Introductory Philosophy

Corneal ulcers are seen commonly in all species. Most heal with minimal veterinary intervention. Therefore, when an ulcer hasn't healed at the first recheck, there is a tendency to throw up our arms and become frustrated. This session will introduce a few "golden rules" of ulcer management, aimed at ensuring ulcers heal before that first recheck and providing a logical approach to the diagnosis and treatment of those ulcers that do not heal as expected. The goal is to turn these potentially frustrating cases into medical success stories.

The Golden Rules

1. Always find and remove the primary cause

All patients with corneal ulcers should undergo a very thorough examination aimed at determining and removing, correcting, or treating the cause. Failure to do so is one of the most common reasons for an ulcer not to heal or to heal but then recur. Because corneal epithelium is constantly being abraded and desiccated, but is protected from excess abrasion by the eyelids and tears, ulcers may be thought of, in a mechanistic sense, as arising when this situation becomes unbalanced (i.e., there is decreased corneal epithelial protection due to tear film or eyelid dysfunction, or increased corneal epithelial loss due to exogenous or endogenous causes). Therefore, causes can be divided into those explained by eyelid, eyelash, or tear abnormalities, foreign bodies, exogenous trauma, or a very limited number of microorganisms (Figure 1).

Figure 1

2. Although trauma is common, it can only be diagnosed by ruling out all other causes

Because of the long list of possible causes (Figure 1), ulceration due to unwitnessed exogenous trauma should be diagnosed only after exclusion of all other potential causes. This requires Schirmer tear testing, assessment of palpebral reflexes, thorough examination of eyelid and conjunctival anatomy and function (including the posterior or bulbar face of the third eyelid), and consideration of infectious causes. Failure to do this (and attributing the ulcer to "a scratch") makes it more likely you will break Rule #1 and that the ulcer will become chronic or progressive.

3. Other than herpes viruses (in "all" species) and Moraxella bovis (in cattle), infection does not CAUSE ulceration

Although secondary bacterial infection is the most feared complication in a corneal ulcer, no bacteria initiate corneal ulcers in small animals. In dogs and cats, the only organisms known to initiate ulcers are feline and canine herpes viruses. Failure to recognize these ulcers leads to failure to use an antiviral drug and again leads to breaking of Rule # 1.

4. Know the speed of normal corneal wound healing

Rate of corneal wound healing depends upon the corneal layer involved. Epithelial healing occurs within hours to days and should leave no long-term scar. Stromal healing requires activation of resting keratocytes into active fibroblasts and/or sometimes fibrovascular ingrowth. This may take weeks to months for a deep ulcer and grey wispy scars are expected. Endothelial cells are post-mitotic in adult animals and regeneration is extremely limited to non-existent, with persistent focal corneal oedema expected following deep ulcers. These healing rates have led to one of the definitions of a complicated ulcer (i.e., one that fails to heal within 7 days).

5. Prior to therapy, always characterize ulcers as "simple" or "complicated"

"Simple" (or "uncomplicated") ulcers, by definition, are superficial and present less than 7 days. If the ulcer fails to fit either of these criteria (i.e., it has been present more than 7 days or is deep), then it is defined as "complicated." Based upon their clinical appearance including their fluorescein staining pattern, complicated ulcers should be further defined as indolent (in dogs only), infected (in cats or dogs), or having their primary cause still present (in cats or dogs) (Figures 2A and B).

Figure 2A

Figure 2B

Each of these ulcer complications has a characteristic appearance:

 Indolent ulcers - also known as refractory or Boxer ulcers, recurrent erosions, or spontaneous chronic corneal epithelial defects (SCCEDs) - are seen in dogs only, typically boxer dogs or corgis of any age or older dogs of any breed. They are superficial, uninfected, chronic or will become chronic, and have a lip of redundant non-healing corneal epithelium that is easily debrided with a cotton-tipped applicator. This lip often produces a characteristic "halo" fluorescein staining-pattern due to leakage of stain under the non-adherent lip. They arise from a failure of replicating and migrating epithelium to complete the final step in healing - to adhere to the underlying stroma via the epithelial basement membrane. Diagnosis is reliant on characteristic signalment, chronicity, appearance and staining-pattern of ulcer, and ease with which the epithelium is manually debrided.

 Ulcers in which the primary cause is still present typically appear like simple ulcers, but remain chronic. That is, they don't necessarily worsen; they just don't heal.

 Bacterially infected ulcers have one or more of 3 features in any combination. These are stromal loss (i.e., the ulcer is deep), corneal malacia (or "melting"), or infiltration of the stroma with white blood cells (which turns the stroma yellow-green).

Treatment

Treatment of Indolent Corneal Ulcers

Grid keratotomy (GK) is the treatment of choice for indolent ulcers. The first step is removal of all redundant, non-adherent epithelium by debridement with a dry cotton-tipped applicator following application of topical anaesthetic. GK is performed following debridement. General anaesthesia or deep sedation is recommended for fractious dogs and when learning this technique. With compliant animals and an experienced operator, topical anaesthesia and good restraint or sedation are all that is required. GK is performed by making linear striations in the cornea in a "cross-hatch" or grid pattern using the tip of a 25-gauge needle. A tuberculin syringe seems to make the ideal "handle" for directing the needle. Striations need to extend from normal adherent epithelium, through the ulcer bed, and emerge in normal adherent epithelium on the opposite side of the ulcer. They must be multiple and deep enough to create visible but very shallow score marks in the corneal stroma. Medical therapy is continued as for any superficial ulcer. Unless there is coincident dry-eye, atropine should be used postoperatively to control reflex uveitis. Topically applied antibiotics are also indicated since loss of epithelium predisposes the corneal stroma to infection. Hyperosmotic (5%) sodium chloride ointment (Muro 128® and others) is recommended if corneal oedema is marked, as this may further decrease already impaired epithelial adhesion. GK may be combined with application of a soft contact lens (Acrivet http://www.acrivet.com/  or Keragenix www.keragenix.com/) and partial temporary tarsorrhaphy. This provides increased protection for the healing cornea, and contact lenses may increase surface tension via a gentle "suction-cup" effect, thereby enhancing epithelial adhesion. When a contact lens is in place, ophthalmic solutions should be used rather than ointments to improve delivery to the corneal surface and to minimize chances of dislodging the contact lens.

A success rate of approximately 80% can be expected using GK alone. Treatment failures tend to arise when patients are "under-treated" by inadequate debridement, or too few, too superficial, and/or too short score marks in the cornea. Indolent ulcers that have not healed 10–14 days after an initial GK may need the procedure repeated. GK is contraindicated in all other ulcer types in dogs and in all ulcers in cats where they are a very "reliable" means of inducing a corneal sequestrum. Indolent ulcers in dogs should probably be pre-treated for a few days with a broad spectrum, bactericidal ophthalmic antibiotic to sterilize the corneal surface before the GK is performed.

Treatment of Herpetic Corneal Ulcers in Cats

As for other viral infections, antiviral therapy is not necessarily instituted at first presentation but, rather, supportive care (topical antibiotics and appropriate analgesia such as atropine) is provided and the cat re-examined to determine if the virus will re-establish latency as before the ulcerative recrudescence. However, with severe, chronic or recurrent disease an antiviral drug is indicated. Full discussion of all antiviral drugs and their indications and contraindications is beyond the scope of this session but, in summary, I have 3 favourite choices:

1.  Topical idoxuridine is inexpensive in the USA and can be compounded as a 0.1% solution or 0.5% ointment. Like all of the antiviral drugs, it is virostatic, which means that for the time they are present on the cornea (minutes per application), they are merely "slowing down" viral replication; not killing viral particles. For this reason idoxuridine must be given very frequently, probably at least 5–6 times daily and, preferably, more often.

2.  Topical cidofovir can be applied less frequently - presumably because it or its metabolites are taken up by and stay to act as a reservoir within ocular surface epithelial cells. Cidofovir is commercially available only in injectable form in the USA, but has been studied as a 0.5% solution diluted with artificial tears (1% carboxymethylcellulose) and topically applied twice daily to cats experimentally infected with FHV-1. Its use in these cats was associated with reduced viral shedding and clinical disease. However, there are reports of its experimental topical use in humans and rabbits being associated with stenosis of components of the nasolacrimal drainage system and it is not commercially available as an ophthalmic agent in humans.

3.  Famciclovir has no antiviral activity itself, but must be metabolized in the plasma, small intestine and liver to penciclovir, which is highly effective against FHV-1. However, cats metabolize famciclovir to penciclovir very poorly compared with humans and therefore appear to require higher doses and more frequent dosing. Recent evidence shows that oral administration of famciclovir at 40 mg/kg PO TID achieves adequate penciclovir concentrations in the tears.

Grid keratotomies should never be performed in cats; however, debridement with a cotton-tipped applicator is indicated.

Treatment of Deep (Infected) Corneal Ulcers

1.  Corneal culture and sensitivity

2.  Frequent (as often as once hourly) therapy with an antibiotic with appropriate spectrum, such as tobramycin, fortified/compounded amikacin or gentamicin, or a fluoroquinolone such as ofloxacin/ciprofloxacin.

3.  I prefer solutions over ointments for deep ulcers at risk of perforation

4.  Surgery for ulcers that are rapidly progressive, have obvious areas of melting, or are deeper than half corneal thickness:

a.  Conjunctival grafts are preferred

b.  Temporary partial (lateral) tarsorrhaphy are a reasonable alternative for owners unwilling to have conjunctival grafts applied, and are performed using 3-0 or 4-0 Vicryl® on a ¾- or ½-curved, cutting micropoint needle, and 3–5 X magnification. The needle is passed through the upper eyelid skin, entering at the haired-non-haired junction approximately 3 mm from the eyelid margin and emerging just anterior to the meibomian (tarsal) gland orifices that appear as a "grey line" of small circles along the margin. Care is taken not to penetrate the conjunctiva, as this will cause suture to rub on the cornea. The suture is then continued through the lower lid entering just anterior to the grey line and emerging at the haired-non-haired junction. A mattress suture is completed by passing the needle back through the lower and then upper lids in an identical manner, approximately 5–7 mm medial to the point where the original "bites" were taken. Usually, one or two mattress sutures in this style beginning at the lateral canthus will close the lids to an extent that still permits monitoring and topical treatment, but provides adequate corneal protection.

c.  I do not recommend third eyelid flaps. They do provide a "bandage," which reduces desiccation and frictional irritation of the cornea by eyelids, but they completely prohibit penetration of medications to the cornea or observation of the disease.

5.  Frequent (as often as once hourly) topical therapy with the patient's own serum

6.  Topical atropine to effect for reflex uveitis