The Eyeball

By | December 23, 2014

The eyeball (bulbus oculi) is formed by three concentric coats: the fibrous tunic (tunica fibrosa bulbi), the middle vascular tunic (tunica vasculosa bulbi), and the inner nervous tunic (tunica interna bulbi). In the dog, the eyeball is nearly spherical, differing little in its sagittal, transverse, and vertical diameters. The size of the eyeball varies among breeds, but the diameter is usually approximately 20 to 22 mm. In one study, the radius of the canine eye varied across breeds from 9.56 to 11.57 mm and was correlated with the width and length of the skull.

The transparent cornea forms the anterior one-fourth of the eyeball, and because it has a smaller radius of curvature (approximately 8.5 to 9 mm) than the rest of the eye, it bulges anteriorly. The vertex of the cornea is designated the anterior pole of the eye (polus anterior). The point directly opposite this is the posterior pole (polus posterior). The latter is a geometric point and does not correspond to the exit point of the optic nerve, which lies ventrolateral to the posterior pole. The line connecting the anterior and posterior poles and passing through the center of the lens is the axis bulbi. In the mesaticephalic dog the axis forms an angle of approximately 30 degrees with the median plane. The angle is greater in the brachycephalic breeds.

Lines connecting the anterior and posterior poles of the eye on the surface of the globe are designated meridians. The equator of the globe is its maximum circumference located midway between the poles. Because the eye is essentially spherical, the common anatomic terms of direction are not applicable for certain structures, such as the retinal layers. In such cases, the terms inner and outer are used with reference to the center of the bulb.

Fibrous Tunic

The fibrous outer tunic of the eye is responsible for the shape of the eye, protection from the external environment, and conduction with refraction (bending) of light rays via the cornea. Additionally, the sclera is the site for insertion of the extraocular muscles. The fibrous tunic is composed of two parts: the opaque sclera, which encloses approximately the posterior three fourths of the globe, and the transparent cornea anteriorly. The junction of the cornea and the sclera is designated the limbus corneae.

Sclera

The sclera consists of a dense network of collagen and elastic fibers and their attendant fibrocytes. It varies in thickness, being greatest in the region just posterior to the corneoscleral junction, where it receives the insertions of the rectus and oblique muscles and contains the scleral venous plexus. The ciliary muscle is attached to a small ridge of fibrous tissue that forms a ring (anulus sclerae) on the inner surface of the sclera posterior to the iridocorneal angle.

The mean scleral surface area of canine eyes is reported to be 12.87 (±2.24) cm2.The thickness of the sclera is only 0.34 (±0.13) mm near the equator. It becomes thicker again on the posterior aspect of the globe. Where the optic nerve leaves the eyeball, the sclera is sievelike (area cribrosa sclerae). Here the collagen, elastic, and reticular fiber bundles of the sclera form a net through the interstices of which the optic nerve myelinated axons pass. The trabeculae of the area cribrosa continue caudally as the prominent connective tissue septae of the optic nerve. The dura mater surrounding the optic nerve (vagina externa n. optici) is continuous with the outer layers of the sclera at the periphery of the area cribrosa, and with the periorbita and dura mater encephali at the optic canal.

The ciliary nerves and the short posterior ciliary vessels enter the eyeball through foramina in the sclera at the periphery of the area cribrosa.

Cornea

The cornea forms the anterior segment of the fibrous tunic. The normally transparent cornea contains 80% (±2%) water. The mean full thickness of the adult canine cornea is approximately 600 µm. In one study, central corneal thickness was reported to be 585 (±79) µm. In dogs less than 1 year of age it was 555 (±64) µm, whereas in older dogs it was 606 (±85) µm. Its thickness increases with age. In another study the mean central corneal thickness of 43 dogs was found to be 611 µm. Measurements made with optical and ultrasonic pachymeters in vivo show the cornea to be uniformly thinner axially than at the limbus. The radius of curvature of the living dog cornea is approximately 8.5 to 9.0 mm. Largebreed dogs have been shown to have a slightly flatter cornea (a larger radius of curvature) than small or medium-sized breeds. The cornea of the dog is very slightly oval; the mediolateral dimension is usually approximately 10% greater than the dorsoventral dimension, which is typically 16 to 18 mm in an average sized dog.

Classically, the cornea is described as consisting of five layers: the anterior epithelium, the anterior limiting lamina (Bowman layer), the substantia propria, the posterior limiting lamina (Descemet membrane), and the posterior epithelium (endothelium). The most variable of these layers among vertebrates is the presence of an anterior limiting lamina. Shively and Epling (1970), in a study of the fine structure of the canine cornea, were unable to demonstrate a distinct layer comparable to the anterior limiting lamina (Bowman layer). This was confirmed by Morrin et al. (1982), who described the ultrastructure of the Beagle cornea. They did describe, however, the subepithelial stroma (for a thickness of approximately 9 µm) as being hypocellular and to contain randomly oriented collagen bundles.

The anterior epithelium of the cornea is approximately 19 cells thick and consists of three distinct layers. A single layer of columnar basal cells attaches to the underlying stroma through a specialization of the extracellular matrix, the anterior corneal basement membrane. The anterior corneal basement membrane of the dog has been documented to possess a rich three-dimensional “felt-like” topographic architecture composed of nanoscale to submicron intertwining fibers, pores, and elevations. The surface topographic features as well as the intrinsic compliance (relative stiffness) of basement membranes have been shown to profoundly modulate a wide menu of corneal epithelial cell behaviors. Over the basal cell layer are approximately three layers of polygonal wing cells. The superficial layers are composed of flattened squamous cells. The most superficial layer of squamous cells is in direct contact with the precorneal tear film and has a microplicated surface. The rugae of this surface are thought to be important in anchoring the precorneal tear film and may also play a role in transport processes by amplification of the membrane surface. Both the anterior and posterior corneal epithelia, but especially the latter, regulate the degree of the hydration of the substantia propria by an active transport mechanism. Disruption of either epithelium results in corneal edema with more severe edema developing with involvement of the posterior epithelium.

The canine corneal epithelium contains carbonic anhydrase, which may facilitate the elimination of metabolic carbon dioxide against small concentration gradients via catalytic conversion to bicarbonate (HCO3 ). The opioid growth factor peptide [met5]enkephalin and its corresponding receptor are found in the canine cornea where they may play a role in homeostasis and repair of the corneal epithelium. Toll-like receptor 4, which is important for recognizing highly conserved molecular patterns of pathogens, is expressed in the canine cornea. The nucleotide-binding oligomerization domain (NOD) proteins NOD1 and NOD2 are also expressed in the canine corneal anterior and posterior epithelia where they serve as signaling receptors of the innate immune system. NOD1 and NOD2 are also found in the conjunctival and nonpigmented iridal epithelium. Cholestyramine, a highly nonpolar dehydration product of cholesterol is present in normal dog corneas where it accounts for 20% to 25% of the total steroid-sterol present. The transparency of the cornea remains incompletely understood. There are three elements thought to participate in achieving and maintaining corneal transparency: (1) uniform sizing and spatial distribution of the collagen fibrils that compose the extracellular matrix of the stroma, (2) the distribution of media of differing refractive indices within the stroma, and (3) the expression of crystallins by the stromal cells of the cornea. Other factors that contribute to corneal transparency are the lack of pigment, vessels, and large myelinated nerve fibers. Any disruption of the highly ordered structure of the collagen fibers, such as by edema or by scar tissue, results in a loss of transparency.

The cornea, normally avascular, is nourished by the capillary loops at the corneoscleral junction (limbus), the precorneal tear film, and the aqueous humor. Recently it has been suggested that the avascularity of the cornea is due to the expression of soluble vascular endothelial growth factor (VEGF) receptor-1 within corneal tissues. This receptor serves as a “trap,” binding available VEGF, preventing it from inciting vessel formation.

The substantia propria is composed of highly ordered collagen fibrils with interspersed cellular elements. These fibrils are of uniform small diameter and are arranged in distinct lamellae. The cornea is easily dissected along these lamellar planes. The majority of fibrils within a lamella run parallel to each other and to the corneal surface, although the fibrils in each lamella run at an angle to those in the other layers. Additionally, although not verified to date in the dog cornea, recent work in the human cornea using second harmonic imaging demonstrates a high degree of lamellar interweaving especially in the anterior stroma. The fibrocytes of the cornea (keratocytes) are flattened between the lamellae.

The posterior limiting lamina (Descemet membrane) is the exaggerated basement membrane of the posterior epithelium of the cornea. It is approximately two times thicker in the dog than in humans. The posterior epithelium of the cornea is composed of a simple cuboidal epithelium, individual cells of which are mostly hexagonal in outline with a mean cell area of 395 (±36) µm2. The mean endothelial cell density of the canine cornea has been reported as 3175 (±776)/mm2 and 2555 (±240) cells/mm2. In dogs less than 1 year of age it has been reported to be 3641 (±752)/ mm2, whereas in older dogs it is 2851 (±634)/mm2. The density of these cells has been shown to decrease with age and following intraocular surgery. The morphologic characteristics of these cells have also been shown to be altered in some disease states such as diabetes. The ability of this layer to regenerate is species variable. Severe trauma to this layer of cells frequently results in chronic corneal edema.

The cornea is innervated by branches of the ciliary nerves that arise from the ophthalmic nerve, a branch of the trigeminal nerve. Nerve branches to the cornea enter the anterior layers of the stroma at the limbus and soon lose their myelin sheaths as they converge toward the vertex. The corneal nerve plexus is formed by thick-, medium-, and thin-diameter nerve bundles. The mean nerve bundle length in 1 mm2 of cornea is 10.32 (±0.11) mm in adult dogs, which is significantly higher than 9.42 (±0.02) mm and 7.75 (±0.14) mm in young and old dogs, respectively (Lasys et al., 2003). In mesocephalic dogs, the mean density of subepithelial and subbasal nerve fibers is 12.39 (±5.25) mm/mm2 and 14.87 (±3.08) mm/mm2, respectively. These values are significantly higher than the corresponding values in brachycephalic dogs of 10.34 (±4.71) mm/mm2 and 11.80 (±3.73) mm/mm2, respectively.

The limbal plexus is a 0.8-1 mm network of superficial nerves around the peripheral cornea. The numerous origins of the limbal fibers include collateral branches of stromal and subconjunctival fibers in passage to the cornea, recurrent collaterals from the peripheral corneal plexus, and perivascular fibers associated with the rich limbal vasculature. The limbal plexus is morphologically subdivided into outer periscleral and inner pericorneal zones. The periscleral zone contains largely perivascular nerve fascicles and a stromal plexus with axons extending randomly through the limbal stroma. The pericorneal zone is a much denser meshwork of highly branched and anastomotic axons and small-diameter fascicles. Many inner zone fibers are intimately associated with vascular elements of the superficial limbal arcade, and others travel through the corneoscleral transition zone and anastomose with axons in the peripheral anterior stromal plexus. The limbal and conjunctival epithelia contain modest numbers of short, wavy, beaded, and mostly radially oriented axons.

Most nerve fibers enter the peripheral cornea at the corneoscleral limbus in a series of 14-18 prominent, radially directed, superficial stromal nerve bundles containing 30-40 axons. These are located at regular intervals around the limbal circumference. Smaller nerve fascicles enter the peripheral cornea between and slightly superficial to the main bundles. Subsequently, the main stromal bundles undergo extensive dichotomous branching to form elaborate axonal trees. The distal branches of these trees are extensively joined at angular junctions to form a dense, anatomically complex stromal plexus that extends uninterrupted to all areas of the cornea. The latter plexus occupies approximately the anterior 0.4-0.5 mm half of the corneal stroma and can be further subdivided into posterior and anterior levels. The posterior level contains modest numbers of primarily smallto mediumdiameter bundles and scattered individual axons. The anterior level is much more densely innervated and morphologically complex. A very fine meshwork of thin, preterminal axons occupies the region immediately beneath the epithelial basement membrane. In contrast to the highly innervated anterior stroma, the posterior corneal stroma of the dog is largely noninnervated.

After entering the basal epithelial cell layer, most intraepithelial axons form preterminal arborizations known as epithelial leashes. Each epithelial leash comprises 2-6 axons attached to a single subepithelial fiber. Individual axons course horizontally to the surface and roughly parallel to each other through the basal epithelial cell layer tangential to the corneal for 1-1.4 mm. Most axons are less than 2.5 µm in diameter but range from 1.2-3.5 µm. As they travel horizontally through the basal epithelium they give rise to an abundance of thin, ascending branches that divide extensively to form irregular clusters of short terminal branches ending throughout the basal, wing, and squamous epithelial layers. Most axonal endings consist of single large bulbous terminal expansions.

Trigeminal nerve innervation of the cornea is essential to maintaining homeostasis. Loss of sensory innervation apparently disrupts a trophic influence normally supplied by the ciliary nerves. Corneal denervation results in corneal ulceration, edema, and loss of stromal tissue (neurotrophic keratitis), even though eyelid function is unimpaired. There is some evidence to suggest that the neuropeptide, substance P, associated with the corneal terminations of the trigeminal nerve, is the neuronal factor necessary to the maintenance of normal corneal health. The cornea also receives sympathetic innervation, and the anterior corneal epithelium of the dog, apparently independent of a neuronal source, is rich in acetylcholine. An extensive review of corneal innervation including the dog is provided by Muller et al. (2003).

At the corneoscleral junction, the anterior corneal epithelium is continuous with the bulbar conjunctiva (see later section on conjunctiva). The collagen fibers of the substantia propria become abruptly less ordered as they approach the sclera, with a resulting loss of transparency. The corneoscleral junction is oblique; the posterior aspect is more peripheral than the anterior. Immediately peripheral to the limbus, the posterior corneal epithelium reflects onto the anterior face of the iris, forming the iridocorneal (filtration) angle.

The iridocorneal angle is a regional term that includes the most anterior internal aspect of the sclera, the most posterior internal aspect of the cornea, the most anterior external aspect of the ciliary body, the root of the iris, and all intervening tissue associated with these structures. In the embryo the iridocorneal angle is a smooth, unfenestrated fornix. Late in gestation and continuing in the early postnatal period, the tissue in this area undergoes progressive rarefaction until a long cleft extends the anterior chamber posteriorly between the base of the iris and the sclera. Examination of 23 normal dogs (46 eyes) that were 5 (±2.73) years of age revealed a mean iridocorneal angle of 12.6 (±5.3) degrees (range, 5-29) and mean angle opening distance of 273.4 (±88.9) µm (range, 107-557). This cleft is bridged by a network of fine collagenous pillars that in aggregate form the pectinate ligament (lig. pectinatum anguli iridocornealis). The heavily pigmented strands of the canine pectinate ligament exhibit large variations in size and thickness. They exist primarily as single strands but may fuse with adjacent strands or ramify into a characteristic branching pattern prior to inserting obliquely onto the corneal limbus. Because the strands are relatively slender and few in number, there are wide intertrabecular spaces. The iridocorneal angle is further divided into corneoscleral trabeculae and deeper uveal trabeculae.

The region of the iridocorneal angle contains Schwalbe line cells, which possess secretory and epithelial characteristics that are associated with the nonfiltering portion of the corneoscleral trabecular meshwork and are considered to be a subpopulation of trabecular cells. The number of Schwalbe line cells declines gradually with age in normal dogs but more rapidly in dogs with glaucoma.

The trabecular cells can actively phagocytose small particulate matter. Samuelson and Gelatt (1984) and Bedford and Grierson (1986) have provided detailed anatomic descriptions of the aqueous outflow pathway in the dog. In many cases, the various reports concerning this region have conflicting findings and the terminology lacks uniformity. Bedford (1977) has described the clinical appearance of the iridocorneal angle using a special goniolens. The aqueous humor leaves the eye by filtering through the spaces between the corneoscleral trabeculae to aqueous collector vessels, the angular aqueous plexus, that join the scleral venous plexus, which, in turn, is drained by the anterior ciliary and vorticose veins. The outermost corneoscleral trabeculae appear to contribute to the canine aqueous outflow barrier by compartmentalizing the glycosaminoglycans in the intervening spaces between trabeculae. They also prevent widening of the angle and hold the initial filtration structures in a relatively compressed state. Dilation of the pupil (mydriasis) impedes the outflow of aqueous humor; the iridocorneal angle is narrowed by the increased thickness of the peripheral iris. Constriction of the pupil (miosis) opens the spaces of the iridocorneal angle and facilitates drainage.

In certain breeds, notably the Basset Hound, the corneoscleral angle is dysplastic. The pectinate ligament is sheetlike with few openings, which impedes the outflow of the aqueous humor. Animals with this condition are thought to be predisposed to developing glaucoma. A positive relationship between pectinate ligament dysplasia and narrowing of the iridocorneal angle with the development of glaucoma has been demonstrated in English Springer Spaniels.

The Eyeball: Vascular Tunic

The Eyeball: Internal Tunic

The Eyeball: Lens

Chambers of the Eye