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Schematic diagram of the <a href="/content/Human_eye" style="color:blue">human eye</a> showing the cornea as separated from the sclera by the <a href="/content/Corneal_limbus" style="color:blue">corneal limbus</a>
Schematic diagram of the human eye showing the cornea as separated from the sclera by the corneal limbus

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. The cornea, with the anterior chamber and lens, refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power.[1][2] In humans, the refractive power of the cornea is approximately 43 dioptres.[3] The cornea can be reshaped by surgical procedures such as LASIK.[4]

While the cornea contributes most of the eye's focusing power, its focus is fixed. Accommodation (the refocusing of light to better view near objects) is accomplished by changing the geometry of the lens. 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 healthy cornea does not have or need blood vessels within it. Instead, oxygen dissolves in tears and then diffuses throughout the cornea to keep it healthy.[5] Similarly, nutrients are transported via diffusion from the tear fluid through the outside surface and the aqueous humour through the inside surface. Nutrients also come via neurotrophins supplied by the nerves of the cornea. 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 most abundant soluble protein in mammalian cornea is albumin.[6]

The human cornea borders with the sclera via the corneal limbus. In lampreys, the cornea is solely an extension of the sclera, and is separate from the skin 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.[7]

The human cornea has five layers (possibly six, if the Dua's layer is included).[8] Corneas of other primates have five known layers. The corneas of cats, dogs, wolves, and other carnivores only have four.[9] From the anterior to posterior the layers of the human cornea are:

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. Research suggests the density of pain receptors in the cornea is 300-600 times greater than skin and 20-40 times greater than dental pulp,[15] making any injury to the structure excruciatingly painful.[16]

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).[10] 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/sub-basal, and epithelial. The receptive fields of each nerve ending are very large, and may overlap.

Corneal nerves of the subepithelial layer terminate near the superficial epithelial layer of the cornea in a logarithmic spiral pattern.[17] The density of epithelial nerves decreases with age, especially after the seventh decade.[18]

Function


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 1.336-1.339, 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 dioptres.[10] The cornea is considered to be a positive meniscus lens.[19] In some animals, such as species of birds, chameleons and a species of fish, the cornea can also focus.[20]

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.[10]

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.[10]

Clinical significance


The most common corneal disorders are the following:

  • Corneal abrasion - a medical condition involving the loss of the surface epithelial layer of the eye's cornea as a result of trauma to the surface of the eye.
  • Corneal dystrophy - a condition in which one or more parts of the cornea lose their normal clarity due to a buildup of cloudy material.
  • Corneal ulcer - an inflammatory or infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal stroma.
  • Corneal neovascularization - excessive ingrowth of blood vessels from the limbal vascular plexus into the cornea, caused by deprivation of oxygen from the air.
  • Fuchs' dystrophy - cloudy morning vision.
  • Keratitis - inflammation of the cornea.
  • Keratoconus - a degenerative disease, the cornea thins and changes shape to be more like a cone.

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. Other methods, such as magnetic deformable membranes[21] and optically coherent transcranial magnetic stimulation of the human retina[22] are still in very early stages of research.

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 cell collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.[23] For corneal epithelial diseases such as Stevens Johnson Syndrome, persistent corneal ulcer etc., the autologous contralateral (normal) suprabasal limbus derived in vitro expanded corneal limbal stem cells are found to be effective[24] as amniotic membrane based expansion is controversial.[25] For endothelial diseases, such as bullous keratopathy, cadaver corneal endothelial precursor cells have been proven to be efficient. Recently emerging tissue engineering technologies are expected to be capable of making one cadaver-donor's corneal cells be expanded and be usable in more than one patient's eye.[26][27]

The majority of ocular therapeutic agents are administered to the eye via the topical route. Cornea is one of the main barriers for drug diffusion because of its highly impermeable nature. Its continuous irrigation with a tear fluid also results in poor retention of the therapeutic agents on the ocular surface. Poor permeability of the cornea and quick wash out of therapeutic agents from ocular surface result in very low bioavailability of the drugs administered via topical route (typically less than 5%). Poor retention of formulations on ocular surfaces could potentially be improved with the use of mucoadhesive polymers.[28] Drug permeability through the cornea could be facilitated with addition of penetration enhancers into topical formulations.[29]

See also


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