Moderator:

Dr. William R. Newman earned his BA from Hofstra University and MD from the State University of New York. With specialty training in nuclear medicine and board certification in radiology, Dr. Newman's career included positions such as Chief of Staff of Sacred Heart Hospital in Cumberland, MD and Vice President of Staff at Memorial Hospital of Bedford County. Retired from practice, he currently serves on the Board of Directors of Memorial Hospital of Bedford County, PA and as the Mayor of Bedford Borough, PA.

Dr. Newman's canine involvement includes membership in and a position on the Board of Directors of the Mastiff Club of America. He has served the club as president, vice president, secretary, show chairman, and newsletter editor and is currently the AKC Delegate and a member of the Delegates' Canine Health Committee. Dr. Newman has bred and/or owned nineteen Mastiffs, including a three time Specialty Winner and thirteen AKC champions. An AKC provisional judge of Mastiffs and Alaskan Malamutes, Dr. Newman is also a member of the English Fox Hound of America and owns a champion English Foxhound as well as the Alaskan Malamute that won Best in Group at the 1998 Westminster Kennel Club Show. Dr. Newman currently serves on the AKC Canine Health Foundation Board of Directors.

Summary:

Significant ophthalmic diseases of the purebred dog that are inherited include the various eyelid and conformational disorders, the glaucomas, cataracts formation, and several retinal diseases (congenital and degenerations). All of these diseases can result in visual impairment to blindness and some conditions result in long-term pain and discomfort. Medical and surgical treatments of these inherited eye conditions can be expensive, frustrating, and of variable success. To significantly decrease the frequency of many of these diseases, we have at our disposal powerful tools, i.e. focused breeding programs and the available genetic/DNA methodologies, to identify affected animals (often years before the diseases appears) and carrier animals, and eliminate these animals from our breeding populations. This presentation will concentrate on these ophthalmic diseases and suggest strategies to address their elimination.

Eyelid and Conformation Disorders Some of the ophthalmic conformation standards for certain breeds are unacceptable by today's standards. Eyes excessively deep within the orbit as well as those more prominent than normal predispose a dog to an entire life of ophthalmic disease (persistent ocular discharge; chronic conjunctivitis; corneal ulceration and pigmentation). Medical and surgical treatments of these conditions are of variable success and expensive. Prominent or protruding nictitating membranes or 'haws' are abnormal and should also be addressed.

Eyelid disorders are also part of several current breed standards and need to be eliminated. The palpebral fissure or eyelid opening is normally a horizontal oval. Selective breeding to create triangular or other abnormally shaped fissures commits these dogs to life-long inflammation, exposure of the conjunctiva and cornea, and intermittent therapy. Often we can surgically correct these lid abnormalities and resolve the persistent external ocular infections, but these surgeries do not affect future generations.

Eye shape and size also directly influence eyelid morphology and function, and the general health of the outer eye. The males of the large and giant breeds with large heads often have deep (enophthalmia) recessed eyes, impaired eyelid function, medial canthal 4 pocket syndrome,' and persistent extraocular inflammations. Breeds with abnormally prominent are eyes predisposed to corneal ulcerations and pigmentation.

Hence, the eyelids, palpebral fissure, nictitans position, orbital depth, and skull shape and size are interrelated, and are determined by the existing breed standards. We need to update any breed standard that requires abnormal ophthalmic structures to promote a healthy and pain-free eye than is also appropriate for that breed.

Breed-Related Primary Glaucomas Glaucoma is defined as an elevation of intraocular pressure (IOP) that is incompatible with the health and normal function of the optic nerve. The primary glaucomas are breedrelated and consist of a group of diseases characterized by an abnormal elevation in IOP due to decreased aqueous outflow without overt ocular disease. These primary glaucomasare categorized further into open-angle, narrow-angle, and closed-angle glaucoma by gonio-scopic examination of the iridocorneal angle, and are breed specific (see below).

The primary glaucomas are dynamic and usually progressive diseases and appear clinically different as the disease advances. Hence, any classification scheme for the dog often lists the same breed with differenttypes of glaucoma; this is probably because the disease is being diagnosed clinically at different stages.

The modes of inheritance of the primary glaucomas for most breeds of dogs are still not determined. In the Beagle, primary open angle glaucoma is inherited as an autosomal recessive trait. The primary angle closure glaucomas in the Great Dane and Welsh Springer Spaniel are thought inherited as autosomal dominants with variable penetrance.

The primary glaucomas are difficult to treat, medically and surgically, and very expensive. Maintenance of vision in affected eyes is often limited to only a few months. Determination of the mode of inheritance and development of genetic/DNA tests are essential steps to address these diseases and reduce their frequency. Also development of more effective medical and/or surgical treatments of the glaucomas is critical.

Secondary Glaucomas and Lens Luxations

In any discussion of the breed-related glaucomas, the inherited lens luxations and their associated secondary glaucomas must be considered because of the high frequencies of these diseases in certain breeds (especially the terrier group). The secondary increase in intraocular pressure seems associated with the lens becoming 'loose' within the eye and causing inflammation and physical barriers to the outflow of aqueous humor from the eye. In the breeds studied, these lens luxations/displacements seem associated with a zonular / vitreous abnormality. This defect also affects both eyes, and is predominately a terrier breed problem (see table below).

Long-term strategies for the lens luxations and these associated glaucomas should be: 1) studies to determine the mode of inheritance in specific breeds and develop genetic/DNA tests for affected and carrier dogs; and 2) develop improved treatments for dogs already affected.

Cataracts

Cataracts are defined as an opacity of the lens or lens capsule. The inherited cataracts in purebred dogs represent a significant problem in America because of their frequencies and they cause visual impairment and blindness. Although cataract surgery is highly successful, these cataracts are preventable in many breeds if we can identify the carrier animals (old method-test breedings and new/future genetic/DNA tests) and the 'pre-breeding affected animals, and remove these animals from the breeding population. Not all cataracts are inherited in the dog! In the diagnosis of the breed-associated cataracts in dogs, use of a number of classification schemes is necessary, and can support diagnosis of the inherited types. The classification schemes most useful for the inherited cataracts are age of onset, and anatomical area of the lens first involved.

Inherited Canine Cataracts Breed Mode of inheritance Age of Onset

For many breeds of dogs we still need breeding studies to prove or disprove inheritance in certain cataractous breeds. Then using genetic/DNA studies (to demonstrate carrier dogs, and affected animals months to years before the cataracts develop), we can markedly reduce the frequency of cataracts in many breeds in the next several years.

Retinal Disorders

The three large and important groups of retinal diseases in the dog, include Collie eye anomaly, the retinal dysplasias, and the dysplasia and degeneration of the outer retinal photoreceptors (broadly grouped as progressive retinal atrophy-PRA).

Collie eye anomaly (CEA) was intensively investigated in the 1960s, and the results are still very valid. Unfortunately this disorder has surfaced in other breeds, such as the Shetland Sheepdog, Border Collie, Australian Shepherd, and recently the Lancaster Heeler in England. Hence, the Collie eye anomaly 'label' may be less appropriate since its presence has been discovered in additional breeds. As the basic eye pathology is focal choroidal hypoplasia and colobomas (optic disc/adjacent retina), perhaps these terms would be suitable.

Unfortunately CEA in the Collie breed is still too common, and we need to work ourselves out of this hole! Ideally only normal eye animals should be used for breeding. As this defect is present at birth (and easily detected at 6-8 weeks), it can be quickly eliminated. But breeders have to decide this is a priority and critical for the future of this breed! In the other breeds CEA is considerably less frequent (less than 5%), and breeding of affected animals and parents that have affected offspring should be discouraged. We should not need to repeat the CEA story again!!

The retinal dysplasias are becoming more common, and in certain breeds can cause visual impairment and blindness. The multifocal retinal dysplasias affect the American Cocker Spaniel, Beagle, Rottweiler, and Yorkshire Terrier; these diseases do not cause blindness but should be eliminated. The total retinal dysplasiasare often associated with other ocular disorders, such as cataracts, microphthalmia, retinal detachments and blindness, and affect the Labrador Retriever, Golden Retriever, English Springer Spaniel, Bedlington Terrier, Sealyham Terrier, Doberman Pinscher, and the Australian Shepherd. These 'blinding retinal dysplasias are infrequent.

One strategy at this time is to eliminate all affected animals, and affected/carrier parents as breeding animals. This strategy could be applied to either the focal or generalized forms of retinal dysplasia, or targeted to those generalized forms that cause blindness. Genetic/DNA tests are future goals that could be applied to a much larger population to identify and removal any carriers.

The retinal photoreceptor diseases (traditionally called progressive retinal atrophy-PRA) are being investigated now with the molecular genetic approach. Experience has demonstrated the process of 'discovery' is slow but rewarding! Those breeds with a significant PRA problem include the Toy and Miniature Poodle, Labrador Retriever, American Cocker Spaniel, Miniature Schnauzer, and Papillon. Other breeds with PRA will undoubtedly be investigated.

Considerable effort, time and support have been directed at the photoreceptor diseases for the past several years and we are making progress! For certain breeds {i.e. Irish Setters and Cardigan Welsh Corgi) the highly specific gene mutation tests are available. For Portuguese Water Dogs, Chesapeake Bay, Retrievers, English Cocker Spaniels, and Labrador Retrievers genetic tests have been developed (all with a marker-based test for prcd). The marker-based test of prcd (genetic markers on the canine chromosome 9) usually indicates the presence of the gene mutation) appears not as sensitive as those that detect the actual gene mutation. Hence, dogs may demonstrate the marker genes but not gene mutation (they will test as false positives). Nevertheless these tests are useful at this time identifying these animal completely clear of these diseases (they are not carriers or affected). The positive results will be either affected, carriers, or false positives! Another test has been recently developed for congenital stationary night blindness (CSNB) for Briards. So our interpretations of these new genetic tests has to become more sophisticated and is based on the exact type of genetic test used!

Summary

Fortunately the time to address and markedly reduce the frequency of 'blinding' inherited eye diseases in purebred dogs is at hand! Many technologies are available and are interrelated. All of the national breed clubs should be sponsors and actively support the Canine Eye Registry Foundation (CERF). Annual CERF eye examinations of all breeding animals is very important, particularly when certain eye diseases occur in later life. The annual CERF reports are important monitors for all breeds and can measure either the increase or decline of all eye diseases in a large population of dogs in America.

Continued careful analysis of pedigrees for multiple generations is critical for the development of eye diseases and their mode of inheritance. The development of additional genetic/DNA tests to detect affected and carrier dogs, and the life-long identification (by tattoos or microchips) of these dogs is critical. The unimpeded exchange of information among breeders and veterinary ophthalmologists can ensure our chance of success, shorten the time for positive results, and control our costs!

Dr. Gelatt's work is supported by the following grant from the AKC Canine Health Foundation:

No. 1607: Hereditary and DNA Studies in Cataracts in the Bichon Frise (Supported in part by the Bichon Frise Club of America)

Biographical Profile

Kirk N. Gelatt, VMD, graduated from Pennsylvania State University (Penn State), and the School of Veterinary Medicine, University of Pennsylvania (VMD; 1965). He received his ophthalmology training at Penn supported by a National Institutes of Health research fellowship. Dr. Gelatt has served as a faculty member at three additional veterinary schools: Kansas State University (1967 -70); University of Minnesota (1970 -76); and the University of Florida (1976 to present).

Dr. Gelatt's more than three decades of work in academia has included didactic and clinical teaching to more than 2,700 veterinary students, and training 34 residents and postdoctoral fellows in comparative ophthalmology. He has presented more than 240 professional talks nationally and internationally. He has published more than 150 refereed articles, 50 abstracts, 90 nonrefereed articles, 45 book chapters, and seven books. He serves as the editor for the reference, Veteranary Ophthalmology,the "gold standard" for this discipline. The third edition of VeterinaryOphthalmology with 37 chapters and 45 different authors was released in January 1999. Dr. Gelatt's research interests have concentrated on the canine glaucomas, inherited cataracts in the dog, clinical pharmacology of drugs that change intra-ocular pressure, and ophthalmic surgeries.

Dr. Gelatt is one of eight veterinarians of the organizing committee that chartered the American College of Veterinary Ophthalmologists in 1970. He served in the different

offices of ACVO, and was President in 1997-78. He currently serves as editor and chief of the new journal, Veterinary Ophthalmology, the official journal of the ACVO

Dr. Gelatt has received the University of Minnesota Phi Zeta Research Award (1976), the Ralston Purina Research Award (1979), Alumni Award of Merit, University of Pennsylvania (1990), Gaines-Cycle-"Fido" Research Award (1991), North American Veterinary Conference Founding Award (1993), Daniel's Senior Clinical Investigator Award (1994), Bourgelatt International Award from the British Small Animal Veterinary Association (1995), and the American Kennel Club's Career Achievement Award (1998). Dr. Gelatt was promoted in 1998 at the University of Florida to "Distinguished Professor of Comparative Ophthalmology."

Dr. Gary Johnson is on the faculty in the Department of Veterinary Pathobiology in the College of Veterinary Medicine at the University of Missouri. He has a Bachelors Degree from Augsburg College, a PhD from Kansas State University and a DVM from the University of Minnesota. He has postdoctoral training from Johns Hopkins University and the New York State Department of Health. His early research was on bleeding diseases of dogs. For the last ten years his research has focused on the use of DNA markers to study inherited diseases and quantitative traits in dogs and cattle. Dr. Johnson is a breeder and exhibitor of Irish Terriers.

George J. Brewer, MD, went to undergraduate school (Pharmacy) at Purdue University, and to medical school at Indiana University and the University of Chicago.. He did residency training at the University of Chicago, and then did a postdoctoral fellowship in Human Genetics at the University of Michigan. He has been on the faculty at the University of Michigan since 1967, and is a Professor of Human Genetics and a Professor of Internal Medicine.

Dr. Brewer's research has involved human genetic diseases, such as sickle cell anemia and Wilson's disease (human copper toxicosis). Over the last fifteen years he has worked extensively in the molecular genetics of canine diseases, such as copper toxicosis, von Willebrand's disease, renal dysplasia, hip dysplasia, cataract, epilepsy and others. He is one of the founders of VetGen, LLC, an Ann Arbor-based company offering a variety of DNA tests for canine diseases and traits.

Gregory M. Acland is a veterinary ophthalmologist at the James A. Baker Institute for Animal Health, in the College of Veterinary Medicine of Cornell University. His

research is undertaken as part of the Center for Canine Genetics and Reproduction directed by Dr. Gustavo Aguirre. Current projects include collaborative efforts to identify the genes for PRA in multiple breeds, for cone degeneration in Alaskan Malamutes, Collie Eye Anomaly, and several forms of cataract; and to evaluated potential therapies for inherited retinal degenerations. Dr. Acland is funded by the American Border Collie Association, the AKC Canine Health Foundation, the Baker Institute PRA/CEA Fund, The Foundation Fighting Blindness, and the National Eye Institute (Grant EY06855).