Immune-mediated keratitis in horses

Getty ImagesImmune-mediated keratitis (IMMK) is a common non-infectious eye disease in horses. Equine veterinarians can recognize it by the chronic corneal opacity without corneal ulceration or significant uveitis.

The four distinct types of IMMK are each characterized by the depth of the corneal lesion. IMMK usually affects only one eye, but it can affect both.

It's important to note that IMMK diseases can be extremely serious, threatening a horse's sight. And yet, “The condition is hard to discuss with equine general practitioners, because they've been trained to look for corneal ulcers, and now we have this nonulcerative disease,” says Dennis Brooks, DVM, PhD, DACVO, professor of ophthalmology at the University of Florida's College of Veterinary Medicine.

Suspected causes

The pathogenesis of many nonulcerative equine keratopathies is believed to be mediated by a dramatic corneal immune response to foreign protein, microbial antigen or a self-antigen, Brooks notes. Suspected IMMK of horses has been classified primarily according to the apparent depth of the inflammatory response.1

The cornea has limited ways it reacts when injured, Brooks continues. It can grow blood vessels into it, even though the cornea is normally avascular. Various types of cells can infiltrate it, although it's normally relatively acellular. And it can imbibe water.

Additionally, a horse's eye is able to slough off damaged cells when the animal has been injured or is sick, which is how the equine cornea heals. While the cornea normally is clear, if it's injured, it turns colors: blue with edema, red from blood vessels, or whitish-yellow from white blood cells infiltrating it, Brooks says.

“The problem is, how does a horse perpetuate corneal disease, as there are both infectious and non-infectious processes?” Brooks asks. “Most veterinarians are more comfortable dealing with infection, because they can treat with antimicrobials and antifungals. But what do you do for a cornea that does not appear to have infection as a component of the disease?”

Brooks answers his own question: “Turning off the horse's immune system to the eye, or at least moderating it with medications, is the key.”

The cornea normally holds a significant amount of water, and that hydration increases when the cornea is injured. The water, in turn, changes the cornea's transparency, and it becomes opaque and appears blue, Brooks states. “A horse's corneas get a lot more blue than human corneas under IMMK conditions,” he says. “It must bother them, and it certainly affects their sight to some degree.”

The types of IMMK are based on clinical signs, response to medical intervention and the specificity of effects on the cornea. Brooks notes the following four distinct types of IMMK.

Epithelial IMMK

Symptoms of this form of the condition (see Photo 1) may include:

• Inflammation of the eyelids (blepharitis)

• Congestion of the blood vessels in the conjunctiva (hyperemia-conjunctivitis is commonly known as “pinkeye”)

• Swelling of the conjunctiva (chemosis).

Photo 1. The epithelial form for IMMK as seen with very faint fluorescein dye staining. Photos 1-4 courtesy of Dr. Dennis Brooks.The superficial opacity seen in epithelial IMMK represents irregular coalescing clumps or islands of the thickened epithelium, with no underlying stromal edema, notes Brooks. “When you shine a light on the cornea, it looks rough instead of smooth and shiny,” he says.

This is the most superficial form of IMMK, as it may seem as if nothing is wrong; notably, there is not a large corneal ulcer. The veterinarian must get the horse into a dark environment, as dark as possible, and shine a light from different angles onto the cornea to see it, he explains.

Epithelial IMMK occurs mostly where the eyelids meet, that is, where the upper eyelid touches the lower lid. “The horse may be a little uncomfortable, the lid might be a little swollen, or maybe not,” Brooks says. “When the practitioner looks at the particular region of the insult, he or she will see this epithelial IMMK. If it's right across the center of the cornea, it's the epithelial form.”

Chronic superficial stromal IMMK

Photo 2. Chronic superficial stromal IMMK is found under the upper lid.This form of IMMK (Photo 2) is characterized by prominent subepithelial arborizing vascularity from the limbus (the blood vessels look like a tree branching out, although it's sometimes hard to see), with yellow-white stromal cell infiltration. The conjunctiva is hyperemic (i.e., showing increased blood flow).

Chronic deep stromal IMMK

Photo 3. An orange-green color is present from capillary leakage of plasma in the chronic deep form of IMMK.In this form, the horse's blood vessels have ruptured, releasing plasma into the stroma, so the cornea shows a greenish-yellow color (Photo 3). Subepithelial bul­lae may form as water accumulates, forming small bubbles. “If the bullae rupture, they may produce significant pain,” says Brooks. “If so, a 5% sodium chloride solution will help reduce the bullae when there is a lot of edema.”

Endotheliitis

This is the most damaging and dangerous type of IMMK, Brooks says. Endotheliitis affects the innermost layer of cells in the cornea, the endothelium. The corneal endothelium's job is to pump water out. If that cell layer gets damaged, it stops pumping out water, and then it starts to turn colors. “The water stays in the cornea instead of getting pumped out, and it's a real problem,” says Brooks.

Photo 4. Vertical corneal edema is present in this eye with endotheliitis, the deep form of IMMK.In many affected horses, it appears as if the corneal edema, or the blue color, is displayed in a vertical pattern (Photo 4). The deepest layer of the cornea is impacted, and when that layer of cells is damaged, the horse doesn't seem to generate any more cell growth to repair the injury. Horses are born with a certain number of endothelial cells and do not develop anymore, actually losing them as they age.

Endotheliitis can cause significant pain in both eyes and does not respond to medication. “It's not the form you want a horse to have, in that generally the other forms of IMMK respond to medication, while endotheliitis does not,” Brooks says. “We're desperate to find something that works. Although people have tried various medications, the horses with endotheliitis do not respond well. Unfortunately, those with endotheliitis can progress to glaucoma.”

Treatment

For veterinarians treating IMMK, it is important to distinguish the condition from other causes of keratitis, especially infectious keratitis. Once the condition is diagnosed, veterinarians should begin with topical NSAIDs and topical cyclosporine A, not corticosteroids.

“Of the four kinds of IMMK, the more superficial the disease the more likely we are to be able to control it,” states Brooks. “And the deeper the disease, it's more likely we will not be able to do so. It is very frustrating as we learn about this disease and get more information about it. We now seem to have hit a crossroads. Although we can control [symptoms] in many cases, the question is, how do we cure these animals?”

The takeaway

For horses with the various forms of IMMK, the sooner they're diagnosed, the more likely their sight can be saved, at least for a period of time, Brooks says, noting the veterinarians should look first for opacification or signs of eye pain.

If a horse presents with signs of endotheliitis, the veterinarian should consult with a veterinary ophthalmologist immediately. “Hopefully in the near future there will be a new treatment regimen to save sight in these horses,” says Brooks, “because right now the vision of horses with endotheliitis is in serious trouble.” 

Reference

1. Brooks DE. How to diagnose and treat immune-mediated keratitis of the horse, in Proceedings. 60th Annu Meet Am Assoc Equine Pract 2014;16-18.

Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.