Understanding Equine Recurrent Uveitis (ERU)
- Oct 1, 2002
Horses exhibit eye pain for a variety of reasons and to varying degrees. As we've discussed previously, the most common cause is corneal ulceration. In this article, we'll discuss uveitis, which requires a very different kind of treatment than that used for ulcers. Uveitis means inflammation inside the eye; it can be combined with other words to describe exactly where in the eye the inflammation occurs. While acute uveitis occurs suddenly and might be caused by a systemic disease or corneal ulcer, it gets better with treatment of the causative condition and does not occur again. Equine recurrent uveitis (ERU) is an autoimmune disease that can be controlled, but occurs again and again.
Equine recurrent uveitis (ERU) can't be cured; it is named for its tendency to recur in one or both eyes. The disease has also been called "moon blindness" and "periodic ophthalmia" because of its erratically recurrent nature, compared by early observers to the phases of the moon. It is a result of an overly aggressive immune system, an autoimmune disease in which the eye's own immune system reacts against normal tissue early in the disease. Various causes are implicated, with Leptospira and other bacteria suspected to be the cause in many horses in the United States and Europe.
Equine recurrent uveitis is one of the oldest diseases known in veterinary medicine. Even ancient Egyptian horses might have been affected, as described in hieroglyphics in the tombs of the pharaohs. In modern times, ERU is one of the most frequent causes of equine blindness (5-25% of U.S. horses might be affected), and treatment costs millions of dollars annually in the United States. Luckily, the great majority are mild or even unrecognized forms of the disease, requiring occasional or no therapy.
The most obvious sign of eye pain is squinting--holding the eyelids closed to some degree (see Figure 1 on page 58). If you think your horse is squinting, compare the upper eyelids and eyelashes of each eye; identify the one with the eyelashes pointed down. Other signs of eye pain include repeated face rubbing and tears overflowing the eyelids. Individual horses express pain differently, and over time they might develop a tolerance and show fewer signs.
In addition to pain, uveitis changes the eye appearance or color. The cornea might be a hazy blue or gray because it has more fluid than normal, the pupil might be small or hard to see due to the cloudy cornea, the iris might change color (Figure 2), and the fluid space in between might be occupied by cells or proteins and appear gray, tan, or even red (Figures 3 and 4). If uncontrolled, this inflammation can result in permanent, even blinding, complications such as cataracts (Figure 5) and retinal detachment.
Of course, many of these signs are also common with corneal ulceration and other eye diseases. A critical point is to differentiate uveitis on its own (primary uveitis) from uveitis due to another eye disease (secondary to an ulcer). Primary uveitis is treated with anti-inflammatory drugs, which could cause catastrophic progression of corneal ulcers or infections if they were also present. It's important to carefully evaluate the cornea and perform a fluorescein dye test (to rule out ulcers) before prescribing these drugs for use on the eye, especially when steroids are used. These drugs reduce the local immune response (which is desirable with primary uveitis), but they risk a corneal infection getting out of control in the case of secondary uveitis. This risk is greatest in the hot and humid southern states, where fungal organisms and infection are more common.
The Eye's Immune System and ERU
The immune system of the eye is specially adapted to maintaining the transparency of the cornea, lens, and vitreous. Intraocular (within the eye) inflammation or uveitis can cause cloudiness of these structures and reduce vision if the immune system is not properly controlled. There are a set of checks and balances that minimize the chance of an unnecessary, overly aggressive immune response inside the eye. However, the immune system is out of balance in ERU; normal eye tissue is mistakenly attacked and damaged due to a failure in differentiating normal from diseased tissue.
Many causes can trigger uveitis. Some are infectious, such as the Leptospira bacteria, and others mimic infection. Cells in the eye recognize abnormal proteins or infectious agents and respond by releasing chemical signals that cause an "alert status" instead of the normal, carefully controlled internal environment of the eye (see "How Exactly Does ERU Occur?" at left). The many iris and ciliary body blood vessels become leaky and allow proteins and white blood cells to freely enter the eye to remove the abnormal material. The anterior and vitreous chambers of the eye literally become sticky from proteins, while immune cells release even more chemicals to help identify and destroy infectious or diseased material.
Unfortunately, this immune process isn't specific against just the perceived threat; normal delicate ocular tissues also can become damaged. The iris might get stuck to the lens or cornea and distort the pupil. The lens can become cloudy and partly block vision. At the very back of the eye, retinal damage can cause death of sensitive nerve cells that perform the very first stages of vision. The same chemicals that direct this process also signal pain. Special muscles in the iris and ciliary body spasm and cramp, and contribute to the small pupil size.
The real problems for the horse eye with uveitis begin when this whole cascade of events occurs for the second, third, or subsequent time. As the immune system of the eye tries to become more sophisticated and efficient, it reduces the checks and balances in the immune system; thus allowing the response to start more easily. Some inflammatory cells stay permanently inside the eye for surveillance against disease. This improves the reaction time when a new problem arises, but it also makes it easy to accidentally trigger an unnecessary attack.
Ultimately, permanent damage starts to add up and includes complete cataract, scars from the inflammation, glaucoma (increased intraocular pressure), death of nerve cells, and shrinkage of tissues--all contribute to vision loss and ongoing pain.
Treatment is aimed at reducing inflammation inside the eye. The initial cause is probably no longer present by this stage. In the mildest cases, treatment might be minimal. If clinical signs worsen, oral anti-inflammatory drugs like phenylbutazone (Bute), or flunixin meglumine (Banamine) are recommended. If that does not clear the problem fairly quickly, specific eye medications will be needed. The affected eye is tested first with fluorescein dye to make sure there are no corneal ulcers, especially if it is blind and more easily injured. Typically, the medication protocol includes an antibiotic and a corticosteroid. Control of inflammation is provided by the steroid, while the antibiotic prevents infection. Corticosteroids include dexamethasone, prednisolone, and possibly betamethasone, but hydrocortisone is rarely powerful enough. If the inflammation or pain is sufficiently severe, the veterinarian also might recommend atropine. This relieves several aspects of the uveitis, most noticeably the pain from muscle spasm, and the pupil becomes dilated.
This treatment can be a pretty big ordeal, both for you and your horse. It becomes even more inconvenient, not to mention uncomfortable, when it happens repeatedly--especially in a blind eye. All drugs have potential side effects when used long-term, so the search for a better method has begun. One of the most exciting developments is a delivery device that is surgically placed inside the eye. The implant leaks tiny amounts of cyclosporine A medication to "turn off" the cells that cause the inflammation in ERU.
The prototype has been successful with few complications, and it has the potential to last five years. Safe and correct cyclosporine A implant placement requires general anesthesia and special training, and like all surgeries, involves some risk of its own. On average, ERU episodes fell 20-fold to under one episode per two years in studies of this treatment method, and some horses had none at all.
An alternative surgery called a vitrectomy removes the cells and gel substance (vitreous) from inside the eye. However, this surgery is more invasive and can cause devastating and painful complications. Soon afterward, many horses develop cataracts that cannot be removed because of the high risk of surgical complications. We no longer recommend this surgery in general, although a very few select blind horses can get good pain relief this way without having the eye removed. In Europe, the vitrectomy surgery is quite successful, so ERU might behave differently depending on your location. It is not known why there is a difference, but some believe that there is a different cause of ERU there. Both surgeries have the best results if done before complications develop.
Appaloosas deserve special mention because they are affected by a particularly severe version of ERU. While many breeds of horses respond to relatively minimal therapy, have infrequent ERU episodes, and only exhibit mild squinting and eye discharge, Appaloosas often require intensive treatment, have more severe clinical signs, and relapse more frequently. The underlying genetic reason for this is not known, but the prognosis for pain control and continued vision is definitely poorer in Appaloosas. We recommend blood tests for Leptospira antibodies in Appaloosas in order to get a prognosis for saving sight. Appaloosas with high antibody levels to Leptospira bacteria need much more aggressive medical and surgical therapy to save sight than Appaloosas with low antibody levels.
If your horse develops a painful eye (or eyes) but hasn't been diagnosed with ERU, the most important step is examination of the eye by your veterinarian. A veterinarian's familiarity with the horse is particularly valuable and will help differentiate a corneal ulcer from primary uveitis or another problem. If ERU is the cause, then the most critical part of management and treatment is early identification and treatment of all future episodes. In most cases, it is safe to begin administering Bute or Banamine right away, until judgment can be made about topical corticosteroids for the eye. Your veterinarian will also advise you about when to seek further help from a veterinary ophthalmologist, and whether you should consider surgical implantation of the constant-release medication device.
There is probably nothing that can be done to prevent horses from becoming affected by ERU. Even though an infection is most likely to be the original cause, you shouldn't be concerned about it spreading to other horses in the barn. Outbreaks of uveitis are quite rare, and are usually obvious. Most times, they don't result in recurrent uveitis.
Brooks, D.E. Equine Ophthalmology Made Easy. Jackson, WY: Teton NewMedia Press, 2002.
Church, S. Surgical Techniques. The Horse: AAEP Convention Wrap-Up 2001. February 2001, 28. Article Quick Find #3329 at www.TheHorse.com.
Dwyer, A.E.; Crockett, R.S.; Kalsow, C.M. Association of leptospiral seroreactivity and breed with uveitis and blindness in horses: 372 cases (1986-1993). Journal of the American Veterinary Medical Association, 207, 1327-1331, 1995.
Fruhauf, B.; Ohnesorge, B.; Deegen, E.; Boeve, M. Surgical management of equine recurrent uveitis with single port pars plana vitrectomy. Veterinary Ophthalmology, 1, 137-152, 1998.
How Exactly Does ERU Occur?
Scientists are still not certain. However, research continues to provide clues that should eventually explain the process. It has long been suspected that an internal infection in the eye is later transformed into an attack on the eye tissues themselves. Currently we think ERU develops like this:
- A mild infection occurs somewhere in the horse's body (not necessarily in the eye). A variety of organisms could be responsible, but Leptospira is the most important.
- An immune response develops that contains, and might kill, the infection.
- Special memory cells keep information about the infection. Each cell recognizes a very specific part (antigen) of the infectious organism, making a faster defense possible next time.
- The iris and ciliary body are invaded by a variety of cells to improve immunity. Some cells also live in the vitreous.
- The next time a similar immune response is triggered, a chemical signal causes an "alert" status. If the chemical signal enters the eye, the immune cells or lymphocytes are activated.
- The immune cells in the eye might not be needed, but they turn on anyway. More chemicals are released. Damage occurs.
- Other cells also respond to the signal and enter the eye, causing more damage.
- Special cells make antibodies against the antigen they recognize. Other cells (neutrophils) also invade and cause widespread destruction of tissue they contact.
- Some infectious organisms disguise themselves with antigens similar to the horse's own retinal nerve cells--then those nerve cells are also killed by the immune system, which can no longer tell them apart.
- Inflammation increases the risk of non-specific damage to all normal cells.
- When the chemical signals decrease, the inflammation gradually resolves.
- Areas badly damaged do not return to normal, but are replaced by scars.
- Not much damage occurs until the next time chemical signals are received by the immune cells in the eye.
- Over time, the "strictness" of the chemical signal might be reduced, resulting in more liberal activation of immune cells and more widespread damage.
- More uveitis cycles mean increasing damage. The more severe the uveitis, the more permanent the damage.
- In the worst cases, the uveitis never totally resolves, but just waxes and wanes.
Cyclosporine A is a drug that inactivates the chemical signal to the immune cells. When it is released constantly inside the eye, the immune response is reduced. Vitrectomy surgery (removal of the cells and gel substance, or vitreous, from inside the eye) attempts to remove all cells to prevent them from responding, but can't stop new cells from arriving.--Tim J. Cutler, MRCVS; Dennis E. Brooks, DVM, PhD, Dipl. ACVO
5 TIPS: Recurrent Uveitis
- Equine recurrent uveitis (ERU) is named for its tendency to reappear repeatedly in one or both eyes.
- ERU has also been called "moon blindness" or "periodic ophthalmia."
- ERU is an autoimmune disease with the eye's immune system reacting against normal tissue early in the disease.
- Appaloosas are often more severely affected by ERU than other breeds.
- The problems with ERU escalate with successive attacks, which result in cumulative damage to the eye.
Dennis E. Brooks, DVM, PhD, Dipl. ACVO, professor of ophthalmology at the University of Florida, authored Equine Ophthalmology. He has lectured extensively--nationally and internationally--on comparative ophthalmology and glaucoma; authored more than 80 refereed articles; and is a recognized authority on canine glaucoma and infectious keratitis, corneal transplantation, and glaucoma of horses.
Tim J. Cutler, MRCVS, recently finished his residency in ophthalmology at the University of Florida and is currently at Carolina Veterinary Specialists in Greensboro, N.C.
About the Author
Dennis E. Brooks, DVM, PhD, Dipl. ACVO, is a professor of ophthalmology at the University of Florida. He has lectured extensively, nationally and internationally, in comparative ophthalmology and glaucoma, and has more than 140 refereed publications. He is a recognized authority on canine glaucoma, and infectious keratitis, corneal transplantation, and glaucoma of horses.
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