OPHTHALMOLOGY
How to Diagnose and Treat Immune-Mediated
Keratitis of the Horse
Dennis E. Brooks, DVM, PhD, DACVO
Author’s address: University of Florida, College of Veterinary Medicine, 2015 SW 16th Avenue,
Gainesville, FL 32608-1166; e-mail: [email protected]. © 2014 AAEP.
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
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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
OPHTHALMOLOGY
Fig. 1. Fluorescein is weakly and transiently retained in the
interstices between the islands of abnormal epithelium in this eye
with epithelial IMMK.
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
Fig. 3. In some eyes with stromal IMMK, a yellow-green tinged
coloration may appear within the midstromal central and paracentral cornea. Some sutures are present following corneal
biopsy.
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.
Fig. 2. The lesions appear to be initially restricted to the area
under the upper lid in stromal IMMK.
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. There is a
deep diffuse fibrocellular infiltrate, opacification,
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OPHTHALMOLOGY
Fig. 4. There is a deep diffuse stromal edema in the central
cornea of this eye with immune mediated endotheliitis.
and stromal edema in the central cornea which may
evolve rapidly into bullous keratopathy (Figs. 4
and 5). Isolated arborizing blood vessels encroach
upon the affected area at the level of Descemet’s
membrane and/or endothelium. In some cases,
dense clumps of cells may be evident adherent to
the endothelium in the region of the terminal blood
vessels. In long-standing cases stromal mineralization can occur. Rapid clearing of the cornea and
regression of the blood vessels using topical dexamethasone occurs in many cases of endotheliitis in
the UK. It is a difficult disease in control in North
America. Endotheliitis may be a precursor to glaucoma in the horse. Treatment should continue for a
weeks following any corneal clearing. Recurrence
of the disease is possible in a small number of long-
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Fig. 5. The other eye in the horse in Fig. 4 has more diffuse
edema.
standing cases. A successful outcome following penetrating keratoplasty has been reported in the U.S.
Acknowledgments
Conflict of Interest
The Author declares no conflicts of interest.
References
1. Matthews AG. The cornea. In: Barnett KC, Crispin SM,
Lavach JD, Matthews AG. Equine Ophthalmology. An Atlas and Text 2nd ed. Philadelphia: Saunders, 2004.
2. Matthews AG. Nonulcerative keratopathies in the horse.
Equine Vet Education 2000;12:271–278.
3. Gilger BC, Michau TM, Salmon JH. Immune-mediated keratitis in horses: 19 cases (1998 –2004). Vet Ophthalmol
2005;8 233–239.