This presentation is intended to familiarize the clinician with the general medical concepts necessary for treating superficial corneal ulcers. Then, selected and unique types of superficial ulcers that require additional specific treatments will be discussed.
General Key Points
Corneal ulcers are among the most common causes of a red and painful eye in domestic pets, and several distinct ulcerative conditions are encountered. Ulcers are most easily classified as either superficial or deep, and complicated or uncomplicated. Complicated ulcers are those that are infected, progress deeply in the cornea, or for which the inciting cause has not been eliminated. Common causes of corneal ulcers in dogs include trauma, dry eye, conjunctival foreign bodies, entropion, and distichia or ectopic cilia hairs. If the cause is not clear, the eyelids and conjunctival fornices (including behind the third eyelid) should be inspected closely for frictional irritants or foreign material. In dogs especially, an assessment of the blink reflex and tear function should be performed routinely. Herpesvirus infection is the most common cause of corneal ulcers in the cat. Aerobic bacterial culture and/or corneal cytologic examination should be performed for rapidly progressive ulcers, or if infection is suspected, to determine the most appropriate antibiotic. The principles of medical treatment are similar for both superficial and deep ulcers. It is primarily the frequency of treatments that change (e.g., TID for a superficial and non-infected ulcer versus hourly for a deep and infected ulcer).
Key Clinical Diagnostic Points
Corneal ulcers are detected by application of fluorescein stain to the eye(s), and excess stain is gently rinsed from the eye using sterile irrigation solution. Using a Finoff transilluminator (Welch-Allyn #41100) and cobalt light filter (Welch-Allyn #41102) for examination, ulcers will appear as a fluorescent green. Three staining patterns are generally recognized:
1. Superficial or stromal ulcers will stain a homogenous green. Ulcers may be circular, irregular, linear, or any combination thereof. Interpretation of depth is subjective by the examiner.
2. A “crater-like” defect that retains stain at the periphery and is clear at the center suggests a descemetocele, as Descemet’s membrane does not retain fluorescein. Descemet’s membrane may be seen bulging anteriorly.
3. A “crater-like” defect which pools stain transiently, but from which stain is easily rinsed, suggests a prior deep ulcer which has re-epithelialized. Such a defect is called a facette and must be distinguished from a descemetocele.
Key Clinical Diagnostic, Etiologic and Pathophysiologic Points
Uncomplicated superficial ulcers will usually heal in about 5-7 days. The cause should be determined when possible, and if still present, it should be corrected. Topical antibiotics and atropine, and oral analgesics, are usually sufficient for therapy. With the exception of refractory ulcers, superficial ulcers do not usually require surgery.
Refractory Ulcers (also Boxer, Indolent, or Recurrent Erosions)
A refractory ulcer is a unique type of superficial ulcer that is frustrating for veterinarians and clients alike. These ulcers are typically chronic, superficial, non-infected (except feline herpesvirus), and minimally to moderately painful. Most are characterized by redundant corneal epithelial edges and, at least in the early stages, an absence of corneal vascularization. Boxers, especially, that have had one of these ulcers for several weeks can have profound corneal vascularization. Refractory ulcers are believed to represent an epithelial/basement membrane corneal dystrophy. Client education is very important, as weeks or months may be required for these ulcers to heal (if surgery is not performed). A refractory ulcer should be suspected if a superficial ulcer persists for more than 7-10 days and no cause for the ulcer is identified. Any dog breed can be affected, and affected dogs are usually middle-aged or older.
Historically, there have been many different recommended treatments for these ulcers. In addition to standard antibiotic and atropine treatments, treatment recommendations have included corneal debridement, chemical cautery (e.g., trichloracetic acid, tincture of iodine) to disrupt the corneal basement membrane and stimulate vascular ingrowth, hyperosmotic agents (e.g., 5% sodium chloride), topical growth promoters (e.g., epidermal growth factor, serum, etc.), application of soft contact lenses or collagen shields, and surgery including a third eyelid flap, punctate or grid keratotomy, or superficial keratectomy. Cats with refractory ulcers may have concurrent herpesvirus infection, and antiviral therapy may then be indicated.
Corneal Debridement
The conventional wisdom is that once a patient is determined to have a refractory ulcer, the loose epithelial edges should be removed to facilitate healing. I perform epithelial debridement as the first step for all refractory ulcers. One study indicated that canine refractory ulcers will heal about 40% of the time after this procedure alone. My experience is that if an ulcer debrides discreetly (i.e., remains relatively small with well defined borders), there is a reasonable chance it will heal with this procedure alone. If much or most of the corneal surface débrides (typical of a Boxer), then you are best to proceed with a keratotomy procedure (see below), as such an ulcer is unlikely to heal with debridement alone.
Contact Lenses
Therapeutic contact lenses act as a bandage to both reduce frictional irritation from the eyelids and reduce pain sensation. They can usually be applied after application of topical anesthetic, and they allow continued visualization of the eye. Determining the proper size for an individual animal comes with experience. If the proper size is not selected, the lens is easily displaced from the eye. The cost is about $13-15/lens. Contact lenses with different diameters (14-19 mm) and base curvature (8.3-12 mm) are available for use in both dogs and cats. Contact lenses with a shorter radius of curvature (i.e., more curved) may provide a better fit for small breed dogs. Lenses can be ordered from Keragenix, Inc. by calling 1-888-521-2020 or by visiting their website at www.keragenix.com.
Absorbable Collagen Patches
These are made of porcine collagen derived from small intestine (Vet BiosistTM, www.globalvetproducts.com or 1-800-410-2711) or urinary bladder (ACell Vet, 1-800-826-2926). They provide a structural matrix for healing, are absorbed into the cornea, and have been advocated for treatment of refractory ulcers as well as deep ulcers. The theory for their use is sound, but they must be sewn to the cornea or held in place by a third eyelid flap. The keratotomy procedure can be performed more quickly, so I do not use collagen matrix for treatment of refractory ulcers.
Keratotomy
In my opinion, keratotomy is the procedure of choice for treatment of refractory (or indolent) ulcers in dogs. This procedure is only intended for the treatment of superficial and non-infected ulcers. It is not recommended in cats, as it may predispose to formation of a corneal sequestrum. Superficial punctate keratotomy (SPK) or grid keratotomy (GK) is performed following debridement of loose corneal edges with a sterile cotton-tipped swab. General anesthesia is recommended for fractious dogs or the first few times this technique is performed. In compliant animals, topical anesthesia and good restraint or sedation are all that is required. In most instances, I administer intravenous butorphanol (0.2 mg/kg) combined with a needle hub of acepromazine. For SPK, multiple superficial punctures of the anterior stroma are made with the tip of a 22 or 25 gauge hypodermic needle applied perpendicular to the surface of the cornea. Deep corneal penetration is to be avoided, and sufficient force is applied to the needle to indent the cornea only slightly. The punctures are made at about 1.0 mm distances from one another throughout the ulcer bed and overlapping normal cornea for 1-2 mm. SPK is too risky for use in most awake animals, so GK is then preferred. This is performed by making linear striations in the cornea in a “cross-hatch” manner using the tip of a 25 gauge needle. I use a tuberculin syringe as a handle with a 25 gauge needle attached, and I drag the needle across the cornea at about a 30 or 45 degree angle. For either SPK or GK, the needle can be secured in a hemostat in such a manner as to limit the depth of corneal penetration, but I find this to be unnecessary. The SPK procedure seems to cause less corneal scarring than the GK.
Punctures or linear striations in the superficial stroma are believed to facilitate epithelial attachment as the ulcer heals. Medical therapy is continued as for any superficial ulcer, and SPK or GK may be combined with another procedure (e.g., contact lens, third eyelid flap, etc). One study indicated a cure rate of approximately 75% using the technique of GK alone. At my clinic, our healing rate after a single keratotomy is about 95% within 10-14 days. An occasional pet may require a second minor “touch-up” procedure.
Miscellaneous Surgery for Refractory Ulcers
After keratotomy, the surgical procedure most commonly performed for treatment of refractory ulcers is probably the third eyelid flap. It serves as a protective bandage and reduces frictional irritation of the eyelids on the cornea (similar to a contact lens). The only time that I perform a third eyelid flap is if general anesthesia is required to perform the keratotomy; I may then place a third eyelid flap on the eye to facilitate healing. Lamellar keratectomy is curative in most cases, but special instrumentation and magnification are required, and it is unnecessary for most pets. Conjunctival flaps will heal these ulcers, but scarring is more pronounced, and the procedure is usually not necessary. Thermal cautery (or thermokeratoplasty) has also been advocated for indolent ulcers, but there is greater risk to injury of the eye using a cautery unit, and the keratotomy procedure works equally well for a majority of dogs with refractory ulcers. The one exception is dogs that have refractory ulcers and concurrent corneal endothelial dystrophy (see below, where thermal cautery may be preferred.
Herpetic Keratitis
As mentioned before, herpesvirus is the most common cause of corneal ulcers in cats. The clinician should have no hesitation about prescribing a topical antiviral drop, notably idoxuridine. Ulcers may occur in young cats or kittens with concurrent upper respiratory disease, but in adult cats, respiratory disease is usually absent. It is often unilateral in adult cats. Two types of keratitis are observed; the ulcerative form is due to direct cytopathic effects of the virus, whereas the non-ulcerative form (stromal keratitis) is believed to be an immune-mediated reaction against viral antigen (refer to section notes on Non-Ulcerative Corneal Disease).Ulcers may be linear or branching (i.e., dendritic), or they may be larger and map-like (i.e., geographic). The type of ulceration may differ between the two eyes. Dendritic ulcers are considered pathognomonic for herpesvirus infection, but they are uncommonly recognized. Special staining of the eyes with rose bengal is often required to detect dendritic ulcers, though they can be seen with fluorescein and magnification. It is unusual for herpetic ulcers to progress deeply unless secondary bacterial infection occurs or they go undiagnosed for an extended period.
Immunofluorescent antibody (IFA) or polymerase chain reaction (PCR) tests can be performed in an attempt to confirm herpesvirus. However, cats often respond to empirical antiviral therapy despite negative IFA or PCR test results. A prior study indicated that some cats with normal eyes are PCR-positive for herpesvirus, whereas other cats with known herpesvirus are often PCR- negative. For this reason, I almost never perform diagnostic tests for FHV, as the clinical assessment is more reliable.
Cats with FHV seem particularly susceptible to stress, and a stressful event can often be identified as having occurred prior to the ulcer. Common stresses that can precipitate herpetic ulcers include the client having been gone on a trip, recent acquisition of a new cat (though the new cat has no eye disease), a recent visit to the veterinarian for dental cleaning, etc., and recent administration of steroid (any route), or topical NSAIDS. I see several cats each year that have been treated for anterior uveitis with either topical steroid or NSAIDs, and if treatment is required for several weeks, they develop herpetic ulcers. Recrudescent infection occurs because most cats already have the virus.
Corneal Endothelial Dystrophy
The corneal edema associated with this condition can cause refractory ulcers in advanced cases. Hyperosmotic treatment with sodium chloride ointment or suspension may facilitate healing and slow progression of the disease. Because of the underlying pathology, the SPK and GK procedures are less effective for treating these ulcers. Thermal keratotomy may be preferred. This procedure involves making multiple superficial corneal stromal burns using a disposable ophthalmic cautery unit. Surgical discretion is advised because the cornea can “melt like butter” under the heat of the cautery unit. In some cases, conjunctival grafts or penetrating keratoplasty (corneal transplant) may be required. Refer to the section notes on Non-ulcerative Corneal Disease for a more detailed discussion of this condition.
Punctate Keratitis
This is a relatively uncommon condition for which the Dachshund appears predisposed. Punctate keratitis appears to be immune-mediated, and this is the one instance of corneal ulceration where topical steroids are indicated. Affected eyes usually have multifocal punctate corneal opacities that retain fluorescein stain, and one or both eyes can be affected. Topical cyclosporine drops or ointment may be effective in treating some of these patients, but I have more consistent results using topical steroid. I will usually use a neo-poly-dex preparation BID-TID, and once a response is noted, the frequency of administration can be reduced to a maintenance level.
Sheltie Corneal Dystrophy
This condition has an obvious breed-predilection for the Sheltie, and the cause is unclear. Affected dogs have multifocal circular opacities of the cornea, many of which may retain fluorescein stain. Secondary lipid degeneration may occur. It can appear very similar to immune-mediated punctate keratitis, and may respond similarly to treatment. However, topical steroid should be used cautiously in these dogs, as their response to steroid is less predictable than in immune-mediated punctate keratitis. Also, my experience is these dogs develop much more corneal scarring and opacity over time if the disease is not controlled. Affected eyes may have marginal tear production and reduced tear film breakup times, but overt dry eye is not a feature of this disease.
Qualitative Tear Deficiency
This can be a difficult condition to diagnose. It should be suspected in any dog (or cat) that has a history of chronic recurrent corneal disease, including ulcers, in the absence of an obvious cause. It should be considered in cats with chronic ulcers that do not improve with topical antiviral treatments. Tear production (or quantity) is normal, and affected animals may have epiphora. With qualitative tear abnormalities, the tear lipid or mucin components are defective, and aqueous tear does not stay on the eyes for normal durations. This results in corneal pathology similar to dry eye (i.e., vessels, pigment, and ulcers). Tear lipids are produced by the meibomian glands, whereas tear mucin is produced by conjunctival goblet cells. The eyelid margins and meibomian gland openings should be scrutinized for focal swellings or inflammation, as marginal blepharitis (or meibomianitis) would be consistent with a lipid abnormality.
Tear film breakup times can be used to facilitate diagnosis of mucin tear deficiency, but magnification is required. When a drop of fluorescein is applied to the eyes with irrigation solution or saline, it forms a homogenous layer over the corneal surface for a specified period of time, prior to breaking up in patches. This can be observed using a cobalt light and some form of magnification. Mean tear film breakup times in dogs are about 19 seconds, but mean normal values are not reported for cats. Tear film break up times are usually less than 5-7 seconds in affected eyes of both dogs and cats. If the condition is due to mucin deficiency, diagnosis can be confirmed by conjunctival biopsy to enumerate the conjunctival goblet cells. Normal goblet cell numbers at selected biopsy sites have been established for both dogs and cats. Fortuitously, in dogs, topical cyclosporine is beneficial for treatment of this disorder, as it is for primary dry eye. Cyclosporine will improve numbers and health of conjunctival goblet cells. Less is known about the benefits of cyclosporine treatment for cats, and topical cyclosporine could cause recrudescent FHV infection. Mucinomimetic tear preparations are those that simulate tear mucin, and these are recommended for treatment of affected animals. Mucinomimetic tear preparations often have a dextran or povidone base, and more viscous substances such as sodium hyaluronate also have mucinomimetic properties. Recommended products include longer acting hyaluronate-containing preparations such as HylashieldTM or i-drop VETTM (I-MED Pharma, Inc.), or solutions that can be obtained over-the-counter at any pharmacy including Tears PlusTM, Tears NaturaleTM, RefreshTM, Moisture DropsTM, etc. If a lipid deficiency is suspected, then an artificial tear ointment containing mineral oil and petrolatum may be preferred. Common brand names include Refresh PMTM, Lacri-LubeTM, DuolubeTM, Hypo TearsTM, etc.
Key Therapeutic Points
Antibiotics
Topically applied antibiotics are indicated in the treatment of all corneal ulcers. Disruption of the corneal epithelium makes the cornea susceptible to microbial infection. The frequency of antibiotic application is determined both by the severity of the condition and the preparation used. Ointments have a longer contact time and should be applied TID to QID, whereas solutions require more frequent application (e.g., 6-8 times daily) in initial therapy. The choice of antibiotic to use for a superficial and non-infected ulcer is based largely on the clinician’s personal preference. The thought that ointments delay corneal healing compared with solutions (drops) is outdated and of minimal significance. Similarly, the thought that chloramphenicol should be used because it penetrates the eye best is outdated. The corneal epithelium is the main barrier to penetration of drugs, so most antibiotics penetrate the cornea when an ulcer is present. Additional criteria to consider when selecting an antibiotic include the most likely offending organism, the client’s ability to apply drops versus ointment, concurrent dry eye (i.e., ointments lubricate and last longer), prior sensitivity to certain antibiotics (e.g., neomycin sensitivity), and culture or cytology results, if available. Antibiotics in common usage include oxytetracycline/polymyxin (Terramycin®), erythromycin, triple antibiotic (neomycin/polymyxin/bacitracin), gentamicin, and tobramycin (Tobrex®). Triple antibiotic is an excellent first choice for treatment of superficial or non-infected ulcers because it is broad-spectrum. The drops are somewhat expensive, but the ointment is economical. I will also commonly use tobramycin, as an inexpensive generic version is now available. It has long been argued that certain antibiotics, notably gentamicin, can delay healing of indolent or refractory corneal ulcers, so other antibiotics may be preferred. My personal opinion is this concept has been overstated.
Atropine
Atropine 1% ointment or solution is used to treat the “reflex anterior uveitis” that occurs with corneal ulcers, where its primary benefit is the reduction of pain. Atropine mydriasis will also reduce the potential for posterior synechia formation that may occur with severe concurrent uveitis, though severe uveitis is not typical of most superficial ulcers. It should be used at a frequency sufficient to effect mydriasis (usually SID or BID) followed by gradual reduction. Atropine should be used sparingly, if at all, for ulcers associated with keratoconjunctivitis sicca (KCS) or dry eye, as atropine will further compromise tear production. A Schirmer tear test should be performed if KCS is suspected as causative of the ulcer. Periodic tear tests may be indicated if atropine is to be used for an extended period of time. Atropine is contraindicated if concurrent elevation in pressure (i.e., glaucoma) is suspected.
Antiviral Agents
Antiviral agents are indicated in the treatment of herpetic ulcers. In my clinic, a cat with a corneal ulcer has feline herpesvirus (FHV) until proven otherwise. One study comparing the efficacy of antiviral drugs against FHV showed that trifluridine > idoxuridine > vidarabine > acyclovir. Idoxuridine 0.1% solution is usually effective and is much less expensive than trifluridine (Viroptic®), so idoxuridine is my first choice. Idoxuridine is no longer commercially available, but it can be obtained from a compounding (I use Wedgewood in New Jersey at 1-800-331-8272, or the Prescription Center in North Carolina at 1-800-682-4664). Antiviral drops should be applied 4-6 times daily until clinical improvement is noted, then the frequency should be gradually reduced. I typically continue antiviral drops at a low frequency (e.g., BID) for 1-2 weeks after clinical signs have subsided. Trifluridine can be obtained by prescription at most pharmacies, but it is very expensive (about $100 for a 7.5 ml bottle), it requires refrigeration, and some cats are very irritated by it.
Oral L-lysine is an amino acid that has antiviral effects when administered at 250 or 500 mg PO BID. It appears safe for extended usage (or even maintenance treatment) in cats, and it may be useful to prevent recrudescent infections. Only recently have palatable commercial L-lysine preparations become available for veterinary use. These preparations are available as a power or gel (Viralys®, VET Solutions) or as an ointment (Enisyl-F®, Vetoquinol N.-A. Inc.). It is generally considered that L-Lysine will lessen the severity and duration of an infection, but during active infections, I use it concurrently with topical antiviral drops. L-lysine by itself would probably not be sufficient to resolve most FHV infections.
Analgesic/Anti-inflammatory Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) are useful both for their anti-inflammatory and analgesic properties. In dogs with corneal ulcers, I routinely use oral Rimadyl® or Metacam® at standard dosages. In cats, I have often used aspirin at 10 mg/kg q48 hrs. The FDA has recently approved Metacam® for use in cats, and this may be preferable to aspirin.
In animals with especially painful eyes, I will also prescribe tramadol (Ultram®) at 2 mg/kg PO BID in dogs, or at 1/4 of a 50 mg tablet PO BID in cats. Tramadol can be obtained with or without acetaminophen, so care must be taken to ensure the pharmacist provides the correct drug.
Systemic corticosteroids can be judiciously used to treat severe concurrent uveitis if the corneal wound is non-infected (e.g., after corneal laceration repair). However, they will impede the vascular ingrowth that may be required for healing of deep stromal ulcers. I only use systemic corticosteroids after corneal laceration repair and favor oral NSAIDs for uveitis related to other types of ulcerative keratitis. Topical corticosteroids are contraindicated in the treatment of corneal ulcers because they predispose to infection, delay corneal healing, and potentiate enzymatic destruction of the cornea. Topical NSAIDs such as flurbiprofen (Ocufen®) and diclofenac (Voltaren®) will delay corneal healing somewhat but are less deleterious that topical steroids. Their routine use is not warranted in treating canine ulcers, and they should not be used for treating feline ulcers, as they potentiate herpesvirus.
Overview and Summary of the Issue
Superficial corneal ulcers are usually easily diagnosed, and their treatment is usually straightforward. However, for the occasional pet (or ulcer) that proves problematic, knowledge of a few selected superficial ulcerative conditions discussed herein should enable the clinician to successfully resolve the ulcer.
Erosions and Superficial Corneal Ulcers
Western Veterinary Conference 2006
B. Keith Collins, DVM, MS, DACVO
Animal Eye Specialists, LLC
Waukesha, WI, USA
