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C H A P T E R

2 Cornea and Sclera

The outer connective tissue coat of the eye has the appearance of two joined spheres. The smaller, anterior transparent sphere is the cornea and has a radius of curvature of approximately 8 mm. The larger, posterior opaque sphere is the sclera, which has a radius of approximately 12 mm (Figure 2-1, A). The globe is not symmetric; its approximate diameters are 24 mm anteroposterior, 23 mm vertical, and 23.5 mm horizontal.1

C O R N E A

CORNEAL DIMENSIONS

The transparent cornea appears from the front to be oval, as the sclera encroaches on the superior and inferior aspects. The anterior horizontal diameter is 12 mm, and the anterior vertical diameter is 11 mm.1,2 If viewed from behind, the cornea appears circular, with horizontal and vertical diameters of 11.7 mm (Figure 2-1, B).1

In profile, the cornea has an elliptic rather than a spherical shape, the curvature being steeper in the center and flatter near the periphery. The radius of curvature of the central cornea at the anterior surface is 7.8 mm and at the posterior surface is 6.5 mm.1,3 The central corneal thickness is 0.53 mm, whereas the corneal periphery is 0.71 mm thick (Figure 2-1, C).1,3-5 (All values given are approximations.)

Clinical Comment: Astigmatism

ASTIGMATISM  is a condition in which light rays coming from a point source are not imaged as a point. This results from the unequal refraction of light by different meridians of the refracting elements. Because it is usually elliptic in profile, the cornea contributes to astigmatism in the eye because it refracts light and helps to focus the rays onto the retina. The curvature of the surface of the cornea (central 3 to 4 mm) can be determined by keratometric measurement to give a clinical assessment of the corneal contribution to astigmatism.

Regular astigmatism occurs when the longest radius of curvature and shortest radius of curvature lie 90 degrees apart. The usual presentation occurs when the radius of curvature of the vertical meridian differs from that of the horizontal meridian. The most common situation, called with-the-rule astigmatism (Figure 2-2, A), occurs when

the steepest curvature lies in the vertical meridian. Thus the vertical meridian has the shortest radius of curvature.

Against-the-rule astigmatism (Figure 2-2, B) is not as common and occurs when the horizontal meridian is the steepest; the greatest refractive power is found in the horizontal meridian. If the meridians that contain the

greatest differences are not along the 180and 90-degree axes (± 30 degrees) but lie along the 45and 135-degree axes (± 15 degrees), the astigmatism is called oblique.

Irregular astigmatism is an uncommon finding in which the meridians corresponding to the greatest differences are not 90 degrees apart.

In addition to the cornea, the lens is a refractive element that focuses light rays and might contribute to astigmatism. In fact, when considering the refractive condition, the tendency of with-the-rule astigmatism to convert to against-the-rule astigmatism with aging is

attributable primarily to the lens, which continues to grow throughout life.

CORNEAL HISTOLOGIC FEATURES

The cornea is the principal refracting component of the eye. Its transparency and avascularity provide optimal light transmittance. The anterior surface of the cornea is covered by the tear film, and the posterior surface borders the aqueous-filled anterior chamber. At its periphery, the cornea is continuous with the conjunctiva and the sclera. From anterior to posterior, the five layers that compose the cornea are epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium (Figure 2-3).

Epithelium

The outermost layer of stratified corneal epithelium is five to seven cells thick and measures approximately 50 μm.1,6 The epithelium thickens in the periphery and is continuous with the conjunctival epithelium at the limbus.

The surface layer of corneal epithelium is two cells thick and displays a very smooth anterior surface. It consists of nonkeratinized squamous cells, each of which contains a flattened nucleus and fewer cellular organelles than deeper cells. Cell size varies but a superficial cell can be 50 μm in diameter and 5 μm

10

12 mm

8 mm

A

11 mm

12 mm

B

.53

.71

C

FIGURE 2-1

Corneal dimensions.A, Radius of curvature of cornea and sclera. B, View from in front of the eye. The sclera encroaches on the corneal periphery inferiorly and superiorly. Dotted lines show the extent of the cornea in the vertical dimension posteriorly. C, Sagittal section of cornea showing central and peripheral thickness (0.53 to 0.71 mm).

CHAPTER 2  t  Cornea and Sclera

11

in height.7 The plasma membrane of the surface epithelial cells secretes a glycocalyx component that adjoins the mucin layer of the tear film.8-10 Many projections located on the apical surface of the outermost cells increase the surface area, thus enhancing the stability of the tear film. The fingerlike projections are microvilli, and the ridgelike projections are microplicae (Figure 2-4).

Tight junctions (zonula occludens) join the surface cells along their lateral walls, near the apical surface. These junctures provide a barrier to intercellular movement of substances from the tear layer and prevent the uptake of excess fluid from the tear film. A highly effective, semipermeable membrane is produced, allowing passage of fluid and molecules through the cells but not between them. Additional adhesion between the cells is provided by numerous desmosomes.

As the surface cells age, they degenerate. The cytoskeleton disassembles and the cytoplasm condenses. The cells lose their attachments and are sloughed off, being constantly replaced from the layers below. On scanning electron microscopy, the corneal surface consists of variously sized cells, ranging from small to large. The lighter cells are newer replacement cells, whereas the darker cells are those that are degenerating and will soon be sloughed.11

The middle layer of the corneal epithelium is made up of two to three layers of wing cells. These cells have winglike lateral processes, are polyhedral, and have convex anterior surfaces and concave posterior surfaces that fit over the basal cells (Figure 2-5). The diameter of a wing cell is approximately 20 μm.7 Desmosomes and gap junctions join wing cells to each other, and desmosomes join wing cells to surface and basal cells.12

The innermost basal cell layer of the corneal epithe­ lium is a single layer of columnar cells, with diameters ranging from 8 to 10 μm (Figure 2-6).7 These cells contain oval-shaped nuclei displaced toward the apex and oriented at right angles to the surface. The rounded, apical surface of each cell lies adjacent to the wing cells, and the basal surface attaches to the underlying basement membrane (basal lamina). The basal cells secrete this basement membrane, which attaches the cells to the underlying tissue through hemidesmosomes. Anchoring fibrils pass from these junctions through Bowman’s layer into the stroma.13 Although less numerous here than in the wing cell layer, desmosomes and gap junctions join the columnar cells; interdigitations and desmosomes connect the basal cells with the adjacent layer of wing cells. The basal layer is the germinal layer where mitosis occurs.

The basal cells are joined to keratin filaments in the basement membrane by hemidesmosomes. Opposite

12 Clinical Anatomy of the Visual System

A B

FIGURE 2-2

Corneal topography provides a map of the corneal surface curvature.A, Corneal topography demonstrating with-the-rule corneal astigmatism. B, Corneal topography demonstrating against-the-rule corneal astigmatism. (Courtesy Patrick Caroline, C.O.T.,   Pacific University College of Optometry, Forest Grove, Ore.)

the plaque, fine anchoring collagen fibrils form a complex branching and anastomosing network that runs from the basement membrane through Bowman’s layer and penetrates 1.5 to 2 μm into the stroma.13-18 The linkage between the hemidesmosome and the anchoring network is likely composed of basement membrane components.5 The anchoring fibrils attach to anchoring laminin-containing plaques of extracellular matrix within the stroma.16,19

Clinical Comment: Evaluation

of Corneal Surface

Fluorescein dye can be used to evaluate the barrier function of the surface layer. When instilled in the tear film, it will not penetrate the epithelial tissue as long as the zonula occludens are intact. If the tight junctions are disrupted, the dye can pass easily through Bowman’s layer and into the anterior stroma. An epithelial defect will usually appear a vivid green fluorescence when viewed with the cobalt blue filter of the slit lamp.

Epithelial Replacement

Maintenance of the smooth corneal surface depends on replacement of the surface cells that are continually being shed into the tear film. This renewal of the stratified epithelium involves cell division, migration, differentiation, and senescence. Cell proliferation occurs

in the basal layer. Basal cells move up to become wing cells, and wing cells move up to become surface cells. Only the cells in contact with the basement membrane have the ability to divide; the cells that are displaced into the wing cell layers lose this ability.20 Stem cells located in a 0.5- to 1-mm-wide band around the corneal periphery are the source for renewal of the corneal basal cell layer. A slow migration of basal cells occurs from the periphery toward the center of the cornea.21,22 Turnover time for the entire corneal epithelium is approximately 7 days, which is more rapid than for other epithelial tissues.23,24 Repair to corneal epithelial tissue proceeds quickly; minor abrasions heal within hours, and larger ones often heal overnight. If the basement membrane is damaged, however, complete healing with replacement basement membrane and hemidesmosomes can take months.14,15

Despite cells constantly being sloughed, the barrier function is maintained as the cell below moves into position to replace the one that has been shed. Tight junctions are present exclusively between the squamous cells that occupy the superficial position. The protein components necessary to form these junctions are not present in the basal cells but are increasingly present as the cells move up to the surface where the zonula occludens junctions become complete.25

The basal cell layer is continually losing and reestablishing the hemidesmosome junctions as cells divide and move up into the wing cell layers. The plaque sites remain present in the stroma for reattachment.15

 

CHAPTER 2  t  Cornea and Sclera

13

 

 

 

 

 

Corneal epithelium

Bowman's layer

Corneal stroma

Descemet's membrane

Corneal endothelium

Anterior chamber

FIGURE 2-3

Light micrograph of corneal layers.

Fine ridges (microplicae) and processes (microvilli) of corneal surface cell

FIGURE 2-4

Scanning electron micrograph of junction of three superficial cells in cornea. (×5000.) (From Krause WJ, Cutts JH: Concise text of histology, Baltimore, 1981, Williams & Wilkins.)

Clinical Comment: Recurrent

Corneal Erosion

RECURRENT CORNEAL EROSION  is a condition in which the corneal epithelium sloughs off either continually or periodically. This condition may occur because of either poor attachment between the epithelium and its basement membrane or poor attachment between the basement membrane and the underlying tissue. Recurrent corneal erosion can occur after incomplete healing of an abrasion in which the hemidesmosomes are malformed, or it may

be caused by an epithelial basement membrane dystrophy stemming from defective nutrition or metabolism.5

Age-related changes also can play a role in recurrent corneal erosion. Epithelium continues to secrete basement membrane throughout life; in the corneal epithelium, the thickness of the basement membrane doubles by 60 years of age. In addition, areas of reduplication of the membrane can occur with aging.26 As the basement membrane thickens or as reduplication occurs, the thickness of the membrane can exceed the length of the anchoring fibrils, allowing sloughing of epithelial layers.

Corneal erosions are very painful because the dense network of sensory nerve endings in the epithelium is disrupted.

A number of treatments may be used. Acute cases may be patched and antibiotic ointment applied to allow healing of the surface without the shearing effect of opening and closing the eyelids. Bandage soft contact lenses or collagen shields often are applied in chronic situations to alleviate pain.26-29 For cases in which the suspected cause is a faulty basement membrane, treatment might include corneal puncture in which multiple perforations are made through the epithelial layers to induce new basement membrane formation and adhesion30-32 (Figure 2-7). If reduplication is the cause of corneal erosion, the doubled membrane can be removed.32

Bowman’s Layer

The second layer of the cornea is approximately 8 to 14 μm thick.1,6,33 Bowman’s layer is a dense, fibrous sheet of interwoven collagen fibrils randomly arranged in a mucoprotein ground substance. The fibrils have a

14 Clinical Anatomy of the Visual System

FIGURE 2-5

Three-dimensional drawing of corneal epithelium showing five layers of cells. Polygonal shape of basal and surface cells and their relative size are apparent. Wing cell processes fill spaces formed by dome-shaped apical surface of basal cells. Turnover time for these cells is 7 days, and during this time the columnar basal cell gradually is transformed into a wing cell and then into a thin, flat surface cell. During this transition, cytoplasm changes and Golgi apparatus becomes more prominent. Numerous vesicles develop in the superficial wing and surface layers, and glycogen appears in surface cells. Intercellular space separating the

outermost surface cells is closed by a zonula occludens, forming a barrier that prevents passage of precorneal tear film into corneal stroma. Cell surface shows extensive net of microplicae

(a) and microvilli that might be involved in retention of the precorneal film. Corneal nerve (b) passes through Bowman’s layer (c); the nerve loses its Schwann cell sheath near basement membrane (d) of basal epithelium. It then passes as a naked nerve between the epithelial cells toward the superficial layers. Lymphocyte (e) is seen between two basal epithelial cells.

Basement membrane is seen at (f). Some of the most superficial corneal stromal lamellae (g) are seen curving forward to merge with Bowman’s layer. The regular arrangement of the corneal stromal collagen differs from the random disposition in Bowman’s layer. (From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.)