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

FIGURE 1-27. The pupillary light reflex. The direct pupillary light reflex is the response shown by the eye being illuminated. The consensual pupillary light reflex is the response shown by the contralateral eye, which is not being illuminated.

is important to protecting the eye, and interference with it (e.g., facial paralysis, trigeminal palsy, local anesthesia) often results in severe ocular damage. Closure of the lids of the stimulated eye is referred to as the direct corneal reflex, and closure of the contralateral lids is termed the consensual corneal reflex. In normal animals, the direct reflex is typically more pronounced than the consensual reflex.

Menace Response

The menace response is a learned response rather than a true reflex, and as such, it may be absent in normal young, naïve, or stoic animals. Therefore lack of this response in such animals should not be taken as definitive proof that they are blind. The stimulus is hand movement across the animal’s visual field, and care must be taken to prevent air currents from stimulating a corneal or palpebral reflex and causing a false-positive response. Motion parallel to the ocular surface (as opposed to directly toward the eye) or application of the stimulus behind a sheet of glass or plastic may prevent air currents from stimulating the corneal reflex and causing a false-positive response. Such false-positive and false-negative responses are often misinterpreted by owners as evidence of sight or blindness in an animal.

PHYSIOLOGY OF THE AQUEOUS

Aqueous humor fills the aqueous compartment, which consists of the anterior chamber between the iris and cornea, and the posterior chamber, between the posterior iris surface and the anterior lens surface. The posterior chamber should not be confused with the vitreous compartment, which is located posterior to the lens (Figure 1-28).

Anterior chamber

Posterior chamber

Vitreous

FIGURE 1-28. The chambers of the eye. The aqueous compartment is subdivided into two chambers by the iris diaphragm. The anterior chamber is anterior to the plane of the iris and pupil (blue), whereas the posterior chamber (green) is posterior to the iris-pupil plane but anterior to the vitreous (white). The retina and optic nerve are in yellow. (Modified from Fine S, Yanoff M [1972]: Ocular Histology: A Text and Atlas. Harper & Row, New York.)

Formation and Composition

In order to maintain the optical clarity of the eye, a series of blood-ocular barriers are present in the normal eye. The bloodaqueous barrier reduces aqueous humor protein concentrations to about 0.5% of plasma concentrations and also prevents many substances, including drugs, from entering the aqueous. Most large molecules, including proteins, are unable to pass through or between cells in the two layers of the ciliary epithelium overlying the ciliary processes because of tight intercellular junctions between cells. Similarly, a blood-retinal barrier formed by the retinal capillary endothelial cells and their basement membrane also limits passage of substances into the retina so as to prevent distortion of the photoreceptors. The exact anatomic location of the barrier, however, is probably different for different substances (e.g., capillary endothelial cells, endothelial basement membrane, or intercellular junctions). Inflammation and certain diseases frequently disrupt the blood-ocular barrier and allow higher amounts of proteins, including immunoglobulins and fibrinogen, to enter the eye.

Aqueous is produced in the ciliary body, by passive (diffusion and ultrafiltration) and active (selective transport against a concentration gradient) processes. Fluid from ciliary capillaries passes into the stroma of the ciliary processes, through the ciliary epithelium, and into the posterior chamber.

An energy-dependent transport mechanism similar to that in the renal epithelium is present in the ciliary body and results in higher concentrations of certain substances (e.g., ascorbic acid) in the aqueous than in the plasma. Sodium and chloride ions are actively pumped into the aqueous and draw water passively along a concentration gradient. Na-K–activated ATPase is present

Table 1-3 Aqueous Humor Statistics

in the inner layer of the unpigmented ciliary epithelium and may be associated with the “sodium pump” that probably accounts for the majority of actively formed aqueous.

Aqueous humor is also produced via the enzyme carbonic anhydrase, which catalyzes the formation of carbonic acid from carbon dioxide and water. Carbonic acid dissociates, allowing negatively charged bicarbonate ions to pass to the aqueous. Positively charged sodium ions, and eventually water, then follow bicarbonate into the posterior chamber. Drugs that inhibit carbonic anhydrase therefore result in decreased aqueous production and a reduction in intraocular pressure (IOP; see later). Aqueous carries nutrients for the tissues it bathes (i.e., iris, cornea) and receives constant contributions of waste products of metabolism. Thus the composition changes as it passes from the ciliary body to the drainage angle.

Aqueous may then leave the eye via several routes. In the conventional or traditional outflow route, aqueous humor passes through the pupil into the anterior chamber, and from there it enters the trabecular meshwork in the drainage (iridocorneal) angle, the blood-free venous angular aqueous plexus, and eventually the systemic venous circulation through a plexus of small veins in the sclera, the scleral venous plexus. Contraction of smooth muscle fibers of the ciliary muscle that insert into the trabecular meshwork are probably capable of increasing drainage of aqueous from the eye by increasing the size of the spaces in the trabecular meshwork. The vast majority of aqueous humor leaves the eye via the traditional outflow route.

An alternative route of drainage—the uveoscleral route— normally accounts for about 3% to 15% of aqueous outflow in most species, and probably more in the horse. Aqueous passes through the ciliary body and choroid via the supraciliary and suprachoroidal spaces, and from there it passes through the sclera into the orbit. Outflow via this route may be substantially increased in certain disease states and in response to some antiglaucoma drugs, such as the prostaglandin derivatives.

Pressure Dynamics

Equilibrium between formation (production) and drainage (outflow) of aqueous results in a relatively constant intraocular pressure (IOP) (Table 1-3). IOP is affected by factors such as age, species, mean arterial pressure, central venous pressure, blood osmolality, and episcleral venous pressure. IOP typically exceeds the pressure in the draining venous system (the episcleral veins) because aqueous humor is actively produced and the trabecular meshwork slows its departure (provides resistance) from the eye. The ease with which aqueous humor leaves the eye is called the facility of outflow (C). The various

IOP = Aqueous secretion + Episcleral venous pressure Outflow facility

or

Po = (F/C) + Pe

where IOP (Po) is expressed in mm Hg, F is the rate of aqueous formation in µL/min, C is the facility of aqueous outflow in ML/min/mm Hg via both the conventional and uveoscleral outflow routes, and Pe is the episcleral venous pressure in mm Hg. These relationships make it clear that there are multiple avenues for decreasing IOP, including decreasing aqueous humor secretion, increasing conventional or uveoscleral outflow, and potentially lowering episcleral venous pressure. They also suggest that (1) IOP can be reduced only to 8 to 9 mm Hg (episcleral venous pressure) by methods that improve outflow via the conventional pathways but that (2) in theory, improving outflow via the uveoscleral pathway can achieve very low IOPs because this route drains into the orbit, which has a pressure of only 1 to 3 mm Hg.

Budras KD, et al. (2002): Anatomy of the Dog: An Illustrated Text. Schlütersche, Hannover, Germany.

Duke-Elder S (1958, 1968): System of Ophthalmology: Vol. 1: The Eye in Evolution, and Vol. IV: Physiology of the Eye and of Vision. Henry Kimpton, London, pp. 605-706.

Evans HE (1993): Miller’s Anatomy of the Dog, 3rd ed. Saunders, Philadelphia. Jacobs GH (1993): The distribution and nature of color vision among the

mammals. Biol Rev 68:413.

Kaufman PL, Alm A (2003): Adler’s Physiology of the Eye, 10th ed. Mosby, St. Louis.

Miller PE, Murphy CJ (1995): Vision in dogs. J Am Vet Med Assoc 207:1623.

Miller PE, Murphy CJ (2005): Equine vision: normal and abnormal, in Gilger BC (editor): Equine Ophthalmology. Saunders, St. Louis, pp. 371-408.

Neitz J, et al. (1989): Color vision in the dog. Vis Neurosci 3:119.

Peichl L (1992): Topography of ganglion cells in the dog and wolf retina. J Comp Neurol 324:603.

Prince JH, et al. (1960): Anatomy and Histology of the Eye and Orbit of Domestic Animals. Charles C. Thomas, Springfield, IL.

Samuelson D, et al. (1989): Morphologic features of the aqueous humor drainage pathways in horses. Am J Vet Res 50:720.

Walls GL (1963): The Vertebrate Eye and Its Adaptive Radiation. Hafner, New York.

DEVELOPMENT

Formation of Optic Primordia

Broadly speaking, the embryonic and fetal development of the eye occurs in three stages:

•Embryogenesis: Segregation of the primary layers of the developing embryo. The period begins with fertilization and ends with differentiation of the primary germ layers.

•Organogenesis: Separation into the general pattern of various organs.

•Differentiation: Detailed development of the characteristic structure of each organ.

It is assumed that the embryonic development of the eye is similar in sequence for all mammalian species and that interspecies differences pertain mostly to the duration of gestation and the age of the various anatomic end points—for example, regression of embryonic vasculature or eyelid opening.

The optic primordia (rudimentary eye) develops from that portion of the embryo that later forms the anterior part of the central nervous system (CNS). The first step in the embryogenesis of the future eye takes place at the embryonic plate stage, when the ectoderm invaginates along the posterior-anterior axis to form the neural groove. The two neural lips of the groove subsequently fuse, thus turning the groove into the neural tube (Figures 2-1 and 2-2). At the site of fusion, between the ectoderm and the neuroepithelium (the epithelium of the neural tube), neuroepithelial cells proliferate to form the neural crest cells and migrate sideways into the paraxial and lateral mesoderm. These neural crest cells mix with mesodermal cells and form the secondary mesenchyme; this secondary mesenchyme forms the main mesodermal structures of the eye. Therefore the eye develops from the neural ectoderm, neural crest, and surface ectoderm, with minor contributions from the mesoderm.

The anterior end of the neural tube enlarges and bends down to form the primordia of the CNS. On its outer surface, on both sides, appear two small pits called the optic grooves or optic pits. These pits, which appear on day 13 of gestation in the dog, are the anlage of the eyes (see Figure 2-2, G).

*The author wishes to acknowledge the contribution of Dr. Robert Barishak, and to thank him for his input throughout the years and to this chapter.

With the closure of the anterior end of the neural tube, intratubular fluid accumulates and its pressure causes the evagination of the optic grooves and their transformation into the two optic vesicles (Figures 2-3 and 2-4). This marks the beginning of organogenesis. In the dog this event occurs on the fifteenth day of gestation. The lumen of the neural tube remains connected to the cavities of the optic vesicles by two optic stalks (see Figure 2-4, D). Under the pressure of the intratubular (intraventricular) fluid, the optic vesicles continue to enlarge and bulge, eventually coming in contact with the surface ectoderm. At the site of contact with the optic vesicle the surface ectoderm thickens and forms the lens placode (Figures 2-3; 2-4, C; and 2-5). The contact of the optic vesicle with the surface ectoderm serves as an induction for the optic vesicle to start invaginating, thus forming the double-layered optic cup (see Figures 2-3 and 2-4, E and F).

The invagination of the vesicle progresses from inferior to superior but is not completed on the ventral side of the optic cup, where a fissure, called the embryonic optic fissure, remains. The double layers of the optic cup are aligned on both sides of the fissure, which extends posteriorly under the optic stalk. This fissure allows the secondary mesenchyme present around the cup to penetrate into the cavity of the optic cup to form the hyaloid vascular system (twenty-fifth day of gestation in the dog) (see Figure 2-4, G and H). This fissure gradually closes leaving a small aperture at the anterior end of the optic stalk, through which the hyaloid artery passes (Figure 2-6). The hyaloid artery supplies the inner layers of the optic cup and developing lens vesicle. The two lips of the optic fissure fuse anteriorly to the optic stalk. The fusion process progresses anteriorly and posteriorly, eventually causing closure of the optic cup and allowing intraocular pressure to build up (see Figure 2-6).

The lens placode thickens to become the lens vesicle. Following the invagination of the optic vesicle, the lens vesicle finds itself embedded inside the cavity of the cup (see Figure 2-4, F and H). Anteriorly, the hyaloid artery gives branches, the tunica vasculosa lentis, which cover the posterior and lateral faces of the lens. This vascular network supplies the metabolic requirements of the lens during development. The hyaloid vascular system disappears at advanced stages of the development or during the postnatal period. In dogs remnants of the hyaloid system might remain visible until the fourth postnatal

Neural crest

Ectoderm

Endoderm

FIGURE 2-1. Developing embryo at the start of neural tube formation. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

DEVELOPMENT AND CONGENITAL ABNORMALITIES 21

FIGURE 2-3. Formation of the optic vesicle, optic cup, and lens vesicle. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

month, whereas in cattle they may persist until 12 months of age. In humans, but not in domestic animals, the caudal portions of the hyaloid artery and vein transform themselves into the central retinal artery and vein.

At this stage of development, organogenesis has been completed and the general structure of the eye has been determined. It is followed by a period of differentiation as the specific structures of the eye begin to form. Their development

is reviewed in the following sections, beginning with the posterior parts of the eye and progressing anteriorly.

Retina

The optic cup is lined by two layers of epithelium of neuroectodermal origin (see Figure 2-4, H). The inner layer, facing the vitreous, is nonpigmented, but the outer layer, facing the

Optic groove

Level of section B

Neural fold

Neural groove

A

Neural tube

Notochord

Forebrain

Mesenchyme

Lens placode

Optic vesicle

C

Mesenchyme

Midbrain

Surface ectoderm

Forebrain

Lumen of optic stalk

Mesenchyme

Hyaloid artery

DEarly stage of optic cup

Outer layer of optic cup

Inner layer of optic cup

Lens vesicle

Optic fissure

Hyaloid artery

Lens vesicle

Wall of brain

Intraretinal space

H

(future) sclera, is pigmented. The anterior rim of the cup will form the anterior uvea (ciliary body and iris), and the posterior part of the cup will form the retina. The two epithelial layers of the optic cup will form the two epithelial layers of the retina and the anterior uvea.

The outer epithelial layer of the posterior optic cup forms the pigment epithelium of the retina. The inner epithelial layer forms the sensory retina (Figure 2-7). The two layers of the posterior optic cup are separated by the intraretinal space representing the cavity of the optic vesicle, which has gradually

Neural

ectoderm Retinal disc

FIGURE 2-5. Light micrograph of 6-mm pig embryo showing thickening of lens placode. (From Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

been obliterated during the invagination of the optic vesicle. Diseases of the posterior segment of the eye cause retinal detachment in this space as the sensory retina separates from the pigment epithelium.

The common neuroblastic layer, which is the nuclear portion of the sensory retina, divides into an outer neuroblastic layer

Lens

Hyaloid vessels

in optic fissure

Level of section B

A

Optic stalk

Lens

Optic fissure closed

Level of section D

C

Hyaloid vessels in optic fissure

DEVELOPMENT AND CONGENITAL ABNORMALITIES 23

and an inner neuroblastic layer (see Figure 2-7). These outer and inner neuroblastic layers are separated by the fiber layer of Chievitz. The cells of the outer neuroblastic layer differentiate into cones and rods externally and horizontal cells internally. The cells of the inner neuroblastic layer differentiate into ganglion cells, amacrine cells, bipolar cells, and Müller’s cells. The rods and cones (i.e., the photoreceptors) form the outer retina and are adjacent to the choroid and sclera (Figure 2-8). The ganglion cell layer, which originated in the inner neuroblastic layer, is called the inner retina because it is adjacent to the vitreous. The resulting retina is called an inverted retina because the photoreceptors are close to the outer layers of the eye and light must pass through all of the retinal layers to reach the photoreceptors. The reason for this arrangement is to place the photoreceptors next to the choroid, thus giving these cells, which have very high metabolic requirements, their own “private” blood supply.

There is species variation in the degree of retinal development present at birth. In dogs it is possible to record electrophysiologic activity of the photoreceptors during the first postnatal week; signals reach adult amplitude by 5 to 8 weeks of age. Similarly, differentiation of the rod and cone inner and outer segments is evident histologically during the first 8 weeks of life.

Optic Nerve

Axons from the ganglion cells grow toward the optic stalk, thus forming the nerve fiber layer, the innermost layer of the retina (see Figures 2-6, B and D; and 2-8). Axons from throughout the entire retina converge on the optic disc, where they form into bundles collectively known as the optic nerve (cranial nerve II)

Lumen of optic stalk

Inner layer of optic stalk (containing axons of ganglion cells)

Mesenchyme

B

Walls of optic stalk continuous with the wall of the brain and the layers of the optic cup

Axons of ganglion cells

Hyaloid vessels

FIGURE 2-7. The two retinal walls. The inner retinal wall shows two zones—an inner, nonnucleated layer and a deeper, nucleated layer. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

(Figure 2-9). The axons of optic nerve extend posteriorly to form the optic chiasm and optic tracts before making their first synapse at the lateral geniculate nucleus.

As the ganglion cell axons collect at the optic disc they displace primitive neuroectodermal cells forward, into the vitreous cavity. These displaced cells form a glial sheath around the hyaloid artery. At the disc, the same cells may form an agglomeration called Bergmeister’s papilla, which protrudes into the vitreous. The papilla may persist into adult life (especially in ruminants), or it may atrophy, thus forming a depression, known as the physiologic optic cup, in the optic disc (Figure 2-10). In newborns this physiologic optic cup may be confused with a coloboma of the optic disc. In patients with glaucoma the physiologic optic cup may enlarge owing to the forces of the increased intraocular pressure on this region of the eye.

A

Sclera

Choroid

Retina

Vitreous

The embryonic vitreous consists of the primary, secondary, and tertiary vitreous (Figure 2-11). The primary vitreous develops with the hyaloid vasculature (Figure 2-12). It has mesenchymal, neuroectodermal, and ectodermal components. The mesenchymal elements enter posteriorly with the hyaloid vessels, and anteriorly through the space between the anterior rim of the optic cup and the lens vesicle. The ectodermal elements are the fibrils produced by the posterior face of the lens. The primary vitreous also contains neuroectodermal elements, which consist of the fibrils produced by the inner limiting membrane of the retina. The secondary vitreous is the “definitive” vitreous that will persist into adulthood. It is denser, is more homogeneous and avascular, and is laid down around the primary vitreous (see Figures 2-11, B, and 2-13). It is also secreted by the inner limiting membrane of the retina. The tertiary vitreous is secreted by the ciliary epithelium. Bundles of fibers extend from the ciliary epithelium toward the lens equator, covering the secondary vitreous anteriorly (see Figure 2-11, C). In the adult they persist as lens zonules (suspensory ligament of the lens).

Lens

As noted earlier, thickening of the lens placode (on the seventeenth day of gestation in the dog) occurs as a result of induction by the optic vesicle. The placode then invaginates, and by day 25 it forms the lens vesicle (see Figures 2-3 and 2-4, D, F, and H). This vesicle is lined by surface ectodermal cells, the apex of which is directed toward the center of the lens vesicle cavity (Figures 2-14 and 2-15). The base of the cells forms the primitive lens capsule. The anterior cells of the lens

B

Retinal pigment epithelium

Photoreceptor layer

External limiting membrane

Outer nuclear layer

Outer plexiform layer

Inner nuclear layer

Inner plexiform layer

Ganglion cell layer

Nerve fiber layer

Internal limiting membrane

Axons of ganglion cells

A

Optic stalk

Lens

Optic nerve

Level of section C

B Central vein and artery of the retina

Sheath of the optic nerve (continuous with the meninges of the brain and the choroid and sclera)

Central artery and

vein of the retina

Axons of ganglion cells

A

vesicle remain cuboidal, but the posterior cells elongate, become columnar, and form the primary lens fibers (Figure 2-16). These fibers extend anteriorly, thus filling the cavity of the vesicle with lens fibers (see Figures 2-14, D and E; and 2-16, C and D). Their nuclei disappear, and these fibers constitute the embryonal nucleus of the lens. As a result, the posterior aspect of the adult lens is devoid of cells and is composed only of a lens capsule. The anterior cuboidal cells, on the other hand, remain as the adult lens epithelium.

The junction between the anterior lens epithelium and the primary lens fibers extends along the equator of the lens and forms the equatorial zone. Epithelial cells in this area form the secondary lens fibers; these fibers extend anteriorly along the lens epithelium and posteriorly along the lens capsule. Secondary lens fibers continue to form throughout

FIGURE 2-10. Optic nerve heads of a dog (A) and a sheep (B). The dark spot in the center of the canine optic nerve head is the physiologic optic cup (arrow). The pink tuft in the center of the sheep optic nerve head is the ovine Bergmeister’s papilla (arrow). (Courtesy University of California, Davis, Veterinary Ophthalmology Service Collection.)

B

life from those equatorial epithelial cells that maintain their lifelong mitotic activity. Successive layers of fibers are deposited on top of preexisting fibers, like the layers of an onion. As a result the embryonal nucleus is surrounded by the fetal nucleus, which in turn is surrounded by the adult nucleus and cortex (Figure 2-17).

Because none of the lens fibers is quite long enough to reach fully from pole to pole, and because the cells are too thick at the ends for all to meet in a single point, they meet in a Y-shaped structure known as the lens suture. The anterior lens suture is an upright Y, and the posterior suture is inverted (Figures 2-16, F and G; and 2-18).

The lens capsule is secreted anteriorly by the anterior lens epithelium. Its formation continues throughout life, and therefore its thickness increases with age. The posterior lens capsule,

Primary vitreous (hyloid artery)

A

Remains of primary vitreous (Cloquet’s canal)

Secondary (adult) vitreous

B

Tertiary vitreous (lens zonules)

Remains of primary vitreous (Cloquet’s canal)

C

Secondary (adult) vitreous

FIGURE 2-11. Scheme of main features in vitreous development and regression of hyaloid system, shown in drawings of sagittal sections. A, Hyaloid vessels and branches occupy much of the space between lens and neural ectoderm, forming the primary vitreous. B, An avascular secondary vitreous of fine fibrillar composition fills the posterior part of the eye. The primary vitreous shown in A is condensed into Cloquet’s canal as the hyaloid vessels atrophy. C, Vessels of hyaloid system atrophy progressively. Zonular fibers (tertiary vitreous) begin to stretch from growing ciliary region toward lens capsule. (Modified from Duke-Elder S [editor] [1963]: System of Ophthalmology. Vol III: Normal and Abnormal Development, Part 1. Embryology. Henry Kimpton, London.)

Tunica vasculosa lentis

Hyaloid artery

FIGURE 2-12. Light micrograph of 25-mm pig embryo showing the hyaloid arterial system filling future vitreal cavity. Vessels are evident extending through the optic stalk, and the vascular network attached to posterior lens is evident. (Modified from Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

FIGURE 2-13. Vitreous development. The primary vitreous and hyaloid artery fill the optic cup. The primary vitreous retracts and the hyaloid artery regresses, while the secondary avascular vitreous develops. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

A

Presumptive fibers

B

C

Elongating posterior

epithelium

D

Lens fibers

E

FIGURE 2-14. A, Formation of lens placode. B, Invagination forming lens vesicle. C to E, Development of embryonic nucleus. C, Hollow lens vesicle is lined with epithelium. D, Posterior cells elongate, becoming primary lens fibers. E, Primary lens fibers fill lumen, forming embryonic nucleus. Curved line formed by cell nuclei is called the lens bow. Anterior epithelium remains in place. (From Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

which is much thinner, is formed by the basal membrane of the elongating primary lens fibers.

Primitive Vascular System

The hyaloid artery, a branch of the internal ophthalmic artery, enters the optic cup through the embryonal optic fissure (see Figure 2-6, A). Its branches continue forward, reach the anterior margin of the optic cup, and anastomose with the annular vessel (see Figure 2-6, C) formed by the choriocapillaris, which is the capillary plexus that surrounds the optic cup. The hyaloid artery is called vasa hyaloidea propria; its anterior dividing branches form a net around the lens called the lateral and