The cornea is the most exposed and most commonly injured structure of the equine eye.
The cornea is the most exposed and most commonly injured structure of the equine eye.
The corneal epithelium consists of eight to 12 cell layers and may be damaged by trauma, excessively drying from inadequate tear coverage, exposure to ultraviolet light or be infected directly with bacteria, fungi or viruses. The tear film is the first ocular defense, lubricating, flushing and carrying immunoglobulins from the lacrimal glands. The corneal epithelium is the second, and provides a complete cellular barrier to separate the external environment from the thickest corneal layer, the largely acellular corneal stroma immediately beneath.
Photo 1: Histopathology of an abscess. The normal acellular corneal lamellae are devastatingly interrupted by this violent war in a microcosm. Vessels, inflammatory cells and organisms cause a dense corneal opacity, which will ultimately become fibrous tissue.
The normal equine cornea is approximately 1 mm (0.04 inches) thick, becoming slightly thinner toward the center. On the inner aspect, Descemet's membrane is a specialized basement membrane that supports the corneal endothelium. The highly specialized corneal endothelial cells border the anterior chamber and, in part, control corneal hydration.
Corneal transparency is related to the exact spacing and parallel orientation of collagen fibrils, a relative state of deturgescence (or dryness), the presence of very few cells (keratocytes and fibrocytes) within the stroma and the absence of corneal vessels and pigmentation. Corneal clarity is lost when these features are altered, which may occur with many corneal injuries, but especially with damage to the stroma.
Uveitis, or inflammation of the uveal tract, is a general response to ocular injury. It may be extensive and severe in the horse with even a relatively minor corneal lesion, and rapidly becomes a major determinant of whether the eye will be visual at the conclusion of the treatment. Early control of uveitis is important, because after complications occur (synechiae, cataract, retinal detachment), they are difficult to control or reverse. If uveitis becomes established it may persist and result in chronic irritation and ultimately in phthisis bulbi (or shrinkage) of the globe.
A corneal abscess (Photo 1) may be identified as a dense opaque mass within the corneal stroma. An abscess is technically a specific cellular response localizing an infectious process and sealing it. In the cornea, its use may be broader and applies to leukocytes accumulating around a presumptive infectious agent. The coloration is typically tan-yellow rather than white or gray, although it may vary.
Photo 1: Corneal stromal abscess. The opaque tan-white area with no fluorescein retention is typical of this lesion. Intact corneal epithelium seals the abscess within the stroma.
In the earliest stages the abscess will be small and irregular with poorly defined hazy edges. The adjacent cornea is often edematous and therefore blue-gray. Small satellite abscesses may appear nearby. Abscesses may be located near the limbus or in the center of a clear cornea.
Stromal abscesses that are identified later in their clinical course may be overwhelmed by vascularization, and the reason for their identification at this stage is a substantial worsening in keratitis and uveitis, which occurs abruptly when the abscess contents are exposed to the immune system via the blood vessels. Vessel perfusion often appears as an intense crimson wave enveloping the ulcer. Some fungal abscesses actually secrete anti-angiogenic factors, and in those situations the vessels will rapidly approach but not invade the abscessed area.
Photo 2: Corneal scar subsequent to partial thickness corneal transplant, 10 weeks post operative. Patient was healed (stopped medications) at 24 days after surgical removal of abscess. Compare to Figure 1, which is the abscess at presentation.
Corneal stromal abscesses may be infected or sterile. The majority appear to begin as a corneal ulcer, which epithelializes and seals infectious agents (and leukocytes) within the stroma. Organism proliferation occurs within this closed environment, limiting direct access by components of the immune system. Some abscesses may occur as a result of systemic delivery, although it appears that this form is rare in horses.
Abscesses near the corneal limbus are perhaps more likely to result from systemic agents. Bacteria are probably the most common cause of abscesses in general. However, if the abscess is deep within the stroma, or involves the corneal endothelium and Descemet's membrane, it is most likely to be fungal in origin.
Fungi have an affinity for the basement membrane (more collagen type IV), and appear to be able to grow there almost without restriction. From a histopathological perspective, there are numerous degenerate neutrophils together with macrophages and in-growth of numerous blood vessels (Photo 1, p. 8E).
Organisms may be difficult to see, or be overwhelmingly numerous. Fungal hyphae are best identified with special silver stains, and are readily seen near Descemet's membrane. Some abscesses appear sterile histopathologically and microbiologically, but whether they were never infected or were originally septic and then resolve, is unclear. The severity of the uveitis is more readily understood when a normal corneal section is compared to an abscess lesion histologically, and the inflammatory response is observed (Photo 2). Our opportunity to improve the outcome, save vision and hasten healing is to understand and redirect these pathophysiological processes in our favor.
Clinically, another condition occurs rarely but appears almost identical to a stromal abscess. It is termed non-ulcerative keratouveitis (NKU). A distinguishing feature is that NKU is dominated by the uveitis rather than the keratitis, and afflicted patients appear tremendously uncomfortable. NKU lesions are near the limbus and tend to be deep within the cornea. The clinical and biological appearance of NKU and a late-stage stromal abscess may be confusing. In each, inflammation is the dominant process, and its control is critical. Referral is indicated when such cases are suspected.
Medications are selected based on abscess location, severity of the lesion and underlying uveitis. For most abscesses, we favor topical antimicrobial therapy alone. Antibiotics of choice include chloramphenicol (bacteriostatic, good epithelial penetration) and neopolygram (bactericidal, poor penetration).
Culture and cytology are warranted if the abscess is accessible, but typically it is sealed beneath more normal cornea. If an epithelial defect is present concurrently, then any bactericidal topical antibiotic may be selected. When the cornea is fluorescein negative, chloramphenicol is preferred because as the keratitis resolves it will continue to penetrate to the stroma.
Oral antibiotics will not access the lesion unless it is well perfused; consequently they are infrequently indicated. Topical antifungals pose more difficult selection criteria. Natamycin® is the drug and formulation of choice, but is expensive. The majority of fungal isolates are sensitive, and it may achieve fungicidal concentrations. The azoles are much less expensive, but the lack of commercial ocular formulations reduces ocular penetration and fungal sensitivity is not as good. Fluconazole is often a poor choice, because many isolates are resistant.
Topical itraconazole-DMSO combinations are favored by some, and may be useful. Topical miconazole is readily available, and many isolates are sensitive. Oral antifungal therapy may be useful, particularly where vessels penetrate the abscess, or the blood-ocular barrier has been breached and will allow entry of the drug into the aqueous humor. Itraconazole (3 mg/kg PO BID with food) is my preferred drug, and may promote a dramatic turnaround of very severely infected corneas. Oral itraconazole is compounded as a suspension but has limited availability [Wickliffe Pharmacy, Lexington Ky., (859)389-7470]. Superficial and proliferative fungal plaques that protrude above the corneal surface will heal faster with a keratectomy to debulk the massive organism load prior to medication. Topical povidone iodine (Betadine®) applied as a 0.5% solution is fungicidal, but may be quite irritating to the conjunctiva. It may be used to supplement therapy, and I use it after a keratectomy on the newly exposed surface of the corneal lesion.
Blindness is the most likely outcome if uveitis is not adequately controlled. Complications of uveitis include synechiae (attachments of iris to other intraocular tissues), condensation of fibrinous membranes or overgrowth of iris vessels to completely occlude the pupil, corneal endothelial opacification and/or fibrosis, glaucoma, retinal detachment and, ultimately, hypotony and globe shrinkage. Chronic and intractable mild to moderate pain may also result. Early and complete control of the uveitis yields the best outcome.
Mydriasis and cycloplegia (paralysis of ciliary muscle) are the major effects of atropine. Ciliary spasm results from a reflex neural pathway and is tremendously painful. Cycloplegia typically is achieved only at a higher drug concentration than mydriasis; thus, incomplete mydriasis probably means insufficient cycloplegia. I prefer the pupil to be totally dilated until the infectious stages of keratitis are resolved, and do not permit the pupil size to oscillate. This may require atropine use four times (or more) per day; under such conditions it is preferable to hospitalize the patient and monitor gastrointestinal function. Handwalking and non-athletic exercise may reduce the risk of colic. Complications of atropine use are idiosyncratic, not dose related, and typically resolve with removal of atropine use.
Flunixin meglumine is considerably more effective than either phenylbutazone or aspirin. Until the abscess is completely controlled, a full dose regimen (1.1 mg/kg PO BID) is strongly recommended. Other potential useful systemic NSAIDs include ketoprofen, carprofen and meloxicam although ophthalmologists have limited experience in determining their relative effectiveness compared to flunixin. The highest tolerated dose should be used initially to achieve control of the uveitis. Reductions in dosage should be performed cautiously, in small amounts and infrequently. Concurrent use of gastroprotectants may be useful. Certain patients that will not tolerate higher doses of oral NSAIDs may be managed with relatively more frequent atropine use and lower NSAID dosage.
Some stromal abscesses prove impossible to manage medically. In response to the repeated loss of vision and chronic pain in eyes affected with stromal abscesses, and in an effort to reduce the number of enucleations performed because of this disease, surgical alternatives have been developed. The difference in results may be impressive.
After surgical removal of the abscess, upward of 95 percent of patients retain vision, in comparison to reported results as low as 50 percent with medication-only management. Even if vision is lost, almost all patients are able to retain the globe.
Average time to healing (cease medication) may be as short as three and a half weeks, with a partial thickness corneal transplant (posterior lamellar keratoplasty), and six weeks with a full thickness transplant (penetrating keratoplasty). The indicated surgical procedure depends on the location and size of the abscess, surgeon preference and stage at referral.
Surgical intervention is often not possible or recommended when the abscess becomes large, and benefits the patient most within the early stages of the disease process (prior to massive antigen presentation to the immune system and severe uveitis). Note that the healing times quoted represent cases with the most severe infections, which frequently persist for 12 to 20 weeks with medication alone. Thus, the time to return to athletic use and comfort may be substantially reduced with surgery.
Other considerations include the need for anesthesia, transfer to a surgical center, and the ability to provide 24-hour care during the most intense medication period. Cost is typically very similar for medical and surgical strategies, if performed early, because of the shortened time to healing, reduced drug consumption and shorter hospitalization. Early surgical intervention is typically the most cost-effective with mid-size or larger deep abscesses.
Keratectomy with or without a conjunctival flap would be effective for the resolution of a superficial corneal abscess, although such abscesses rarely require surgical intervention. This surgery is highly effective and commonly indicated for expedited resolution of the fungal plaque, which is not considered an abscess but rather is a prolific growth of fungal hyphae on the anterior corneal surface. Medical treatment of these lesions may be quite extended without a keratectomy to reduce the fungal burden.
Ultimately, the outcome with corneal stromal abscesses is most dependent on speed of identification, and the aggressiveness of therapy. The worst cases, which probably represent less than 5 percent, may be extremely challenging and arguably respond best to early surgical therapy. After surgery, those cases may be managed at home in conjunction with a specialist.
Medical management alone of corneal stromal abscesses may be of long duration, and be tiresome for the client, patient and veterinarian. With unlimited resources, the vast majority of clinical cases may be successfully resolved and preserve vision with little more than a corneal scar to identify it.
Regardless of the severity, as soon as a corneal stromal abscess is diagnosed, aggressive early control of the disease yields the best outcome, least long-term complications and shortest medication time as well as improved quality of life for the patient that experiences the pain. Day-to-day monitoring in the early stages is critical to ensure complete control of the uveitis, and to prevent explosive growth of microorganisms. Drawings and photographs during treatment assist substantially to identify progress or lack thereof, and are strongly encouraged.
Dr. Cutler is associated with the Animal Eye Specialty Clinics in West Palm Beach, Deerfield Beach and Wellington, Fla. He is board certified by the American College of Veterinary Internal Medicine and by the American College of Veterinary Ophthalmologists. He received his veterinary degree from the Veterinary College of Ireland, University College Dublin, and his MS degree and residencies from the University of Florida. His interests include corneal disease and surgery, particularly corneal transplantation. The Animal Eye Specialty Clinics schedule equine referral patients for routine and emergency appointments as requested. Visit http://www.animaleyedocs.com for more information.