Glaucoma is one of the leading causes of blindness. While glaucoma can develop in anyone, people over age 60, who have a family history of glaucoma, or who are African-American are at especially high risk. Certain types of medical conditions, such as diabetes or extreme near-sightedness, can also increase the risk for glaucoma.
Glaucoma is actually a term used to describe several types of eye conditions that affect the optic nerve. In many cases, damage to the optic nerve is caused by increased pressure in the eye, also known as intraocular pressure (IOP).
Primary Open-Angle Glaucoma
- Primary open-angle glaucoma is the most common type of glaucoma.
- In primary open-angle glaucoma, poorly functioning drainage channels prevent fluid from being released from the eye at a normal rate. This in turn causes a rise in intraocular pressure.
- People with primary open-angle glaucoma usually experience few or no symptoms until the later stages of the disease, when vision loss becomes apparent.
There is no cure for glaucoma, but treatment can help reduce intraocular pressure thus preventing optic nerve damage and blindness. Glaucoma is usually treated with medications, although surgery may also be recommended for some patients.
Most glaucoma medications are usually given in the form of eye drops. Make sure your doctor or ophthalmologist explains to you the correct way to administer these drops.
A number of different medications are used to treat glaucoma. They include:
- Beta-blockers, such as timolol (Timoptic, Betimol)
- Prostaglandins, such as latanoprost (Xalatan)
- Carbonic anhydrase inhibitors, such as dorzolamide (Trusopt) and brinzolamide (Azopt)
- Adrenergic agonists, such as apraclonidine (Iopidine) and brimondidine (Alphagen)
Glaucoma is a disease of the optic nerve, in which the nerve cells in the front of the optic nerve (the ganglion cells) die. The process is irreversible. Previously, it was believed that glaucoma was almost always due to increased intraocular pressure. However, glaucoma can occur in patients with normal and even low eye pressure, so damage to the optic nerve is now key for diagnosis.
The Aqueous Humor. To understand glaucoma, it is important to first consider aqueous humor, the clear, watery fluid that circulates continuously through the front (anterior) chamber of the healthy eye and is a primary focus of glaucoma research. (This fluid is not related to tears, nor is it the dense jelly-like substance called vitreous humor that is contained in the rear chamber.)
Aqueous humor serves two important functions in the eye:
- Nourishing the area around the colored iris and behind the cornea
- Exerting pressure to help maintain the eyes shape
Draining the Fluid and Intraocular Pressure. The aqueous fluid is continuously produced within the front of the eye, causing pressure known as intraocular pressure (IOP). To offset the in-flowing fluid and to maintain normal IOP, the fluid drains out between the iris and cornea (an area known as the drainage angle). It does so through two channels within this angle:
- The trabecular meshwork, a sponge-like, porous network, and its connecting passageways are referred to as the "conventional" outflow pathway. Most of the eye fluid outflow occurs in this region and flows from the trabecular meshwork to a group of vessels encircling the anterior chamber, called Schlemm's canal. From here, the fluid enters collection chambers and then flows out into the general blood circulatory system of the body.
- The uveoscleral pathway is located behind the trabecular meshwork and is called the "unconventional" pathway. Up to 30% of the fluid flows out through this channel.
Intraocular Eye Pressure. Increased IOP is, indeed, present in most cases of glaucoma, but some patients have normal IOP, which is usually maintained at measurements of 10 - 20 mmHg. Higher IOP measurements increase the risk of glaucoma, but do not necessarily mean that the patient has glaucoma.
Primary Open-Angle Glaucoma
Most people with glaucoma have the form called primary-open-angle glaucoma (also called chronic open-angle glaucoma). Open-angle glaucoma is essentially a plumbing problem.
The disease process may occur as follows:
- The drainage angle remains open, but tiny drainage channels in the trabecular meshwork pathway become clogged. This pathway is responsible for most aqueous humor fluid outflow. An imbalance then occurs as fluid continues to be produced but does not drain out efficiently.
- The fluid in the eyes anterior chamber builds up and increases pressure within the eye (intraocular pressure).
- The intraocular pressure exerts force on the optic nerve at the back of the eye.
- Over time, the persistent pressure or other factors irreversibly damages the delicate long fibers of the optic nerve, called axons, which convey images to the brain.
- As these axons die, the small cup-like head of the optic nerve may eventually collapse into an enlarged irregular shape.
Optic nerve damage is the basic glaucoma condition. If it is untreated, eventually the nerve deteriorates until a person loses sight, first in the peripheral vision (the vision in the "corner of the eyes"). If it becomes severe, the person loses central vision (in the middle of the eyes), and may eventually become blind. (Blindness is fortunately nearly always preventable with early treatment.)
Primary open-angle glaucoma tends to start in one eye but eventually involves both. About half of patients have generalized (spread out) nerve damage. In the other half the disease is localized, causing wedge-shaped abnormalities in the nerve fiber layers of the retina.
Normal Tension Glaucoma
Intraocular eye pressure is normal (12 - 22 mmHg) in about 25 - 30% of U.S. glaucoma cases, a condition known as normal-tension glaucoma. Other factors are present that cause optic nerve damage but do not affect IOP.
Closed-angle glaucoma (also called angle-closure glaucoma) is responsible for 15% of all cases. It is less common than open-angle glaucoma in the U.S., but it constitutes about half of the world's glaucoma cases because of its higher prevalence among Asians. The iris is pushed against the lens, sometimes sticking to it, closing off the drainage angle. This can occur very suddenly, resulting in an immediate rise in pressure. It often occurs in genetically susceptible people when the pupil shrinks suddenly. Closed-angle glaucoma can also be chronic and gradual, a less common condition.
Congenital glaucoma, in which the eye's drainage canals fail to develop correctly, is present from birth. It is very rare, occurring in about 1 in 10,000 newborns. This may be an inherited condition and often can be corrected with microsurgery.
The Light-Processing Parts. To understand sight, one begins with light and its passage through the eye's sensitive camera-like structures:
- Light first passes through the cornea, a clear tissue at the front of the eye.
- Behind the cornea, the iris (the colored tissues of the eye) opens and closes like a camera shutter to regulate the passage of light.
- The lens, located behind the iris, focuses the light, which then hits the retina.
- The retina is an electric fragile membrane of nerve cells called photoreceptors that receive light and translate it into signals.
- A layer of cells, called the retinal ganglia, receive signals from the retina. These nerve cells are the front ends of the optic nerve cable, which, in turn, receive the signals.
- The optic nerve is actually a cable of about 1.2 million nerve fibers called axons. It carries the signals to the brain, which interprets them as images.
- They exit the eye through the optic disc, located in the back of the eye.
The Supportive Chambers. To help support and protect these sensitive structures, the eye contains two fluid-filled chambers:
- The posterior (rear) chamber is the large area behind the iris.
- Fluid passes from the posterior into the anterior (forward) chamber located in the bulging area between the iris and the front of the eye.
Causes of Primary Open-Angle Glaucoma
The exact cause of primary open-angle glaucoma is unknown. A number of conditions, alone or in combination, are needed to trigger the processes leading to increased pressure and then to the nerve damage that destroys sight. The damage done to the optic nerve in glaucoma is triggered in most cases by the excessive pressure on the optic nerve that, over time, causes damage. Because optic nerve damage occurs in patients with normal as well as high intraocular pressure, however, there are other factors that occur and can damage the optic nerve.
Causes of Closed-Angle Glaucoma
People with acute closed-angle glaucoma often have a structural defect that causes a narrow angle between the iris and cornea where the aqueous humor circulates. Conditions that suddenly dilate the pupils may cause this shallow angle to close and precipitate attacks of acute glaucoma in susceptible people. Such conditions may include:
- Certain drugs such as antihistamines, tricyclic antidepressants, some asthma medications (nebulized ipratropium), some anti-seizure drugs (topiramate)
- Emotional stress
Causes of Secondary Glaucoma
When glaucoma is caused by other diseases or conditions, it is known as secondary glaucoma. Both open-angle glaucoma and closed-angle glaucoma can be a secondary condition.
Medical Conditions. A number of diseases can contribute to the development of glaucoma:
- Diseases that affect blood flow to the optic nerve (such as diabetes, high blood pressure, and migraine; people with type 2 diabetes should be regularly screened for glaucoma.)
- Sleep apnea
- Physical injury in the eye
- Extreme nearsightedness (myopia)
- Previous eye surgery
- Other disorders, including leukemia, sickle cell anemia, and some forms of arthritis
Corticosteroids. Corticosteroids, commonly called steroids, have multiple effects on the trabecular meshwork. Steroids pose a higher or lower risk depending on the form:
- Taking topical steroid treatments in the eye poses the highest risk. Use of topical steroids must be monitored carefully since, in some cases, damage may be permanent.
- Taking oral corticosteroids, particularly in high doses or for long periods, increases the chance of glaucoma. In such cases, the eye disorder typically develops almost immediately and reverses within 2 weeks after the drug has been withdrawn.
- Inhaled steroids do not appear to cause glaucoma, but there may be some risk in people with a family history of glaucoma and other risk factors.
Syndromes Associated with Increased Optic Pressure and Glaucoma
Specific syndromes have been identified with glaucoma. Many have an inherited component, although in most cases other factors must be present to activate the disease process.
Pseudoexfoliation Syndrome. Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk. PEX has a strong genetic component but other factors (possibly sunlight, an autoimmune response, or slow virus) may be needed to trigger the disease.
Pigment Glaucoma. Pigment glaucoma starts with a condition called pigment dispersion syndrome, an inherited condition in which granules of pigment (the substance that colors the iris) flakes off into the intraocular fluid. These fragments clog the trabecular meshwork and pressure builds up, causing glaucoma.
Irido Corneal Endothelia Syndrome. In irido corneal endothelial syndrome (ICE), cells on the back surface of the cornea spread to the drainage angle, sometimes forming scars that connect the iris to the cornea.
Neovascular Glaucoma. Neovascular glaucoma is always associated with other disorders, usually diabetes, that result in abnormal formation of new blood vessels on the iris and in the drainage system.
Aniridia. Aniridia is a rare inherited disorder in which the iris is abnormal and increases the risk for glaucoma.
Congenital Glaucoma. When an infant is born with glaucoma (congenital glaucoma), it is usually caused by an inherited genetic abnormality that affects the drainage canal.
About 4 million Americans have open-angle glaucoma, the most common type of glaucoma (accounting for about 90% of all glaucoma cases). Half of these people w are unaware they have glaucoma because the condition causes no pain or visual changes in its early stages.
Risk factors for glaucoma include:
Increased Intraocular Pressure (IOP)
Elevated intraocular pressure in the eye increases the risk of optic nerve damage and glaucoma.
The risk of developing glaucoma increases with age. Everyone over age 60 is at risk of developing glaucoma. People in certain racial or ethnic groups are at higher risk of developing glaucoma at younger ages.
Race and Ethnicity
Compared to Caucasians, African-Americans have five times the risk of developing glaucoma, and four times the risk of becoming blind because of it. African-Americans are also much more likely than Caucasians to develop glaucoma at younger ages. For African-Americans, the risk of developing glaucoma begins at age 40. According to the U.S. National Eye Institute, African-Americans ages 45 - 64 are 15 times more likely to become blind due to glaucoma than Caucasians in the same age group.
People of Asian descent have a slightly greater risk than other racial groups of developing closed-angle glaucoma.
Glaucoma tends to run in families. Brothers and sisters of patients with open angle glaucoma are 5 times more likely to develop glaucoma by the time they are 70 years old than people whose siblings do not have the disease. Previous studies have also found that people with family histories of glaucoma are more likely to already have some vision loss when they are first diagnosed with glaucoma.
People with certain medical or physical conditions, including diabetes, migraine, nearsightedness, and sleep apnea, appear to have a higher risk for glaucoma. High blood pressure may be a risk factor. Conditions that require the use of any oral or inhaled steroid, particularly high doses for prolonged periods of time, can cause glaucoma. Previous eye surgery also puts people at risk, as does nearsightedness.
Symptoms of Open-Angle Glaucoma
Open-angle glaucoma is a chronic condition that slowly progresses over many years. In its earliest stages, it produces no pain, visual changes, or other symptoms. As the condition progresses and the optic nerve becomes damaged, the following symptoms appear in either one or both eyes:
- Peripheral vision (vision from the side of the eyes) gradually decreases. Patients develop tunnel vision, the ability to only see straight ahead.
- Eventually, straight-ahead vision decreases.
If left untreated, blindness results.
Symptoms of Closed-Angle Glaucoma
In acute closed-angle glaucoma, the pressure inside the eye increases quickly, and the symptoms are dramatic. Intense pain in the eyebrow area and blurred vision develop usually in one eye, and the patient often feels like the eye will burst (although it won't). The eye usually reddens. A person may see rainbow-like halos around lights. Sometimes nausea and vomiting occur. These symptoms may occur on and off and not appear as a full attack. In either case, they indicate a medical emergency. In chronic closed-angle glaucoma, the process is gradual and painless.
Symptoms of Congenital Glaucoma
Although congenital glaucoma is usually present at birth, symptoms generally dont develop in the infant for a few months. If parents notice that an infants eyes are enlarging, becoming cloudy, often watering, or tending to close in the presence of light, they should have an ophthalmologist examine the childs eyes. Port-wine stains on an infants face could indicate Sturge-Weber syndrome, a disorder that occasionally causes glaucoma.
A diagnosis of glaucoma no longer simply relies on the presence of pressure within the eye. Optic nerve damage or a strong suggestion of damage must also be present. This damage can be clearly seen during a dilated eye examination of the optic nerve. In general, the hallmark sign of this condition is a loss of peripheral vision. With peripheral vision loss, a person can see in front of him- or herself but has lost the vision to the side.
Because chronic glaucoma has no warning symptoms, half of patients are unaware they have the condition. Early diagnosis is the key to successful treatment of glaucoma and prevention of blindness.
Recommendations for Glaucoma Screening
There has been debate about the relative benefits and risks of routine glaucoma screening in adults. Glaucoma screening in adults can help identify signs of increased intraocular pressure (IOP) and the early stages of primary open-angle glaucoma (POAG). However, treatment of IOP and early POAG can potentially result in harmful effects, such as eye irritation and increased risk for cataracts. Because of this uncertainty, the United States Preventive Services Task Force has not found sufficient evidence to recommend for or against routine screening for glaucoma in adults.
In contrast, the American Academy of Ophthalmology strongly supports glaucoma screening, with the following specific recommendations:
- Everyone over age 65 and African-Americans over 40 years old should have periodic eye exams, including tests for glaucoma, every other year.
- African-Americans ages 20 - 39 should have eye examinations every 3 - 5 years.
- Other people at higher risk (people with diabetes, history of eye injuries, a family history of glaucoma, or those taking corticosteroid medications) should have eye examinations every year after age 35.
- People with known glaucoma should have frequent examinations to check peripheral vision and to be sure treatment is maintaining a safe eye pressure. After such examinations, the ophthalmologist will assess current treatment and make necessary adjustments.
Tonometry and Pressure Tests
Doctors determine the intraocular pressure (IOP) of the aqueous humor inside the eye using a painless procedure called tonometry, which measures the force necessary to make an indentation in the eye. A tonometer (small smooth instrument) may be used. There are several methods and the doctor may apply anesthetic eye drops to first numb the eye:
- In the applanation (Goldman) method, uses a blue-light filter and slit-lamp, which is moved forward toward the patient's face.
- Electronic indentation tonometry uses an electronic pen with a digital read-out.
- The noncontact approach does not use a tonometer. It applies a puff of air to measure the force needed to indent the eye.
- In the Schiotz method, the doctor presses very lightly against the eye with the tonometer. IOP is measured by the weight needed to flatten the cornea. This method is not considered as accurate as the others.
In general, normal IOP is usually maintained at measurements of 10 - 20 mmHg. Intraocular pressure over 21 mmHg indicates a potential problem. The test is not completely accurate, however. Only about 10% of people with IOP levels of 21 - 30 mmHg will actually develop glaucoma and optic nerve damage. On the other hand, many people with glaucoma have normal pressure, at least for part of the time.
Changes in posture may also affect IOP. A recent study indicated that IOP increases during sleep or when a person is lying down. As IOP tests are generally given in a doctors office when a patient is sitting up, they may not provide a completely accurate evaluation of eye pressure.
Measurement of Cornea Thickness (Pachymetry)
Cornea thickness is an important indicator of disease progression in patients with elevated IOP. The doctor first applies numbing drops to the eye and then uses an ultrasonic wave instrument to measure cornea thickness.
Tests for Optic Nerve Damage
To check for damage in the optic nerve, the doctor first uses eye drops to dilate (widens) the pupils and then examines the eyes with a magnifying lens instrument such as an ophthalmoscope, which has a light on one end.
Damaged nerve fibers may be indicated by:
- An asymmetrical or elongated cupped optic nerve. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.)
- The optic nerve color may be pale or an unhealthy-pink.
Visual Field (Perimetry) Tests
The doctor will conduct tests of the visual fields (the areas that the patient can see). In most people with glaucoma, the first areas to become noticeably impaired are the peripheral visual fields (areas of sight that are not directly in front of a person but more to the sides). Perimetry tests are used to check peripheral vision. The patient looks straight ahead and is asked to indicate when a moving light appears on the side.
Tests for Closed-Angle Glaucoma
Using an instrument called a gonioscope, ophthalmologists can inspect the front of the eyes and assess the drainage angle between the cornea and the iris and the channels in the trabecular meshwork. This test can differentiate between closed- and open-angle glaucoma.
Glaucoma cannot be cured, but treatment may help delay disease progression. Most treatments for glaucoma aim to reduce ocular pressure and its fluctuations. Early treatment with medications, surgery, or both can nearly always maintain safe pressure of the aqueous humor, thus preventing optic nerve damage and blindness.
Decision to Start Treatment
Many people have high IOP but no sign of nerve damage. Over the course of 20 years, only 10 - 30% of these people will actually develop glaucoma. Nevertheless, once glaucoma has destroyed optic nerve fibers, no known treatment can reverse the damage.
However, not all individuals with early signs of glaucoma (elevated IOP or normal-tension glaucoma) develop optic nerve damage and serious vision problems. Nor does treatment prevent progression in some patients. Medications used for glaucoma also can carry significant side effects and risks.
Some doctors recommend treatment only for people with early signs of glaucoma who have risk factors for progressive disease and vision loss (thinner corneas, larger cup to optic disc ration, older age, and elevated pressure).
Considerations for Drug Treatments
A number of effective drugs are used to treat glaucoma. The drugs reduce pressure in the eye but all have a number of side effects that affect other parts of the body. Some of these side effects can be quite severe. Many of the drugs used for glaucoma also interact with common medications for other conditions. To compound the difficulties, many patients require multiple drugs. As a result, only about half of patients comply with their treatments.
Doctors generally recommend topical drugs (such as eye drops or ointments) first.
- Topical beta-blockers are the standard first-line drugs, most commonly timolol (Timoptic). Newer beta-blockers include betaxolol (Betoptic), levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol has been used for years, and these other drugs are also well tolerated.
- Topical prostaglandins are alternatives if beta-blockers fail. They include latanoprost (Xalatan) and unoprostone (Rescula). Of the standard drugs used for glaucoma, these drugs have the greatest effect on lowering IOPs. They also have fewer widespread effects than beta-blockers.
- Topical carbonic anhydrase inhibitors (CAIs) are less effective than standard beta-blockers or prostaglandins but have fewer widespread effects than the beta-blockers. They may be helpful in certain cases. Topical forms are dorzolamide (Trusopt) and brinzolamide (Azopt). (Oral CAIs are available and more effective, but they have severe side effects and are rarely used for the long term.)
- Alpha2-adrenergics, also called selective alpha adrenergics, are effective but may not be as well tolerated as timolol. They include brimonidine (Alphagan).
- Miotics, which include pilocarpine and others, were the standard drugs before the introduction of topical beta-blockers. They have now been largely replaced by timolol and others, although they are sometimes used in combinations.
- Beta-blockers and newer drugs (prostaglandins, topical CAIs, and selective alpha adrenergics) are now preferred over older drugs, which include miotics, oral CAIs, and nonselective alpha adrenergics. Some drugs may be given in combination.
Treating Pregnant Patients. Considerations for a pregnant woman with glaucoma can be complicated. All of the drugs used for glaucoma are absorbed by the body, cross the placenta, and are excreted in breast milk. Many have effects that can interfere with or adversely affect pregnancy.
Women should discuss going off medication, particularly during the first trimester, and be monitored during that time for increasing eye pressure. IOP tends to drop during pregnancy, although usually not to a significant degree. In addition, changes in IOP and visual loss vary greatly. Some women have no IOP change or visual loss during pregnancy, while others may experience an increase in IOP or worsening of visual loss. Your ophthalmologist must carefully consider your case and talk with you about the risks and benefits of continuing glaucoma medication during pregnancy. If women need to take medications, they should try to take the lowest effective dose possible.
Considerations for Surgery
The goal of standard glaucoma surgery is to reduce pressure in the eye by increasing the outflow of the aqueous fluid. Two methods are commonly used:
- Filtration surgery (trabeculectomy). This uses standard surgical instruments to open a passage in the eye for draining fluid.
- Laser trabeculoplasty. This procedure uses a laser to burn tiny holes in the drainage area.
Both are effective, but certain patient groups may respond to one more than the other. For example, African-Americans may do better with laser surgery while trabeculectomy may be a better choice for Caucasians with no serious medical problems.
In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs.
In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs. Surgery does not cure glaucoma, and over half of patients will need medication within 2 years.
Nearly all glaucoma medications are prescribed for reducing eye pressure.
Beta-blockers (Timolol and Others)
Topical beta adrenoceptor blockers (commonly called beta-blockers) are the drugs most often prescribed to treat glaucoma. They lower the pressure inside the eye by inhibiting the production of aqueous humor.
Brands. These drugs are categorized as either nonselective or selective beta-blockers:
- Nonselective adrenoceptor beta-blockers. Timolol (Timoptic, Betimol) has been the standard beta-blocker for years. Newer nonselective drugs include levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). A few studies suggest some are more beneficial than timolol with similar side effects.
- Selective beta1-adrenoceptor blockers. Betaxolol (Betoptic) and levobetaxolol (Betaxon) are selective beta-blockers. These drugs appear to have fewer adverse effects on the heart than the nonselective beta-blockers, although they still have widespread effects. Studies also suggest that they slow progression more than timolol, although timolol is more effective at lowering IOP. Selective beta-blockers may also have nerve-protecting properties.
All beta-blockers work well and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for patients who also have cataracts.
Side Effects and Complications. After the beta-blocker is administered, only a tiny amount of the drug is absorbed by the cornea. Most of it enters in the bloodstream. These drugs, therefore, can cause side effects in parts of the body other than the eyes ("systemic" side effects):
- Systemic side effects may include reduced sexual drive, fatigue, depression, anxiety, and breathing difficulties.
- Beta-blockers affect the heart. They lower heart rate and reduce blood pressure.
- Beta-blockers can worsen severe asthma or other lung diseases.
- A patient switching to a beta-blocker from other glaucoma medication may feel a sudden rise in eye pressure. It is important that the pressure be checked shortly after the other drug has been withdrawn.
- When beta-blockers are used to treat one eye, the other (contralateral) eye also experiences a lesser, but still significant reduction in IOP.
Interactions with Other Medications. The effects of the eye medication can interact with other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. People with diabetes who take insulin or hypoglycemic medications should realize that beta-blocker side effects may mask the symptoms of hypoglycemia (low blood sugar).
Prostaglandins are hormone-like substances that help open blood vessels. Drugs that resemble prostaglandins increase outflow of aqueous humor (the watery substance in the eye). Drainage of aqueous humor helps reduce intraocular pressure.
Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands. Latanoprost was the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), may help some patients who do not respond to latanoprost. These drugs may also benefit patients with normal-tension glaucoma.
Side Effects. These drugs do not slow down the heart rate and also appear to be safe for people with asthma. Side effects include itching, redness, and burning during administration. Muscle and joint pain may also occur. All of these drugs may permanently change eye color from blue or green to brown.
Carbonic Anhydrase Inhibitors
Carbonic anhydrase inhibitors (CAIs) decrease eye pressure by reducing the fluid in the chambers of the eye (aqueous humor). These drugs are used for glaucoma when other drugs do not work. They may be combined with other medications.
CAIs may also improve blood flow in the retina and optic nerve (beta-blockers do not). Improving blood flow can keep the disease from getting worse.
Brands and Side Effects. CAIs are available in the following forms:
- Eye-drop CAIs include dorzolamide (Trusopt) and brinzolamide (Azopt). About 10% of patients report fatigue, stinging in the eye, and loss of appetite using dorzolamide. Taste changes can occur. Brinzolamide is a newer medication that may cause less stinging than dorzolamide.
- Forms taken by mouth (oral) include acetazolamide (Diamox), methazolamide (Neptazane), and dichlorphenamide (Daranide). Although they are more effective than eye drops, they have significantly more side effects and are rarely used for long-term treatment. The oral forms have very unpleasant side effects, including frequent urination, depression, stomach problems, fatigue, weight loss, sexual dysfunction, and, in infants, failure to thrive. Long-term use of the oral forms, in rare cases, can cause serious anemia and kidney problems, including the risk for stones. They can also produce a toxic reaction when taken with large doses of aspirin.
Adrenergic agonists activate muscles in the eye that dilate pupils and, therefore, increase outflow of aqueous fluid. Newer variations called alpha 2-adrenergic agonists reduce production of aqueous humor and also increase outflow through the uveoscleral pathway (the alternative channel to the trabecular meshwork).
Apraclonidine (Iopidine) and brimonidine (Alphagan) are alpha 2-adrenergic agonists. These are generally been used before glaucoma surgery, but may be useful as primary therapy when used in combination with beta-blockers or other standard drugs.
Brimonidine is proving to be particularly effective for long-term therapy. (Apraclonidine is used for the short term.) It also may have nerve-protecting properties and may be safer than other drugs during pregnancy and for patients with asthma.
The most common side effects of brimonidine and apraclonidine are dry mouth and altered taste. They also commonly trigger an allergic reaction that causes red and itching eyes and lids,. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure.
Miotics (Pilocarpine and Others)
Miotics, also called cholinergic agonists, narrow the iris muscles and constrict the pupil. This action pulls the iris away from the trabecular meshwork and allows the aqueous humor to flow out through the drainage channels, reducing the pressure inside the front of the eye.
Brands. Pilocarpine (Pilocar, Adsorbocarpine, Almocarpine, Isoptocarpine, Ocusert) was the most widely used anti-glaucoma drug before timolol was introduced. It is the preferred miotic. Because pilocarpine is used up by the body fairly quickly, however, patients must take it several times a day; many people, therefore, fail to take their medication regularly. A combination of timolol or latanoprost with pilocarpine is more effective than either drug used alone. Carbachol is another miotic.
Epinephrine and its derivatives are the older anticholinergics. Epinephrine is now rarely prescribed because of side effects. Dipivefrin (Dipivefrin), a newer form of epinephrine, remains inactive until it reacts with enzymes in the cornea. It is effective in low doses and causes few systemic side effects.
Side Effects. Side effects include:
- Teary eyes, brow-aches, eye pain, and allergic reactions.
- A miotic narrows the pupil and so can cause nearsightedness. Vision can also become dim and it may difficult to see in darkened rooms or at night, when driving could be hazardous.
- Anticholinesterase miotics increase the risk of cataract development and are therefore used mostly in patients in whom cataracts have already been removed. Retinal detachment is an uncommon but dangerous side effect in susceptible individuals. Excessive use of these miotics may cause toxic reactions, including convulsions, muscular paralysis, and even death from respiratory failure.
- Epinephrine can produce burning in the eyes, enlarged pupils, and allergic reactions. Occasionally it can cause anxiety and headaches. Rare side effects include high blood pressure and disturbances in heart rhythm. It is rarely prescribed now. Although dipivefrin, the newer form of epinephrine, has fewer systemic side effects, it still causes problems in the eyes similar to those of epinephrine.
Managing Drug Regimens
Studies indicate that many patients skip doses of their glaucoma medications, sometimes because of side effects and sometimes because of confusing or time-consuming regimens. Skipping even a few doses can greatly increase the risk of visual loss. It is essential that patients tell their doctor if they are not regularly taking their medication. Otherwise, the doctor may increase the dosage, thereby causing unwelcome side effects.
Patients who do not regularly take their glaucoma medication are at high risk for blindness. If you have problems taking your medications or sticking to the dosing regimen, talk with your doctor.
Hints for Managing a Regimen.
- Pharmaceutical manufacturers use colored tops, yellow for timolol, for example, and green for pilocarpine, to help prevent mix-ups. Creating a chart scheduling each drug by color can be helpful.
- Small electronic timers are available that will signal times for taking the medications. The timing of these combinations is important.
- Some patients may be candidates for single medications that combine two drugs, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice per day. Patients who need additional glaucoma drugs, however, will need to take these two drugs separately.
- When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss with the doctor reducing the dosage or trying other drugs.
Administering Eye Drops. A common reason that medicine does not work is that patients do not take it correctly. Patients should ask the ophthalmologist to watch while they place the drops in their own eyes to make sure the procedure is being done correctly. The following are some recommended steps:
- If you use both ointments and eye drops, take the eye drops first.
- Wash your hands before applying eye drops.
- Hold the bottle upside down.
- Tilt your head back and, with one hand, pull the lower eyelid down to form a pocket.
- With your other hand, hold the bottle as close as possible to your eye. Dont let the bottle directly touch your eye or eyelid.
- After you have placed the drop, close your eye or press your index finger against the corner of the eye near your nose. Gently move the lower lid upward until the eye is closed. Keep your eye closed for at least 1 minute. This prevents the drop from draining out.
- Wait at least 5 minutes before applying another drop or a different medication
Drug Therapy for Acute Closed-Angle Glaucoma
Acute closed-angle glaucoma is an emergency situation. Doctors may administer a combination of two or more anti-glaucoma medications to reduce eye pressure quickly before it can damage the optic nerve and cause visual loss. Apraclonidine (Iopidine) is a powerful drug used before and after laser surgery to prevent an increase in fluid pressure and is more effective than other medications. In addition to standard drugs, doctors may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.
If medications do not control eye pressure, or if they create intolerable side effects, surgery may be necessary in a small percentage of people with glaucoma. The standard procedures are usually one of the following:
- Filtration surgery (trabeculectomy). This procedure opens the full thickness of the drainage area.
- Laser trabeculoplasty. This procedure partially opens the drainage area. It does not reduce pressure to the extent of trabeculectomy but it has fewer adverse effects.
Filtration Surgery (Trabeculectomy)
The Procedure. Filtration surgery has been used for more than 100 years with only minor modifications. It uses conventional surgical techniques known as full-thickness filtering surgery or guarded filtering surgery (trabeculectomy).
- The surgeon creates a sclerostomy, a passage in the sclera (the white part of the eye) for draining excess eye fluid.
- A flap is created that allows fluid to escape without deflating the eyeball.
- The surgeon may also remove a tiny piece of the iris (called an iridectomy) so that fluid can flow backward into the eye.
- A small bubble called a bleb nearly always forms over the opening, which is a sign that fluid is draining out. Although surgeons aim for a thick bleb, which poses less risk than a thin one for later leakage, paradoxically the ideal operation would have no bleb at all.
The procedure has a high success rate. About 50% of patients no longer need medication after surgery. Thirty-five to 40% of those who still need medication have better control of their glaucoma.
A newer instrument called a trabectome has allowed for a less invasive type of trabulectomy surgery. The trabectome procedure appears to be a safe and simple way to lower eye pressure. It can be performed before a traditional trabulectomy, if needed.
Side Effects. Many of the serious side effects or complications that occur with filtration surgery involve blebs (blister-like bumps).
- Bleb Leaks and Infections. Blebs, particularly thin ones, commonly leak. Leakage can occur early on or sometimes as late as months or years after surgery. Untreated, such leaks can be serious and even cause blindness. Late-onset leakage significantly increases the risk for infection as well as a number of other serious conditions, including bleeding, a flattening of the eye ball, and harmful inflammation. Surgical repair is the most effective way of managing leaking blebs, although drug therapies, pressure patching, and other nonsurgical techniques may be tried first. Due to the dangers of leaking blebs, doctors recommend lifelong monitoring after surgery. Unfortunately, the incidence of late-onset leaking blebs is increasing due to the use of drugs used in filtration surgery to prevent scarring, another complication.
- Scarring. In up to 20% of cases, scars form around the incision, closing up the drainage channels and causing pressure to rebuild. Scarring is a particular problem in young patients, African-Americans, and patients who have taken multiple drugs, have had an inflammatory disease, or have had cataract surgery. Releasing the surgical stitches used in the procedure may help prevent scarring and pressure build-up. A second procedure called bleb needling sometimes can open up the scarred area and restore drainage. With this technique, the tip of a very fine hypodermic needle is used carefully to cut loose the particles closing off the drainage area.
- Cataracts. The procedure is highly associated with the development of cataracts over time. Because cataracts are associated with glaucoma anyway, it is not entirely clear whether the cataracts are caused by the surgery or would develop in any case.
Supportive Medication for Preventing Scarring. Specific drugs, usually mitomycin C, are often used in conjunction with the procedure to prevent scarring and closure. A large review of studies of mitomycin C supported its effectiveness in increasing surgical success in nearly all patients. Fluorouracil (5-FU) appears to be similar in effectiveness but has a high risk for complications and is not used as often as in the past.
The Procedure. Laser trabeculoplasty involves the following steps:
- The procedure uses an instrument, usually a YAG laser, to burn 80 - 100 tiny holes in the drainage area.
- A tiny scar forms, which increases fluid outflow.
- The procedure takes 15 minutes, causes almost no discomfort, and has very few complications.
Laser surgery is not a cure. Patients still need to take anti-glaucoma eye drop medications every day. Within 2 - 5 years, about half of patients need either additional surgery or new medications.
Complications. In about 35% of patients, pressure increases after surgery. In most cases it is temporary, but in rare cases the increased pressure is permanent and vision loss can occur. Use of the drug apraclonidine (Iopidine) or pilocarpine can help prevent this elevated pressure. About a third of patients also develop adhesive-like substances called peripheral anterior synechiae that cause the iris to stick to part of the cornea.
Drainage Implants (Tube Shunts)
Drainage implants, also known as tube shunts, may be used to drain fluid in certain cases, such as if glaucoma is not responsive to any standard procedure or is caused by certain conditions.
Candidates. Drainage implants may be useful in the following conditions:
- Glaucoma caused by swelling in the iris
- Glaucoma caused by abnormal vessel formations
- Iridocorneal endothelial (ICE) syndrome
The Procedure. In general, the procedure involves:
- An implant, most commonly a 1/2 inch silicone tube, is inserted into the eye's front chamber (anterior).
- The tube drains the fluid onto a tiny plate that is sewn to the side of the eye.
- Fluid collects on the plate and then is absorbed by the tissues in the eye.
Complications. Complications include:
- Hypotony (very low eye pressure) is a serious complication that has been reduced using better techniques and improved implants.
- Cataracts, detached retina, breakdown of the cornea, and bleeding are potentially significant complications.
- There is also a risk for eye movement disorders, such as strabismus (crossed eyes) or diplopia (double-vision).
The implant often becomes blocked, and additional surgery may be needed.
Nonpenetrating Surgical Techniques: Deep Sclerectomy and Viscocanalostomy
Deep sclerectomy and viscocanalostomy are less invasive techniques than filtering surgery that leave the anterior chamber (front of the eye) intact and avoid creation of blebs.
In both deep sclerectomy and viscocanalostomy, the surgeon creates a flap in the outer part of the sclera (the white part of the eye) and then removes a deep piece of the sclera underneath.
Many variations are under investigation. In general, the procedures have fewer complications afterward than standard filtering surgery, although they require excellent surgical skill. Nonpenetrating techniques do not lower IOPs as much as conventional surgery does, however.
Treatment for Patients with both Glaucoma and Cataracts
Cataracts and Glaucoma. For patients with both glaucoma and cataracts, doctors recommend:
- In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. Typically the patient will first have a trabeculectomy for glaucoma, followed by cataract surgery such as phacoemulsification (lens removal through ultrasound). Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure.
- Phacoemulsification is sometimes combined with viscocanalostomy in a procedure called phacoviscocanalostomy.
- In patients who have cataracts plus either closed-angle glaucoma or open-angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.
Some evidence indicates that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. However, it is still unclear which specific type of surgical procedure works best. [For more information, see In-Depth Report #26: Cataracts.]
Laser Cyclophotocoagulation (Cycloablation) for End-Stage Glaucoma
Diode laser transscleral cyclophotocoagulation (TSCPC), also called laser cycloablation, reduces aqueous production by destroying the muscles that control the lens for near and far vision (the ciliary body). There is a chance of vision loss with this procedure, so it is generally reserved for people with end-stage glaucoma or those who fail to benefit from any other therapies.
Surgery for Acute Closed-Angle Glaucoma
For an acute closed-angle glaucoma attack, emergency microsurgery is usually necessary after reducing pressure with medications.
Iridotomy or Iridectomy. Either laser (iridotomy) or conventional (iridectomy) surgery may be used. With either procedure an ophthalmologist makes a tiny opening in the iris to let the aqueous humor flow out more freely. Because acute glaucoma commonly occurs later in the other eye, surgeons will often recommend surgery in the unaffected eye to prevent a second attack.
Laser iridotomy almost never requires hospitalization, and postsurgical treatment includes only aspirin and eye drops. It has almost completely replaced conventional surgery, which requires anesthesia and hospitalization.
Vision will be blurred, and recovery can take 4 - 8 weeks. Following surgery, patients can usually safely use previously restricted anticholinergic medications, such as antihistamines and certain antidepressants.
Phacoemulsification and Intraocular Lens Implantation. Phacoemulsification and intraocular lens implantation, a procedure ordinarily used for cataracts, may prove to be beneficial for some patients with acute angle-closure glaucoma requiring surgery. [For more information, see In-Depth Report #26: Cataracts.]
Studies suggest that patients with open-angle glaucoma who exercise regularly (at least 3 times a week) may be able to reduce their intraocular pressure by an average of 20%. If they stop exercising for more than 2 weeks, pressure increases again. (Although not confirmed by any evidence, yoga or other exercises that involve head-down or inverted positions may be harmful for patients with glaucoma and should be discussed with the doctor.)
Exercise has no effect on closed-angle glaucoma. It may, in fact, increase eye pressure in patients with pigmentary glaucoma. Vigorous high-impact exercise may cause more pigment to be released from the iris in these patients. Patients should talk to their doctor about an appropriate exercise program.
Antioxidants in Foods and Supplements. Diet most likely plays very little role in glaucoma. There has been no definitive evidence for an association between important nutrients associated with protection against other eye disorders, including vitamins C, E, A, and carotenoids.
Caffeine. Some studies have shown that large amounts of caffeine drunk in a short period of time can elevate eye pressure for up to 3 hours.
Fluids. Drinking large amounts (a quart or more) of any liquid within a short time, about 30 minutes, appears to increase pressure. Patients with glaucoma should have plenty of fluids, but they should drink them in small amounts over the course of a day.
Glaucoma can cause the eyes to be very sensitive to light and glare. Medications can worsen this problem. Sunglasses solve this problem and are important for prevention of cataracts. Protective sunglasses do not have to be expensive. But it is important to select sunglasses whose product labels state they block at least 99 percent of UVB rays and 95 percent of UVA rays.
Polarized and mirror-coated lenses do not offer any protection against UV radiation. It is not clear if blue light-blocking lenses, which are usually amber in color, provide UV protection.
Herbs and Supplements
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.
A number of herbal and nontraditional remedies have been advertised as glaucoma remedies. A few studies have reported that the herbal remedy ginkgo biloba may have properties that offer benefits to patients with glaucoma, including increasing blood flow in the eye without altering overall blood pressure, heart rate, or intraocular pressure. More research is, however, needed. There is no evidence that bilberry, another popular herbal remedy for eye disorders, is effective in preventing or treating glaucoma.
- www.glaucoma.org -- Glaucoma Research Foundation
- www.nei.nih.gov -- National Eye Institute
- www.glaucomafoundation.org -- The Glaucoma Foundation
- www.aao.org -- American Academy of Ophthalmology
- www.glaucomaweb.org -- American Glaucoma Society
- www.lighthouse.org -- Lighthouse International
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.