Periodic Ophthalmia (Moon Blindness)
Periodic ophthalmia, otherwise known as recurrent uveitis, uveitis, or moon blindness, can be a devastating disease of the equine eye. It also, unfortunately, is a disease that we really don't know much about. The hypothetical causes have been sporadically researched over the years, but we aren't really much closer to understanding this inflammatory ocular disease.
Classic appearance of long-standing uveitis. Note the scarring of the iris and the white reflective cataract. Photo by Dr. Michael A. Ball
The term moon blindness comes from the ancient belief that the disease was associated with the changes of the lunar cycles. The "recurrent" or "periodic" part of the disease is the result of the propensity of this disease to recur in a rather unpredictable manner after the animal has once experienced the disease. The medically descriptive name for this disease is uveitis (pronounced you-vee-itis), and I will refer to it by that name for the rest of this article.
The uvea is an anatomical name for certain parts of the interior eye and, of course, "itis" means inflammation--so uveitis is an inflammation of the uvea. The uvea includes most of the interior parts of the eye that have a large blood supply. This is especially true for the iris--the colored part of the eye surrounding the pupil.
Who Suffers From Uveitis?
All species of animals, including humans, can suffer from some form of uveitis, but the horse has been plagued with the recurrent form of this disease for some time. In fact, this disease was recorded by veterinarians attending horses of Alexander the Great. The disease is reported to have a worldwide distribution, but it appears to be more common in North America than in Australia, the United Kingdom, or South Africa. This disease probably suffers from more folklore, ignorance, misconception, and anecdotal causes, cures, and treatments than any other human or veterinary disease. Unfortunately, the bottom line is that we really don't know very much about recurrent uveitis. Although there are many "predisposing" factors scattered about in the lay literature as well as specific horse predispositions, there is no age, sex, breed, moon cycle, or any other proven predisposing factor. It has been reported that up to 12% of a given population of horses in some areas of the eastern United States can suffer from uveitis. The specific proven causes and those under investigation will be discussed next.
The Suspected Causes
As already mentioned, uveitis is a generic term that describes inflammation of the uvea. Uveitis can be caused by anything that causes inflammation within the eye and does not necessarily have to be associated with "recurrent" uveitis. Trauma to the eye can induce uveitis. Blunt trauma, e.g., a pop in the eye with a polo ball, can create inflammation and propagate uveitis. If the trauma involves a wound of any sort to the eye, then uveitis can be caused by infection. If a corneal ulcer caused by bacteria, fungi, or yeast becomes severe enough and starts to involve the deeper layer of the cornea, it can induce uveitis. Sometimes these corneal infections can rupture into the anterior chamber and cause a very severe uveitis. In addition, severe systemic infection (most typically neonatal septicemia) can have a uveitis component; the presence of uveitis in a neonate might be an indication of a systemic disease.
With respect to recurrent equine uveitis or periodic ophthalmia, the currently suspected causes with research to support their validity are related to infection with the bacteria Leptospira, affliction with the parasite Onchocerca cervicalis, and, potentially, infection with the bacteria Streptococcus equi (the cause of strangles). The most commonly held explanation is that inflammation of the uvea is caused by a delayed hypersensitivity reaction or is an autoimmune mediated phenomenon. A delayed hypersensitivity reaction is one of the four classic immune responses to a foreign substance in our body. Essentially there is an immune mediated reaction developing after exposure to a foreign substance. Some of the immune cells have a memory for the foreign substance and are suspected to persist on the uveal tissue. Then, when the horse (and subsequently the immune cells) are exposed to the same foreign substance at some time in the future, the reaction stimulates inflammation.
The autoimmune phenomenon occurs when the immune system, for whatever reason, stops recognizing a part of the body as part of the family and starts to reject it. It might be possible that after infection with one of the suspected causes of recurrent uveitis, immune proteins (antibodies) are produced that target the uveal tissue. If the protein structure of part of the infectious agent is similar to the protein structure of part of the uveal tissue, this situation might occur. A classic example of this in people is rheumatic fever, where the heart valves are attacked by the immune system after infection with the bacteria that causes strep throat.
Bacteria of the leptospira family cause a contagious disease of animals, including people. There is a wide variety of leptospiral organisms (more than 175 different strains) that get their name in part due to their spiral shape when viewed under the microscope. Many infections are asymptomatic, but several different disease conditions can be associated with infection. Leptospiral infection can cause fever, jaundice (a yellowing of the tissue associated with liver or red blood cell damage), blood in the urine, abortion, and even death. With respect to the eye, it has been observed that ocular lesions occur one to two years after infection with the bacteria leptospira. This also is similar to what is observed in people, but the time interval from infection to onset of ocular lesions is typically greater in horses. The strain of leptospira that is most commonly incriminated with recurrent uveitis is called Leptospira interrogans serovar pomona.
There have been numerous studies evaluating leptospira infection in horses, especially with respect to asymptomatic horses and blood titers indicating exposure to the bacteria. Some reports indicate that up to 30% of some horse populations have a blood titer compatible with exposure and potentially prior infection. As a result of this, it is difficult to prove a cause and effect relationship in horses suffering from uveitis and having a concurrent positive blood titer for leptospira.
One study by Ann Dwyer, DVM, of the Genessee Valley Equine Clinic, Rochester, N.Y., was reported in a 1995 issue of the Journal of the American Veterinary Medical Association evaluating blood testing for leptospiral titers in horses suffering from uveitis in upstate New York. Dwyer observed that 53% of more than 100 horses had a positive blood titer for leptospirosis as compared to 9% of more than 200 horses with clinically normal eyes. (More on leptospirosis in in next month's issue.)
The parasite Onchocerca is a uniquely disgusting worm that ends up living in the thick ligament (the nuchal ligament) located along the top of the neck. The ligament acts like a suspension cable attaching from the withers to the back of the skull--it actually holds the head up. The baby forms of this parasite are transmitted by sand flies and mosquitoes. The cycle goes from the sand flies' and mosquitoes' injecting the babies into the horse's blood stream to their ending up in the nuchal ligament. When the parasite becomes an adult and produces babies, they migrate out of the ligament to the skin in the head area, actually penetrating the skin and some end up in the connective tissue surrounding the eye. As an immune reaction develops, one of the consequences can be uveitis. Although confirmed as a causative agent in some cases of uveitis, there are many cases that have no evidence of parasite migration.
As mentioned earlier, there are many other potential causes of uveitis in the horse. With respect to the causes of classic recurrent equine uveitis or periodic ophthalmia, there has been very little new information generated over the past decade. There have been many suspected causes that have been all but eliminated as possibilities. Hopefully, the near future will bring more research that will lead to a better understanding of the disease, allowing for the development of more effective treatments or preventions.
Clinical signs for this disease actually can be broken up into those observed during an acute flare-up of the disease and those observed that indicate that the disease has occurred in the past. The primary sign of uveitis is eye pain as manifested by squinting, tearing, and an increased sensitivity to light. Other observed signs are a very constricted pupil (even in a dark stall), cloudiness within the eye (will be difficult to see the iris and pupil with a distinct haze present--the so-called "aqueous flare"), and potentially the presence of solid material (protein) attached to the iris. As the inflammation occurs within the eye, irritating chemicals are produced and released into the fluid in the anterior chamber (the space between the inside of the cornea and the iris which is filled with a clear fluid).
In addition to the inflammatory chemicals being released, white blood cells and protein leak from the inflamed blood vessels into the anterior chamber fluid--a fact that creates the haze (aqueous flare) within the anterior chamber. In severe cases of uveitis, the white blood cells will settle and collect in the floor of the anterior chamber. One of the proteins that leaks into the anterior chamber is called fibrin. Fibrin is a light, fluffy, cotton candy-like substance that is one of the components of a blood clot and is a precursor to a dense connective tissue scar. If the fibrin production in the eye is heavy and goes without treatment, fibrin can cause a significant amount of scarring within the eye. Matured fibrin can glue the iris to the lens, thus preventing it from opening in lower light situations, or it can cover the lens and greatly affect vision. In addition, the cornea might be ulcerated or become cloudy and opaque. If left untreated, the inflammation within the eye associated with uveitis can have a devastating impact on vision.
The signs of a prior bout of uveitis can be more subtle and require extensive examination of both the outer and inner areas of the eye. This examination is an important part of the pre-purchase examination due to the recurrent nature of uveitis. Unfortunately, it is impossible for your veterinarian to predict if uveitis will recur or not. The disease might never happen again, or it could recur next week. There really is no way to predict that. All your veterinarian can do is attempt to determine how whatever damage has been done currently affects vision and document the extent of the lesions.
The most subtle of signs is a darkening of the iris to a deep, dark chocolate color with or without obvious scarring of the iris itself. In advanced cases, it can appear very moth-eaten and scarred. The edge of the iris might be irregular and roughened. Remember the little punching bag-like gizmos (nigra bodies) on the iris are normal and must be differentiated from abnormal structures.
The surface of the lens (within the area of the pupil) might have a piece of brown iris stuck to it (or the iris itself) or other scar tissue from the previous inflammation. Sometimes there are white strands of scar tissue darting about inside of the anterior chamber. The most crucial part of the examination with respect to prepurchase is deep inside the eye. It is possible to have none of the other telltale signs and have significant scarring in the back of the eye. The lesions caused by uveitis in the back of the eye (where the light-sensing retina is located) are reflective scars surrounding the optic disk (optic nerve as it enters the eye). These lesions are referred to as "butterfly" lesions, since they often appear in the shape of a butterfly. The scarring in the back of the eye, depending on the degree of it, can cause a visual deficit or blind spot. Partial blindness can be extremely difficult to detect, let alone determine to what degree vision is affected.
Many horses can compensate for partial (and even full) blindness in one eye in an amazing way. I have uncovered complete blindness in more than one horse (that had been that way for some time) where the owners/handlers had no idea of a problem.
In more chronic cases of uveitis, the iris can become very scarred and light in color. The border of the iris generally is very irregular and glued down to the lens; the lens often is opacified by the presence of a cataract, the eye itself might be abnormally large and firm or abnormally small and soft, and vision can be severely impaired. Also, in advanced cases the cornea might not be healthy and could have an ulcer. One eye or both eyes can be affected.
Before the treatment of uveitis is initiated, it is imperative that the diagnosis be made by a veterinarian and that the cornea be evaluated for the presence of a corneal ulcer. The two main drugs used in the treatment of uveitis are atropine and corticosteroids. The atropine serves several important purposes. Atropine works by paralyzing some of the muscles of the iris, thus stopping the painful spasm and allowing the pupil to dilate. The dilation of the pupil is very important because if it stays constricted and in contact with much of the lens in the presence of inflammation, the chances are greater for the iris to become scarred and attached to the lens. Sometimes if the atropine alone does not dilate the pupil, another drug will be used that actively dilates the pupil.
The corticosteroids are potent anti-inflammatory drugs that are typically necessary to quench the inflammation of a uveitic eye. As mentioned before, the main theoretical causes of uveitis involve an immune mediated inflammation--suppression of the ocular immune system is generally necessary to control uveitis.
Corticosteroids do not come as a risk-free treatment. Due to their potent immune suppressing abilities, the corticosteroids, if used on an eye in the presence of a corneal ulcer, can predispose the eye to a fungal infection. Approximately 65% of horses which develop fungal eye disease have been treated with a topical corticosteroid. Despite this risk, the corticosteroids are necessary to control the inflammation associated with uveitis.
In addition to these two main treatments for uveitis, topical antibiotics, topical antifungal, and topical non-steroidal anti-inflammatory drugs often are used. In addition, systemic pain medication often is necessary.
Remember that the greater the fibrin content in the anterior chamber, the greater the chance of permanent scarring and visual deficit. There is a unique (but unfortunately expensive) treatment used if the fibrin content in the anterior chamber is severe. A drug called TPA (tissue plasminogen activator), which is used as a clot buster in human heart attack and stroke patients, can be injected directly into the eye to dissolve the fibrin. The administration of low dose aspirin might be of benefit in decreasing the production of fibrin within the eye.
Another treatment that might be considered is removal of a severely affected eye. This can be a very difficult decision to make for the owner, but sometimes can be the best option for the horse. A chronic uveitis eye can be chronically painful and require substantial treatment to give the horse even marginal comfort, with no vision. If the eye is blind and painful, the best way to remove the pain could be to remove the eye.
Hopefully in the near future, there will be a research breakthrough in the prevention or treatment of uveitis, but until then, uveitis will remain the leading cause of blindness in horses.
About the Author
Michael A. Ball, DVM, completed an internship in medicine and surgery and an internship in anesthesia at the University of Georgia in 1994, a residency in internal medicine, and graduate work in pharmacology at Cornell University in 1997, and was on staff at Cornell before starting Early Winter Equine Medicine & Surgery located in Ithaca, N.Y. He is also an FEI veterinarian and works internationally with the United States Equestrian Team.
Ball authored Understanding The Equine Eye, Understanding Basic Horse Care, and Understanding Equine First Aid, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.