Peter G.C. Bedford, BVetMed, PhD, FRCVS, DVOphthal, DECVO, ILTM
Ulcerative keratitis is a major ocular disease entity, its common occurrence and the inherent difficulties met in its treatment assuring its significance in both the canine and feline species. Aetiologies may vary but there are common denominators in both the principles of treatment and the disastrous outcome which can occur only too frequently.
In corneal ulceration there is a loss of epithelium plus varying amounts of stroma. A progression of superficial ulceration through deep ulceration to descemetocele formation and corneal rupture with uveitis and possible endophthalmitis can occur. The aetiology is complex, but trauma, collagenase activity and bacterial/viral infections are obvious therapeutic considerations. Mycotic infection is not a feature in the U.K.
Specificity in diagnosis is always required and the following features will be recognised.
1. Pain--witnessed by excessive lacrimation, photophobia and blepharospasm
3. Corneal oedema around the ulcer site
4. Vascularization--usually superficial, but it can be deep too. The presence of granulation tissue indicates repair attempts by second intention
5. Descemetocele formation
6. Fluorescein staining
The diagnosis of corneal ulceration is usually quite straightforward and the use of fluorescein should be routine in any patient presenting with anterior segment pain. Blepharospasm may complicate the examination procedure but a topical analgesic agent usually allows adequate examination of the cornea. Superficial ulcers may/may not be seen with the naked eye, but the use of the biomicroscope or the +12d lens of the direct ophthalmoscope is helpful and the uptake of the fluorescein by the denuded stroma is easily noted. A variable degree of ocular pain accompanies corneal ulceration. Superficial lesions are more painful than deep because the sensory nerve endings are within the epithelium. A reflex uveitis can accompany ulceration, trigeminal feedback initiating iridocyclitis, miosis and ciliary spasm. Its presence contributes to the overall discomfort or pain.
The location of the ulcer site may say something about its aetiology. Central ulcers are usually associated with exposure or trauma whilst ulceration of the nasal quadrants suggests entrapped foreign bodies behind the membrana nictitans. Ulceration associated with eyelid abnormalities (distichiasis, entropion) can be confined to the peripheral areas of the cornea. Limbal ulceration is rare, and is immune mediated.
Uncomplicated superficial ulcers should heal rapidly within a few days at most if managed medically, and there is 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. There are three important considerations:
A. - Identify and remove/correct the cause
The common causes include:
1. Trauma--lacerations, foreign bodies.
2. Eyelid abnormalities--entropion, ectopic cilia, trichiasis, lagophthalmos.
3. Precorneal tear film disorders, particularly KCS.
4. Irritants--chemical burns.
a. The primary agents are viral (FVH1 in cats).
b. Bacteria are usually secondary contaminants.
c. Fungal infections are rare in the U.K.
6. Epithelial dystrophy
7. Immune-mediated ulceration--severe, perilimbal ulceration that is rare.
B. - Treat established or potential infection
It is usual to use a broad spectrum antibiotic initially and to run sensitivities to select the specific antibiotic where indicated.
C. - Create a healthy environment
1. Prevent self trauma and contaminant infection :
a. Elizabethan collar
b. Contact lens bandage
c. Membrana flap
d. Topical antibiosis
2. Relieve pain and discomfort atropine (reflex uveitis)
a. Possible use of systemic NSAIDs
Treatment involves both medical and surgical considerations. Antibiosis, atropine, antiproteases, wetting agents, the membrana nictitans flap and conjunctival flaps are the common therapies utilised.
N.B. topical corticosteroids are only used once epithelialisation has occurred (check with fluorescein). Their use during ulceration slows epithelialisation and potentiates collagenase release.
A small superficial ulcer which is not infected should heal within days once the cause has been identified and removed, but self trauma can complicate the picture. Elizabethan collars can help prevent this damage, and the use of a corneal lens bandage or a membrana flap will render the patient comfortable. The refractory ulcer and the recidivistic corneal erosion will require surgical debridement to remove all the necrotic and devitalised tissue and a lens bandage or the use of the membrana flap is again advocated. Grid or punctate keratotomy is suggested as a way of enhancing re-epithelialisation too. Deep ulceration always presents the clinician with difficulty for rupture is always a possibility. Intensive medical therapy is required where bacterial infection is suspected or confirmed. Fortified topical antibiotic preparations are usually required. Ciprofloxacin (Ciloxan) is useful against Staphs and Pseudomonas, but tobramycin (Tobralex) or fortified gentamicin (40mg i/v gentamicin into 5ccs of 0.3% drops) is useful for specific gram (-)ve infections. Fortified Cephalosporin (500mg Cefuroxime in 15ml hypromellose) is good for gram (+)ve infections (stable for 48 hrs). The membrana flap is contraindicated - there is no physical support and the inability to observe the ulcer site dictates strongly against its use in this situation. Again the corneal lens bandage is best used only where the ulceration is superficial. Cyanoacrylate adhesives (Histoacryl : Braun) can be used for deep ulceration and descemetocele treatment, but care is the requirement with their use. A thin layer is used to cover the defect, for excessive deposits cause possible necrosis as the result of toxicity. By and large the use of a conjunctival flap usually proves essential in providing the cornea with support and vascularisation. Several flaps are possible, but the author favours the use of a pedicle flap with the conjunctiva being lifted from the dorsal bulbar region of the eye and sutured directly into the ulcer site. The flap strengthens the cornea and seals the anterior chamber should rupture occur. It brings a blood supply and with it collagenase inhibition. The base of the pedicle is transected after three weeks or when healing is well established. Alternatively a free graft of bulbar or membrana conjunctiva can be sutured directly into the ulcer site but this lacks a blood supply to maintain its viability. With both techniques there may be considerable scarring but rupture will be prevented and sight will be preserved. Superficial keratectomy 8 or 9 months after the repair can help restore corneal transparency should the scar be large. Descemetoceles should be treated in the same way and rupture usually requires the removal of the prolapsed iris and corneal suturing will be necessary.
Systemic antibiotic therapy can be provided and is particularly important where there is a risk of corneal perforation.
Anticollagenase therapy is essential to treat melting ulcers, where there is progressive dissolution of the corneal stromal collagen by proteases. 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, heparin, sodium citrate, and cold serum or plasma (containing µ2-macroglobulins) have all been advocated in the management of progressive stromal ulcers. Initially, after samples have been taken for cytology and microbiology, the ulcer may be cleansed with dilute (e.g., 1:20-1:50) 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.
In all ulcer situations the possible complication of uveitis should always be considered and therapeutic measures taken. Topical 1% atropine relieves ciliary spasm and reduces the risk of posterior synechiae formation. Systemic NSAIDs are also used.
Corneal epithelium loves to repair and it will do so very rapidly given the right kind of environment. It is the loss of stromal tissue and the associated activity of collagenase and protease enzymes which complicate the simple ulcer and can lead to rupture and loss of eye. Collagenase inhibition is a significant part of therapy and the use of the conjunctival pedicle flap will often turn potential disaster into success.