Cornea

Corneal Anatomy and Physiology as Applied to Refractive Keratotomy
(condensed from Refractive Keratotomy by George O Waring-1992)

FUNCTIONS OF THE CORNEA

Refractive keratotomy works by altering corneal anatomy to create a new shape—flatter in the center and steeper in the periphery. The cornea protects the intraocular contents and refracts light. To accomplish these functions the cornea must maintain its strength and transparency which is no easy task for an avascular connective tissue. The cornea is 550 um thick centrally and 700 pm thick peripherally and has a 12 mm diameter horizontally and a 11 mm diameter vertically.  For comparison a credit card is about 800 um thick; a dime is 13 mm in diameter.

The cornea must be strong. Contrary to the layperson's concept that the eyeball is a delicate structure, the corneoscleral connective tissue shell can withstand considerable blunt force (approximately 5 kg/cm2) before rupturing and can resist lacerating insults, both accidental and surgical. The major structural component of the cornea is the collagenous connective tissue stroma, which is confluent with the sclera at the limbus. The incisions made during refractive keratotomy weaken this structure.

The cornea must remain transparent. It is remarkable that this epithelium-lined connective tissue has a specialized structure and function that maintains functional optical clarity.  Any opacity of the cornea, such as the scars from keratotomy wounds, scatters light, both degrading the geometric image and decreasing contrast sensitivity.

One can consider the cornea fancifully as a sandwich dipped in nutritious soup. Two surface layers, the epithelium and the endothelium, contain a central filling, the stroma. All three layers receive nourishment and oxygen from the tears, aqueous humor, and limbic vessels. More precisely the structure of the cornea fits that of many other tissues. The surface epithelium and endothelium rest on basement membranes (the epithelial basement membrane and Descemet's membrane) that lie in turn on a layer of connective tissue, the stroma.

Translating this basic structure into histologic terms, the five-layered stratified squamous epithelium maintains a smooth optical surface and blocks the penetration of water and solutes from the tears into the stroma. In the stroma, proteoglycan molecules hold collagen fibrils in orderly lamellar array to maintain structural strength and optical clarity. To accomplish this the proteoglycans must remain relatively dehydrated. The single layer of endothelium performs this dehydrating function by partially blocking the flow of aqueous humor into the stroma and continuously removing water from the stroma. To nourish the cornea, the tear film conveys oxygen and the aqueous hum or provides amino acids, carbohydrates, and lipids.

 

CORNEAL EPITHELIUM

The corneal epithelium has the following three major functions
1. Formation of a mechanical barrier to foreign material and microorganisms
2. Creation of a smooth, transparent optical surface to which the tear film can
adhere
3. Maintenance of a barrier to the diffusion of water, solutes, and drugs


After a keratotomy incision the epithelium migrates into the incision and fills it with an epithelial plug. Because the epithelium remains present within the incision for months to years, a basement membrane, complete with the hemidesmosomal attachment, is laid down along the wall of the incision. 

B O W M A N 'S LAYER


Bowman's layer is a compact feltwork of fine, randomly oriented collagen fibrils that lies between the epithelial basement membrane and the cellular stroma . This acellular, 12 um thick tissue probably helps maintain corneal shape, although the details of its biomechanical properties and its function are unknown.
  It is not elastic.  Because Bowman's layer is acellular, it cannot regenerate.  In every case of keratotomy, Bowman's layer is permanently cut and does not heal. The cut ends of Bowman's layer assume a variety of configurations— end-to-end approximation, overlapping, and bending down into the incision. The space between the cut ends of Bowman's layer fills with cellular scar tissue that creates a permanent opacity.

CELLULAR CORNEAL STROMA


The structural components of the stroma, Keratocytes (also called corneal stromacytes or fibrocyles) synthesize the extracellular matrix of the stroma. The collagen fibrils are of relatively uniform diameter and are stacked in orderly sheets that form approximately 200 layers.

In terms of refractive keratotomy the most important material in the cornea is the stromal collagen because the collagen fibrils, including Bowman's layer, provide the structural strength and dimensional stability of the cornea.   The corneal stroma has little elasticity and stretches only by approximately 0.25% in the range of normal intraocular pressure. Therefore the cornea can maintain a reasonably constant shape and curvature.

 

It is certain, however, that when a refractive keratotomy incision is made through Bowman's layer and approximately 90% of the stroma, the remaining 10% of the posterior stroma and Descemet's membrane must support the intraocular pressure. These tissues cannot support the pressure without deformation, and therefore the cornea bows forward paracentrally and peripherally, producing gaping of the incisions and compensatory flattening of the central cornea. Once the structural integrity of the anterior layers of the cornea has been severed by the first few incisions, the forces are taken up by the remaining stroma and the further change in the shape of the cornea is not affected much by additional cuts.

The tensile strength of the corneal stroma is high; blunt injury to the cornea seldom ruptures the globe through the cornea, but rather usually through the thinner sclera near the equator of the globe or around the optic nerve.  However, the collagen fibrils severed by keratotomy never heal end-to-end, and the intervening corneal scar, which creates the new configuration of the cornea by filling in and maintaining the gap within the incision, never regains the tensile strength of the normal cornea. Therefore the probability of rupture of the cornea from blunt injury is increased after keratotomy.

CORNEAL ENDOTHELIUM AND DESCEMET'S MEMBRANE


The corneal endothelium is the most posterior layer of the cornea and comprises approximately 350,000 cells at birth. The major function of the corneal endothelium is to maintain corneal hydration at a fixed level, preserving corneal transparency.

The endothelium and refractive keratotomy collided in the hands of T.Sato and his colleagues, who practiced posterior keratotomy in the 1940s and 1950s, time when the function of the endothelium was largely unknown.  The insults gradually took their toll and reduced the number of endothelial cells to the point that stromal edema appeared in many cases.

Descemet's membrane forms the scaffolding on which the endothelial cells spread themselves. The mechanism by which the endothelium attaches lo Descemet's membrane is unknown.

CORNEAL THICKNESS

Measurement of the corneal thickness is a fundamental activity in keratotomy surgery because it forms the basis for setting the length of the knife blade in an attempt to make uniformly deep incisions through approximately 90% of the cornea.  Setting a knife blade at a given length will not necessarily produce an incision of exactly that depth, because of variability in knife blade configuration and sharpness and also because the stromal collagen is relatively resistant to cutting, so some of the posterior collagenous lamellae in the stroma are displaced rather than cut by the knife.

 

SPECIES DIFFERENCES IN CORNEAL STRUCTURE


There is considerable variability among species in the anatomy, physiology, and biomechanical properties of the cornea. For example. Bowman's layer is present only in primate, chicken, and goose corneas, so one might expect the biomechanical properties of these corneas to differ from those without a Bowman's layer. The rabbit cornea is a poor model for keratotomy surgery because it is thinner (300 um) centrally, does not thicken peripherally, has no Bowman's layer, is more elastic and pliable than human corneas and heals more rapidly (including the endothelium) than the human cornea. The cat cornea is as thick as the human cornea, but little is known about its response to corneal surgery.  Even the monkey cornea seems to have different biomechanical properties, such as being more elastic than the human cornea, with differences among monkey species. This type of variability is one reason why the results of research on laboratory animals cannot be directly translated to human surgery.

UNFINISHED BUSINESS


Understanding the structure of the cornea continues to challenge clinicians and researchers, even though the tissue itself appears reasonably simple. For example, what is the function of Bowman's layer? Is it structural? Is it to separate the epithelium from the keratocytes? Does it play a special role in the maintenance of corneal curvature? The answers to such simple questions have remained elusive. What latitude does the structure and function of the corneal epithelium have? What is the limit of the nutrients it needs from the aqueous humor to remain structurally normal, and how thin can the cornea get (is one layer adequate?) before it ceases to perform its barrier and protective functions?— a question pertinent to those who would place refractive lenticules within the cornea. The structure of the anterior corneal stroma differs from that of the posterior corneal stroma, both in terms of lamellar organization and proteoglycan content. Do these differences play a role in corneal function, and do they have applications to lamellar refractive surgery, or are they vestigial reflections of the ontogeny of the cornea? Is there really a circular ligament around the cornea that plays a role in modulating corneal curvature and shape? How docs light get through the cornea with minimal scattering so as to form an acceptable image on the retina, and what are the limits of light scattering within the cornea that are compatible with normal visual acuity and contrast sensitivity?  Such questions intrigue any refractive surgeon who creates corneal scars.  Fundamental studies on corneal anatomy and biophysics may have practical implications for refractive surgery.