How to Diagnose and Treat Immune-Mediated Keratitis of the Horse

1. Introduction

The pathogenesis of many nonulcerative keratopathies of horses is believed to be mediated by a dramatic corneal immune response to a foreign protein, microbial antigen, or a self-antigen.^1,2  Such suspected immune-mediated keratitis (IMMK) of horses has been classified primarily according to the apparent depth of the inflammatory response.³  Geographic differences in primary corneal insult, antigen exposure, and in the duration of the IMMK prior to its recognition have led to some discrepancy in the clinical presentations and responses to therapy. It does seem that the more chronic the duration of IMMK, the poorer response to medical therapy. The diagnosis of IMMK is based on clinical signs and response to therapy.

2. Epithelial IMMK

This is a unilateral disease affecting horses of any age. Vascularization is not a prominent feature of the disease. There is a diffuse central superficial corneal opacity usually associated with very slight blepharospasm and discomfort. There may be some slight associated conjunctival hyperemia or chemosis. The superficial opacity represents irregular coalescing clumps or islands of thickened epithelium with no underlying stromal edema. The unaffected areas of cornea appear normal. Fluorescein is weakly and transiently retained in the interstices between the islands of abnormal epithelium Fig. 1. Topical dexamethasone results in rapid corneal clearing in most cases and the disease has not been observed to recur after successful treatment. 

A Note of Caution

Subepithelial keratomycosis has recently been identified in Florida, Canada, Brazil, Mexico, Denmark, and Germany. It looks identical to some cases of the epithelial keratitis form of IMMK. Biopsy and response to topical antifungal therapy are factors in making the diagnosis of subepithelial keratomycosis. It does seem capable of self-resolution in a few cases which is quite confounding!!

3. Chronic Superficial Stromal IMMK

This disease is characterized by an insidious onset with affected eyes showing only slight to moderate discomfort. The lesions appear to be initially restricted to the area under the upper lid (Fig. 2) and, less frequently, the third eyelid and lower lid. The paracentral cornea is commonly involved in the U.S. There is prominent subepithelial arborizing vascularization from the limbus, perivascular epithelial edema, and a superficial yellow-white stromal cell-infiltrate. Tear production is normal and no fluorescein uptake occurs. The apposing palpebral conjunctiva is moderately hyperemic.

The disease is initially unilateral but the contralateral eye may become affected with time. Topical treatment with cyclosporine A twice daily usually results in clearing of the cornea in 7 to 10 days in cases of short duration. Long-standing cases may be refractory to CsA. Most cases of chronic superficial keratitis are not responsive to topical corticosteroids. Subconjunctival CsA implants are helpful for this condition. Successful resolution of refractory cases of chronic superficial keratitis in the U.S. required superficial keratectomy and conjunctival grafting.
 

4. Chronic Deep Stromal IMMK

This is an episodic keratitis recurring at irregular intervals of up to several years. There is frequently history of initiating ocular trauma and the disease may derive from a local adaptive response to autoantigen in an immunocompetent cornea.

In the acute or active phase of the disease there is an extensive and dense, deep, stromal edema, white cellular infiltrate, and fibrovascular response with isolated blood vessels encroaching on the affected stroma at various levels. The intensity of the stromal changes varies between cases and between episodes. Despite the dramatic appearance of affected eyes, the disease is associated with no ocular pain. Subepithelial bullae may form and rupture, however, to create fluorescein positive superficial erosions that are associated with transient ocular discomfort. In some eyes, a yellow-green tinged coloration may appear within the midstromal central and paracentral cornea (Fig. 3). The ventral paracentral cornea is most commonly affected. Subepithelial calcium deposition may occur in some eyes. In the quiescent or inactive phase of the disease there is a modest diffuse stromal fibrosis with some superficial vascularization.

The therapeutic benefit of topical corticosteroids is very limited in acute episodes of chronic deep keratitis although they may slowly accelerate clearing of the cornea. Topical cyclosporine A twice daily results in significant suppression of the acute corneal reaction and clearing of the cornea within 10 to 14 days in eyes with chronic deep keratitis. However, treatment may need to be maintained for long periods to prevent recrudescence of the disease. Spontaneous clearing of the cornea can also occur. Topical and/or systemic doxycycline aids healing of chronic deep keratitis with the yellow-green stroma. Topical NSAIDs are also often beneficial. Superficial keratectomy and conjunctival grafting are necessary for healing of cases of chronic deep keratitis in a few cases.
 

5. Endotheliitis

This type of IMMK is characterized by acute, uni- or bilateral, central edema, and deep vascularization. Endothelial immunoreactivity to a persistent, possibly viral, heteroantigen may be involved in the pathogenesis. Affected eyes are nonpainful with no evidence of anterior uveitis in the UK, but can be very painful in horses in North America. [...]