Equine Ophthalmologist Quests for Corneal Cures
By Audrey Pavia
Published in Veterinary Product News, 2000
Dennis Brooks has a real passion for eyes – equine eyes in particular. "I just can't stand it when goes blind," he says. "When a horse can't see, it can't run. And I love to watch horses run." This sensibility, simple as it sounds, is what drives this veterinary ophthalmologist to find cures to diseases that most researchers would rather not deal with.
Brooks developed his fervor for ophthalmology as a young boy growing up in western Illinois. "I was always fascinated with eyes and drawn to veterinary ophthalmology," he says. "I think my interests developed in this area because I wore glasses since I was very young, and was always attracted to the eye and how it worked."
Graduating in 1980 with a D.V.M. from the University of Illinois, Brooks went on to obtain his Ph.D. in ophthalmology from the University of Florida in 1987. After working as an ophthalmology consultant for several practices in Tennessee and teaching at the University of Tennessee, Brooks returned to the University of Florida in 1990 as an associate professor and ophthalmology service chief. Since that time, Brooks has been treating and conducting extensive research on equine eye problems at the University, concentrating primarily on corneal disease and glaucoma, while studying other areas like equine recurrent uveitis and cataracts as well.
Brooks research has resulted in some astounding revelations, particularly in the area of ulcerative keratitis. By studying the tears collected from the affected and contralateral eyes of seven horses with ulcerative keratitis, and from 33 normal eyes of 17 control horses with no evidence of ocular disease, Brooks discovered why some ulcers refuse to heal despite the fact that the offending infecting organism has been removed from the eye.
"The microbes typically associated with corneal ulceration induce leukocytes in the tear film to release enzymes that elicit inflammatory and degradative processes," he says. "Normal turnover of the corneal stroma occurs through degradation and subsequent replacement of extracellular matrix components (ECM). This process is mediated, in part, by proteases. Proteases are enzymes produced and released by a variety of cells including corneal epithelial cells, corneal stromal fibroblasts, leukocytes, and some bacterial and fungal pathogens. These enzymes normally exist in balance with inhibitory factors that serve to prevent excessive degradation of normal tissue. In pathologic processes such as ulcerative keratitis, however, excessive levels of certain proteases can lead to rapid degeneration of collagen and other components of the ECM, potentially inducing keratomalacia or corneal 'melting.' "
In research conducted in 1998, Brooks discovered that two major families of proteases may affect the horse cornea, including the matrix metalloproteinases (MMP) and the serine proteases. "Matrix metalloproteinases are a family of zinc-dependent enzymes including collagenases, gelatinases, and stromelysins," he says. "Serine proteases include trypsin, chymotrypsin, and elastases, with neutrophil elastase being the most relevant of these enzymes where corneal disease is concerned.
"Our hypothesis is that there is a significant difference in the concentrations of MMP-2, MMP-9, and neutrophil elastase found in the tears of horses with ulcerative keratitis versus normal controls. By identifying the specific types and relative concentrations of proteases present in equine ulcerative keratitis, we hope to set the stage for future studies designed at targeting the major offending proteases with specific antiprotease therapy. This, in turn, may eventually lead to improved clinical management of equine ulcerative keratitis."
Another discovery recently made by Brooks and his team at the University of Florida concerns the bacteria usually associated with corneal ulcers in horses.
"Although gram positive bacteria predominate in the normal conjunctival microflora of horses throughout the world, gram negative bacteria and fungi are more often isolated from equine ulcers," says Brooks. "Beta-hemolytic Streptococcus spp. are associated with a very aggressive ulcerative keratitis with the capability to digest conjunctival graft tissue. Clinical signs are pronounced. Aggressive surgical and intensive medical therapy with topical antibiotics and protease inhibitors is indicated in these situations."
Brooks' other area of interest, glaucoma, has received considerable attention at the University of Florida. In fact, according to Brooks, the University clinic is particularly good at treating this problem in horses. "We treat glaucoma with laser surgery here," he says. "A horse's sight can be preserved for quite a long time using this method – which works better in horses than in dogs, by the way."
"In the past, most people didn't think horses could get glaucoma, but this has turned out not to be true at all," says Brooks. "It's a much more common disease than the older textbooks mentioned." The frustrating condition of equine recurrent uveitis has also received research attention from Brooks, who has studied a surgical procedure called core vitrectomy that can help alleviate the pain and inflammation associated with ERU.
"With ERU, inflammation in the iris and ciliary body causes debris consisting of proteins, white blood cells, antibodies, scar tissue, and bacteria (in some cases) to be trapped inside the vitreous," says Brooks. "The presence of these abnormal substances is the reason for the recurrent attacks of uveitis in ERU, and why medicine cannot cure ERU.
"Surgical vitrectomy procedure involves removing as much of this entrapped debris as possible," he says. "A specialized needle is used. It is attached to a vitrectomy hand piece and a special vitrectomy surgical unit that simultaneously puts fluid inside the vitreous eye cavity, chews up the vitreal debris, and then sucks out the vitreal debris."
While Brooks has made considerable headway in discovering the causes and treatments of various equine eye diseases, he believes that much more research in these areas is needed. "It's frustrating that there isn't more money available for research in equine eye problems," he says. "This is especially true considering that the National Animal Health Monitoring System's 1998 Equine Study showed that eye problems were the fourth most common cause of illness in American horses. Only trauma, leg and hoof problems and colic came out ahead."
Lack of funding is not the only difficulty in Brooks' chosen line of work. "Treating eye disease is an emotional roller coaster," he says. "The lows are very low. It's definitely the wrong profession to be in if you are a perfectionist. On the other hand, when the victories happen, they are so great, they make it all worthwhile. I love to see horses run."