Ординатура / Офтальмология / Английские материалы / Slatter's Fundemental of Vetrinary Ophthalmology 4th edition_Maggs, Miller, Ofri_2008

In some animals only small tapetum “islands” may be seen (Figure 15-26). In canine toy breeds the tapetum is frequently small. Primates (see Figure 15-7, F), pigs, most rodents (see Figure 15-7, E), and many nonmammalian species (see Figures 15-10, B, and 15-11) lack a tapetum all together.

Nontapetum

In most mammals, the tapetum covers approximately the dorsal third of the fundus. The rest of the fundus is called the nontapetum. Here the underlying RPE is pigmented, giving this area its characteristic dark appearance (see Figure 15-7, A, C, and D). However, the amount of the pigmentation may vary. Moderate amounts of RPE pigment in the nontapetal area give this region a light brown (chocolate) shade rather than the characteristic black appearance. Lack of pigment in the pigment epithelial cells of the nontapetal retina is a common variation (see Figures 15-24, B, and 15-27) and is frequently seen in subalbinotic or color-dilute animals (e.g., Siamese cat,

appaloosa, merle collie). If there is no pigment in the RPE, the underlying choroid and sclera may be visualized in the nontapetal area (tigroid fundus).

Optic Disc

The location of the optic disc in the eye is fixed because it is determined by the location of the underlying optic foramen through which the optic nerve exits the orbit. However, the size of the tapetal and the nontapetal regions may vary, so the disc may be visualized in the tapetal area (if the tapetum is large), in the nontapetum (if the tapetum is small), or in their junction.

The presence of myelin determines the size and shape of the optic disc. In the cat, myelination of the optic nerve fibers begins posterior to the disc, and therefore the disc is round and dark (similar to an atrophied canine disc) (see Figure 15-7, B). In dogs, myelination of the fibers usually begins at the level of the disc, giving it a characteristic triangular shape and pink shade (see Figure 15-7, A). However, variations in size, shape,

FIGURE 15-25. Localized absence of the tapetum in a yearling. Although the retinal pigment epithelium (RPE) in the nontapetum is pigmented, the RPE overlying the region of tapetal aplasia is unpigmented, allowing visualization of the underlying choroidal vessels, which can be seen as broad red bands. This is a normal variation. (From Rubin LF [1974]: Atlas of Veterinary Ophthalmoscopy. Lea & Febiger, Philadelphia.)

FIGURE 15-26. In the fundus of this dog, only a few tapetal “islands” are visible through the pigmented retinal pigment epithelium. Myelination of the nerve fibers can be seen as white streaks radiating from the disc. This is a normal variation.

FIGURE 15-27. Fundus pictures of two animals in which the retinal pigment epithelium in the nontapetum does not contain melanin. Its absence allows visualization of the underlying choroidal vessels, which can be seen as broad red bands. In both cases, the tapetal area is normal. A, A domestic shorthair cat; B, a horse. (From Rubin LF [1974]: Atlas of Veterinary Ophthalmoscopy. Lea & Febiger, Philadelphia.)

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and color of the optic disc, based on the extent of myelination, are common in the dog. The disc may also be surrounded by a ring of pigment or hyperreflectivity, both of which are considered normal variations. A dark spot may be seen in the center of the disc, the physiologic cup representing the origin of the embryonic hyaloid vascualture.

Blood Vessels

As noted previously, the blood vessels seen ophthalmoscopically are those supplying the inner retina and midretina. The large, straight vessels are the veins. There are usually three veins, although it is not uncommon to see four or more large veins. In the cat the veins stop at the edge of the disc, but in dogs they cross over its surface and usually form a vascular ring (see Figure 15-7, A and B). In dogs in which the veins stop abruptly on the disc surface, a coloboma or glaucomatous cupping should be suspected.

Arteries are the smaller vessels. They are more numerous (10 to 20) and usually more tortuous than veins. In dogs arteries usually stop at the disc rim and do not cross the disc surface as do the veins. It is important to learn to distinguish arteries from veins, because arteries are the first vessels to undergo attenuation in cases of inherited retinal atrophies.

Myelination of Nerve Fiber Layer

Myelination of canine optic nerve fibers usually begins at the optic disc. Occasionally myelination spreads into the nerve fiber layer of the retina, appearing as white fan-shaped streaks radiating from the optic disc (see Figure 15-26). These are differentiated clinically from papilledema and optic neuritis (see Table 16-10 in Chapter 16).

PATHOLOGIC MECHANISMS

Ischemia

The retina has a bipartite blood supply, because the choroid supplies the outer retina, and the inner retinal vessels (visible ophthalmoscopically radiating from the disc) supply the inner retina and midretina. Owing to its high metabolic rate, the retina is particularly susceptible to interruptions in blood supply. After hypoxia begins, death of retinal cells follows rapidly, intracellular and extracellular edema occurs, neural elements disintegrate, and atrophy and gliosis of the retina result. Many disease processes

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(e.g., anemia, inflammation, retinal detachment, increased intraocular pressure, decreased orbital circulation after trauma) may result in decreased retinal circulation and tissue hypoxia.

Repair Processes

Like other neural tissues, the retina has limited or no regenerative capacity. Changes in photoreceptor and neural elements are almost always irreversible, limiting the scope of treatment for many disorders to prevention of further damage. Repetitive or chronic stimuli thus result in cumulative damage until vision is affected.

Retina–Optic Nerve Interaction

Diseases that result in severe and widespread retinal lesions, especially of the ganglion cell layer, eventually also cause lesions of the axons of these cells in the optic nerve—the clinical disorder of optic atrophy. Similarly, lesions to the optic nerve fibers (e.g., in chronic optic neuritis) eventually cause death of the ganglion cell body. This is believed to be due to interruptions of axoplasmic flow—the flow of solutes along the axon both toward and away from the cell body.

A process of transsynaptic atrophy also takes place across the various layers of the retina. Lesions of the photoreceptors in the outer retina eventually result in damage to the intermediate layers and loss of ganglion cells with optic atrophy. Conversely, although glaucoma is primarily a ganglion cell and optic nerve disease, damage to the outer retina may be observed in chronic cases.

Interactions with Choroid

Because of their proximity, inflammation of the choroid frequently extends to involve the retina, and vice versa. Common examples are hematogenous bacterial and viral infections of the choroid (feline infectious peritonitis [FIP]), bovine malignant catarrhal fever) that extend to the retina, thereby causing chorioretinitis. Neurotrophic viral retinitis (e.g., canine distemper) may proceed from retina to choroid, thereby causing retinochoroiditis. However, the distinction between retinochoroiditis and chorioretinitis is somewhat semantic, as clinically it is impossible to distinguish between the two. The inflammation invariably results in a breakdown of the bloodocular barrier and spreads to both the retina and choroid. The

consequences of many of these disorders are often much more devastating to the retina than to the tissue from which they arose.

Primary Photoreceptor Disease

Many disorders in the group of “retinal atrophies” primarily affect the photoreceptors. In most cases the disease process begins in the more peripheral retina and in its early stages may be visualized as discoloration of the peripheral tapetum. However, with time the disease progresses to involve the entire retina. As the retina atrophies, it becomes thinner, resulting in increased tapetal reflectivity. If the tapetum and transparent retina are compared to a mirror (tapetum) and curtain (retina), when the curtain is removed (retinal atrophy), reflectivity is increased (Figure 15-28). This increased reflectivity is visible ophthalmoscopically (Figure 15-29; compare it with Figure 15-7, B).

The second ophthalmoscopic sign associated with retinal atrophy is gradual vascular attenuation. Vascular attenuation is secondary to the atrophy, rather than its cause. Blood supply diminishes as the atrophic retina has fewer metabolic requirements (see Figures 15-29, B, and 15-30; compare them with Figure 15-7, B and A, respectively). The attenuation may be observed as a decrease in both the diameter and number of vessels. Arteries are affected before veins, and small vessels are affected before larger vessels are affected.

Reactions of Pigment Epithelium

Besides its roles in metabolic support and photopigment recycling, the RPE has potential phagocytic activity. Therefore inflammation or infection of the retina is frequently accompanied by a phagocytic reaction of the RPE, with cells undergoing hypertrophy, proliferation, and migration to the diseased area where they phagocytose inflammatory debris. Subsequently, the RPE may also undergo atrophy.

Reactions of pigment epithelium are frequently visible ophthalmoscopically. If atrophy of the pigment epithelium occurs over the tapetum, it is not readily apparent because it is nonpigment (and hence invisible ophthalmoscopically) in this region. However, if it occurs in the nontapetal area, the affected region is visible as a depigmented or pale area, giving the nontapetal fundus a mottled appearance (Figures 15-31 and

FIGURE 15-28. Pathogenesis of increased tapetal reflectivity in cases of retinal atrophy. A thinner (atrophied) retina absorbs less light; hence more light reaches the tapetum and is reflected toward the observer.

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B

FIGURE 15-29. Fundus picture of retinal atrophy in two Abyssinian cats. Compare these pictures with the normal feline fundus in Figure 15-7, B. A, A moderately advanced case. Note the hyperreflectivity of the tapetal fundus, observed most clearly in the upper midperipheral area. See also Figure 15-47, which shows the histopathologic changes in this retina. B, Advanced stage. Note the hyperreflectivity next to the optic disc, and the further attenuation of the blood vessels. (Courtesy Kristina N. Narfström.)

FIGURE 15-30. Vascular attenuation in a poodle with progressive retinal degeneration. Compare diameter of blood vessels with those seen in Figure 15-7, A.

FIGURE 15-31. Focal loss of pigment (arrow) from pigment epithelial cells in the nontapetal area in a dog with progressive retinal degeneration.

FIGURE 15-32. Ophthalmoscopic appearance of paler “punched-out” area of depigmentation of the pigment epithelium in the nontapetal fundus in progressive retinal degeneration.

FIGURE 15-33. Hypertrophy of pigment epithelial cells (arrows) and atrophy of the underlying retina as a result of chorioretinitis in a dog.

FIGURE 15-34. Three areas of inactive retinitis in the tapetal dog fundus. In each area, the atrophied retina is visible as a hyperreflective region, the center of which is occupied by a pigment clump. This clump is retinal pigment epithelium that migrated to this region to phagocytose inflammatory debris. (Courtesy University of California, Davis, Veterinary Ophthalmology Service Collection.)

15-32). When proliferation of pigment epithelial cells occurs, with either hyperplasia or hypertrophy, the results are visible ophthalmoscopically as focal areas of increased pigmentation, or pigment clumps. These areas are most readily visible in the tapetal fundus (Figures 15-33 and 15-34). If the primary cause is an inflammation of the retina, the hypertrophy and hyperplasia of pigment epithelial cells are often accompanied by loss of adjacent rods and cones. In such cases, areas of pigment clumping may be surrounded by focal regions of tapetal hyperreflectivity, similar to the hyperreflectivity seen in inherited photoreceptor diseases.

Perivascular Cuffing

In inflammatory and neoplastic diseases, inflammatory cells frequently accumulate around retinal vessels, as they do in any other tissue. However, in the eye, unlike any other organ, this reaction can be visualized in vivo using an ophthalmoscope (Figure 15-35). The vasculitis, or “perivascular cuffing,” is visible

as a white or gray sheath around vessels that sometimes obscures their color (Figure 15-36).

Retinal Hemorrhages

Hemorrhages into and around the retina occur in many diseases and conditions, such as anemia, coagulopathy, systemic hypertension, hyperviscosity, and systemic infectious diseases such as canine ehrlichiosis and bovine thromboembolic meningoencephalitis (see also Chapter 18). Based on their ophthalmoscopic appearance, it is possible to localize the position of these hemorrhages to the layer involved, that is, subretinal (between the retina and choroid), intraretinal, nerve fiber layer, or preretinal (between the retina and vitreous) (Figure 15-37). The localization helps in identifying the source of the blood because subretinal hemorrhages originate in the choroidal vessels, whereas preretinal hemorrhages originate in the ophthalmoscopically visible vessels of the inner retina.

15-35. Perivascular cuffing of inflammatory cells around retinal vessels in a cat diagnosed with feline infectious peritonitis. (Courtesy University of California, Davis, Veterinary Ophthalmology Service Collection.)

FIGURE 15-36. Perivascular cuffing forming a gray-white sheath around retina vessels of a dog with systemic mycosis. (Courtesy University of Wisconsin–Madison Veterinary Ophthalmology Service Collection.)

Gliosis

In many acute, severe insults, neural elements of the retina may be lost early, but the more resistant glial Müller’s cells survive and may proliferate to fill spaces left by neural cells. The end stage of many chronic retinal disorders is often a glial scar replacing the retina (Figure 15-38).

CONGENITAL RETINAL DISORDERS

Retinal Dysplasia

Primary retinal dysplasia is a congenital, developmental abnormality of the retina. It occurs in all species but is of greatest clinical significance in dogs, being of lesser importance in cats and cattle. It has been defined as an anomalous differentiation, characterized histologically by linear folding of the sensory retina and formation of rosettes containing variable numbers of neuronal retinal cells around a central lumen (Figure 15-39). The most significant forms of canine retinal dysplasia are

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hereditary, although dysplasia may also be found with maternal viral infections (e.g., canine herpes, feline panleukopenia, ovine blue tongue, bovine viral diarrhea), toxicities in utero, and multiple ocular anomalies. Cases of noninherited retinal dysplasia are frequently accompanied by other developmental neurologic abnormalities, notably cerebellar hypoplasia.

Inherited canine retinal dysplasia occurs most commonly in American cocker spaniels, English springer spaniels, beagles, Labrador retrievers, miniature schnauzers, Australian shepherd dogs, Rottweilers, and Bedlington, Sealyham, and Yorkshire terriers, but it can occur in any breed. It can be subdivided into the following three forms:

•Focal or multifocal retinal dysplasia: Retinal folds and rosettes are seen as areas of reduced tapetal reflectivity, as gray streaks in the tapetal area, and as gray or white streaks in the nontapetal area (Figure 15-40). The streaks may be linear or Y- or V-shaped. They are most commonly found in the central fundus, in the tapetal area. Vision is usually normal. This form is seen in spaniels, beagles, Rottweilers, and Labrador retrievers.

•Geographic retinal dysplasia: Irregular or U-shaped areas are seen in the tapetal fundus. Elevated and thinned parts of the retina may be present, with gray or black areas delineating the affected retina (Figure 15-41). Areas of hyperreflectivity may also be present. Retinal pigment epithelial hypertrophy may be indicated by areas of increasing pigmentation. Vision may be severely affected, depending on the size of the lesion. The commonly affected breeds include the spaniels and Labrador retriever.

•Complete retinal dysplasia with detachment: A completely detached neural retina attached at the optic nerve head is seen. Vitreous dysplasia, leukocoria, rotatory nystagmus, and hemorrhages may be seen in affected animals. Blindness or severe visual impairment is usual. This form is seen in Bedlington and Sealyham terriers, English springer spaniels, and also in Labrador retrievers and Samoyeds when combined with skeletal chondrodysplasia. In the retinal dysplasia with associated chondrodysplasia in Labrador retrievers and Samoyeds, ocular lesions include cataracts, vitreous strands, persistent hyaloid remnants, retinal folds, retinal dysplasia, peripapillary hyperreflectivity, and rhegmatogenous retinal detachments. Skeletal effects include short forelimbs and abnormal morphology of the radius and ulna. The condition is due to one abnormal gene, which has recessive skeletal effects and incompletely dominant ocular effects.

The most common reasons for presentation of animals with inherited retinal dysplasia are blindness and intraocular hemorrhage in puppies, although these occur only in a small proportion of affected dogs. Milder forms of dysplasia and folds may be seen during routine screening programs for hereditary ocular defects in puppies and older dogs. Because the mild forms of the disease have minimal effect on vision, owners will frequently breed them even though the offspring may be affected with severe forms of the disease. Dysplasia is usually transmitted as a simple recessive trait, although dominant inheritance with incomplete penetration may afflict the Labrador retriever.

Animals with retinal dysplasia should not be bred.

FIGURE 15-38. Glial band replacing the retina in chronic glaucoma.

FIGURE 15-39. Retinal folds and rosettes in a kitten whose dam was affected with panleukopenia during pregnancy. Cerebellar hypoplasia was also present. (Courtesy Drs. G.A. Severin and Julie Gionfriddo, Colorado State University.)

FIGURE 15-41. Geographic retinal dysplasia in the German shepherd. (From Geographical retinal dysplasia in the dog. American College of Veterinary Ophthalmologists, 1999.)

FIGURE 15-42. Choroidal hypoplasia temporal to the optic disc in a collie with collie eye anomaly. Owing to the hypoplasia, choroidal vessels may be visualized as thick red bands. These vessels are abnormal in number and shape (compare them with the choroidal vessels in Figure 15-27, A).

FIGURE 15-40. Foci of retinal dysplasia in a 7-month-old American cocker spaniel. Areas overlying the tapetum appear as dark streaks, surrounded by a narrow zone of hyperreflectivity. (Courtesy Dr. A. MacMillan.)

Collie Eye Anomaly

Collie eye anomaly (CEA) is an inherited, congenital disorder that affects collies, Shetland sheepdogs, Lancashire heelers, and Australian shepherds. It has also been reported in several nonshepherd breeds, including long-haired whippets and Nova Scotia duck-tolling retrievers. The disease has worldwide distribution, with prevalence of 30% to 85% reported in various countries. Its defining feature is choroidal hypoplasia in the region temporal to the disc. Within this area, focal absence of tapetum and RPE

pigment allows visualization of abnormal choroidal blood vessels (Figure 15-42). The vessels appear wider, fewer in number, and irregularly oriented. Up to 35% of CEA cases may also be affected by optic nerve head colobomas (Figure 15-43). A coloboma can be seen as a gray indentation of variable depth in the optic disc and is further described in the following section. Other clinically significant features are intraocular hemorrhages and retinal detachments, which may be partial or complete, although these are far less frequent and occur in less than 10% of affected dogs. Tortuous blood vessels, retinal dysplasia, and microphthalmia may also be present. Dogs with complete retinal detachment are blind, whereas those with optic nerve coloboma or partial detachment have visual deficits. However, choroidal hypoplasia by itself does not cause any visual deficits, leading some breeders to downplay the significance of CEA.

The inheritance mode of CEA is still being studied. Simple autosomal recessive transmission has long been suspected, but recent evidence suggests that the disease is polygenic, thus

FIGURE 15-43. Coloboma of the sclera and optic nerve in a collie with collie eye anomaly. Retinal vessels reaching the edge of the disc coloboma disappear from view as they “dive” into the coloboma.

FIGURE 15-44. Coloboma in a basenji pup with persistent pupillary membrane. Note the retinal rosettes on the right side of the coloboma beneath the retina.

hindering attempts to reduce the prevalence of CEA through selective breeding. Another complicating factor in the control of the disease is the “go normal” phenomenon. In maturing puppies, the characteristic choroidal hypoplasia may be covered by RPE pigment, which masks the underlying lesion (thus making the eye appear to “go normal”). In Norway it has been shown that approximately half the CEA cases may be masked after 3 months of age. Therefore it is recommended that puppies be screened for the disease at 7 to 8 weeks of age. The advent of genetic testing for CEA may help in the control of the disease, although large-scale studies of its accuracy are still lacking.

Coloboma

Colobomas are congenital malformations caused by incomplete closure of the embryonic optic fissure (see Chapter 2). As a result, a section of the uvea, retina, choroid, sclera, and/or optic nerve may be missing. Colobomas of the iris or lens appear as actual notches in these organs. Colobomas of the retina and choroid appear as focal areas of hypopigmentation. Colobomas of the optic nerve appear as gray indentation in the optic disc. Their depth is variable and may be estimated using a direct ophthalmoscope. Blood vessels may be seen disappearing over the coloboma as they “dive” into the pit. Colobomas of the optic nerve are seen in CEA (see Figure 15-43), in basenjis in association with persistent pupillary membranes (Figure 15-44), and in Charolais cattle. Isolated colobomas are uncommon but are seen occasionally in all species (Figure 15-45). Scleral colobomas appear as actual indentation in the wall of the globe.

RETINOPATHY

Retinopathies can be divided into the following four major classes:

•Inherited dystrophies, dysplasias, degenerations and atrophies: For example, progressive rod-cone degeneration (prcd) in the poodle and American cocker spaniel, rod dysplasia in the Norwegian elkhound, etc. (discussed next)

•Acquired retinopathies: These retinopathies are secondary to systemic diseases, such as infectious diseases of the

15-45. Giant coloboma of the optic nerve head in a cat. The patient also suffered from a coloboma (agenesis) in the lateral aspect of both upper eyelids. (Courtesy University of Wisconsin–Madison Veterinary Ophthalmology Service Collection.)

choroid and/or retina (e.g., canine distemper, fungal disease, FIP) and cardiovascular diseases (e.g., systemic hypertension, anemia, hyperviscosity) (see Acquired Retinopathies in this chapter and Chapter 18).

•Specific retinopathies: Atrophy secondary to glaucoma (see Chapter 12), uveodermatologic syndrome (see Chapter 11), and SARD (see later).

•Retinopathies of miscellaneous causes: Causes may be nutritional deficiency (e.g., taurine deficiency in cats, hypovitaminosis A in cattle), storage diseases (e.g., ceroid lipofuscinosis in dogs, cats, and sheep, or mannosidosis in Aberdeen Angus cattle and cats), or drug or plant toxicity (e.g., bracken fern poisoning in sheep, oxygen toxicity in premature human infants and in animal models, including kittens and puppies).

Inherited Retinopathies

Historically, all inherited retinopathies were given the collective name retinal atrophy. However, this broad definition encompasses a large group of diseases that differ in the age of onset, the breed and cells they primarily affect, mode of inheri-

tance, and genetic and molecular pathogenesis (Table 15-5). The situation is further complicated by the fact that classification and subdivision of retinal disorders in dogs continue to evolve as detailed genetic, electron microscopic, and electroretinographic studies are performed on specific disorders in different breeds. Therefore the list in Table 15-5 should by no means be regarded as final. Based on clinical examinations, many other dog breeds are suspected of being affected by inherited retinopathies, and it is possible that future studies will lead to their inclusion in this list (see the Appendix). Furthermore, inbreeding in existing breeds and “development” of new breeds may cause the disease to appear in additional breeds.

Table 15-5 Classification of Inherited Retinopathies

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Classification of Inherited Retinopathies

AGE OF ONSET. Broadly speaking, inherited retinopathies can be classified as dysplasia or degenerative. Rod-cone dysplasia (rcd) (which should not be confused with retinal dysplasia, the abnormal differentiation and folding of the retina described previously in the section on congenital diseases) is defined as atrophy of the photoreceptors that occurs before they have completed their development. Examples of photoreceptor dysplasia are the rcd type 1 in the Irish setter, rcd type 2 in the collie, rod dysplasia in the Norwegian elkhound, and photoreceptor dysplasia in the miniature schnauzer.

Degenerative retinopathy, on the other hand, is defined as an inherited atrophy of the photoreceptor that takes place after the cells have completed their development. Therefore it is a late-onset disease, although the age of onset may vary greatly among breeds. For example, cone-rod degeneration (crd) may be diagnosed by age 4 to 6 months in the miniature longhaired dachshund, and early retinal degeneration (erd) may be observed before 1 year of age in the Norwegian elkhound (Table 15-6). On the other hand, progressive rod-cone degeneration (prcd), which is probably the most common form of inherited retinal degeneration, is typically diagnosed in dogs older than 3 years, although it may also be diagnosed in elderly dogs. The disease affects at least 20 breeds, including popular breeds such as the toy and miniature poodles, Labrador retriever, and American and English cocker spaniels.

AFFECTED CELLS. Inherited retinopathies may initially affect the rods, cones, or RPE. The name of the disease is commonly indicative of the cell that is primarily affected. Thus in both rcd and prcd the disease process initially involves the rods and then spreads to the cones. Cone degeneration (cd) in the Alaskan malamute and German shorthaired pointer is a nonprogressive disease that affects only the cones, whereas crd in the dachshund and pit bull terrier spreads from cones to rods. RPE dystrophy (RPED) is a disease that affects primarily the RPE.

MODE OF INHERITANCE. The great majority of the inherited retinopathies are autosomal recessive diseases, with some exceptions. RPED may be a dominant disease with variable penetrance in the Labrador retriever. PRA is inherited as a dominant disease in the mastiff and the bullmastiff, and it is X-linked in the Siberian husky and Samoyed. Sometimes the same breed may be afflicted with two different forms of the disease. The Abyssinian cat, for example, is afflicted with both early-onset rcd, which is inherited as an autosomal dominant disease, and a late-onset rod-cone degeneration, which is inherited as an autosomal recessive disease.

GENETIC AND MOLECULAR PATHOGENESIS. The list of breeds in which retinal atrophy is suspected to be a hereditary disease is very long (see the Appendix). During the last decade the genetic, molecular, and biochemical abnormalities that cause inherited retinopathies have been the subject of intensive research in scores of dog breeds. Obviously, the great variation in the phenotypic appearance of inherited retinopathies reflects a wide variety in the genotype of the disease. At least seven forms of PRA have been identified, based on the mutated gene

or the mutation locus. Thus, for example, rcd1 in the Irish setter and rcd2 in the collie present with similar clinical, ERG, and histopathologic findings, but they differ as to which gene is mutated. Mating of affected dogs from the two breeds therefore produces normal offspring that are carriers of both diseases. Generally speaking, however, all of the inherited rod-cone retinopathies are caused by mutations in one of the enzymes responsible for the phototransduction process. The mutation causes disruption of the biochemical cascade that takes place in the outer segment of the photoreceptor. The disruption results in accumulation of one of the substrates (e.g., a mutation in cGMP phosphodiesterase causes elevation of cGMP), eventually leading to cell death.

Clinical Signs

A comprehensive discussion of the clinical signs associated with each form of inherited retinopathy is beyond the scope of this book. As noted previously, one of the largest variables is the age at which clinical signs appear. However, regardless of the age of onset or the exact genetic mutation and mode of inheritance, most inherited retinopathies (with some notable exceptions, such as cd and RPED, which are discussed later under Specific Forms of Inherited Retinopathy) give rise to similar clinical signs, as listed here. The disease invariably affects both eyes.

PROGRESSIVE LOSS OF VISION. Early stages of inherited retinopathy are characterized by loss of night vision (nyctalopia) due to early degeneration or dysplasia of rods (Figures 15-46 and 15-47). Affected animals often have difficulty seeing moving objects. As the disease progresses cones are also affected and day vision is also lost, making the animal blind. At the time of the initial diagnosis it is difficult to estimate how long it will take for the dog to become totally blind. Patients frequently have severe visual defects before any change is noticed by the owner, which often happens when the dog is taken out of its familiar environment—for example, on vacation or for grooming or boarding. Therefore owners complaining of “acute vision loss” should be carefully questioned about events surrounding the onset of blindness. Further inquiries may sometimes disclose that the loss of vision is associated with a change in the dog’s surroundings, and ophthalmoscopic examination will reveal signs of long-standing, progressive disease. On the other hand, many owners will have noticed the gradual progression from