The known hereditary diseases of the canine eye
P.G.C. Bedford, BVetMed, PhD., DVOphthal, DipECVO, FRCVS
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. Excluding adnexal problems, in the U.K. some 47 of approximately 200 breeds currently Kennel Club registered are involved in 9 proven primary ocular disease conditions. These include defects of the uveal tract, the lens and the retina and several breeds are affected with more than one disease. The possibility of hereditary disease is being investigated in some 46 other breeds, and the range of ocular structure additionally involved includes the cornea and the optic nerve. Currently it is regular clinical examination which represents the most effective way of attempting disease control but for the future the development of DNA-based tests will help identify carrier animals and predict those affected clinically in maturity through puppy screening. Several gene mutation and linkage analysis tests already exist for inherited retinal disease, and more will come with the passage of time. Sadly ocular disease control is not practised as widely as perhaps it should be : in the United Kingdom, for example, in 1995 12,000 dogs were examined under the auspices of the joint Kennel Club/British Veterinary Association certification scheme, 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. The promise of DNA based tests will allow the accurate determination of genotype in the dog which is clinically normal at the 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.
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.
There are several adnexal conditions that are readily recognised as being inherited within specific breeds, but sadly the patterns of inheritance are not known. Conditions like entropion, ectropion and euryblepharon (diamond eye) are related to the required appearance of the dog, and their control necessitates changes in these requirements. For example, the combined entropion/ectropion defect in the Clumber Spaniel or the Neapolitan Mastiff will require the appearance of a more prominent eye with a smaller palpebral fissure. Other adnexal conditions that demonstrate breed predisposition are not related to appearance, and problems like distichiasis and trichiasis require the avoidance of affected lines in breeding programmes.
The congenital primary ocular diseases in the dog are retinal dysplasia, Collie Eye Anomaly (CEA), cataract, and the persistence of elements of the foetal tunica vasculosis lentis, persistent hyperplastic primary vitreous (PHPV) and persistence of the pupillary membrane (PPM). Congenital glaucoma per se is not inherited, but goniodysgenesis, 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 are not congenitally present include the various eyelid and other adnexal problems, hereditary cataract (HC), lens luxation (LL), primary glaucoma (PG), progressive retinal atrophy (PRA) and retinal pigment epithelial dystrophy (RPED, formally CPRA). With the exception of the eyelid and other adnexal problems, known to be inherited, the BVA/KC/ISDS Eye Examination Scheme certifies clinical status with respect to these 9 inherited disease problems.
Retinal Dysplasia describes those inherited conditions in which abnormal retinal 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 to be 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 sometimes referred to as rosettes, but classification is often confused. 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 Golden 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 which is seen in addition to simple neuroretinal folds in the Cavalier King Charles Spaniel, the Golden Retriever and the Labrador Retriever. To date total retinal non-attachment has only been described in the Bedlington Terrier and the Sealyham Terrier, whilst in the Labrador Retriever it has been seen both in dogs with and without skeletal abnormalities.
Collie Eye Anomaly enjoys high incidence in the Rough Collie and Shetland Sheepdog breeds in the U.K, but it 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 6 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 the congenital presence and a known mechanism of inheritance.
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 whereas cataract extraction is possible, corneal opacity is not treatable.
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 aging adults from approximately 6-8 months to 9 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 8 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 or Labrador 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 which directs the diagnosis towards an hereditary lesion. Differentiation of primary from secondary cataract is usually easily achieved and, of course, essential in terms of disease control.
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 : it usually affects dogs at 3 to 4 years of age. Unfortunately, the premonitory signs are short lived and it is the presence of the glaucoma which 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) are seen as the vital premonitory signs. The glaucoma is treated by removal of the lens, but such surgery must be completed quickly if sight is to be preserved.
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, nineteen breeds are involved in the PRA story in the United Kingdom and its possible presence is being investigated in another four 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 end point. For example, the rod/cone dysplasia of the Irish Setter results in blindness at 8 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 5 or 6 years of age. The actual gene mutations have been determined for very few of the PRA’s, but where they have the resultant DNA tests can be both 100% specific and accurate. The most celebrated test is that for the cyclic GMP phosphodiesterase defect in the rod/cone dysplasia of the Irish Setter, and this has been joined by tests for similar defects in the PRA of the Cardigan Welsh Corgi and the Sloughi. Linkage analysis tests based on the identification of a marker polymorphism are less accurate, but they have been developed for breeds like the Labrador Retriever and the Miniature and Toy Poodles. The appearance of PRA on a world wide basis involves many breeds and in the U.K., for example, in addition to the Irish Setter, the Miniature Poodle and the Cocker Spaniel, PRA has been described in the Australian Cattle Dog, Rough Collie, the Miniature Long-Haired Dachshund, the Elkhound, The Irish Wolfhound, the Lhasa Apso, the Miniature Schnauzer, the Toy Poodle, the Chesapeake Bay Retriever, the Golden Retriever, the Labrador Retriever, the American Cocker Spaniel, the English Springer Spaniel, the Tibetan Spaniel, the Tibetan Terrier and the Welsh (Cardigan) Corgi. Secondary cataract is commonplace in many affected dogs.
Retinal pigment epithelial dystrophy is due to an inability of the retinal pigment epithelial cells to support the neuroretina metabolically and as such there ensues secondary photoreceptor degeneration. The 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. Thus the dog collides with a stationary object but will detect movement. The disease is currently considered to be due to a defect in antioxidant activity within the retina and vitamin E has been shown to be the cause in some breeds. 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, there being as much as 18 months to 2 years between the initial appearance of the pigment foci and noticeable increased reflectivity. RPED can be detected as early as 17 months of age, but may not make its 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 Cardigan Welsh Corgi breeds in the United Kingdom and its possible inheritance in the Polish Lowland Sheepdog is being investigated.
Primary glaucoma is due to inherent defect within the aqueous drainage pathway. Open angle glaucoma due to a progressive loss of outflow facility through the endothelial meshwork part of the aqueous drainage pathway 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 4 to 6 months of age by gonioscopy and the disease has been described in the Basset Hound, the Flat Coated Retriever, the Siberian Husky, the American Cocker Spaniel, the Cocker Spaniel and the Welsh Springer Spaniel in the United Kingdom. Its possible presence as an inherited defect, but not necessarily the same aetiology as a mechanical angle closure, is currently being investigated in the Dandie Dinmont Terrier, the Elkhound, the Great Dane, the Hungarian Vizsla, the Golden Retriever, the English Springer Spaniel and the Welsh Terrier.
The control of inherited disease is the responsibility of the breeder and his breed society, but the veterinary profession and Kennel Club authorities have their roles to play. As far as the eye is concerned, such control is currently 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 certificated clinical examination 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 a problem for the whole breed and, as such, control measures must be accepted by the whole breed working in unison. Routine examination, the development of DNA based testing, and the publication of results in an open registry are essential if the propagation of inherited disease is to be denied.