Chapter 13 Lens
Development of the lens is described in Chapter 2. The lens is a transparent, avascular, biconvex body with an anterior surface that is flatter or less curved than the posterior surface (Figure 13-1). The centers of the surfaces are called the anterior and posterior poles. The rounded circumference is the equator, which has numerous irregularities where zonular fibers attach. Its anterior aspect is in contact with the posterior surface of the iris and fills the pupil. Its posterior aspect is in contact with the vitreous or, more specifically, a depression in the vitreous called the hyaloid (patellar) fossa.
The lens consists of the capsule, anterior epithelium, and lens fibers. It is divided into two general regions, the cortex (outer areas near the capsule) and the nucleus (central area) (Figure 13-2). As the lens grows throughout life, layers of fibers are produced in the equatorial area and are laid down on top of the former layers, forcing older fibers toward the lens center in a process resembling the formation of rings in tree trunks. These successive layers are visible clinically with biomicroscopy. They are called the adult, fetal, and embryonal nuclei, respectively (Figure 13-3).
Figure 13-2 The adult lens, showing the nuclear zones, cortex, anterior epithelium, and capsule. Epithelial cells can be seen undergoing transformation into lens fibers at the equatorial region. The varying thickness of the lens capsule in various zones is also shown.
(Modified from Hogan MJ, et al. : Histology of the Human Eye. Saunders, Philadelphia.)
Figure 13-3 Optical section of normal adult lens. 1, Anterior capsule; 2, anterior line of disjunction (anterior epithelium); 3, anterior surface of adult nucleus; 4, anterior surface of fetal nucleus; 5, anterior (upright) Y suture; 6, inner layer of posterior half of fetal nucleus, containing posterior (inverted) Y suture; 7, posterior surface of fetal nucleus; 8, posterior surface of adult nucleus; 9, posterior line of disjunction; 10, posterior capsule.
(From Remington LA : Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)
The lens is supported at the equator by the lens zonules, or suspensory ligaments—collagenous fibers that attach to the processes of the ciliary body and suspend the lens in the middle of the pupil (Figure 13-4). Alterations of tension in these fibers alter the refractive (optical) power of the lens. To view nearby objects, the animal accommodates through contraction of the ciliary body muscles, mediated by parasympathetic stimulation. In primates and birds, this contraction leads to an increase in the curvature of the lens (i.e., it becomes more spheroid), thus increasing its refractive power (Figure 13-5). In carnivores, the contraction of the ciliary muscle results in forward movement of the lens in the eye, allowing the animal to accommodate for nearby objects. To view distant objects, sympathetic stimulation causes the animal to disaccommodate by relaxing its ciliary muscle. In primates and birds the relaxation results in a flatter lens with reduced refractive power. In carnivores it results in posterior movement of the lens in the eye. In general, the accommodative ability of birds and primates is superior to that of carnivores; most herbivores, reptiles, and rodents possess virtually no accommodative capabilities. However, it is worth remembering in this context that the cornea is the most important refracting surface in the eye, accounting for the majority of the optical power (because light undergoes significant refraction as it passes from air into the cornea). The lens accounts only for 30% to 35% of the eye’s refractive power and is used for fine adjustment for objects at different distances.
(From Streeton BW , in Jakobiec FA [editor]: Ocular Anatomy, Embryology, and Teratology. Harper & Row, Philadelphia.)
(From Yanoff M, Duker JS : Ophthalmology, 2nd ed. Mosby, St. Louis.)
The capsule is a transparent, elastic envelope surrounding the lens (Figure 13-6). It provides insertion for zonular fibers that suspend the lens in the eye. In primates, the capsule regulates lens shape through its elasticity. The capsule is impermeable to large molecules (e.g., albumin, globulin) but allows water and electrolytes to pass. The anterior lens capsule, which is associated with the underlying epithelium, is much thicker than the posterior lens capsule, which lost its underlying epithelium during embryonic development (see also Figure 13-2).
Cuboidal epithelial cells lie beneath the anterior capsule (see Figure 13-6). Toward the equator, the cells proliferate (through mitosis), become more columnar, and elongate into new lens fibers (see Figure 13-2). Because of mitotic activity in this area, these cells are susceptible to toxic and pathologic influences, which may become apparent as equatorial opacities. The lens epithelium is important in transport of cations through the lens capsule. The posterior lens epithelium, which transforms into lens fibers of the embryonic lens nucleus, is not seen in newborns and adults.
Lens fibers make up the substance of the lens and are arranged in interdigitating layers (Figure 13-7). These fibers stretch from the equatorial region toward the anterior and posterior poles of the lens. However, they do not quite reach the poles but instead meet fibers from the opposite equator and form a Y-shaped suture pattern with them (Figure 13-8). The suture pattern may become visible as a prominent upright (anterior) or inverted (posterior) Y if the lens becomes cataractous (see Figures 13-1 and 13-3). Because new lens fibers are formed throughout life, the older fibers in the (central) lens nucleus are denser and less transparent than the younger fibers laid down around them in the cortex. This difference between nucleus and cortex becomes more pronounced as the animal ages and may result in the formation of nuclear sclerosis (see later).
(From Krause WJ, Cutts JH : Concise Text of Histology. Williams & Wilkins, Baltimore.)
Figure 13-8 Embryonal and adult lens showing sutures and arrangement of lens cells. A, The embryonal nucleus. The anterior Y suture is at a, and the posterior at b. The lens cells are wide, shaded bands. Cells attaching to tips of Y sutures at one pole of the lens attach to the fork of the Y at the opposite pole. B, Adult lens cortex. The anterior and posterior organization of the sutures is more complex. Lens cells arising from the tip of a branch of the suture insert farther anteriorly or posteriorly into a fork at the posterior pole. This arrangement conserves the shape of the lens. This drawing shows the suture lying in a single plane for pictorial reasons, but it extends through the cortex and nucleus down to the Y sutures in the embryonal nucleus. The exact shape of the adult sutures varies in domestic species, but in young animals especially, the Y shape of the embryonal nucleus predominates and must be distinguished clinically from pathologic lens opacities (cataract).
(Modified from Hogan MJ, et al. : Histology of the Human Eye. Saunders, Philadelphia.)
Because the lens is avascular, its metabolic needs are met by the aqueous humor. Therefore lens metabolism is precarious and depends on constant composition of the aqueous. Disturbances in aqueous composition (resulting from anterior uveitis) affect lens metabolism and transparency.
Metabolism of glucose provides most of the energy requirements of the lens. Glucose enters from the aqueous by both diffusion and assisted transport. Most of the glucose is broken down anaerobically to lactic acid via the hexokinase (pentose phosphate) pathway, although some aerobic glycolysis occurs via the citric acid cycle. Elevation in glucose levels (in diabetic patients) inhibits the hexokinase enzyme, and the glucose is diverted into the sorbitol shunt, where it is converted by aldose reductase into sorbitol (Figure 13-9).
(From Yanoff M, Duker JS : Ophthalmology, 2nd ed. Mosby, St Louis.)
The lens is high in protein (35%) and water (65%) and low in minerals. The proteins are divided into soluble proteins, or crystallins, and insoluble, or albuminoid, proteins. The former constitute approximately 85% of the lens protein content, but their proportion varies with species, location within the lens, age, and, most significantly, disease. The proportion of soluble proteins drops with age, and a similar process occurs when the lens becomes cataractous, as the proportion of insoluble proteins rises. During cataract formation, the lens proteins break into polypeptides and amino acids that diffuse through the lens capsule into the anterior and posterior chambers. Because these molecules are usually not recognized by the eye’s immune system, the breakdown and diffusion of cataractous lens protein usually trigger an inflammatory reaction known as lens-induced uveitis (LIU).
Throughout life, new lens cells are produced at the equator, forcing older cells toward the nucleus (see Figures 13-2 and 13-3). As the older cells become more tightly packed, the nucleus becomes denser and harder. In dogs, after about 6 years of age this greater nuclear density becomes visible as a grayish blue haze known as nuclear sclerosis (Figure 13-10). This haze is probably associated with increased insoluble proteins and decreased soluble crystallins (γ-crystallin) in the lens nucleus. Advanced nuclear sclerosis may appear similar to cataract, and in fact, the two are frequently confused by owners and practitioners. However, use of mydriatics and retroillumination (illumination of the lens by reflection of strong light from the tapetum) can help in differentiating between the two entities. The retroillumination will highlight the cataractous opacities, easily distinguishing them from the transparent nuclear sclerosis. In most animals, except for the most severe cases, the effect of nuclear sclerosis on vision is minimal, and the fundus can be readily visualized.
Figure 13-10 Nuclear sclerosis in a dog. The blue haze is a dense lens nucleus, containing lens fibers that have been pushed and compacted at the lens center throughout life. Although seemingly dense, the nucleus is usually transparent, and it rarely affects vision.
(Courtesy University of Missouri Veterinary Ophthalmology Case Photo Collection.)
The term cataract comprises a common group of ocular disorders manifested as loss of transparency of the lens or its capsule. The opacities may be of varying sizes, shapes, location within the lens, etiology, age of onset, and rate of progression.
A recent large-scale retrospective study covering 40 years and 230,000 dogs has shown that the prevalence of canine cataracts in North America has slowly been increasing and is reportedly 2.42% in the last decade. The increased prevalence is attributed to improved training and diagnostic techniques in veterinary ophthalmology and to the increased popularity of purebred dogs during the twentieth century. The overall prevalence of cataracts in mixed breed dogs, which presumably are not affected by hereditary cataracts, is 1.61%.
Lens biochemistry is complex, as are the many different causes of cataract. With the exception of diabetic, galactosemic, and experimental cataracts, the exact biochemical dis-orders responsible for the formation of cataracts in domestic animals are imperfectly understood. However, in general it may be stated that noxious influences affecting any of the following lens functions may result in opacity:
Once these disturbances occur, they will cause irreversible changes in lens protein contents, metabolic pumps, ionic concentrations, and antioxidant activity. The proportion of nonsoluble (albuminoid) proteins in the lens increases at the expense of the soluble (crystallin) protein fraction. Epithelial Na+/K+ adenosine triphosphate pump activity decreases, resulting in a shift in the ionic balance within the lens, and antioxidant activity in the lens likewise diminishes. At the same time, proteolytic enzyme activity increases in the lens, causing breakdown of cell membranes and degradation of lens protein. All of these events amplify and cascade as the cataract progresses, causing visible changes in the lens. These changes are caused by morphologic changes in the lens capsule, epithelium, and fibers that accompany the molecular events. The end result is loss of transparency due to lens fibers rupture, cell death, and water-cleft formation. The clinical picture is determined by the nature and position of these opacities. They seldom appear simultaneously throughout the whole lens cortex. Sometimes they remain stationary for a long time and interfere little with vision. At other times, when they are associated with considerable imbibition of fluid into the cortex, complete opacification may be rapid. Degeneration of all the cortical cells then may occur with rapid liquefaction of the fibers.
Cataract refers to a group of lens disorders of varying age of onset, speed and extent of progression, appearance, and etiology. Because of the variable nature and appearance of cataracts, numerous methods of classification are commonly used (Table 13-1).
|FEATURE||SUBCLASSIFICATION OF TERMS|
|Stage of development (maturity)||Incipient, immature, mature, hypermature, morgagnian|
|Position within the lens||Anterior capsular, anterior subcapsular, cortical, equatorial, nuclear, posterior subcapsular, posterior capsular|
|Age of development||Congenital, developmental, juvenile, senile, acquired|
|Etiology or pathogenesis||Primary: inherited|
|Secondary: traumatic, intraocular disease (uveitis, infection), nutritional, radiation, diabetic, toxic, congenital abnormalities, senile|
|Consistency||Fluid, soft, hard|
Cataracts may be classified according to cause. In many canine breeds, inheritance is the most common cause of cataracts. Additional causes are metabolic, traumatic, toxic, and developmental disorders of the eye. Cataracts also may be caused by nutritional deficiencies or may be secondary to other ocular diseases. Causes of cataracts are discussed in detail in a later section.
Cataracts may also be classified according to the location of the initial opacity (e.g., nuclear, cortical, anterior/posterior subcapsular). Many inherited canine cataracts are characterized by a typical initial location (see later), and therefore an opacity in a characteristic location in the lens of a susceptible breed should be suspected to be hereditary. Metabolic cataracts may also be classified according to typical location, with the vacuoles that characterize diabetic cataracts initially appearing in the equatorial cortex. Cataracts may also be classified according to age of onset. Some cataracts, usually developmental, toxic, or inherited, may be congenital. Others may appear in juvenile, adult, or elderly patients. Once again, in many dog breeds inherited cataracts are characterized by a typical age of onset (see later).
However, in many ways, the most relevant method of classifying cataracts is according to their stage of development (maturation), which determines the extent of visual deficits, the onset of lens-induced uveitis, and the time of surgical intervention.
Figure 13-12 Immature cataract. Though most of the lens is involved, it is still mostly transparent, and the animal still has vision. Note the vacuoles in the periphery, which indicate that this cataract is secondary to diabetes. These vacuoles will not be seen unless the pupil is dilated.
It should be noted that in young dogs the resorption can be extensive enough to involve most (or all) of the cataractous lens, thus allowing the animal to regain vision. Once again, however, the resulting secondary inflammation must be treated aggressively. Some lens resorption also occurs in elderly dogs affected by mature cataracts. However, in these patients its extent is limited. The resorption will trigger LIU but will rarely lead to regaining of vision.
LIU is an inflammation of the eye caused by a reaction to the presence of lens antigens in the aqueous humor. The antigens usually leak from the lens into the anterior chamber following the degradation of lens protein in cataracts, thus causing phacolytic uveitis. The degradation and resulting LIU are limited in mature cataracts and more extensive in hypermature cataracts. Phacolytic uveitis is a humoral and cell-mediated immune reaction of the uvea to the released lens protein. The inflammation is a result of the fact that lens proteins are separated from the immune system before birth and are regarded as foreign. These antigens—especially the α-crystallins—are organ specific rather than species specific and cross species lines. Reaction to their presence is less severe in younger animals. A more severe form of granulomatous LIU may occur in older dogs with hypermature cataracts.
Clinical signs of uveitis include photophobia, blepharospasm, corneal edema, ciliary injection, aqueous flare (reduced transparency of aqueous humor due to leakage of inflammatory cells and mediators to the anterior chamber), miosis, a dark iris, and hypotony (reduced intraocular pressure [IOP]).
This inflammation must be treated medically (see Chapter 11) because it may gravely affect the prognosis of cataract surgery. Furthermore, the inflammation may cause secondary complications, including glaucoma and posterior synechia.
LIU may also occur after traumatic rupture of the lens capsule with subsequent exposure of lens protein to the aqueous humor. This inflammation is known as phacoclastic uveitis. The difference between phacolytic uveitis and phacoclastic uveitis has been proposed to be that in phacolytic uveitis (via leakage), only recrystallized lens proteins are presented to the immune system; in phacoclastic uveitis (with capsule rupture), intact lens antigens including membrane-associated antigens are released and are able to interact with Class II major histocompatibility T cells and macrophages, resulting in a cell-mediated or delayed-type hypersensitivity reaction, sustained by massive and long-term antigen release.
In many pure breed dogs, inheritance is probably the most common cause of cataracts. The large-scale study cited earlier found 59 dog breeds that have a prevalence of cataracts higher than the “baseline” prevalence of 1.61% reported in mixed breed dogs. Seven breeds, including the toy and miniature poodle, had a cataract prevalence greater than 10%. Obviously, any breed in which the prevalence of a disease is higher than that of the general population should be suspected of being genetically susceptible to the disease. However, just as with any other disease, the inheritance of cataracts can be proven conclusively only through identification of a responsible gene, or by rigorous inheritance testing, including repeat breedings and cross-matings, over several generations. Such testing has demonstrated the inheritance of cataracts in several equine and bovine breeds and in approximately 20 canine breeds, including the Afghan hound, American cocker spaniel, bichon frise, Boston terrier, Chesapeake Bay retriever, German shepherd, golden retriever, Labrador retriever, miniature schnauzer, Old English sheepdog, toy and miniature poodle, Sealyham terrier, Staffordshire bull terrier, and wirehaired fox terrier (Table 13-2). Hereditary (and acquired) cataracts are very rare in cats.
In each of these 20 breeds the cataract is characterized by a typical age of appearance, initial opacity location within the lens, and rate of progression (or lack thereof) (see Table 13-2). Careful examination of young animals with inherited cataracts often demonstrates early, minute changes, but behavioral signs of visual impairment may not become evident until much later. Hereditary cataracts can be either recessive or dominant genetic traits. However, determining the genetics of a particular cataract in one breed does not exclude another genetic factor from causing a different type of cataract in the same breed. For example, there is evidence that both dominant and recessive cataracts are present in the golden retriever.
It is likely that the list in Table 13-2 is by no means final. On the basis of a very high cataract incidence and the same criteria (typical age, location, and progression), it is likely that cataracts are inherited in many additional canine breeds that have a cataract prevalence greater than 1.61%, including numerous terriers, spaniels, sheepdogs, and retrievers (see the Appendix).
Although a detailed discussion of the characteristic pathogenesis of cataracts in each breed is beyond the scope of this book, their early recognition has significant implications for prognosis and prevention. If a clinician recognizes a lenticular opacity in a characteristic location in a purebred dog of the right age, it may be assumed that the cataract is inherited in origin. Client education about cataract progression in this breed, as well as recommendations concerning neutering, should be provided. Such counseling is not required if there is evidence that the cataract is secondary to some nonhereditary cause.
Congenital cataracts begin during fetal life, are present at birth, and may be stationary or progressive. They may be inherited, secondary to other ocular developmental abnormality, or the result of maternal influences.
Not all congenital cataracts are inherited, and in fact, the majority are not genetic. It is important to breeders to determine whether genetic factors are involved. A thorough history is needed to better determine inheritance.
A thorough ocular and physical examination should be performed. If a genetic cause cannot be eliminated, repeat breeding of the parents may be necessary to determine whether a genetic influence is involved.
Persistent pupillary membrane (PPM) (see Chapter 11) is inherited in the basenji, but familial and noninherited PPMs may be found in any dog breed and in numerous species. PPM may cause cataracts or corneal endothelial dystrophy, or both. Stationary anterior capsular cataracts develop if a strand of membrane adheres to the lens. The strand may or may not be absorbed before maturity; in either case, it will leave a permanent capsular opacity that may interfere with vision. Adhesion of a strand of pupillary membrane to the corneal endothelium results in permanent corneal endothelial dystrophy, which will similarly affect vision. Strands are not clinically significant if both ends attach to the iris or if one end is free in the anterior chamber. Some clinicians advocate surgical treatment of severe cases through corneal transplantation or cataract extraction. Others argue against surgery due to the stationary character of the cataract and corneal lesions, and because the PPM may be patent and ocular hemorrhage could occur during surgery. Medical treatment, using topical 1% atropine applied every 2 or 3 days to dilate the pupil and help vision, has also been suggested. However, many cases receive no medical or surgical treatment.
Persistent hyaloid artery and persistent hyperplastic primary vitreous are discussed in detail in Chapters 2 and 14. When the remnants of the embryonic blood supply contact the lens, cataracts of the posterior capsule and/or cortex result. The extent of visual interference depends on the size of the opacity. The remnants may persist as any of the following: