Introduction

The anterior segment of the eye includes the lens of the eye and every structure anterior to the lens.  This would include the lens, the iris, the anterior chamber, the ciliiary body, and the cornea.  The anterior segment can be divided into two chambers, the anterior chamber and the posterior chamber.  The anterior chamber contains all structures anterior to the iris, but the term is often used to refer only to the space that contains aqueous.  The posterior chamber contains the lens.

The Cornea

The cornea is the window to the eye.  It is analogous to the front lens of a multi-element camera lens.  It is a five layer tissue structure that is remarkable in that it is crystal clear in its normal state.  The cornea provides two-thirds of the refractive power of the eye, about 42 diopters worth.

The horizontal diameter of the cornea is about 12mm and the vertical diameter is about 11mm.  The cornea is thicker at the edge, about 1mm, than it is in the center, about .53mm.  The shape of the cornea is not spherical, it is aspherical, meaning the shape is steeper at the center and it flattens out toward the edge.  The steep central portion is called the corneal cap and it is about 4mm wide. 

The shape of the corneal cap is what is measured by the keratometer.   If the cap is spherical, then the cornea is said to be spherical.  If the cap is not spherical, then the cornea is said to be astigmatic.  Astigmatism means that the curvature of the cap is steeper in one primary meridian than it is in the other primary meridian.  If the astigmatism is regular, then the primary meridians are 90 degrees apart (e.g. 90 and 180).  If astigmatism is irregular, then the primary meridians are not exactly 90 degrees apart.  For more information on clinical optics and astigmatism, see Modules 16 and 19. 

How is it that the cornea is clear?

1. There are no blood vessels in the cornea.  The cornea receives most of its oxygen from the air, through the tear layer.  What blood supply there is comes from capillaries that barely cross the limbus and then loop back.  Some nourishment is received via the aqueous.  The oxygen supply to the cornea can be compromised by contact lens wear.  If oxygen deprivation is severe, the cornea will grow new blood vessels (neovasularization) into the corneal tissue to try to increase the oxygen supply.

2. The nerves (trigeminal) that supply the cornea are de-myelinated once they cross into the corneal tissue.  Myelin is an insulating sheath that is present on most of the nerves in the body. 

3. The normal state of the corneal tissue is that of relative dehydration.  In this state, the corneal fibrils, which are collagen tissue similar to the tissues of the sclera, are clear.  If the corneal tissue becomes hydrated due to injury or disease, then the tissue becomes opaque.

The Five Layers of the Cornea

1. Epithelium:  This is a thin layer of cells on the outer-most cornea.  The outer cells of the epithelium produce a layer of mucin that integrates with the mucin layer of the tears.  Sensory nerve fibers run through the epithelium, so damage to this layer can be painful.  The life cycle of the epithelial cells is about one week, with older cells being carried away by the tears and new cells being produced constantly.  A damaged epithelium can regenerate in about 24 hours, without scarring.

2. Bowman's Membrane:  This thin layer between the epithelium and the deeper stroma acts as a barrier to microorganisms.  If damaged, this layer layer cannot regenerate and a scar is formed.

3. Stroma:   The stroma makes up the bulk (~85%) of the thickness and structure of the cornea.  It is composed mostly of collagen fiberils arranged in a non-interweaving matrix that contributes to the clarity of the cornea. 

4. Descemet's Membrane:  This thin layer acts as a protective barrier on the posterior side of the cornea.

5. Endothelium:  This a layer of single cell thickness that interfaces with the aqueous of the anterior chamber.  It has two major functions.  Each cell has microvilli that extend into the aqueous and exchange waste and nutrients.  The cells also pump water out of the stroma, keeping the cornea dehydrated and clear.  Endothelial cells do not regenerate and they are lost naturally with age.  As they die, the surrounding cells expand to take over the space of the dead/departed cells.  Disease processes, trauma, and surgical procedures can speed the cell destruction process.  If enough cells are lost, the remaining cells cannot cover the increased space, the pump system can become deficient, and the cornea may become edematous.  The condition of the endothelium can be monitored by doing an endothelial cell count.  This is accomplished by photographing (specular microscopy) the polygon shaped endothelial cells and counting how may there are in a given area of the cornea.

    

   

The Tear Film

The tear film covers the corneal epithelium and it has the following functions:

• It is the initial refractive interface of the eye.  In order to provide optimum optical performance, the tear film must be clear and perfectly smooth.

• It provides metabolic functions to the outer corneal tissues, bringing nutrients and oxygen, and carrying away waste products.

• It provides some antibacterial proteins that serve as a barrier to disease for the cornea.

• It provides moisture for the epithelial cell layers.

The tear film has three layers: 

• The lipid (oily) layer is the outermost layer.   It is produced by the meibomian glands of the eyelids.  This layer retards evaporation of the tears and promotes a smooth surface area.  Blepharitis and Rosacea are common causes of a disruption in the lipid layer.  Rosacea is a skin disease of the face.  The oil being secreted by the meibomian glands becomes thickened and has difficulty being expressed from the glands.  The tear layer then does not have a normal lipid coating and the tears evaporate quickly.  The result is an irritated cornea with dry eye symptoms that are not relieved well by artificial tears.  Treatment includes warm compresses to the lids and oral doxycycline, which help the function of the meibomian glands.

• The aqueous layer is the middle layer of the tear "sandwich".  This layer provides the bulk of the tear volume and serves to transport nutrients and oxygen to the outer corneal tissues.  It is produced by the lacrimal gland and by the accessory lacrimal glands in the conjunctiva.  The lacrimal gland produces "reflexive" tears.  These are the tears that flood the eye when there is irritation to the cornea or an emotional disturbance (crying).  The accessory lacrimal glands in the conjunctive provide the "baseline" level of aqueous tear production.  A decrease in lacrimal gland production, causing dry eye symptoms, responds well to the use of artificial tears.  The eye drop Restasis works by promoting an increase in tear production by the accessory lacrimal glands.

Aqueous layer deficiency can be multi-factorial.  Some more common causes are:

• Collagen vascular diseases such as rheumatoid arthritis and systemic lupus erythematosus

• Vitamin A deficiency

• Sjogren's syndrome, which mostly affects women and is characterized by an aqueous tear deficiency and dry mouth (xerostomia)

• Conjunctival scarring, which can be caused by disease, such as trachoma, and by chemical or thermal burns

• Systemic drugs such as oral contraceptives, antihistamines, and beta-blockers.

• Mucins play a role in tear film stability and they can be found in different concentrations in the aqueous layer.  The highest concentration of mucins, forming the "mucin layer",  is found at the corneal surface, next to the corneal epithelium.  Mucins are produced by goblet cells in the conjunctiva.  The corneal epithelial cells produce a substance called glycocalyx that bind the mucin cells to the corneal epithelial cells.  It is this mucin binding that creates a smooth sheet of tear film on the corneal surface.  Any disruption in this binding causes a break up in the tear film, as measured by "tear break up time".  A break up of the tear film causes dry eye symptoms and inflammation of the cornea.  Artificial tears help the situation but need to be applied frequently.  The lubricating eye drop Systane is designed to adhere to the corneal surface and has been shown in studies to work better than some other artificially tears at extending tear break up time, but even this drop loses its maximum effectiveness after only 20 minutes.

A chemical burn to the eye can destroy the goblet cells in the conjunctiva (which produce mucin), creating a chronic severe dry eye condition.  Vitamin A deficiency (usually caused by chronic malnutrition) decreases the production of mucin, causing dry eye syndrome.

Examination of the Cornea

The primary instrument used to examine the cornea is the slit lamp biomicroscope.  This instrument is essentially a microscope, an illumination source with various modalities, and a head rest to position the patient.  Slit lamp biomicroscopy will be covered in another module. 

The keratometer is used to measure the curvature of the primary meridians of the corneal cap.  This information is used in contact lens fitting, refractive surgery, intra-ocular lens power calculations, and in refractometry.

Corneal Disorders

 (This is not a comprehensive list, including only some of the more common diseases)

Because the cornea is a major refractive tissue of the eye, diseases that affect the cornea can result in reduced vision, glare, halos, and distorted vision.  Some corneal diseases can change the shape of the cornea, causing astigmatism.  Corneal diseases can also cause pain, tearing, and light sensitivity.

Many corneal disorders can either be classified as a dystrophy, or as a type of infection/inflammation.

Corneal Dystrophies: A corneal dystrophy is an inherited disease process that results in the atrophy or degeneration of corneal tissue over time.  The severity and duration of the process is variable.  A dystrophy can cause opacities and edema that affect the vision of the eye.  They can also cause recurrent corneal erosions that cause pain, redness, and photophobia (light sensitivity).  Treatments can include the use of hypertonic drops and ointment, patching, debridement, a bandage soft contact lens, or keratoplasty in severe cases.  Dystrophies can affect each of the corneal layers. 

• Epithelial dystrophies include Cogan's (basement membrane) microcystic epithelial dystrophy and Meesmann's epithelial dystrophy.

• Reis-Bucklers' is a dystrophy of Bowman's membrane.

• Stromal dystrophies include granular dystrophy and lattice dystrophy. Granular dystrophy is pictured below.

   

  

   

• Endothelial dystrophies include posterior polymorphous dystrophy, congenital hereditary endothelial dystrophy (CHED), and Fuch's dystrophy.  Corneal dystrophies can be very subtle.  A cornea with Fuch's dystrophy is pictured below.  You have to look very closely to notice an abnormality.  The dystrophy can be seen more clearly in the the Photoshop enhanced image picture.

Keratoconus is a corneal dystrophy (ectactic dystrophy) that results in a thinning and stretching of the cornea into a cone shape.  The apex of the cone is usually on the inferior, nasal aspect of the cornea.

Manifestations of keratoconus include decreased vision, increased myopia and astigmatism,  a scissors type retinoscopy reflex, and irregular keratometry mires that show steepening over time.  Significant keratoconus can be seen with the slit lamp and will produce a characteristic image on a corneal topography map.  Rigid gas permeable lenses can improve vision and severe keratoconus can be treated by keratoplasty.

An inflammation of the cornea is called a keratitis.  Inflammation and infection of the cornea can also result in ulceration of the cornea.  A corneal ulcer results when the epithelium and Bowman's layer are broken and there is destruction of cells in the stromal layer.  Keratitis and ulcers can be caused by bacteria, a protozoa, a virus, or a fungus infection.  The mode of entry is often trauma or irritation of the corneal surface (e.g. contact lens wear).  Keratitis can also be caused by exposure.  Keratitis is often accompanied by conjunctivitis (bacterial or viral).

• Bacterial keratitis usually results from a break in the corneal surface that allows entry.  Examples of infectious bacterial agents are staphylococcus, pneumococcus, and pseudomonas.  Infiltrates appear in the corneal structure, edema is present, and there may be flare or cells in the anterior chamber. It is usually not necessary to know the offending bacteria because antibiotic and antibiotic/steroid combination medications are "broad spectrum", meaning they are effective against a wide variety of bacteria.

A bacterial corneal ulcer.  Notice the red (injected) conjunctiva.  This is what is sometimes called an "angry eye".

• Acanthamoeba is a protozoa that rarely infects the cornea, but the damage spreads rapidly and it is difficult to treat.  It has been associated with poor disinfection of soft contact lenses.

• Viral keratitis can be caused by the Herpes simplex and Herpes zoster viruses.  A viral corneal ulcer has a "dendrite" or branch-like appearance when stained with fluorescein (pictured below).  Treatment can include anti-viral drops and antibiotic drops to prevent a secondary bacterial infection.

Photo courtesy of Ted Montgomery (www.tedmontgomery.com)

• Fungal keratitis can result from Fusarium, Aspergillus, Cephalospovium, or Candida fungi.  Corneal trauma from vegetable matter (e.g. a scratch from a tree branch) is a common mode of entry.  A fungus can also take residence in a cornea already compromised by another infection or treatment, particularly if topical steroids have been used for a prolonged period.  The cornea is scraped and the sample is sent to a lab for diagnosis.  Debridement is sometimes needed if antifungal drops are ineffective.

• Exposure keratitis most often results from inadequate lubrication of the cornea due to incomplete closure of the lids.  A seventh nerve palsy can create this condition.  Treatment includes liberal use of artificial tears during the day and lubricating ointment at night.  Lid surgery is sometimes indicated.  Another common cause of keratitis is exposure to ultraviolet light.  A long day at the beach or snow skiing without sunglasses can result in that gritty feeling in your eyes that resolves within 24 hours.  A more severe UV corneal burn occurs when welding without eye protection.  The symptoms do not begin for several hours, but the pain will send the welder to the emergency room in the middle of the night.  Treatment is antibiotic ointment and pressure patching (so the lids do not move over the cornea) for 24 hours.

Irregular Astigmatism

Irregular astigmatism can have a significant effect upon visual acuity and the quality of vision, even to the point of visual disability.  An astigmatic cornea is present when the corneal surface is not perfectly spherical.  Regular astigmatism is present when there are two meridians of curvature and they are exactly 90 degrees apart.  Irregular astigmatism is present when the primary meridians of curvature are not 90 degrees apart, or there are more than two meridians of curvature.  When irregular astigmatism is present, the corneal surface can be thought of as being "bumpy".

Causes of irregular astigmatism include disease process already discussed, such as keratoconus, infectious keratitis, anterior membrane dystrophies, and trauma.  The condition is common after keratoplasty.  It can occur after refractive surgery and can result from contact lens wear.

Slight to moderate irregular astigmatism can be difficult to detect, yet have a significant impact upon the quality of vision.  Signs and symptoms include photophobia, a poor retinoscopy reflex, inability to refract the eye to the vision obtained through a pinhole, and inability to superimpose keratometry mires.  Corneal topography can be used to confirm an advanced condition.

Over-refraction with a hard contact lens can be used to confirm irregular astigmatism.  The tear lens of the hard contact lens will "smooth out" the irregularities in the corneal surface and improve the visual acuity.  Fitting the cornea with a rigid gas permeable contact lens can be an effective treatment for the condition.  Intacs, deep anterior lamellar keratoplasty, or penetrating keratoplasty can be used to treat keratoconus if a contact lens is not effective/tolerated.

Keratoplasty

Keratoplasty is the replacement of opaque and/or diseased corneal tissue with healthy corneal tissue from a donor (cadaver) eye.  The procedure is also referred to as corneal transplantation or corneal grafting.  The graft can be full thickness (penetrating) or partial thickness (lamellar).

Keratoplasty is most commonly performed for pseudophakic bullous keratopathy (PBK), which results from trauma to the corneal endothelium during complicated corneal surgery (the incidence is less than 1% of cataract surgeries).  Keratoplasty is also performed for keratoconus, corneal degenerations and dystrophies, and scarring secondary to trauma or keratitis.

Until recently penetrating keratoplasty (PK, or PKP) or lamellar keratoplasty where the only options for corneal tissue replacement.  Now another procedure is available, called Descemet Stripping Automated Endothelial Keratoplasty (DSAEK).  Whereas penetrating keratoplasty replaces a button of full thickness corneal tissue, DSAEK replaces only a central section of Descemet's membrane and endothelium, leaving the outer layers of the cornea intact.  Thus, DSAEK is very useful for treating PBK and endothelial dystrophies such as Fuch's.

Penetrating Keratoplasty (PK or PKP)

The graft is usually between 7.5 and 8.5 mm in diameter.  Larger graft sizes are prone to complications such as increased IOP, synechiae, and vascularization.  Smaller graft sizes are more prone to astigmatism.

The donor button is cut (trephination) slightly larger than the planned recipient opening.  A partial thickness trephination is performed first on the recipient eye, followed by a full thickness cut.  The button is at first held in place by four sutures, and is then secured by running sutures around the edge.  The anterior chamber is reformed by injecting balanced salt solution.

A thin button (lamella) of endothelial tissue is removed from the donor cornea with a special instrument.  The recipient cornea is entered via two small incisions near the limbus.  Descemet's membrane (recipient eye) is scored (cut) and stripped using an instrument.  The endothelial lamella from the donor eye is folded and inserted into the anterior chamber of the recipient eye through one of the incisions.  The lamella is smoothed into place over the area of stripped endothelium.  An air bubble is introduced into the anterior chamber to keep the tissue in place.

Compared to PK, DSAEK uses a smaller corneal incision with no corneal sutures.  This provides more rapid visual rehabilitation for patients with endothelial disease.  For patients needing donor tissue due to diseases of the anterior layers of the cornea, PK is still necessary.

The excimer laser can be used to produced a smoother, clearer cornea in some cases of corneal disease.  This is the laser that is used in refractive surgery.  In fact, PTK can be used in combination with PRK (photorefractive keratectomy).  This procedure is useful in treating shallow corneal scars, recurrent epithelial erosion syndrome, and some corneal dystrophies. 

The procedure is similar to PRK.  The corneal epithelium is removed.  The corneal tissue is ablated (vaporized) with the laser, and the patient wears a bandage contact lens until the epithelium regenerates.  Recovery time is about a month.

Alternatives to this procedure are manual corneal scraping and corneal transplant (PK).

Dry Eye and Keratoconjunctivitis Sicca (KCS)

Dry eye is a very complicated disease state that can have many causes (see the discussion on the tear film).

Dry Eye symptoms are very common in the over 40 crowd.  As we age, tear production decreases and the cornea does not always receive sufficient lubrication.  For most of us, the symptoms are occasional periods of that burning, gritty feeling in the eyes.  The symptoms can sometimes be relieved by the use of artificial tears. 

There are factors that can make the dry eye condition worse:

• Environmental factors such as sun, wind, low humidity, air pollution (including smoking), and cold.

• The decreased estrogen in the post-menopausal female.

• Contact lens wear.  Hard lenses are generally better tolerated than soft lenses. Lower water content soft lenses are generally more comfortable than higher water content soft lenses. (The dry eye "sucks" the water out of the contact lens.)  Both hard and soft lenses cause an increase in tear evaporation.  Contact lens wearers should not use artificial tears while wearing the lenses, but should use contact lens lubricating drops specifically made for the type of lenses that they wear.

• Some medications decrease tear production, particularly those that take water out of the body (diuretics).  Antihistamines and birth control pills are particularly troublesome.

• Some diseases, in particular Sjogren's syndrome, lupus, and rheumatoid arthritis are associated with dry eye symptoms.  Sjogren's syndrome mostly affects women and is characterized by an aqueous tear deficiency and dry mouth (xerostomia).

There are two types of tear production, baseline (lubricating) and reflex.  Baseline tears provide lubrication to the eyes.  Reflex tears have a "washing" effect and are produced by irritation to the eyes or by emotion.  An eye that is "watery" from reflex tears can actually be suffering from Dry Eye Syndrome (DES).  The eye becomes irritated because of a lack of lubricating tears, and the irritation produces reflex tearing.

When dryness of the cornea results in chronic disruption (inflammation) of the corneal surface,  the condition is called keratoconjunctivitis sicca (KCS).  Symptoms can range from mild to severe.  The patient may experience burning, a foreign body sensation, and light sensitivity, a mucoid discharge, and excessive tearing from reflex tear secretion.  The eye may appear red, and slit lamp examination may show the following:

• a decrease in the tear meniscus (this is the area of wetness found at the junction of the lower lid with the cornea)

• debris in the tear film

• superficial punctate keratopathy (SPK)

• strands of mucous

• filaments on the cornea

• small corneal ulcerations in more advanced cases

The following tests are used to confirm KCS:

• Tear break up time (BUT) is probably the most commonly used test for evaluating dry eye because it is a simple and fast test.  Normally, blinking will provide a even, smooth coat of tears on the corneal surface.  If blinking is interrupted, the tears will eventually evaporate, leaving one or more dry spots on the cornea.  The time from the end of the blink to the appearance of a dry spot is called the "tear break up time".  For the eye with normal tear production, the time is 15 to 45 seconds.  An eye with KCS will have a much shorter BUT, generally in 5 to 10 seconds.

• Rose bengal stain is used to confirm a disrupted or exposed corneal epithelium.  Rose bengal was once thought to stain only damaged epithelial cells, but a study demonstrated that rose bengal will stain damaged or healthy epithelial cells that are not protected by the mucin tear layer.

• Schirmer tear testing with and without anesthetic.  With anesthetic, less than 5mm of wetting is abnormal.  Without anesthetic, less than 10 mm of wetting is abnormal.  If Schirmer I testing is abnormal, Shirmer II testing is done, with a wetting of less than 15mm being abnormal. Click here for instructions on how to perform Schirmer tear testing.

Treatment of DES and KCS

Underlying problems and conditions, as previously discussed, are treated if possible. 

DES and mild to moderate KCS are primarily treated with lubricating drops and ointments.  To be effective, drops are used from 4 to 12 times a day.  There is a great variety of drops available with differing viscosities, some with preservatives and some preservative free.  Choosing an effective viscosity is mostly a matter of trial and error with samples.  The gels last longer in the eye but may blur the vision. The ointments are usually reserved for use at bedtime because of blurring.

Artificial tears with preservatives can be used by DES patients who uses the drops less than 5 times a day, but heavy users should use preservative free drops.  Patient's with KCS must use preservative free drops because the preservatives are toxic to the exposed or damaged corneal cells.

The more severe cases can be treated with punctal occlusion, which blocks the tear the ducts and keeps what tears there are from draining away.  The procedure is non-surgical, performed quickly, and is reversible.  Small silicone plugs are placed in the punctums.