Inherited Disease of the Canine Eye
Peter Bedford United Kingdom
The spectrum of inherited ocular disease in the world of the pedigree dog involves many breeds and all parts of the eye. Both disease type and incidence vary geographically, as does breed popularity. Currently, it is regular clinical examination which represents the most effective way of attempting disease control, but in the future, the DNA-based genetic tests will play an increasingly significant role. In 1995, some 12,000 dogs were examined under the official control scheme in the UK, recording an overall failure rate of 4.23%. Under-subscription in some areas means that unfortunately accurate incidence figures for some of the diseases are rarely available. Of course, clinical examination has its limitations and can only confirm genotype directly in the presence of disease. For the future the promise of DNA based tests will allow the accurate determination of genotype in the dog which is clinically normal at time of examination. However, irrespective of the mechanism of diagnosis, successful disease control means the acceptance of hereditary disease as a breed problem and wholesale subscription to the current control schemes is required if such schemes are to prove successful.
Diseases with Proven Mechanisms of Inheritance
Inherited or primary ocular disease may be present as a congenital defect or may develop clinically in adolescence or later in life. The exact mode of inheritance may or may not have been defined, but marked breed predisposition clearly demonstrates a genetic base. The congenital primary ocular diseases in the dog include retinal dysplasia, Collie Eye Anomaly (CEA), cataract, and the persistence of elements of the primary vitreous (PHPV) and elements of the pupillary membrane (PPM). Congenital glaucoma per se is not inherited, but goniodynesis, abnormal development of the iridocorneal or drainage angle, is inherited in certain breeds and this congenital defect may predispose to primary angle closure glaucoma, usually in middle-aged or older dogs. Several types of progressive retinal atrophy find origin in congenital abnormality of the photoreceptor units of the retina, but the associated disease does not make its clinical appearance until several months of age. The inherited diseases which develop after birth, include the various eyelid and other adnexal problems, hereditary cataract (HC), lens luxation (LL), primary glaucoma (PG), progressive retinal atrophy (PRA), and retinal pigment epithelelial dystrophy (RPED, formally CPRA).
1. Retinal Dysplasia
Retinal Dysplasia describes those inherited conditions in which abnormal differentiation results in neuroretinal fold and rosette formation, degeneration or non-attachment. The effect ranges from no noticeable impairment of sight through to blindness. All forms of RD are considered simple recessive traits. A simple fold may be linear, Y shaped or circular and results from the non-attachment of the neural part of the retina, the neuroretina, to the underlying retinal pigment epithelium in that area. Complicated folds in which there is a proliferation of photoreceptor and RPE elements are referred to as rosettes. Folds may be accompanied by variable degrees of retinal detachment and degeneration.
In the United Kingdom R.D. has been recorded in the Bedlington Terrier, the Cavalier King Charles Spaniel, the Hungarian Puli, the Labrador Retriever, the Rottweiler, the Sealyham Terrier, the American Cocker Spaniel and the English Springer Spaniel. Its potential presence as an inherited disease is being investigated currently in another eight breeds including a geographic form that is seen in addition to simple neuroretinal folds in the Cavalier King Charles Spaniel, the Golden Retriever and the Labrador Retriever.
2. Collie Eye Anomaly
Collie Eye Anomaly enjoys high incidence in the Rough Collie and Shetland Sheepdog breeds in the U.K, but is also seen in the Smooth Collie and the Border Collie. It was recently recorded in a non-collie breed, the Lancashire Heeler. Again, the disease is considered to be inherited as a simple recessive trait and exhibits pleiomorphism. All affected dogs demonstrate choroidal hypoplasia to varying extent, with some 30% being additionally affected by colobomatous defects of the optic disc and peri-papillary sclera. Blindness is seen in approximately 6% of affected eyes as the result of either congenital neuroretinal non-attachment or the early onset of neuroretinal detachment usually within the first two to three years of life. Haemorrhage can complicate the presenting clinical picture. Disease control is complicated by the fact that as many as 30% of those puppies which exhibit the ophthalmoscopic signs of choroidal hypoplasia at six weeks of age, mask this lesion by pigmentation in the adult fundus, the so called �go normal� phenomenon. Thus, the phenotype appears normal but, of course, the genotype is that of disease. It follows that disease control must start with litter screening for a combination of �go normal� and carrier offset the advantages of congenital presence and a known mechanism of inheritance.
3. Persistent Hyperplastic Primary
Persistent Hyperplastic Primary vitreous is due to the retention of elements of the foetal vascular supply to the lens, the tunica vasculosis lentis. The lesions seen are variable amounts of fibrovascular plaque on the posterior lens capsule and possible posterior cortical cataract. The effect on sight can range from nothing to blindness. Removal of the diseased lens can be complicated by any vascular involvement. Persistent pupillary membrane is of the same origin, but this time remnant strands of the anterior part of the tunica vasculosis lentis remain attached to the iris and may occasionally interfere with sight as the result of associated lens or corneal opacities. Again, any effect on sight is variable, but cataract extraction is possible, whereas corneal opacity is not treatable.
4. Hereditary Cataract
Hereditary Cataract may be congenitally present as a nuclear opacity or may develop variably in terms of position, extent and age in both young and ageing adults from approximately 6�8 months to nine years of age. Currently, some 17 breeds are affected in the UK with the Boston Terrier and the Miniature Schnauzer each being affected with two types of inherited cataract. The possibility of HC is currently being investigated in another eight breeds of dog.
Cataract is defined as any opacity of the lens and/or its capsule. Thus, the clinical features seen range from pinhead marks to total lens opacity. The larger the cataract, the more severe the effect on sight. Congenital cataract is usually static, allowing vision through the adult cortical portion of the lens. As such, it can often be managed medically and surgery may never prove necessary. Hereditary cataract in young and adult dogs may or may not cause blindness depending on the amount of lens involved. For example, the posterior polar cataract of the Golden Retriever is static, but in 5% of affected dogs, there is subsequent cortical opacitation and surgery is necessary to restore sight. In the Siberian Husky and the Norwegian Buhund, the cataract is usually confined to the posterior cortex, but the amount of change is variable and surgery seldom proves necessary. Throughout the affected breeds, it is the pattern of the cataract together with age of involvement that directs the diagnosis towards a hereditary lesion. Differentiation of primary from secondary cataract is usually easily achieved, and of course, essential in terms of disease control.
5. Lens luxation
Lens luxation is the displacement or dislocation of the lens from its position on the anterior face of the vitreous due to the degeneration of its suspensory apparatus. In most patients, the lens moves into the pupil or the anterior chamber resulting in secondary glaucoma. Lens luxation is recessively inherited in several Terrier breeds and the Border Collie and usually affects dogs at three to four years of age. Unfortunately, the premonitory signs are short lived; the presence of the glaucoma dictates the diagnosis. Usually there is a lag of days to weeks before the second eye involvement and it is during this time that the presence of vitreous in the pupil or marked iridodenesis (iris tremble) is seen. The glaucoma is treated by removal of the lens, but such surgery must be completed quickly if sight is to be preserved and chronic glaucoma avoided.
6. Progressive Retinal Atrophy
Progressive Retinal Atrophy covers a number of inherited neuroretinal degenerations, some of which are due to primary photoreceptor dysplasia, whilst others are due to photoreceptor degeneration of, as yet, undetermined aetiologies. Currently, fifteen breeds are involved in the PRA story in the United Kingdom and its possible presence is being investigated in another six breeds. All types of PRA are inherited as recessive traits and all are characterised ophthalmoscopically by increased tapetal reflectivity and blood vessel degeneration. The age of onset varies, but total blindness is the common endpoint. For example, the rod/cone dysplasia of the Irish Setter results in blindness at eight to 12 months of age, whilst the rod/cone degeneration of the Miniature Poodle or Cocker Spaniel may not demonstrate clinical effect until the affected dog is five or six years of age. Aetiology is only completely understood for the Irish Setter and it has been possible to develop a DNA-based test to identify the defective genetic material in this breed. No such test currently exists for the other types of PRA and disease control is confounded by carriers and late onset. In addition to the Irish Setter, the Miniature Poodle, and the Cocker Spaniel, PRA has been described in the Rough Collie, Miniature Long-Haired Dachshund, Elkhound, the Miniature Schnauzer, Toy Poodle, Chesapeake Bay Retriever, Labrador Retriever, American Cocker Spaniel, English Springer Spaniel, Tibetan Spaniel, Tibetan Terrier, and Welsh (Cardigan) Corgi. Secondary cataract is commonplace in many affected dogs.
7. Retinal Pigment Epithelial Dystrophy
Retinal pigment epithelial dystrophy is due to an inability of the retinal pigment epithelial cells to supply nutrients to the neuroretina and as such, there ensues secondary photoreceptor degeneration. Its effect is largely confined to the non-pigmented part of the retina within the tapetal fundus and, as such, affected dogs rarely lose their peripheral vision. The initial ophthalmoscopic change is the appearance of light brown pigment foci within the tapetal fundus. Histology demonstrates that the foci are due to accumulating lipopigment within the retinal pigment epithelial cells. The lipopigment is phagocytosed photoreceptor outer segment material that accumulates within the cytoplasm of these cells, rather than being broken down by lyzosomal activity and recirculated into the neuroretina for new outer segment production. It is the ongoing accumulation of the pigment that stops the adequate nutrition of the photoreceptors by the retinal pigment epithelium and leads to their degeneration. This degeneration is seen ophthalmoscopically as increased tapetal reflectivity; as much as 18 months to two years can pass between the initial appearance of the pigment foci and noticeable increased reflectivity. Because the pigmented retinal pigment epithelial cells remain relatively immune to lipopigment accumulation, affected dogs only effectively lose their central vision. For example, the dog collides with a stationary object, but detects movement. RPED can be detected as early as 17 months of age, but may not make an appearance until the ninth year of life. The mechanism of inheritance is unknown and this together with a possible late onset can render disease control difficult.
RPED is currently described in the Border Collie, Briard, Rough Collie, Smooth Collie, Golden Retriever, Labrador Retriever, Shetland Sheepdog, Cocker Spaniel, English Springer Spaniel and Welsh Corgi breeds in the United Kingdom and its possible inheritance in the Polish Lowland Sheepdog is being investigated. Recent work in the Cocker Spaniel breed has shown that this disease is associated with low levels of plasma alpha- tocopherol and that the inherited defect is likely to be a deficiency of a liver derived tocopherol transfer function.
8. Primary Glaucoma
Primary Glaucoma is due to inherent defect within the aqueous drainage pathway. Open angle glaucoma is uncommon in the canine population, but an angle closure glaucoma, consequent to a goniodysgenesis in which there is abnormal differentiation of the pectinate ligament, is inherited in several breeds of dog. This latter disease is characterised by sudden onset loss of sight and pain due to spontaneous closure of the ciliary cleft. The goniodysgenesis can be detected at four to six months of age by gonioscopy and the disease has been described in the Basset Hound, Flat Coated Retriever, Siberian Husky, American Cocker Spaniel, Cocker Spaniel, and Welsh Springer Spaniel in the United Kingdom. Its possible presence as an inherited defect, but not necessarily the same aetiology, is currently being investigated in the Dandie Dinmont Terrier, Elkhound, Great Dane, Hungarian Vizsla, Golden Retriever, English Springer Spaniel, and Welsh Terrier.
The control of inherited disease is the responsibility of the breeder and his breed society, but the veterinary profession and the national kennel clubs have their roles to play. As far as the eye is concerned, such control is based upon regular clinical examination, particularly of the breeding stock. In the future, DNA based tests will play an increasingly significant role, but for the present and the immediate future, an awareness of the diseases and the use of the official certification schemes represent the most significant features of disease control. The presence of an inherited disease is not only a problem for the affected dog, but also a problem for the whole breed, and as such, control measures must be accepted by the whole breed working in unison. Routine examination and the publication of results in an open registry are essential if the propagation of inherited disease is to be denied.
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