CORNEAL WARS: A NEW HOPE, CORNEAL WARS: OPACITY STRIKES BACK, CORNEAL WARS: RETURN OF THE TRANSPARENCY GUY CLARE

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1 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

2 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: 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

3 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)

4 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

5 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

6 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

7 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

8 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

9 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

10 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)

11 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

12 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

13 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)

14 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 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

15 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

16 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).

17 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

18 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

19 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

20 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

21 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: 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

22 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

23 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)

24 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

25 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