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					Corneal Erosion and Ulceration in the Brachycephalic Breeds Peter G C Bedford Chair of Veterinary Ophthalmology Royal Veterinary College, University of London Hawkshead Lane North Mymms Hatfield, Herts AL9 7TA Introduction Ulcerative keratitis is one of the most common ocular diseases encountered in veterinary practice and there is marked predisposition to this disease in the brachycephalic types as the result of corneal prominence and lagophthalmos. A loss of corneal epithelium and variable amounts of stroma leads to an irregular corneal surface, oedema of the surrounding cornea and, if chronic neovascularisation and/or pigmentation. A variable degree of ocular pain is present, the more superficial lesions tending to be more painful due to the relatively superficial location of sensory nerve endings within the cornea. A reflex uveitis is commonly associated with ulcerative keratitis. When irritated, trigeminal sensory fibres in the cornea initiate reflex miosis, iridocyclitis and cilary spasm. Corneal ulcers should be described in terms of their topographic location (e.g. axial, ventronasal etc.) and depth. In those cases in which there is only loss of the most superficial layers of epithelial cells, the defect is described as an erosion. Ulcers may be described as superficial stromal (anterior 1/3 of cornea) and mid- to deep stromal (>1/3 of corneal depth). A descemetocoele results from a loss of corneal stroma down to the level of Descemet’s membrane – such ulcers are at serious risk of perforation. Fluorescein dye is used to aid in the diagnosis of corneal ulceration and helps to determine the depth of lesions. Fluorescein is a lipophobic dye which will not stain corneal eptithelium or Descemet’s membrane but stains the hydrophilic corneal stroma bright green. Thus, very superficial erosions do not stain. Descemetocoeles have a characteristic pattern of fluorescein uptake with no staining at the clear base of the ulcer, surrounded by a ring of fluorescein uptake by the exposed stroma of the “walls” of the defect. Causes a) Trauma – corneal foreign bodies, lacerations.

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b)

Eyelid abnormalities – e.g. entropion, ectopic cilia, nasal fold trichiasis, neoplasia. Pre-corneal tear film disorders – exposure keratitis and KCS. Irritants – e.g. chemical burns, foreign bodies. Epthelial Basement Membrane Dystrophy – indolent ulcers in the Boxer. Immune-mediated – severe ulceration in the peripheral, perilimbal cornea is extremely rare.

c) d) e) f)

g)

Endothelial dystrophy in the Boxer breed (or old subjects) can lead to the formation of anterior stromal bullae which can rupture to mimic ulcerative keratitis. Infection – in dogs bacterial infection is usually a secondary complication in ulceration. Fungal keratitis is very rare.

h)

Basic Principles of Therapy a) b) *Identify and address the inciting case* Control infection – topical antibiotic . NB. Topical antibiotics are mildly epitheliotoxic. Ointments impair healing more than drops. c) d) Control reflex uveitis – atropine alone is usually sufficient. Create an optimum environment for healing – e.g. Elizabethan collar to prevent self-trauma, therapeutic soft contact lens, third eyelid flap etc. e) Do not use topical corticosteroids –corticosteroids retard epithelialisation, predispose to infection and potentiate the action of protease exzymes which can rapidly destroy the corneal stroma. Medical Treatment a) Superficial ulcers Superficial lesions should heal rapidly within a few days, at most, if managed medically, with no need for surgical intervention. Failure to heal within this time frame should prompt thorough reassessment of the case in order to identify and address any complicating factors. Therapy consists of topical antibiosis and occasionally 1% atropine is also utilised. b) Indolent Ulcers Also known as recurrent epithelial erosions or “Boxer ulcers”, these refractory superficial lesions (involving only epithelium +/- basement membrane) can be recognised by their characteristic appearance. These ulcers 2

are characterised by a lip of loose, underrun, non-adherent epithelium around their margins. Without specific therapy, indolent ulcers may persist for many months, with variable degrees of superficial corneal vascularisation, local oedema and associated discomfort. In the Boxer and Corgi breeds this type of ulcer appears to be due to an epithelial basement membrane dystrophy which results in production of abnormal basement membrane by basal epithelial cells and a paucity of hemidesmosomes which are responsible for their attachment to the underlying stroma. A similar clinical picture, of refractory/recurrent superficial ulceration, is relatively common in middle aged and older dogs of other breeds (including cross-breeds). This lesion should be managed by extensive debridement or keratectomy (keratotomy is much heralded, but adequate debridement should suffice). A topical broad spectrum antibiotic and a membrana flap (contact lens bandage) are also involved. (polysulphated glycosaminoglycan, apronitin and epidermal growth factor can all be used additionally as topical therapy). c) Deep Ulcers These are always a clinical challenge as corneal rupture is a possibility, especially if the ulcer is progressive or has reached Descemet’s membrane. If rapid progression is a feature, particularly if there is significant, profuse, purulent discharge, intraocular inflammation and a very cloudy ulcer bed, then bacterial infection should be suspected. Rapidly progressive ulcers with evidence of corneal liquefaction are termed “melting ulcers”. Intensive topical antibiosis should be started immediately, with frequent application (e.g. hourly). Antibiotic used should ideally be selected on basis of culture and sensitivity. Although collagenases produced by Pseudomonas have been traditionally implicated in the aetiology of melting ulcers, grampositive organisms (particularly Staphs) may be involved. Therefore, gramstained smears should also be prepared from swabs taken from the edge of the ulcer. Ciprofloxacin (Ciloxan) has good efficacy against such gram positive and gram negative organisms, however, tobramycin (Tobralex) or fortified preparations of gentamicin (e.g. 40mg i.v. gentamicin injected into 5ml bottle of 0.3% drops, after removal of appropriate volume) may be useful for specific gram negative infections and fortified preparations of cephalosporins (e.g.

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500mg cefuroxime reconstituted in 15ml artificial tears – stable 48 hours) for gram positive infections. Systemic antibiotic therapy is usually also provided and is particularly important where there is a risk of corneal perforation. Melting ulcers require the additional use of collagenase inhibitor. Protease enzymes may be produced by some bacteria, devitalised corneal epithelial cells and fibroblasts, polymorphonuclear leukocytes and possibly some fungi. Although the efficacy of collagenase inhibitors in canine ulcerative keratitis is questionable, agents such as acetyl-cysteine, disodium EDTA, herparin, sodium citrate, and cold serum or plasma (containing α2-macroglobulins) have all been advocated in the management of progressive stromal ulcers. I routinely use serum administered topically every 2 hours. Initially, after samples have been taken for microbiology, the ulcer may be cleansed with dilute (e.g. 1:2u – 1.50) povidone-iodine solution in sterile saline in order to reduce the burden of bacteria, and remove debris containing devitalised corneal cells and PMNs which may all contribute to further melting. Topical 1% atropine drops should be used “to effect” to relieve painful ciliary spasm and minimise the risk of synechia formation. In addition, parenteral NSAIDs are frequently administered. Surgical Treatment a) Debridment This is done most effectively using a scalpel blade. Keratotomy is far from essential and serial debridement should not prove necessary. b) The membrana flap This technique is reserved for the treatment of superficial corneal defects only. It is contraindicated for deep ulcers as the flap does not provide a blood supply, there is no physical support for the weakened cornea and it is impossible to monitor progression. I use 1 control mattress and 2 single interrupted sutures to suture the membrane to the dorsal bulbar conjunctiva. The sutures do not penetrate the full thickness of the membrana. Therapeutic soft contact lenses (Protex bandage lenses, Veterinary Speciality Products) are now available in a wide range of sizes to fit animal patients from 4

small cats to large horses and are useful in the management of superficial ulcers. However, they should not be used where corneal infection is suspected or where tear production is subnormal. c) The conjunctival pedical graft These are used where the ulcer has depth. The weakened cornea is physically supported and the flap has the advantage of providing an immediate vascular supply to the ulcer, bringing blood-associated immune components and growth factors, anticollagenase activity (α2- macroglobulin), and systemic antibiotics to the diseased tissue. The surgical technique is relatively simple but requires good illumination and magnification and appropriate surgical instrumentation and expertise in order to accurately place sutures in the cornea. Conjunctival pedicle grafts are also useful in the management of descemetocoeles and corneal perforations. The graft pedicle is generally transected under topical anaesthesia after several weeks. Significant scarring may result with this technique, however, vision is usually preserved around the scar. Eight months later a superficial keratectomy may remove any severe opacity. d) The conjunctival island graft Isolated conjunctival grafts which do not have blood supply. The graft simply strengthens the cornea. e) Corneoscleral (conjunctival) transposition This technique is excellent for the repair of the deep ulcer in that scarring and opacitation are minimal. f) The Autogenous corneal graft Autogenous lamellar corneal grafts are used, but the disadvantage is that this weakens the donor site. Frozen or fresh cornea may be preferable. Other treatment modalities a) Chemical debridement – iodine, phenol etc. Damage to normal tissue and post operative discomfort are the obvious disadvantages. b) c) d) Collagen shields Cyanoacrylate tissue adhesives “glue” Multiple punctate or grid keratotomy. These techniques increase the surface area for epithelial adhesion.

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e)i)

Fibronectin – a plasma glycoprotein which promotes epithelial attachment (it is in serum) Epidermal growth factor – enhances epithelial regeneration Apronictin – inhibits plasmin (high levels found in indolent ulcers).

ii) iii)

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