Section I: Cataracts – Clinical Findings

The lens is the transparent, biconvex, avascular, and highly structured tissue located in the anterior segment of the eye, and is partly responsible for the refraction of incoming light rays to a point source on the retina. The crystallin lens represents a unique tissue in light of its embryologic development, retention of old cells and nuclear makeup, transparent nature, immune privileged status, and metabolic restrictions. Its unique anatomical structure englobes a nucleus, cortex, and an external capsule composed of basement membrane, epithelia, and differentiated lens fibers (Figure 12.1). The lens is suspended by many dense zonular ligaments that, by directly connecting the ciliary body with the equatorial capsule, induce subtle changes in the lens curvature.

Despite this simplistic anatomical structure, the lens has a highly refined and elegant series of biochemical processes that must function correctly throughout life of the animal to maintain clarity. This transparency is a crucial property of the lens that is achieved, in part, by the absence of light‐scattering organelles within the lens fibers. New lens fibers are generated from the equatorial cells of the lens epithelium, which elongate, synthesize crystallins, and finally lose their nuclei as they become mature lens fibers. The crystallins, which make up over 90% of the proteins in the lens, are specially adapted to contribute to the maintenance of transparency by forming soluble, high molecular weight aggregates that need to stay in solution for the duration of an individual’s life. Loss of transparency is the common denominator of all lens diseases. Due to the high prevalence of heritable cataracts in dogs, this is the most common of all intraocular diseases and a leading cause of vision loss in this species. Cataract surgery is the most frequent and important intraocular surgery that defines veterinary ophthalmology. Advances in cataract removals, such as phacoemulsification and implantation of intraocular lenses (IOLs), have markedly increased the success rate and restoration of vision.

Primary lens displacement (or luxation) is the second most common threatening lens condition in dogs as well as the most frequent secondary glaucoma. In addition, infrequent congenital lenticular disorders, as well as lens conditions secondarily to intraocular or systemic diseases, although less commonly seen, can also affect visual acuity. Breed‐related cataracts in dog are the majority type of lens opacity. This section of the chapter focuses on the clinical manifestations of congenital, developmental, and acquired diseases of the lens, and their appropriate medical management.

Lens Examination

Initial lens exams involved pupillary dilation, head loupes, and the otoscope or penlight to illuminate the lens and permit inspection of the entire lens. Any opacity can interfere with the light beam and permit both direct and indirect visualization. The Sanson–Purkinje images are light reflections from the cornea, anterior lens capsule, and posterior lens capsule that help identify the thickness of the lens and aid in the localization of opacities within the lens. The otoscope can also provide limited magnification for the viewer.

In the framework of a complete ophthalmic examination by the veterinary ophthalmologist, the complete lens evaluation can be achieved by slit‐lamp biomicroscopy using different widths of light beams and magnifications to visualize the different regions of the lens and precisely localize any opacity within the lens. Precise localization of these opacities can provide important clues as to their genesis and possible cause. Inherited cataracts in many canine breeds affect the same region of the lens and often with the same relative age range.

Normal Findings by Age

Before examining a lens, the examiner should review the parameters of what is considered within the “normal limits” in the species, so as to separate those conditions from true disease processes. In young animals, the suture lines of the lens, usually shaped as a “Y” anteriorly and as an “inverted Y” at the posterior pole, can often be observed as faint lines when examined under the biomicroscope. These lines, or arrowhead opacities, often disappear with age and should not be mistaken for congenital cataracts (CCs). In addition, in the very young dog, a visible nuclear ring can be occasionally seen and should not be mistaken for CCs.

Since lens transparency changes with age, understanding the aging lenticular changes in the dog is mandatory before issuing a diagnosis, as the majority of cataracts develop in dogs older than five to seven years. Nuclear sclerosis is a normal aging feature of the lens due to the compression of fibers in the nuclear region. Although it has little or no effect on vision, the blue‐gray appearance of the lens may prompt a misdiagnosis of cataract by inexperienced veterinarians. While cataract results in a black shadow against the reflection from the fundus, nuclear sclerosis presents no barrier to the fundus reflection.

Congenital Lens Abnormalities

Congenital anomalies of the lens can be divided into (i) those that involve abnormalities in the formation and differentiation of the lens placode and subsequently the lens epithelial cells (LECs); (ii) those that are associated with anterior segment dysgenesis; (iii) those that are associated with abnormalities of the fetal vasculature; and (iv) those that are associated with the zonule formation (tertiary vitreous). The first group includes aphakia, microphakia, CC, and posterior lenticonus/lentiglobus. The second group includes a spectrum of abnormalities related to incomplete or late separation of the lens vesicle from the surface ectoderm; most are capsular/subcapsular cataracts associated with dysplastic pupillary membranes (PMs). The third group includes posterior capsular opacities (PCOs), posterior capsular defects, and retrolental choristomatous plaques (persistent embryonic vasculature). Finally, the last group of congenital anomalies encompasses lens luxations, lens coloboma, spherophakia, and microphakia. In addition, congenital abnormalities affecting the lens may be caused by genetic and/or exogenous factors. Because proper development of the lens is crucial in the orchestration of intraocular embryogenesis, eyes with lens anomalies often exhibit multiple ocular defects.

Aphakia

Congenital aphakia or congenital absence of the lens is an extremely rare anomaly in the dog that occurs through failure of contact of the optic vesicle with the surface ectoderm during a critical inductive period of embryogenesis with subsequent failure of lens placode formation. In primary aphakia, there is no lens induction of the surface ectoderm, while in secondary aphakia, lens development takes place, but later is resorbed or expelled in utero. Embryonic lens tissues have a major influence on the development of the optic cup. As a result, aphakia has been reported in association with multiple ocular defects such as microphthalmia, deformities of the anterior segment (e.g., Peters’ anomaly and acorea), retinal dysplasia, retinal detachment, and staphylomas.

Lens Coloboma

A coloboma of the lens is also a rare congenital condition characterized by equatorial notching. Like lens spherophakia and microphakia, coloboma is related to problems of zonular development (local absence or marked deficiency of the zonular fibers [zonular aplasia or marked hypoplasia]) in a specific region, rather than to an incomplete embryonic fissure closure during development. Thus, when compared with other ocular colobomas (iris, optic nerve, scleral, etc.), a lens coloboma is not a true coloboma. As such, lens notching can occur secondary to different etiologies causing focal weakened or deficient zonules.

Colobomas can be either typical (6‐o’clock position) or atypical (other locations), the latter not always being apparently associated with overt lens zonule defects. Based on size, colobomas can be further classified into focal or extensive. Furthermore, lens colobomas may be seen alone or associated with other congenital anomalies such as colobomas of the uvea, MOD (merle ocular dysgenesis), or persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic vitreous (PHTVL/PHPV). When alone and focal, they may go unnoticed until cataracts develop, but when extensive, they may be associated with lens displacement.

Embryonic Vascular Abnormalities

The main vascular supply of the lens, present during prenatal development, derives from the intravitreal hyaloid vascular system. At about day 25 of gestation, the hyaloid artery (HA) branches to create a capillary network on the posterior surface of the lens capsule, the tunica vasculosa lentis (TVL). These capillaries grow toward the equator of the lens, where they anastomose with a second network of capillaries, called the PM, which covers the anterior surface of the lens. Once the ciliary body begins actively producing aqueous humor, the hyaloid vascular system is no longer needed and starts to regress. Some remaining parts of the PM–TVL–HA system that are still present by eight weeks after birth will not undergo further regression and will persist throughout life, thus the term “persistent.” Sometimes, a short remnant of the HA may be seen as a very small, white, spiral‐shaped strand on the posterior pole of the lens (Mittendorf’s dot). Persistent PM (PPM) is a common congenital ocular anomaly seen sporadically in many breeds, presumably as a nonhereditary trait. Nevertheless, in breeds with a higher prevalence or more severe manifestations of PPMs (Basenji, Bloodhound, and English Cocker Spaniel, among others), a hereditary predisposition is likely although, unfortunately, its mode on inheritance has not been yet elucidated (Table 12.1). Arising from the iris collarette, PPMs may show three different presentations that may affect the lens (dysplastic PMs): (i) pigmented strands attached to the anterior lens capsule, inducing varying degrees of focal or multifocal lenticular opacities (Figure 12.3a); (ii) PPMs may appear as multiple, punctate pigment foci on the central anterior lens capsule, which are a common incidental finding in many breeds of dogs (Figure 12.3b); and (iii) total PPM covering the entire pupil, which is extremely rare.

PHTVL/PHPV is the most severe congenital lesion associated with abnormal development of the intraocular vasculature leading, in most cases, to posterior or complete cataract (Figure 12.4). The condition may occur unilaterally or bilaterally and appear alone or concurrently with microphthalmia or other multiple inherited eye anomalies.

The first canine case was reported in 1969 in a Greyhound and subsequently the Doberman breed. Incidence of PHTVL in the Doberman has been reported to be as high as 42.6% in the Netherlands, 14.5% in Norway, 9% in Finland, and 3.3% in Germany. All the other forms (grades 2–6) were bilateral and eventually resulted in progressive cataract and, subsequently, severe impairment or loss of vision. Conversely, in the Staffordshire Bull Terrier, the condition has been rarely associated with progressive secondary cataracts.

Although the disease has been suspected to be inherited in more than 35 breeds of dogs, its mode of inheritance has been elucidated only in 5 breeds (Table 12.2), being considered as an incomplete autosomal dominant trait in the Doberman, English Toy Spaniel, and Staffordshire Bull Terrier, and suspected to be an autosomal recessive trait in German Pinscher (Miniature and Standard) and Miniature Schnauzer. Breeding programs in the Doberman breed in the Netherlands have resulted in a decreased incidence of severely affected dogs from 5% to 1%.

The diagnosis of PHTVL/PHPV is based on history, clinical examination with complete mydriasis, exclusion of other causes of leukocoria, and often ocular ultrasonography (US). Color Doppler imaging and contrast‐enhanced US can be useful to assess the blood flow in the vascular remnants and evaluate the likelihood of surgical complications.

Canine breeds affected by PHPV/PHTVL	Inheritance
American Staffordshire Terrier	Unknown
Australian Cattle Dog	Unknown
Basset Hound	Unknown
Bouvier des Flandres	Not Defined
Boxer	Unknown
Braque d’Auvergne	Familial predisposition
Bull Terrier	Unknown
Cavalier King Charles Spaniel	Unknown
Dobermann	Presumed dominant, incomplete penetrance
Dutch Partridge Dog	Unknown
English Toy Spaniel (King Charles)	Presumed dominant/incomplete penetrance
German Pinscher (Standard and Miniature)	Presumed Autosomal recessive
German Shorthaired Pointer	Unknown
Grand Anglo‐Français, Anglo‐Français de Petite Vénerie	Unknown
Great Dane	Unknown
Greyhound	Unknown
French Pointing Griffon Korthals	Unknown
Grand Griffon Vendéen	Unknown
Japanese Chin	Unknown
Labrador Retriever	Unknown
Labradoodle (Australian)	Unknown
Leonberger	Unknown
Maremma Sheepdog	Unknown
Miniature Schnauzer	Autosomal recessive
Neapolitan Mastiff	Unknown
Newfoundland	Unknown
Old English Sheepdog	Unknown
Pug	Unknown
Pyrenean Shepherd	Unknown
Schnauzer (Standard)	Unknown
Shih Tzu	Unknown
Siberian Husky	Unknown
Staffordshire Bull Terrier	Autosomal dominant with incomplete penetrance
Sussex Spaniel	Unknown
Tibetan Terrier	Unknown
Vizsla	Unknown
Welsh Terrier	Unknown
West Highland White Terrier	Unknown

Although surgical success rates for restoration of vision were low in the pre‐phacoemulsification era, surgical results have markedly improved in the recent years. Combination of phacoemulsification, posterior capsulectomy, and placement of an IOL has been successfully used.

Congenital Lens Luxation

Lens luxation is the displacement or dislocation of the lens from its normal position and implies lack or rupture of zonules. Occasionally, lens luxation may be a congenital condition, which may occur alone or, more often, associated with other, usually multiple, congenital defects, such as lens coloboma, microphakia, or spherophakia. There are no reports of inherited congenital luxations equivalent to congenital ectopia lentis in humans.

Congenital Cataract

CC refers to a lens opacity present at birth or, in altricial animal species, when the eyelids open for the first time. When presented as the only clinical sign, cataracts should be diagnosed prior to eight weeks of age in order to be considered as congenital. CCs, whether unilateral or bilateral, have a broad spectrum of causative factors contributing to their formation, such as DNA mutations (random or hereditary), infectious diseases of the dam during pregnancy, teratogenic drugs, irradiation exposure, metabolic disease, and malnutrition during gestation. Based on its triggering condition, CC may be classified into primary or secondary, depending on whether there is a direct or indirect effect to the lens, respectively.

Primary Congenital Cataract

Primary CCs can be classified into inherited or noninherited, based on the mutation nature (inherited or random, respectively). CCs may be an incidental finding in any dog breed (Figure 12.5). The causes of CCs have been the source of much speculation and research but, unfortunately, the majority have no identifiable cause, being usually the result of lens random dysgenesis (primary noninherited CC).

Clinical and morphological features of CCs vary among breeds. They may appear as small nonprogressive or slowly progressive opacities in the suture lines or in the fetal nucleus or as larger opacities in the posterior lens pole. This latter form may be nonprogressive or progressive, leading to complete blindness in some cases. To simplify understanding, CCs are grouped according to the dog’s weight/size.

Clinical and Morphological Features of Primary Congenital Cataracts in Small Breeds (<10 kg)

In small dogs, CCs were first reported in the Miniature Schnauzer. In this breed, CCs are frequently bilateral and involve the nucleus and, to a lesser extent, the posterior cortex. Its progression is variable, but in some dogs may progress to complete cataracts as early as six weeks of age. Microphthalmia, microphakia, and lenticonus are commonly associated findings. Nonprogressive cataracts affecting the tips of the posterior “Y” suture lines occur in West Highland White Terriers. An autosomal recessive mode of inheritance has been postulated for both of these breeds. In Cavalier King Charles Spaniels, CCs affecting the cortex and nucleus have been reported; however, although suspected to be inherited, the mode of inheritance has not been elucidated. In affected animals, a rapid progression to complete cataract occurs.

Clinical and Morphological Features of Primary Congenital Cataracts in Medium Breeds (10–20 kg)

CCs in American Cocker Spaniels have a central nuclear discoid shape, are bilateral and nonprogressive, and may be detected as early as four weeks of age. The nuclear distribution favors the lower proportion of cataractous to normal lens as the pups mature. Color variants of this breed manifest different and quite varied forms of primary CC with respect to location within the lens, even in closely related dogs, suggesting that the phenotype does not segregate according to familial lines. Similarly, English Cocker Spaniels also have CCs and non‐CCs, but, in this breed, CCs are mainly located in the anterior capsule and commonly associated with microphthalmia and dysplastic PMs (secondary CC).

Primary congenital capsular opacities have also been described in Beagles, although they seem to represent a transient growth phase variant, as they gradually disappear by six to eight months of age. Conversely, congenital posterior cortical cataracts, concurrent with multiple dysplastic ocular abnormalities (e.g., microphthalmia, lens luxation, dysplastic PM, choroidal hypoplasia, scleral thinning, and atypical coloboma of the posterior segment), have been described in Soft‐Coated Wheaten Terriers, English Cocker Spaniels, and Red Cocker Spaniels. Although suspected to be inherited, the mode of inheritance has not been yet established for any of the previously listed breeds.

Clinical and Morphological Features of Primary Congenital Cataracts in Large Breeds (>20 kg)

In large dog breeds, CCs may show two distinct phenotypic presentations. The first presentation consists of small, white, dense opacities located in the suture lines, the embryonic or fetal nucleus, or at attachment points of associated anomalies (e.g., dysplastic PMs and PHTVL). These cataracts are mostly nonprogressive or very slowly progressive and do not interfere with vision.

Congenital posterior polar cataracts have been described in German Shepherds, and Golden and Labrador Retrievers. These are generally bilateral and nonprogressive or slowly progressive, although occasional unilateral cataracts and extensive progression to complete cataract may be observed. Although suspected to be dominant with incomplete penetrance in Labrador Retrievers, the mode of inheritance for CC has been only definitively established in German Shepherds, being inherited as an autosomal dominant trait. Conversely, in the German Shepherd breed in England, an autosomal recessive trait has been reported and a severe progression of the posterior polar cataract to complete cataract and vision impairment has been described. Concomitant microphthalmia has been described only in the Golden Retriever. In addition, cortical CCs have been described in Labrador Retrievers with appendicular skeletal growth retardation, persistent hyaloid remnants, and rhegmatogenous retinal detachment, as well as in short‐limbed dwarfed Samoyeds in conjunction with vitreal liquefaction, hyaloid remnants, and retinal detachment.

Australian Shepherds affected by MOD may also show CC as one of the signs of their clinical picture (e.g., microphthalmia, microcornea, colobomas of the iris, retina, choroid, and/or sclera, and retinal dysplasia with or without detachment). This ocular syndrome is inherited as an autosomal recessive trait.

Nonprogressive congenital nuclear cataracts, in association with concurrent ocular signs (e.g., wandering nystagmus, entropion, microphthalmia, PPM, and multiple retinal folds), have been described in Chow Chows. In addition, CCs have been associated with retinal dysplasia in breeds such as the Bedlington Terrier, Sealyham Terrier, Akita Inu, Beagle, Bloodhound, Samoyed, Old English Sheepdog, and Labrador Retriever.

Finally, an autosomal dominant cataract has been reported in Norwegian Buhunds. The cataract appears as small dots in the fetal nucleus, and progresses over four to five years to assume a pulverulent (“candy floss”) appearance.

Secondary Congenital Cataract

Secondary CCs can be classified into inherited or noninherited. The former group encompasses all the ocular congenital diseases that induce secondary cataracts (e.g., PPM and PHTVL/PHPV). Secondary noninherited cataracts have been previously associated with infectious diseases of the dam during pregnancy, teratogenic drugs, irradiation exposure, metabolic disease, and malnutrition during gestation.

Acquired Lens Abnormalities

Acquired lens abnormalities are common in the dog, and include cataracts, lens sclerosis, and lens displacement as the most commonly reported conditions.

Cataracts

Acquired cataracts are lens opacifications diagnosed after the arbitrary cutoff of eight weeks of age in dogs. Nevertheless, an exception can be made for all those cataracts that even diagnosed after the cutoff show distinct proofs of congenital in origin (e.g., associated PPM and PHTVL/PHPV).

Classification of Canine Cataracts

Cataracts are classified according to different criteria: age at onset, anatomical location, degree of maturation, and etiology. Based on the age of onset, cataracts can be graded as congenital, developmental, and senile. Based on location, cataracts are classified into capsular, subcapsular, cortical (these three areas are further divided into anterior and posterior), nuclear (embryonic, fetal, infantile, or adult), and suture lines. Cataracts can also be categorized as axial, paraxial, or inferior/superior equatorial.

Based on the degree of opacity and progression (probably the most useful), cataracts may be further classified as incipient (see Figure 12.5), immature, mature, hypermature, intumescent, and Morgagnian (Figures 12.6–12.10). Tapetal reflection is used as a classifying tool for most cataracts. An incipient cataract is the earliest stage of opacification and does not/minimally affect the tapetal reflection (<10–15%). In this type of cataract, small lens opacities are often only seen under magnification with a dilated pupil, and vision is not noticeably affected.

A more advanced cataract is described as immature, in which the tapetal refection is reduced, but still present. Immature cataracts can be further categorized into early immature (affects 15–50% of the tapetal reflection) or late immature (affects 50–99% tapetal reflection) (see Figure 12.6b). When vision no longer exists, no tapetal refection is visible, and inspection of the fundus is no longer possible, the cataract is then referred to as mature (see Figure 12.10). Later, the cortex may liquefy (hypermature cataract) and adopt a crystalline appearance with wrinkling of the lens capsule. Limited vision and tapetal reflection may return (especially with mydriasis). In the end stage, total liquefaction of the cortex allowing the nucleus to sink inferiorly may occur in some middle‐aged/old dogs (Morgagnian cataract) (see Figure 12.10d). In some young animals, the liquefied contents escape through the capsule, resulting in cataract resorption, which restores partial vision. Spontaneous cataract resorption is rarely seen in geriatric dogs, but is not uncommon in young dogs (1–3 years old). In cases in which the only abnormality is a cataract, the pupillary light reflexes should remain normal regardless of maturity.

Detailed Description of Acquired Cataracts

Like CCs, acquired cataracts can be further classified into primary and secondary. Primary cataracts include lens opacifications induced by a lenticular metabolic abnormality (hereditary or not in nature) and those age‐related (senile). Secondary cataracts are those induced by other ocular or systemic conditions, such as ocular trauma, glaucoma, uveitis, lens luxation, progressive retinal atrophy (PRA), nutritional or metabolic disorders, infectious diseases, and toxins.

Acquired Primary Cataracts

Acquired primary cataracts are further classified into those appearing from eight weeks of life to middle age, which in the dog is considered about six to seven years of age (developmental cataract), and senile cataract, most commonly seen in dogs older than eight to nine years.

Developmental Cataracts

Developmental cataracts are defined as a primary opacification of the lens that displays a variable presentation among breeds but, at the same time, shows marked intrabreed specificity in their ophthalmoscopic appearance, age of onset, rate of progression, and degree of binocular symmetry, indicating their genetic homogeneity within a breed. They are considered nowadays as one of the most important causes of blindness in purebred dogs, with more than 180 breeds affected (Table 12.3). In some cases, more than one form of cataract occurs in the same breed.

Developmental cataracts may be classified into early form (juvenile) and late form, according to the age at which it is first diagnosed. Often, cataract changes develop early in life, at about 12 months of age. The clinical and morphological features of developmental cataracts have been described for many breeds of dogs. It should be noted that the phenotypic expression of heritable cataract in dogs, most notably age of onset and progression, can vary within a breed, and the expression can be influenced by other modifying genes or environmental factors. In many breeds, posterior polar cataract is the most common manifestation, primarily affecting the cortex and sparing the nucleus in the initial stages. Those cataracts might only progress to a limited extent, rarely affecting the lens completely. Nevertheless, many different presentations have been described for developmental cataracts in the dog.

Clinical and Morphological Features of Developmental Cataracts in Small Breeds (<10 kg)

Grossly, developmental cataracts tend to occur most frequently in the smaller canine breeds. Among the affected breeds, it is worth noting the Miniature Schnauzer, Standard Poodle, Bichon Frise, Boston Terrier, and West Highland White Terrier, of which specific reports on phenotypic lenticular appearance and its progression have been described.

In the Miniature Schnauzer, apart from the well‐known congenital form, a juvenile developmental cataract has also been described. This form has an age of onset of six months and primarily affects the posterior lens cortex, with no nuclear involvement. Its progression is variable.

Juvenile cataracts have also been described in the Standard Poodle and Afghan Hound in which lens opacification affects the equator and tends to impair vision by 6–18 months of age. Bichon Frise shows a late‐onset developmental cataract (two to eight years of age) that affects the anterior and posterior cortices.

Two distinct types of developmental cataracts have been described in Boston and West Highland White Terriers. In the Boston Terrier, the first form, originally described in 1978 by Barnett, is bilateral and begins at the suture lines, affecting the nucleus, as well as the posterior cortex. Despite its early age of onset (8–12 weeks), it is considered as a developmental cataract and tends to progress to maturity. The other form has a late onset (three to four years of age), involves the equator and anterior cortex, and has a very slow progression. In the West Highland White Terrier breed in Sweden, the two types of developmental cataracts also clearly differ: one involves the tips of the posterior Y‐sutures primarily, and the other affects the complete lens structure.

Affenpinscher (a1, b) Afghan Hound (a1, b) Airedale Terrier (a2, b) Akbash Dog (a2, b) Akita Inu (a2, b) Alaskan Malamute (a2, b) American Cocker Spaniel (a1, b) American Eskimo Dog (a2, b) American Hairless Terrier (b) American Staffordshire Terrier (a1, b) American Water Spaniel (a1, b) Australian Cattle Dog (a1, b) Australian Kelpie (a2, b) Australian Shepherd (Standard, Miniature, and Toy) (a1, b) Australian Terrier (a2, b) Barbet (a1) Basenji (a2, b) Basset Artésien Normand (a1) Basset Hound (a1, b) Beagle (a1, b) Bearded Collie (a1, b) Bedlington Terrier (a1, b) Belgian Malinois (a2, b) Belgian Sheepdog (a2, b) Belgian Tervuren (b) Bernese Mountain Dog (a2, b) Bichon Frise (a1, b) Black and Tan Coonhound (a1, b) Black Russian Terrier (a2, b) Bloodhound (a1, b) Blue de Gascogne (a1) Bolognese (a1, b) Border Collie (a1, b) Border Terrier (a2, b) Borzoi (a1, b) Boston Terrier (a1, b) Bouvier des Flandres (a1, b) Boxer (a1, b) Boykin Spaniel (a2, b) Bracco Italiano (a1, b) Braque de l’Ariège (a2) Braque d’Auvergne (a1) Briard (a1, b) Brittany Spaniel (a1, b) Brussels Griffon (a1, b)

Dachshund (a1, b) Dalmatian (a1, b) Doberman Pinscher (a2, b) Dogue de Bordeaux (a1, b) Dutch Partridge Dog (a2) English Cocker Spaniel (a1, b) English Pointer (a1, b) English Setter (a1, b) English Springer Spaniel (a1, b) English Toy Spaniel (a1, b) Entlebucher (a1, b) (Eurasier a1) Field Spaniel (a1, b) Finnish Lapphund (a2, b) Finnish Spitz (b) Flat‐Coated Retriever (a1, b) Fox Terrier (Wire and Smooth) (a1, b) French Bulldog (a1, b) French Shorthair Pointer (a1) French Spaniel (a1) French Pointing Griffon Korthals (a1) German Pinscher (a1, b) German Shepherd Dog (a1, b) German Shorthaired Pointer (a1, b) German Wirehaired Pointer (a1, b) Giant Schnauzer (a1, b) Glen of Imaal Terrier (a2, b) Golden Retriever (a1, b) Gordon Setter (a2, b) Great Dane (a1, b) Great Pyrenees (a1, b) Greater Swiss Mountain Dog (a1, b) Greyhound (a2, b) Groenendael (a1) Harrier (b) Havana Silk Dog (b) Havanese (a1, b) Ibizan Hound (a1, b) Icelandic Sheepdog (a2, b) Irish Setter (b) Irish Soft‐Coated Wheaten Terrier (a1, b) Irish Water Spaniel (a1, b) Irish Wolfhound (a1, b) Italian Greyhound (a1, b)

Maltese (a1, b) Manchester Terrier (a1) Maremma Sheepdog (a1) Markiesje (a2) Mastiff (a2, b) Mi‐Ki (a2, b) Miniature Bull Terrier (b) Miniature Pinscher (b) Münster Spaniel (a1) Neapolitan Mastiff (a1, b) Newfoundland (a1, b) Norbottenspets (a2, b) Norfolk Terrier (a1) Norwegian Buhund (a1, b) Norwegian Elkhound (a2, b) Norwich Terrier (a1, b) Nova Scotia Duck Tolling Retriever (a1, b) Old English Sheepdog (a1, b) Papillon (a1, b) Parson Russell Terrier (a1, b) Pekingese (a1, b) Pembroke Welsh Corgi (b) Petit Basset Griffon Vendéen (a1, b) Pharaoh Hound (b) Picard Spaniel (a1, b) Polish Lowland Sheepdog (a1, b) Pomeranian (a1, b) Poodle (a1, b) Polish Tatra Sheepdog (a1) Portuguese Water Dog (a1, b) Portuguese Pointer (a1) Pug (a1, b) Puli (a1, b) Pyrenean Shepherd (a1, b) Rat Terrier (b) Rhodesian Ridgeback (a1, b) Rottweiler (a1, b) Saint Bernard (a1, b) Saluki (a1, b) Samoyed (a1, b) Saarloos Wolfhound (a1) Sarplaninac (a1) Schapendoes (a1) Schipperke (a1, b)

Bull Terrier (a1, b) Bulldog (a1, b) Bullmastiff (a2, b) Cairn Terrier (a1, b) Cane Corso Italiano (a1) Canaan Dog (b) Cardigan Welsh Corgi (a2, b) Cavalier King Charles Spaniel (a1, b) Chesapeake Bay Retriever (a1, b) Chihuahua (a1, b) Chinese Crested Dog (a2, b) Chinook (b) Chow Chow (a1, b) Cirneco dell’Etna (a1) Clumber Spaniel (a2, b) Collie (a2, b) Coton de Tulear (a2, b) Curly‐Coated Retriever (a1, b)

Jack Russell Terrier (a1, b) Japanese Chin (a1, b) Jagdterrier (a1) Karelian Bear Dog (a2) Keeshond (a1, b) Kerry Blue Terrier (a1, b) Komondor (a1, b) Kuvasz (a1, b) Labradoodle Australian (b) Labrador Retriever (a1, b) Lagotto Romagnolo (a1, b) Lakeland Terrier (a1) Leonberger (a1, b) Lhasa Apso (a1, b) Lowchen (a2, b)

Schnauzer Miniature and Standard (a1, b) Scottish Deerhound (a1) Scottish Terrier (a1, b) Sealyham Terrier (a1, b) Segugio Maremmano (a1) Shar‐Pei (a1, b) Shetland Sheepdog (a1, b) Shiba Inu (a1, b) Shih Tzu (a1, b) Siberian Husky (a1, b) Silky Terrier (a1, b) Skye Terrier (a1) Soft‐Coated Wheaten Terrier (b) Spinone Italiano (a1, b) Staffordshire Bull Terrier (a1, b) Sussex Spaniel (a1) Standard Schnauzer (b) Swedish Vallhund (b) Tibetan Spaniel (a1, b) Tibetan Terrier (a1, b) Vizsla (a1, b) Volpino Italiano (a1) Weimaraner (a1, b) Welsh Corgi Pembroke (a1) Welsh Springer Spaniel (a1, b) Welsh Terrier (a1, b) West Highland White Terrier (a1, b) Whippet (a1, b) Yorkshire Terrier (a1, b)

(a1) Published studies referenced in the “ECVO Manual of Presumed Inherited Eye Diseases,” ECVO Genetics Committee, 2017. (a2) Nonpublished reports considered in the “ECVO Manual of Presumed Inherited Eye Diseases,” ECVO Genetics Committee, 2017. (b) Published studies and nonpublished reports referenced in “Ocular Disorders Presumed to Be Inherited in Purebred Dogs,” ACVO Genetics Committee, 2015.

Clinical and Morphological Features of Developmental Cataracts in Medium Breeds (10–20 kg)

Medium breed dogs are also commonly affected by developmental cataracts, but studies describing the disease in each breed individually are less common. The most frequently affected breeds include Staffordshire Bull Terrier, German Pinscher, and American and English Cocker Spaniel.

In Staffordshire Bull Terriers, developmental cataract is described as bilateral and symmetrical, located primarily in the nucleus and posterior capsule of the lens and progressing to blindness by two to three years of age.

German Pinchers in Finland are affected by a late‐onset developmental cataract (nine years old at diagnosis) that primarily affects the posterior and subcapsular area. Conversely, in dogs bred in Germany, developmental cataracts are seen significantly earlier in life (median age 3.9 years) with a predisposition for the anterior cortical area followed by the posterior pole. The reason for these significant geographic differences is unknown.

The American Cocker Spaniel, apart from the previously mentioned CC, also shows a developmental cataract that affects the cortex, with the posterior aspect most commonly affected, and the anterior cortex and the equator involved less frequently. They can appear as early as six months of age and have variable progression depending on age of onset. Progression tends to be rapid in dogs with early onset (<3.5 years of age) and slower in cases of late onset (>3.5 years of age). Both presentations seem to be genetically distinct. Cortical cataracts are also seen secondary to PRA in the American Cocker Spaniels.

Clinical and Morphological Features of Developmental Cataracts in Large Breeds (>20 kg)

Large breed dogs are commonly affected by developmental cataract, with the posterior area the most frequently involved. In the Golden and Labrador Retriever, apart from the previously described congenital form, a late‐onset form of developmental cataract has also been described. In these breeds, cataracts are cortical, most commonly located in the posterior polar cortex, and viable in progression. In the Labrador Retriever, dogs with posterior polar cataracts produce affected offspring with both focal and diffuse forms of cataract, suggesting the two forms cannot be considered totally separate entities.

Equatorial and posterior subcapsular cataracts occur in the Siberian Husky. These cataracts are considered to be juvenile onset, as they appear at 6–18 months of age and are typically slowly progressive.

Developmental cataracts suspected to be inherited have also been described in the Chesapeake Bay Retriever and Labradoodle, both showing multiple lens locations without a clear phenotypic predisposition.

In the German Shepherd breed in England, developmental cataracts have been reported at 8–12 weeks of age, as small dot opacities in the posterior cortex that can involve the Y‐sutures and nucleus. With progression, by one year of age, nuclear and cortical cataracts with vision impairment can be present. No progression is noted after one to two years of age.

Cataracts in the Norwegian Buhund exhibit moderately large posterior polar cataracts with occasional extensions around the suture lines, as well as occasional vacuoles in the peripheral cortex and rapid progression to blindness. A different type of cataract was described in this breed in 1995, which was termed pulverulent nuclear cataract. The term pulverulent means “dust‐like” and is commonly used in human ophthalmology. The cataracts may be visible as early as 6.5 weeks of age as small dots parallel to the suture lines behind the nucleus. By the age of 4–5.5 years, the opacities progress to involve the fetal nucleus that then resembles a ball of “candy floss.” The adult nucleus and the cortex remain clear.

In the Entlebucher Mountain Dog, developmental cataract is the most frequently observed hereditary eye disease with a prevalence of 23.5%. Most of the affected dogs develop bilateral symmetric opacifications, which are mostly capsular and subcapsular in the posterior polar part of the lens along the suture lines. The first sign of cataracts can be seen at a mean age of 5.5 ± 2.6 years and PRA may be concurrent.

Nuclear, posterior nuclear, and posterior polar subcapsular cataracts have been identified in closely related Leonbergers in the United Kingdom. Similarly, triangular‐shaped polar (anterior and posterior) and complete cataracts have been described in Rottweilers of different ages, with the youngest at 10 months of age. In the Welsh Springer Spaniel, a bilateral, symmetrical, progressive cataract affecting the nucleus and posterior cortex has been described in a pedigree of three generations. Equatorial cataracts can occur as early as four months in the Afghan Hound. Progression is rapid in this breed, with visual impairment often present by two years of age. In the Old English Sheepdog, developmental cataracts have also been described, with the location of the opacity within the lens and the age of onset highly variable.

Mode of Inheritance and Affected Genes in Hereditary Cataracts

The paucity of canine cataract mutations reported in the literature, compared to those associated with, for example, inherited retinal degenerations in the dog, is testament to the fact that hereditary cataract (HC) is probably a genetically complex disorder in most dog breeds, and studies to date have not included the analysis of sufficient numbers of cases and controls to identify DNA variants associated with the disease. Indeed, although presumed HCs have been described in more than 180 canine breeds, the mode of inheritance has been established only in 17 breeds (Table 12.4).

Canine breeds affected by HC	Inheritance	Available genetic tests
Australian Shepherd	Autosomal dominant with incomplete penetrance	HSF4‐2
Border Terrier	Autosomal recessive	HSF4‐1
Boston Terrier	Autosomal recessive	HSF4‐1 for early onset presentation
Chesapeake Bay Terrier	Autosomal dominant with incomplete penetrance	–
American Cocker Spaniel	Autosomal recessive	–
Entlebucher Mountain Dog	Autosomal recessive	–
French Bulldog	–	HSF4‐1
German Shepherd Dog	Congenital: autosomal dominant Noncongenital: autosomal recessive	–
Australian Labradoodle	Autosomal dominant with incomplete penetrance Autosomal recessive Not defined	–
Labrador Retriever	Autosomal dominant with incomplete penetrance Autosomal recessive Not defined	–
Miniature Australian Shepherd	Autosomal dominant with incomplete penetrance	HSF4‐2
Miniature Schnauzer	Autosomal recessive	–
Norwegian Buhund	Autosomal dominant	–
Staffordshire Bull Terrier	Autosomal recessive	HSF4‐1
Toy Australian Shepherd	Autosomal dominant with incomplete penetrance	HSF4‐2
Welsh Springer Spaniel	Autosomal recessive	–
West Highland White Terrier	Autosomal recessive	–

In humans and mice, several mutations in limited different genes have been linked to both autosomal dominant and recessive HC. Different studies have evaluated the role of these mutations in the development of HC in the dog. More than 21 candidate genes have been investigated in several canine breeds, but to date, only 2 genes, the heat shock transcription factor 4 (HSF4) and the Sec1 Family Domain Containing 2 (SCFD2), have been associated with the developmental HC in dogs. One study demonstrated a nearly complete linkage with microsatellites adjacent to exon 9 of HSF4 of chromosome 5 in Staffordshire Bull Terriers, Boston Terriers, and Australian Shepherds. The two gene mutations described in these breeds are predicted to alter the reading frame of the protein transcript and introduce a premature stop codon, which results in truncated and aberrant crystalline proteins. These abnormal proteins are the common final result of two possible HSF4 exon 9 mutations: a 1‐bp insertion seen in Staffordshire Bull Terriers and Boston Terriers (HSF4‐1), and a 1‐bp deletion detected in Australian Shepherds (HSF4‐2).

More recently, a mutation in the intron 5 of the SCFD2 gene on chromosome 13 has been associated with bilateral posterior polar cataracts in Australian Shepherd dogs. The SCFD2 gene encodes a sec1 family domain‐containing protein 2, a molecule that may be involved in protein transport, although very little is reported on its function. Many other genes causing cataracts in humans have been tested in different canine breeds with no significant linkage or association.

Breeding Strategies and Genetic Tests Available for HC

Currently, there are only two DNA‐based tests available for the diagnosis of HC in dogs (see Table 12.4): the HSF4‐1 (exon 9 1‐bp deletion in Border Terrier, Boston Terrier, French Bulldog, and Staffordshire Bull terrier) and the HSF4‐2 (exon 9 1‐bp insertion in Australian Shepherd). The high frequency of HSF4 mutations and their significant association with HC in the above‐mentioned breeds call for careful planning of breeding strategies.

Age‐Related Cataracts

Cataracts are commonly seen in the aged dog and are often classified as age‐related cataracts (ARCs) or senile cataracts, if no other antecedent cause is apparent. The age of onset at which a cataract should be considered age‐related is arbitrary (often >10 years) and breed‐related. In fact, different studies show that body size, life expectancy, and ARC incidence are interrelated in dogs, body size being negatively correlated to longevity, and this in turn positively correlated with the age at which prevalence of cataract is 50% (C50).

While the clinical appearance and rate of progression of ARC can vary, they often are seen initially as an increase in relucency in the adult nucleus of the lens, generally occurring concurrent with or following dense nuclear sclerosis (Figure 12.11). Cortical cataractous changes may also occur to varying extents, either concurrent with or separate from nuclear cataracts. The rate of progression of these classic ARCs in dogs is often slow, requiring many months to several years to result in demonstrable vision loss.

Acquired Secondary Cataracts

Cataracts Associated with Medications and Other Toxic Substances

Cataracts have been associated with medications (drug‐induced cataracts), and a number of pharmacological agents have been reported to produce cataracts in dogs (Box 12.1). As this species is commonly used in toxicological screenings of new pharmacological agents and chemicals, numerous cataractogenic agents have been noted in the laboratory dog. Drug‐induced cataracts tend to be bilateral and dose‐related, and although initially appear at a variety of locations within the lens, often begin in either the anterior and posterior cortical region near the equator or the Y‐suture regions. This type of secondary cataract is often associated with lens vacuole formation and reported to be reversible if the drug insult is removed. In laboratory dogs, cataracts have been described with the chronic use of antihypertensive agents such as diazoxide and phenylpiperazine. Induced lens opacities are progressive for phenylpiperazine, but transient and reversible for diazoxide. The administration of high dosages of cholesterol‐lowering drugs such as hydroxymethylglutaryl‐CoA (HMG‐CoA) reductase inhibitors or drugs inhibiting oxidosqualene cyclase have also been described to produce cataracts, seen initially as accentuation of the suture lines that finally progress to anterior and posterior subcapsular areas. One exception from the HMG‐CoA reductase inhibitors group is atorvastatin that does not seem to have cataractogenesis effects in the dog. The hypocholesterolemic drugs are thought to have a cataractogenic effect by inhibition of cholesterol synthesis in the outer cortical regions of the lens, where cholesterol is critical for the newly synthesized lens fibers’ cell membranes. Chronic topical and oral administration of dimethyl sulfoxide (DMSO) in dogs (dosage of 2.5–40 g/kg) has been associated with unusual lens changes with an unexplained pathogenesis. The lens alteration was characterized by a reduction in the refractive index of newly synthesized lens fibers in the cortex causing them to appear optically clear instead of relucent. Cataractogenesis in dogs has also been associated with the administration of oral contraceptives and with disophenol.