Clearly an abscess: changes in corneal clarity

Clearly an abscess: changes in corneal clarity

Nov 01, 2003

The cornea is the most exposed and most commonly injured structure of the equine eye.

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 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.

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.

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.
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.

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.

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.
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.

EtiologiesCorneal 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.

Treatment 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.

Uveitis controlBlindness 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.