Cornea

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. While the cornea contributes most of the eye's focusing power, its focus is fixed. The curvature of the lens, on the other hand, can be adjusted to "tune" the focus depending upon the object's distance. Medical terms related to the cornea often start with the prefix "kerat-" from the Greek word κέρας, horn.

Structure
The cornea has unmyelinated nerve endings sensitive to touch, temperature and chemicals; a touch of the cornea causes an involuntary reflex to close the eyelid. Because transparency is of prime importance the cornea does not have blood vessels; it receives nutrients via diffusion from the tear fluid at the outside and the aqueous humour at the inside and also from neurotrophins supplied by nerve fibres that innervate it. In humans, the cornea has a diameter of about 11.5 mm and a thickness of 0.5–0.6 mm in the center and 0.6–0.8 mm at the periphery. Transparency, avascularity, the presence of immature resident immune cells, and immunologic privilege makes the cornea a very special tissue. The cornea has no blood supply; it gets oxygen directly through the air. Oxygen first dissolves in the tears and then diffuses throughout the cornea to keep it healthy.

It borders with the sclera by the corneal limbus.

The most abundant soluble protein in mammalian cornea is albumin.

In lampreys, the cornea is solely an extension of the sclera, and is separate from the skin lying above it, but in more advanced vertebrates it is always fused with the skin to form a single structure, albeit one composed of multiple layers. In fish, and aquatic vertebrates in general, the cornea plays no role in focusing light, since it has virtually the same refractive index as water.

Layers
The human cornea, like those of other primates, has five layers; the corneas of cats, dogs, wolves, and other carnivores only have four. From the anterior to posterior the five layers of the human cornea are:


 * 1) Corneal epithelium: a thin epithelial multicellular tissue layer (non-keratinized stratified squamous epithelium) of fast-growing and easily regenerated cells, kept moist with tears.  Irregularity or edema of the corneal epithelium disrupts the smoothness of the air-tear film interface, the most significant component of the total refractive power of the eye, thereby reducing visual acuity.  It is continuous with the conjunctival epithelium is composed of about 6 layers of cells which are shed constantly on the exposed layer and are regenerated by multiplication in the basal layer.
 * 2) Bowman's layer (also erroneously known as the anterior limiting membrane, when in fact it is not a membrane but a condensed layer of collagen): a tough layer that protects the corneal stroma, consisting of a similar irregularly arranged collagen fibers, mainly type I collagen fibrils, essentially a type of stroma. These fibrils interact with and attach on to each other. This layer is eight to 14 micrometres thick and is absent or very thin in non-primates.
 * 3) Corneal stroma (also substantia propria): a thick, transparent middle layer, consisting of regularly arranged collagen fibers along with sparsely distributed interconnected keratocytes, which are the cells for general repair and maintenance. They are parallel and are superimposed like book pages The corneal stroma consists of approximately 200 layers of mainly type I collagen fibrils. Each layer is 1.5-2.5μm. Up to 90% of the corneal thickness is composed of stroma. There are 2 theories of how transparency in the cornea comes about:
 * 4) The lattice arrangements of the collagen fibrils in the stroma. The light scatter by individual fibrils is cancelled by destructive interference from the scattered light from other individual fibrils.(Maurice, 1957)
 * 5) The spacing of the neighboring collagen fibrils in the stroma must be < 200 nm for there to be transparency. (Goldman and Benedek)
 * 6) Descemet's membrane (also posterior limiting membrane): a thin acellular layer that serves as the modified basement membrane of the corneal endothelium, from which the cells are derived. This layer is composed mainly of collagen type IV fibrils, less rigid than collagen type I fibrils, and is around 5-20μm thick, depending on the subject's age.
 * 7) Corneal endothelium: a simple squamous or low cuboidal monolayer, approx 5μm thick, of mitochondria-rich cells. These cells are responsible for regulating fluid and solute transport between the aqueous and corneal stromal compartments. (The term endothelium is a misnomer here. The corneal endothelium is bathed by aqueous humor, not by blood or lymph, and has a very different origin, function, and appearance from vascular endothelia.)  Unlike the corneal epithelium the cells of the endothelium do not regenerate.  Instead, they stretch to compensate for dead cells which reduces the overall cell density of the endothelium and has an impact on fluid regulation.  If the endothelium can no longer maintain a proper fluid balance, stromal swelling due to excess fluids and subsequent loss of transparency will occur and this may cause corneal edema and interference with the transparency of the cornea and thus impairing the image formed.

The mnemonic "EBSDEin", read as "Ebstein" can be used to remember the layers in sequence.

Another Mnemonic is "ABCDE": Anterior epithelium, Bowman's layer, Corneal stroma, Descemet's membrane and Endothelium

Keeping the cornea transparent
Upon death or removal of an eye the cornea absorbs the aqueous humor, thickens, and becomes hazy. Transparency can be restored by putting it in a warm, well-ventilated chamber at 31 °C (88 °F, the normal temperature), allowing the fluid to leave the cornea and become transparent. The cornea takes in fluid from the aqueous humor and the small blood vessels of the limbus, but a pump ejects the fluid immediately upon entry. When energy is deficient the pump may fail, or works too slowly to compensate, causing swelling. This could arise at death, but a dead eye can be placed in a warm chamber and the reservoirs of sugar and glycogen can keep the cornea transparent for at least 24 hours. The endothelium controls this pumping action, and as discussed above, damage thereof is more serious, and is a cause of opaqueness and swelling. When damage to the cornea occurs, such as in a viral infection, the collagen used to repair the process is not regularly arranged, leading to an opaque patch (leukoma). When a cornea is needed for transplant, as from an eye bank, the best procedure is to remove the cornea from the eyeball, preventing the cornea from absorbing the aqueous humor.

Innervation
The cornea is one of the most sensitive tissues of the body, as it is densely innervated with sensory nerve fibres via the ophthalmic division of the trigeminal nerve by way of 70–80 long ciliary nerves and short ciliary nerves. The ciliary nerves run under the endothelium and exit the eye through holes in the sclera apart from the optic nerve (which transmits only optic signals).

The nerves enter the cornea via three levels; scleral, episcleral and conjunctival. Most of the bundles give rise by subdivision to a network in the stroma, from which fibres supply the different regions. The three networks are midstromal, subepithelial/Bowman's layer, and epithelium. The receptive fields of each nerve ending are very large, and may overlap.

Corneal nerves of the subepithelial layer terminate near superficial epithelial layer of the cornea in a logarithmic spiral pattern. The density of epithelial nerves decreases with age, especially after the seventh decade.

Refractive nature
The optical component is concerned with producing a reduced inverted image on the retina. The eye's optical system consists of not only two but four surfaces—two on the cornea, two on the lens. Rays are refracted toward the midline. Distant rays, due to their parallel nature, converge to a point on the retina. The cornea admits light at the greatest angle. The aqueous and vitreous humors both have a refractive index of 1.336, whereas the cornea has a refractive index of 1.376. Because the change in refractive index between cornea and aqueous humor is relatively small compared to the change at the air–cornea interface, it has a negligible refractive effect, typically -6 diopters.

Surgical procedures
Various refractive eye surgery techniques change the shape of the cornea in order to reduce the need for corrective lenses or otherwise improve the refractive state of the eye. In many of the techniques used today, reshaping of the cornea is performed by photoablation using the excimer laser.

If the corneal stroma develops visually significant opacity, irregularity, or edema, a cornea of a deceased donor can be transplanted. Because there are no blood vessels in the cornea, there are also few problems with rejection of the new cornea.

There are also synthetic corneas (keratoprostheses) in development. Most are merely plastic inserts, but there are also those composed of biocompatible synthetic materials that encourage tissue ingrowth into the synthetic cornea, thereby promoting biointegration.

Non-surgical procedures
Orthokeratology is a method using specialized hard or rigid gas-permeable contact lenses to transiently reshape the cornea in order to improve the refractive state of the eye or reduce the need for eyeglasses and contact lenses.

In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.

General references

 * Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. "Collagen fibrils in the human corneal stroma: structure and aging." Invest Ophthalmol Vis Sci. 1998 Mar;39(3):644-8. PMID 9501878.
 * Daxer A, Fratzl P. "Collagen fibril orientation in the human corneal stroma and its implication in keratoconus." Invest Ophthalmol Vis Sci. 1997 Jan;38(1):121-9. PMID 9008637.
 * Fratzl P, Daxer A. "Structural transformation of collagen fibrils in corneal stroma during drying. An x-ray scattering study." Biophys J. 1993 Apr;64(4):1210-4. PMID 8494978.