The Cornea and Corneal Disease

The cornea is the transparent tissue that covers the front of the eye (see diagram). An easy way to locate the cornea is simply to look at your eye in the mirror. You will notice a clear surface covering the iris (the colored part of the eye) and pupil. This is the cornea.

What is the function of the cornea?

Because the cornea is as smooth and clear as glass but as strong and durable as plastic, it helps the eye in two ways:

The cornea provides a physical barrier that shields the inside of the eye from germs, dust, and other harmful matter. It shares this protective task with the sclera (the white of the eye).

It acts as the eye's outermost lens. When light strikes the cornea, it bends--or refracts--the incoming light onto the crystalline lens. The lens then focuses the light onto the retina, the paper-thin tissue at the back of the eye that starts the translation of light into vision.

Although much thinner than the lens, the cornea provides about 65 percent of the eye's power to bend light. Most of this power resides in the center of the cornea, which is rounder and thinner than the outer part of the tissue and is thus better suited to bend lightwaves.

How important is the cornea to good vision?

The cornea is essential to good vision. As the eye's outermost tissue, the cornea functions like a window that controls the entry of light into the eye. For example, the cornea filters out some of the most damaging ultraviolet (UV) wavelengths in sunlight. Without this protection, the crystalline lens and the retina would be highly susceptible to injury from UV radiation.

If this "window" is curved too much, as is the case in some nearsighted people, faraway objects will appear blurry because distant light waves will refract imperfectly on the retina. If this "window" has imperfections or irregularities, as is the case in people with an astigmatism, light will refract unequally, causing a slight distortion of the visual image. But, if this "window" is of normal shape and curvature, light will refract with exquisite precision to the crystalline lens.

STRUCTURE OF THE CORNEA

Although the cornea is clear and seems to lack substance, it is actually a highly organized group of cells and protein. The cornea receives its nourishment from the tears and aqueous humor that fills the chamber behind it. Unlike most tissues in the body, the cornea contains no blood vessels to nourish or protect it against infection. It must remain transparent to refract light properly, and the presence of even the tiniest capillaries would interfere with this process.

The tissue is arranged in three main regions, or layers:

EPITHELIUM As the cornea's outermost region--comprising about 10 percent of the tissue's thickness--the epithelium functions primarily to: (1) block the passage of foreign material--such as dust or water--into the eye and other layers of the cornea, and (2) provide a smooth surface that absorbs oxygen and other needed cell nutrients that are contained in tears. This layer, which is about five cells deep, is filled with thousands of tiny nerve endings that make the cornea extremely sensitive to pain when rubbed or scratched.

STROMA Located behind the epithelium, the stroma comprises about 90 percent of the cornea. It consists primarily of water (78 percent); layered protein fibers (16 percent) that give the cornea its strength, elasticity, and form; and cells that nourish it. The unique shape, arrangement, and spacing of the protein fibers are essential in producing the cornea's light-conducting transparency.

ENDOTHELIUM This single layer of cells is located between the stroma and the aqueous humor (see diagram). Because the stroma tends to absorb water, the endothelium's primary task is to pump excess water out of the stroma. Without this pumping action, the stroma would swell with water, become hazy, and ultimately opaque.

What problems may affect the cornea?

The cornea copes very well with minor injuries or abrasions. If dirt scratches the highly sensitive cornea, epithelial cells slide over quickly and patch the injury before infection occurs and vision is affected.

But if the scratch penetrates the cornea more deeply, the healing process will take longer, resulting in greater pain, blurred vision, tearing, redness, and extreme sensitivity to light. These symptoms require professional treatment. Some of the more serious problems that affect the cornea are:

Microbial Infections (keratitis)

When the cornea is damaged, such as after a foreign object has penetrated the tissue, bacteria or fungi can pass into the cornea, causing a deep infection and inflammation. This condition may cause severe pain, reduce visual clarity, produce a corneal discharge, and perhaps erode the cornea.

As a general rule, the deeper the corneal infection, the more severe the symptoms and complications. It should be noted that microbial infections, although relatively infrequent, are the most serious complication of contact lens wear.

Minor corneal infections are commonly treated with anti-bacterial or anti-fungal eye drops. If the problem is more severe, a person may receive more intensive antibiotic treatment to eliminate the infection and may need to take steroid eye drops to reduce inflammation. Frequent visits to an eye care professional may be necessary for several months to eliminate the problem.

Conjunctivitis ("pink eye")

This term describes a group of inflammatory and often contagious diseases of the conjunctiva (the protective membrane that lines the eyelids and covers exposed areas of the sclera, or white of the eye). These diseases can be caused by a bacterial or viral infection, drug allergy, environmental irritants, or a contact lens product.

At its onset, pink eye is usually painless and does not adversely affect vision. The infection will come and go in most cases without requiring medical care. But for some forms of pink eye, such as epidemic keratoconjunctivitis, treatment will be needed. If treatment is delayed, the infection may worsen and cause corneal inflammation and a loss of vision. Depending on the type of pink eye that a person develops, treatment often consists of antibiotics and steroids.

Ocular Herpes

Herpes of the eye is a recurrent viral infection that affects an estimated 400,000 Americans with herpes. Although ocular herpes can result from the sexually transmitted herpes simplex II virus, it is usually caused by herpes simplex virus I (HSV I), the virus responsible for cold sores. In about 12 percent of those with ocular herpes, both eyes are involved.

Ocular herpes produces a relatively painful sore on the surface of the cornea. Prompt treatment with anti-viral drugs helps to stop the herpes virus from multiplying and destroying epithelial cells. In time, the infection may also spread into the stroma, causing the body's immune system to attack and destroy stromal cells. This more severe infection, called herpes simplex stromal keratitis, is harder to treat and can scar the cornea, causing vision loss. It may also produce an infection of the inside of the eye.

Like other herpetic infections, herpes of the eye remains a controllable, but incurable, problem. For those who lose vision to ocular herpes, it usually results from recurrent attacks that lead to severe stromal keratitis. Studies indicate that after a person has had an initial outbreak of ocular herpes, he or she has better than a 50 percent chance of having a recurrence of the disease. This second outbreak could come weeks or decades after the initial attack. In one large study, researchers found that recurrence rates were 10 percent after one year, 23 percent at two years, and 63 percent at 20 years. Some factors associated with recurrence include fever, stress, sunlight, and trauma. Anyone with ocular herpes should avoid using over-the-counter steroid eye drops. Steroids cause the virus to multiply and the infection to worsen.

Herpes Zoster (shingles)

This infection is produced by the varicella-zoster virus, the same virus that causes chicken pox. After an initial outbreak of chicken pox (often during childhood), the virus remains dormant within the nerve cells of the central nervous system. But in some people, the varicella-zoster virus will reactivate at some time during their lives. When this occurs, the virus travels down long nerve fibers and infects some part of the body, producing a blistering rash (shingles), fever, painful inflammations of the affected nerve fibers, and a general feeling of malaise.

Varicella-zoster virus may travel to the head and neck, perhaps involving an eye, part of the nose, mouth, cheek, and forehead. In about 40 percent of those with shingles in this area, the virus infects the cornea. These zoster-related corneal lesions will usually clear up on their own. But without early anti-viral treatment, a person runs the risk of the virus infecting cells deep within the tissue, causing inflammation and scarring of the cornea. The disease may also cause decreased corneal sensitivity. For many, this decreased sensitivity will be permanent.

Although shingles can occur in anyone exposed to the varicella-zoster virus, several studies have established two general risk factors for the disease: (1) advanced age and (2) a weakened immune system. Studies show that people over age 80 have a five times greater chance of having shingles than adults between the ages of 20 and 40. Unlike herpes simplex I, the varicella-zoster virus does not usually flare up more than once in adults with normally functioning immune systems.

Be aware that corneal complications may arise months after the shingles are gone. For this reason, it is important that patients schedule followup eye examinations.

Corneal Dystrophies

There are over 20 corneal dystrophies that affect all parts of the cornea. Some of the most common are:

Keratoconus

The disorder arises when the middle of the cornea thins and gradually bulges outward, forming a rounded cone shape. This abnormal curvature changes the cornea's refractive power, producing moderate to severe distortion (astigmatism) and blurriness (near- and farsightedness) of vision. These changes may also disrupt the normal, light-conducting arrangement of corneal protein, causing swelling and a sight-impairing scarring of the tissue.

Studies indicate that keratoconus stems from one of several causes: (1) an inherited corneal abnormality. About 7 percent of those with the condition have a family history of keratoconus; (2) an eye injury, i.e., excessive eye rubbing or wearing hard contact lenses for many years; (3) certain eye diseases, such as retinitis pigmentosa, retinopathy of prematurity, vernal keratoconjunctivitis; or (4) systemic diseases, such as Leber's congenital amaurosis, Ehlers-Danlos Syndrome, Down's syndrome, osteogenesis imperfecta, and Addison's disease.

Keratoconus usually occurs during puberty, or shortly thereafter. At first, people can correct their vision with eyeglasses. But as the astigmatism worsens, they must rely on specially fitted contact lenses to reduce the distortion and provide better vision. Finding a comfortable contact lens can be an extremely frustrating and difficult process. However, it is crucial because a poorly fitting lens could further damage the cornea and make wearing a contact lens intolerable.

In most cases, the cornea will stabilize after a few years without ever causing severe vision problems. But in about 10 to 20 percent of people with keratoconus, the cornea will eventually become too scarred or will not tolerate a contact lens. If either of these problems occur, a person will probably need to replace the diseased tissue with a donor cornea, called a corneal transplant.

This operation is successful in about 9 out of 10 people with advanced keratoconus. Several studies have also reported that about 80 percent of these patients have 20/40 vision or better with contact lenses after the operation. In fact, about 60 percent of transplant recipients will need to wear contact lenses after the surgery to correct astigmatism and nearsightedness.

For those with no scarring near the center of the cornea and 20/40 vision or better with contact lenses, another option is surgically grafting a layer of epithelial cells to flatten the cone-shaped cornea. This process is called epikeratophakia. It has comparable results to corneal transplantation and, if unsuccessful, it can be followed with corneal transplantation.

Map-Dot-Fingerprint Dystrophy

The epithelium is separated from the stroma, in part, by a membrane. It serves as the foundation on which the epithelial cells anchor and organize themselves. In map-dot-fingerprint dystrophy, the membrane develops abnormally. Like building a house on a damaged foundation, the epithelial cells anchor to an irregular membrane that, in turn, may make the epithelium slightly irregular.

The condition, which tends to occur in both eyes, usually affects adults between the ages of 40 and 70. It is also occasionally inherited--in which case it arises at about age 6.

Map-dot-fingerprint dystrophy gets its name from the unusual appearance of the cornea during an eye examination. Most often, the epithelium will have a map-like appearance, i.e., large, slightly cloudy bodies that look like a continent on a map. This configuration is actually the irregular pattern of the membrane extending into the epithelium. There may also be a sequence of opaque dots--formed from cellular debris--underneath or close to the map-like patches. Less frequently, the irregular membrane will form concentric lines in the central cornea that resemble small fingerprints.

Most people will never know that they have this corneal dystrophy, since they will never have any pain and vision loss.

But for others, the disease will cause recurrent epithelial erosions--possibly from poor epithelial adhesion to the membrane.

These erosions can be a chronic problem. They alter the cornea's normal curvature, causing periodic blurred vision. They may also expose the nerve endings that line the tissue, causing moderate to severe pain for several days. Generally, the pain will be worse in the morning. Other symptoms include: sensitivity to light, excessive tearing, and foreign body sensation in the eye.

Typically, the problem will flair up occasionally for a few years in adults and then go away on its own, with no lasting loss of vision.

However, if treatment is needed, the doctor will try to control the pain associated with the corneal erosion. He or she may do this by patching the eye to immobilizeit or by prescribing lubricating eye drops and ointments. With effective care, the pain will subside in about 10 days, although periodic flashes of pain may occur for several weeks thereafter.

Fuch's Dystrophy

Fuch's dystrophy is a slowly progressing disease that usually affects both eyes and is slightly more common in women than in men. Although doctors can often see early signs of Fuch's dystrophy in people in their 30s and 40s, the disease rarely affects vision until a person reaches their 50s and 60s.

Fuch's dystrophy occurs when endothelial cells gradually deteriorate without any apparent reason, such as trauma or inflammation. As more endothelial cells are lost over the years, the cornea becomes less efficient at pumping water out of the stroma. This causes the cornea to swell and to distort vision. Eventually, the epithelium also takes on water, resulting in great pain and severe visual impairment.

Epithelial swelling damages vision in two ways: (1) changing the cornea's normal curvature, and (2) causing a sight-impairing haze to appear in the tissue. Epithelial swelling will also produce tiny blisters on the corneal surface. When the blisters burst, they are extremely painful.

At first, a person with Fuch's dystrophy will awaken with blurred vision that will gradually clear during the day. This occurs because the cornea is normally thicker in the morning, and it retains fluids during sleep that evaporate in the tear film while we are awake. But as the disease worsens, this swelling will remain constant and reduce vision throughout the day.

When treating the disease, doctors will try first to reduce the swelling with ointments or soft contact lenses. They may also instruct a person to use a hair dryer, held at arm's length or directed across the face, to dry out the epithelial blisters. This can be done two or three times per day.

But when the disease makes even the most simple tasks hard to complete, a person may need to consider having a corneal transplant to restore sight. The short-term success rate of corneal transplantation is quite good for people with Fuch's dystrophy. But, some studies do suggest that the long-term survival of the donor cornea can be a problem.

Lattice Dystrophy

Although lattice dystrophy can occur at any time in life, the condition usually arises in children between the ages of 2 and 7. It is characterized by an accumulation of abnormal protein fibers (amyloid) throughout the middle and anterior stroma. However, the disease is NOT related to amyloidosis, a serious systemic disease.

Lattice dystrophy gets its name from the amyloid deposits, which during an eye examination can appear as clear, comma-shaped dots and branching filaments that overlap each other in the stroma, creating a lattice effect. Over time, the lattice lines will grow opaque and involve more of the stroma. They will also gradually coalesce, giving the cornea a slight cloudiness that may also reduce vision somewhat.

In some people, abnormal protein also accumulates under the epithelium. This may result in poor adhesion between the stroma and epithelium, causing periodic epithelial erosions. The erosion will: (1) alter the cornea's normal curvature, resulting in temporary vision problems such as astigmatism and nearsightedness, and (2) expose the nerves that line the cornea, causing severe pain. In fact, even the involuntary act of blinking can be painful.

To ease this pain, a doctor may prescribe eye drops and ointments to reduce the friction on the eroded cornea. In some cases, an eye patch may be used to immobilize the eye. With effective care, the pain will subside in about 10 days, although occasional sensations of pain may occur for about the next 6 to 8 weeks.

By about age 40, some people will have scarring under the epithelium. As a result, a haze will develop on the cornea that can greatly obscure a person's vision. In this case, a corneal transplant may be needed. Patients with lattice dystrophy have an excellent chance for a successful transplant with good vision. However, in as little as three years, lattice dystrophy may also arise in the donor cornea. In one study, in fact, about half of the transplant patients with lattice dystrophy had a recurrence of the disease from 2 to 26 years after the operation. Of these, 15 percent required a second corneal transplant.

CURRENT CORNEAL RESEARCH

Although vision researchers have learned much about the structure and function of the cornea in health and disease, many important scientific questions remain to be answered. For example, vision researchers supported by the National Eye Institute, one of the Federal government's National Institutes of Health, are beginning to identify the specific genes that are activated, or switched on, in corneal cells. By understanding more about these genes and how they produce and maintain a healthy cornea, it will help immensely in understanding and treating corneal disease.

Although about 90 percent of all corneal transplant operations are successful, it is preferable for people to retain their natural corneas. For this reason, vision researchers continue to investigate ways to enhance corneal healing and eliminate the sight-threatening scarring that can complicate this process. NEI-supported scientists took an important step forward in describing this process when they recently developed a method of culturing rabbit cornea tissue that allows the researchers to measure cell movement rapidly during healing. The culture is also being used to study drugs and biochemicals that may promote or slow corneal healing and identify those agents that promote better wound healing.

Another area of research interest is laser therapy. Several small-scale studies show that lasers may be effective in sculpting the cornea to improve its ability to refract light in people with myopia and astigmatism. While this news is hopeful, many questions need to be answered about its short and long-term benefits before laser therapy can be recommended as a safe and effective treatment.

The NEI also supports the Herpetic Eye Disease Study (HEDS), a group of clinical trials that is designed to study various treatments for severe ocular herpes. Recently, HEDS researchers reported that orally administered acyclovir, a drug widely used for genital herpes, had no significant effect in treating herpes simplex stromal keratitis. The HEDS should provide eye care professionals with valuable information about when to use and not to use specific antiviral drugs for this condition. But, more importantly, these clinical trials will improve care for people with advanced ocular herpes.

Revised May 1994