR TEST INTERPRETATION

Readings of 15mm and >15mm represent normal aqueous phase (assuming there is no reason

for the eye to produce more tears than normal i.e. in the absence of eye pain / tear

secretagogue)

Readings of 11mm to 14mm inclusive represent sub-optimal aqueous phase

Readings of 10mm or < 10mm are diagnostic for dry eye

CONSEQUENCES OF KCS

What is the relevance for the eye when there is too low aqueous tear production (KCS): -

Reduced oxygen transfer to the cornea à corneal hypoxia

Profuse mucopurulent ocular discharge (the eye’s only available response is to produce more

of the mucoid and lipid phases of the tear film in a failing attempt to minimise the KCS impact)

Decreased optical uniformity à poorer vision

Stimulation for corneal neovascularisation à poorer vision

Stimulation for pigment keratitis à poorer vision

Stimulation for corneal scarring à poorer vision

The stimulation of pain receptors à ocular pain

Decreased pathogen protection à ocular ulceration

Decreased lubrication à foreign body / ocular irritation

SUMMARY FOR THE CLINICAL SIGNS ASSOCIATED WITH KCS

1. Pain (blepharospasm, photophobia, increased blink rate)

2. Ocular discharge (the only response the eye has is to produce more mucus and lipid phases in

an attempt to get some corneal ‘wetting’) 3.Corneal opacification: - 1.Corneal

neovascularisation Corneal scarring (opacification of the cornea)

3. Corneal pigment deposition (pigment keratitis)

4. Ultimately a blind, painful eye with ocular discharge

IMMUNE MEDIATED KCS SIGNALMENT

STRATEGY FOR STT-1 RESULTS <15MM

10mm or <10mm: -

1.Cyclosporine 0.2% (OPTIMMUNE) topically q 12h BOTH eyes

2.+ VISCOTEARS (carbomer gel) q 6h

3.+ Sodium hyaluronate 0.15% or >0.15% q 6h

–Re-assess after 14d (ask the client not to put any medication in that morning). If STT normal then you

can reduce the tear replacement topicals. If abnormal continue and re-assess every 4 weeks

•14mm à 11mm: -

1.VISCOTEARS (carbomer gel) q 12h

–Re-assess every 3 months

CLINICAL RELEVANCE: SCLERA

•Scleritis itself is a very rare condition in dogs and hasn’t been reported in cats

CORNEAL OPACITY MENACES

CORNEAL DIMENSIONAL MENACES

CORNEAL EXAMINATION

•EXAMINIG THE CORNEA CAN BEST BE ACHIEVED WITH THE AID OF MAGNIFICATION AND A GOOD

LIGHT SOURCE

•CONSIDER USING THE OTOSCOPE ATTACHMENT

•ADDITIONAL TESTS CAN INCLUDE: -

•Bacteriology – culture, sensitivity, PCR

•Cytology

•Schirmer Tear Test

•Tonometry

•Fluorescein

KNOW YOUR FOE

•DARTH’S SIDIOUS, MAUL & VADER: PALOUR; NEOVASCULARISATION & DARKENING

•THE ‘DARK SIDE OF THE FORCE’ HAS THE ABILITY TO CREATE OPACITY AND CAUSE CORNEAL

DIMENSIONAL DISTORTION

THE AETIOLOGY FOR CORNEAL OEDEMA CAN ONLY BE DUE TO A LESION (OR LESIONS) ASSOCIATED

WITH: -

1.THE EPITHELIUM

2.THE ENDOTHELIUM

CORNEAL OEDEMA

ULCER DIAGNOSIS

1.TECHNIQUE: Fluorescein stain

1.Use a wetted strip or a pippette touched to the conjunctiva

2.Close or ‘blink’ the lids to distribute dye over the cornea

3.Flush the green dye from the eye

4.View under blue light

Aetiology of corneal ulceration: - –

Breed – Boxers, Corgis, SBT, Bug-

Eyed

–Aberrant hair abrasion

–Nerve palsy: -

–VII: motor to orbicularis oculi

–V: sensory to cornea)

–Dry eye

–Irritants (acid / alkali), Immune mediated, Iatrogenic, Infective (not in the dog) & Idiopathic

–Trauma / foreign body

ABERRANT HAIRS

Clinically significant abrasion of the cornea by aberrant hairs can be due to: -

•Entropion

•Distichiasis

•Ectopic cilia

•Dermoid (congenital defect)

•Less commonly trichiasis (secondary to eyelid agenisis)

NERVE PALSY

Nerve V palsy

–n.V provides sensory information from the cornea to the CNS

–n.V palsy à neurotrophic keratopathy: -

–This can result in punctate epithelial defects, but can later progress to deeper lesions and corneal

oedema

–N.B. A dog with a n.V palsy should still have a Menace Response, and normal Dazzle & PLR

Nerve VII Palsy

–Menace test: afferent arm n.II, efferent arm n.VII to orbicularis

–Palpebral reflex: afferent arm n.V, efferent arm n. VII to orbicularis

–Dazzle reflex: afferent arm n.II, efferent arm n.VII to orbicularis

–N.VII palsy à NEGATIVE Menace, Palpebral & Dazzle i.e. The patient CANNOT blink

IF YOUR PATIENT IS UNABLE TO BLINK then it is likely à EXPOSURE KERATITIS à ULCERATIVE KERATITIS

i.e. BE VERY, VERY WORRIED ABOUT THE POSSIBILITY FOR CORNEAL ULCERATION!

•Even when we use hourly Viscotears we have still had corneal ulceration secondary to a nerve VII

palsy

DRY EYE

With virtually all ulcers (unless there was a risk of perforation in an ulcerated eye) I perform a

Schirmer Tear Test (over 60sec) in BOTH eyes

•AETIOLOGY FOR DRY EYE

•CONGENITAL v. ACQUIREDCONGENITAL DRY EYE: -

•Lacrimal gland aplasia

•Lacrimal gland hypoplasia

•YOUNG DOGS WITH DRY EYE!

•ACQUIRED DRY EYE

•IMMUNE MEDIATED

•NEUROGENIC

•IATROGENIC

•TRAUMA

•Traumatic ulcers tend to fall into 2 groups: -

–Linear wounds (scratches)

–Puncture / penetrating wounds

•Foreign bodies can be superficially ‘stuck onto the cornea’ or can be grass seeds

ULCER AETIOLOGY SUMMARY

CORNEAL ULCERATION

I believe there are 3 clinically important types of canine ulcer: -

1.Those that heal quickly with supportive treatment (< 72h)

2.Indolent / Non-healing / Boxer / SCCED

3.Stromal

CORNEAL EPITHELIAL UNDER-RUNNING

•Following fluorescein staining the diagnosis is made with the observation of: -

1.Epithelial under-running i.e. areas of non-adherent epithelium

2.Any breed is susceptible, however the Boxer and Pembroke Corgi are over-presented

3.Therefore if you are suspicious of under-running, add a topical local anaesthetic and attempt cotton

wool bud debridement. Re-stain and show the results to the owner. If the ulcer has increased in size

there was underrunning and this should be treated as an indolent ulcer

•Indolent ulcers are epithelial defects

•What you are seeing taking up stain is the basement membrane of the epithelium

•The under-running represents non-adherent areas of epithelium

•The basal epithelial cells have not formed the necessary junctional complexes (hemi-desmosomes)

that anchor it through the basement membrane to anterior stroma

KEY POINT ON INDOLENT ULCERS

•These ulcers occur in dogs that dog have a corneal healing issue and are PAINFUL!!

•This is not thought to be a bacterial problem

•USA – known as SCCED ulcers (Superficial Spontaneous Chronic Corneal Epithelial Defect)

•I actually prefer: Spontaneous Chronic Corneal Epithelial Defects instead of Superficial Chronic

Corneal Epithelial Defect

•You now need to discuss with the owner the following areas: -

• We don’t know why it has happened

•Because their pet has a healing problem then the time frame for healing is extremely unpredictable

(weeks to months)

•Conservative Treatment options: -

Conscious animal: -

1.Topical debride, grid keratotomy, contact lens,

2.Topical Tx: -

1.Sodium hyaluronate 0.15% or >0.15% (Eyesoothe, Blink)

2.Chloramphenicol eye drops (covering antibiotics)

3.Mydriatic (Tropicamide 0.5 or 1% = Mydriacyl) BEWARE ATROPINE AS IT WILL à REDUCED TEAR

PRODUCTION

3.Systemic Tx: -

NSAID

•Antibiotics are important to stop secondary invaders, however there is no real rationale for changing

antibiotics after a few weeks, if the ulcer hasn’t healed

•If these ulcers are not getting better you need to stimulate healing more (not change the antibiotic)!

Surgical treatment following GA: -

1.Superficial keratectomy, grid keratotomy & third eyelid flap (TEF),

2.Chloramphenicol, mydriatic, NSAID

3.RV for POC @ 3-5d – should have a ‘normal’ palpebral fissure

4.RV 14d – 17d after initial surgery for TEF removal, continue with topicals

5.RV + 7d, may or may not add in a topical steroid (Maxitrol q 8h) depending on the degree of corneal

neovascularisation or scar AND assuming the cornea is fluorescein negative

Surgical tips: -

•Try a ‘one touch’ technique by grasping bulbar conjunctiva at the medial quadrant between the third

eyelid and the globe

•I debride using the back of a No 11 scalpel blade & use a 25G for the grid

•THERE HAS NOT BEEN ONE OCCASION WHERE ALL THE EPITHELIUM HAS NOT EASILY BEEN STRIPPED

TO THE LIMBUS 360º

THE DON’TS

•DO NOT USE A THIRD EYELID FLAP IF YOU ARE NOT 100% HAPPY WITH YOUR DIAGNOSIS. IN MY

OPINION THEY

ARE CONTRA-INDICATED IF THERE IS STROMAL INVOLVEMENT IN THE ULCER

•DO NOT USE GRIDS IN CATS WITHOUT WARNING OF THE POSSIBILITY OF A CORNEAL SEQUESTRUM

AND ALL THAT THAT MAY ENTAIL!

MY THOUGHTS ON OWNER MANAGEMENT

1.In my hands there is a >95% success rate that a single anaesthetic and surgery will be sufficient for

healing of the ulcer

2.I offer the owners a 50% reduction if any additional surgery at the same eye, for the same condition,

is required within 6 months

3.Warn the owner that the other eye may well get this at some point in the future and there is

nothing we can do to prevent it (approximately 35%)

STROMAL ULCERS HAVE CORNEAL OEDEMA

•The amount of corneal oedema will give you a big clue, together with the appearance of an ‘ulcer pit’

•Remember the epithelium is only 5 cells thick and occupies approximately 10% of the total corneal

thickness

OPACITY & DIMENSIONAL MENACES CORNEAL OEDEMA

•Corneal ulcers that disrupt the epithelium and it’s basement membrane à corneal oedema

•Corneal oedema occurs with increased water content of the extra-cellular matrix

STROMAL ULCERS: HOW TO GAUGE DEPTH

•This may sound stupid, but if it looks deep it is!

•The breed of dog will also give you a clue – ‘Bug-eyed’ dogs are massively over-presented

•You can use the vertical slit on the direct ophthalmoscope to assess how much the light bends going

‘into’ the ulcer

‘ORDER 66’

•Because the stromal ulcer can à PROTEASE ACTIVATION

•This can result in the rapid progression of an ulcer à perforation à bigger problems to manage

PROTEASE SOURCES

1.Normal epithelium has a cell turnover and for this to happen there are naturally occurring epithelial

collagenases, which help regulate this. When there is damage these can get ‘switched on’

2.Keratocytes release Matrix Metallo-Proteases (MMP’s)

3.Bacteria: especially Pseudomonas spp (releases enzymes that degrade collagen – elastase has a

direct action and also converts the inactive iMMP’s into their active form)

4.Leukocytes involved in the inflammatory response will release factors that are pro-lytic

5.Tear film (normal proteinase inhibitors can become over-whelmed in damaged corneas with a

switch to proteinase activity).

Assume ALL stromal ulcers are going to liquify / melt due to ‘ORDER 66’ à action of proteases

•Direct therapy at turning ‘off’ protease activity

Therapy for stromal ulcers: -

•Assume ALL stromal ulcers are going to melt, therefore treat aggressively q 2h for at least 48h

•Topical antibiotics directed against Pseudomonas spp. ofloxacin (OCUFLOX / EXOCIN), ciprofloxacin

(CILOXAN), tobramycin (TOBREX) gentamicin (TIACIL, CLINAGEL),– there is now considerable

Pseudomonas spp. gentamicin resistance

•Systemic antibiotics can be used, but in my experience, are less important and add considerable cost

Autogenous plasma / serum / blood combined with EDTA

•I collect in Lith hep, spin down, draw-off the plasma and place the plasma in an EDTA tube and invert

to create the plasma / EDTA in the mixture

•Refrigerate between applications

•Plasma / serum / blood has the VERY POTENT anti-collagenase alpha-2 macroglobulin

•EDTA, because this chelates divalent ions. These are necessary cofactors for the MMP’s

•ANOTHER Ca2+ CHELATOR OPTION

•Oral doxycyline 10mg/kg PO q 24h

–Topical mydriatic (tropicamide 0.5 or 1.0% (MYDRIACYL) or atropine

–Topical & systemic NSAID’s are controversial

–I would advocate checking these cases at least q 24h

DO NOT USE A THIRD EYELID FLAP WHEN THERE IS STROMAL INVOLVEMENT OR IF YOU ARE UNSURE

OF YOUR DIAGNOSIS

•Remember the ‘ORDER 66’ Proteases x5 and counter with 5 classes of therapeutics: -

1.Anti-proteases - plasma*

2.Calcium chelator - EDTA* / doxycycline#

3.Topical antibiotics*

4.Mydriatic*

5.+ / - NSAID*#?

•(* = topical, # = systemic)

CHALLENGING ULCERS

Occur when the ulcer has formed a Descematocele, however the intra-ocular pressure causes the

descematocele to bulge anteriorly ‘through’ the ulcer

COMPLICATIONS ASSOCIATED WITH CONJUNCTIVAL PEDICLE GRAFTS ARE RARE

•Compliations include

•Conjunctival pedicle graft dehiscence

•Stromal melting peripheral to the limits of the graft

•Vascularisation of a sectioned pedicle graft

•Lipid keratopathy associated with corneal neovascularisation

•Pigment keratitis secondary to melanocyte migration onto the cornea via the conjunctival pedicle

graft

SX: CORNEO-CONJUNCTIVAL TRANSPOSITION (CCT)

•For corneal lesions where there in no melting or little keratomalacia, corneo-conjunctival

transposition (CCT) replaces the lesion with clear cornea (following lesion removal by keratectomy)

•CCT involves creating a parital thickness autologous graft from cornea

•The corneal advancement graft is created by continuing through the limbus into the sclera for 2-3mm

and then cutting the sclera, whilst keeping the conjunctiva attached

CORNEAL OEDEMA DIAGRAM

ENDOTHELIAL DERIVED OEDEMA – UVEITIS

•UVEITIS CAN DISRUPT THE NUTRITIONAL SUPPLY TO THE CORNEAL ENDOTHELIUM

•AS A CONSEQUENCE THE ENDOTHELIAL ‘PUMPS’ LOSE THEIR EFFICIENCY à DIFFUSE CORNEAL

OEDEMA

•CLINICALLY UVEITIS à PAIN, MIOSIS, EPISCLERAL CONGESTION

•CORNEAL ULCERATION CAN à UVEITIS

ENDOTHELIAL DERIVED OEDEMA – GLAUCOMA

•GLAUCOMA IS WHEN INTRA-OCULAR PRESSURE (IOP) BECOMES TOO HIGH (>30mmHg)

•AS A CONSEQUENCE THE ENDOTHELIAL ‘PUMPS’ CANNOT ‘WORK’ AGAINST THE RAISED IOP à

DIFFUSE MORE

INTENSE CORNEAL OEDEMA

•CLINICALLY GLAUCOMA à PAIN, MYDRIASIS, EPISCLERAL CONGESTION & SIGNALMENT WILL GIVE A

MASSIVE CLUE

•GLAUCOMA CAN BE PRIMARY OR SECONDARY, BUT MOSTLY à UNCONTROLLABLE PAIN AND EYE

REMOVAL

ENDOTHELIAL DERIVED OEDEMA – CORNEAL ENDOTHELIAL DYSTROPHY / DEGENERATION

•CORNEAL ENDOTHELIAL DYSTROPHY (BREED ASSOCIATED) OR DEGENERATION (OTHER BREEDS) IS A

DISEASE

WHERE THERE IS PROGRESSIVE REDUCTION IN ENDOTHELIAL CELLS

•AS A CONSEQUENCE THE ENDOTHELIAL ‘PUMPS’ OVERLOADED à CORNEAL DECOMPENSATION

àCORNEAL OEDEMA

•CLINICALLY à MOSTLY NON-PAINFUL & IN OLDER PATIENTS

•DIAGNOSIS BY EXCLUSION, BOSTON TERRIER IS THE ‘CLASSIC’ BREED FOR CORNEAL ENDOTHELIAL

DYSTROPHY

TREATMENT FOR CORNEAL ENDOTHELIAL DEGENERATION / DYSTROPHY MEDICAL V. SURGICAL

•TOPICAL OINTMENT HYPER-OSMOTIC 5% SODIUM CHLORIDE OINTMENT/DROPS

•THERMAL KERATOPLASTY

•The Boston Terrier is the ‘Classic’ breed that suffers from Corneal Endothelial Dystrophy. Other

breeds include the Chihuahuas; Dachsund and both German Short-haired and Wire-haired Pointers

•Bullous keratopathy occurs when the progressive corneal waterlogging forms ‘water pockets’ termed

bullae. The bullae can rupture on the epithelial surface forming an ulcer and this is termed bullous

keratopathy

CORNEAL DIMENSIONAL MENACE

CORNEAL LIPID ACCUMULATION

Clinical diagnosis based on ‘brilliant white’ individual lesions – ‘snow flakes’

•Note whether there is another corneal lesion associated with the area: -

•No other lesion à corneal lipidosis

•Other lesion often vascular à lipid keratopathy

RARELY IS AN AETIOLOGY FOUND OR TREATMENT REQUIRED

CORNEAL CALCIFICATION

Pale opacification: Calcium

•The appearance is of ‘dull-white’ granular particles of dust – a powder appearance

•The location is often epithelial and may be associated with corneal ulceration

•This tends to be present in ‘aged’ corneas

•Will complicate the healing of the epithelium if associated with an ulcer

Calcium can also be associated with the cornea following a parotid duct transposition (PDT) due to the

increased levels of calcium present in saliva à precipitation

•Calcium deposition can be treated by the application of EDTA (made-up by the addition of sterile

saline to a blood tube, or from Moorfield’s Eye Hospital Pharmacy T: 02076847592 as a 5%

preparation)

•ACULAR EYE DROPS (ketorolac) has EDTA as a preservative

•Doxycycline PO can be used 10mg/kg/24h

CORNEAL SCAR

The appearance is of ‘dull-white’ linear or branching lesion with a distinct border

•This represents an area where the normal stromal collagen orientation has become randomised

secondary to a previous insult

•Scar can often be reduced with the application of topical steroids (after having checked that fluor –

ve)

CORNEAL ABSCESS

•The appearance is of a diffuse yellow discolouration of the stroma secondary to PNL accumulation

•These eyes are painful

•Often surgery with a conjunctival pedicle graft and intensive topical medication is required to try and

preserve a functional eye

CORNEAL EPITHELIAL INCLUSION CYST

•These are benign, raised, solitary white to pink corneal masses

•They are non-painful and usually unilateral

•They may arise in any layer of the cornea

It is postulated that following traumatic injury epithelial cells are deposited into deeper cornea, where

epithelial cells replicate forming a cyst with central proteinaceous material

•Treatment is by excision +/- support with a conjunctival pedicle graft (definitive diagnosis shows an

cyst lined by non-keratinizing squamous epithelium)

POSTERIOR POLYMORPHOUS DYSTROPHY

This is a multi-focal endothelial problem that has been reported in the American Cocker Spaniel

•This doesn’t case corneal oedema, rather areas of endothelial opacification

KERATIC PRECIPITATES (KP’s)

These are congregations of fibrin and inflammatory cells on the corneal endothelium following uveitis

•They adhere characteristically at the medial quadrant and are often multiple 0.1-3mm circular pale

structures

•They represent intra-ocular breakdown in the blood/aqueous barrier

•Can occur in dogs and cats

CORNEAL NEOVASCULARISATION

•Are vascular or blood associated lesions and can be termed: -

•Corneal neovascularisation

•Arborising vascularisation

•Corneal granulation

•Pannus – Bilateral immune-mediated phenomenon, starting laterally, but progressing to involve the

whole cornea. GSD, Chow Chow, Border Collie and Greyhounds are over-presented

•Corneal haemorrhage (rare as a result of damage to limbal vessels)

The limbus must be crossed for vascular in-growth

•After a 48h lag following corneal trauma vessel migration starts

•Assuming appropriate growth factor release this continues at a rate of 1mm every 24-48h

•Neovascularisation can be superficial or deep

•Neovascularisation results from inflammatory or hypoxic stimulation à release of angiogenic factors

•The source of angiogenic factors are: corneal epithelium; keratocytes; tears & infiltrating WBC (PNL

and Macrophages)

Angiogenic factors (fibroblast growth factor, IL-1, VEGF) stimulate a localized enzymatic degradation

of the basement membrane of perilimbal vessels at the apex of a vascular plexus loop à migration and

proliferation of vascular endothelial cells to form new blood vessels

•Neovascularisation represents a repair phase associated with a corneal lesion

•Once the repair has been achieved then it can be reduced with the application of: -

•Topical steroid (NaPO4 salt remains superficial i.e. MAXIDEX)

•Topical cyclosporine 0.2% (OPTIMMUNE)

PIGMENT KERATITIS

•Pigment keratitis can be superficial (epithelial) or deep (endothelial - rare)

•It is a non-specific lesion associated with chronic irritation / inflammation

•It results from the migration of melanocytic cells from the limbal and per-limbal tissues

•Deposition occurs at the basal columnar epithelial cells or anterior stroma

•Treatment can be very frustrating, however addressing underlying causes and ‘down-regulating’ the

limbus with topical cyclosporine 0.2% ointment (OPTIMMUNE) can help some cases

CORNEAL DARK OPACIFICATION

•Black opacification of the cornea can also result from the adhesion of uvea,(anterior synechiae) or

uveal remnants to corneal endothelium

•In the cat there is a specific disease entity of corneal necrosis à black plaque (1 report in the horse). If

the eye is painful removal is recommended due to the long time frame of the disease (12-18 months)

CONGENITAL CONDITIONS AFFECTING THE CORNEA

•The following congenital conditions are known to affect the cornea: -

•1. Corneal size (micro (-) or megalo (+) cornea. This may be associated with other abnormalities

•2. Dermoid: is a choristoma = normal cells / tissue in an abnormal location (Tx by surgical excision +/-

support with conj. Pedicle graft)

•3. Infantile corneal dystrophy: subepithelial, transient corneal non-inflammatory deposit. It slowly

resolves by 16wks and doesn’t require Tx

•4. Corneal opacities associated with persistent pupillary membranes

•5. Congenital oedema associated with congenital glaucoma

•6. Congenital corneal melanosis

CORNEAL MASSES

•The following neoplastic diseases have been documented at the cornea: -

•PRIMARY CORNEAL NEOPLASIA IS RARE

1.Corneal viral papilloma

2.Corneal squamous cell carcinoma

THE EYE AS A METASTATIC SITE

1.Systemic lymphosarcoma may invade cornea

2.Systemic haemangiosarcoma

EXTENSION ONTO THE CORNEA FROM LOCAL SITE IS PROBABLY THE MOST COMMON NEOPLASTIC

CONDITION

1.Conjunctival Haemangioma (CHA) / Conjunctival Haemangiosarcoma (CHSA) of the conjuctival

limbus may invade the cornea

2.Limbal melanoma may invade the cornea