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An in-depth report on the causes, diagnosis, treatment, and prevention of glaucoma.


Nearly all the medications for glaucoma are aimed at reducing eye pressure. Lowering IOP is even proving to be beneficial for about two-thirds of patients with normal pressure glaucoma.

Beta Blockers (Timolol and Others)

Topical beta adrenoceptor blockers (common 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 agents 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 agents are 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 blocker. These agents 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 does, although timolol is more effective at lowering IOP. Such findings indicate that these selective beta blockers may also have nerve-protecting properties.

All beta blockers are effective and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for glaucoma 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 agents, therefore, can cause side effects in parts of the body other than the eyes, called systemic side effects:

  • Common systemic side effects include reduced sexual drive, fatigue, depression, anxiety, severe nausea and vomiting, and breathing difficulties.
  • Beta-blockers affect the heart. They lower heart rate and reduce blood pressure. (The newer selective beta-1 blockers may not have as adverse effects on the heart as the nonselective beta blockers.) They may also cause unhealthy cholesterol and triglyceride changes.
  • All beta-blockers can worsen severe asthma or other lung diseases. Beta-blockers should only be used very cautiously or not at all by anyone with asthma, emphysema, bronchitis, or heart disease. Lung function was found to be reduced in 40% of elderly people who took timolol, even those without previous symptoms of lung problems. (Selective beta blockers may produce fewer of these adverse effects.)
  • If the patient is switching to a beta blocker from other glaucoma medication, there may be a sudden rise in eye pressure. It is important, therefore, 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 may be additive to other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. Diabetics on insulin or hypoglycemic medications should realize that timolol side effects may resemble and mask the symptoms of hypoglycemia.


Prostaglandins are hormone-like substances that help open blood vessels. Agents that resemble prostaglandins increase outflow through the uveoscleral pathway (not the trabecular meshwork). Some experts believe that the uveoscleral pathway may be responsible for up to 50% of outflow in healthy eyes, which could explain the very large benefit produced by drugs acting on this channel.

Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands.Latanoprost is the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), are showing great promise and may effective in some patients who do not respond to latanoprost. These agents may also benefit patients with normal-tension glaucoma. Latanoprost, travoprost, and bimatoprost need to be taken only once daily. Unoprostone needs to be taken twice a day and is not as effective as others, but it still can reduce IOP significantly and is the least expensive of these agents.

Latanoprost has been shown to reduce pressure by between 45% and 71%. Some, but not all studies, have suggested that newer prostaglandins travoprost (Travatan) and bimatoprost (Lumigan) are more effective than latanoprost, but the older agent appears to be better tolerated. All of these agents may be more effective than timolol in lowering IOP. The newer prostaglandins may be especially superior to timolol in treating African American patients. In comparison studies, latanoprost achieved better IOP pressure reduction than brimonidine. Studies in 2003 suggest that bimatoprost is more effective in lowering eye pressure than a combination of timolol and dorzolamide (Cosopt). Studies have been mixed on whether latanoprost is superior to the combination.

Side Effects. These agents do not slow the heart rate down 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 agents may permanently change eye color from blue or green to brown. To date, such color changes do not seem to be hazardous. (The only significant problem appears to be cosmetic in people who treat only one eye, since the color may differ from the other.) These agents can increase blood flow in the eye and also make eyelashes become thicker and longer in some patients. (These latter effects are more common with bimatoprost and travoprost than with latanoprost.)

Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors (CAIs) reduce aqueous humor flow by as much as 40% and are now used for glaucoma when other drugs are not effective. They are also useful in combinations. These agents may improve blood flow in the retina and optic nerve (which beta blockers do not) and so theoretically may slow down progression of the disease even in patients with normal-tension glaucoma.

Brands and Side Effects. CAIs are available in the following forms:

  • Topical 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 Trusopt. Taste changes can occur. Azopt is a newer medication that was chemically designed to be closer in pH to human tears and may cause less stinging than Trusopt.
  • Oral forms. Oral forms 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 that include 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

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). Older adrenergic agonists include epinephrine.

Alpha 2-Adrenergic Agonists. Apraclonidine (Iopidine) and brimonidine (Alphagan, Allergan) are alpha 2-adrenergic agonists. These have generally been used before glaucoma surgery, but a number of studies are indicating that they may even 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 agents during pregnancy and for patients with asthma.Studies are finding that brimonidine was as effective and resulted in a better quality of life than the newer beta-blocker betaxolol. Comparison studies indicate that the combination of brimonidine and latanoprost is superior to timolol/dorzolamide (Cosopt) in lowering IOP.

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, a major drawback. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure. It also appears to remain effective longer.

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) and 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.

Demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine) are a group of long-acting drugs known as anticholinesterase miotics. Because of their potential for serious side effects, however, some authorities even prefer surgery to their use.

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 the following:

  • 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. A gel form administered once a day or wafer placed under the lid once a week may help reduce these side effects. Small amounts of an adrenergic drug, such as epinephrine, may also help.
  • The 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.

Experimental Therapies

A number of agents are under investigation. Some research is focusing on developing drugs that can directly protect the eye from nerve damage or even repair this destruction. The following are a few of them:

Glatiramer Acetate. Glatiramer acetate (Copaxone) is a synthetic molecule that is being used in multiple sclerosis to reduce the immune attack on nerve cells. It is now being investigated in glaucoma as a vaccination that may help prevent the immune system from triggering the release of the toxin glutamate, which cause major damage to the optic nerve.

Cannabinoids. Cannabinoids, compounds in marijuana (cannabis), are being studied for their effects on glaucoma. For example, oral or inhaled tetrahydrocannabinol (THC), the active ingredient in marijuana, has been shown to reduce IOP in 60% to 65% of glaucoma patients. The effects of smoking marijuana on IOP last only three hours, however. THC also increases the release of glutamate--a nerve protecting chemical. Experts are hoping that topical use of THC or other cannabinoids may help prevent optic nerve damage without the widespread effects of oral or inhaled administration.

Citicoline. Citicoline is a drug used in neurologic disorders, including stroke and Parkinson's disease. The agent contains factors that build and repair cell membranes and also has a positive effect on certain neurotransmitters. Small studies are suggesting that it may improve the visual pathways in some patients with glaucoma.

Managing Drug Regimens

Reasons for Noncompliance

Studies have revealed that more than 40% of patients miss 10% of their doses, and 15% miss more than half. Noncompliance is very high for many reasons:

  • People with chronic glaucoma who are on medication must use eye drops or take pills one or more times a day, usually for the rest of their lives.
  • Many people require a multi-drug regimen, two or more different kinds of medications that can be used in various combinations, such as eye drops, ointments, or time-release wafers inserted under the eyelid. Such regimens can be very confusing.
  • The side effects of the drugs are more unpleasant than the disease itself, which has no symptoms until vision is lost. The treatment then does not usually produce any noticeable improvement, and the consequence of not taking the drugs, blindness, seems far in the future.
  • Skipping even a few doses can greatly increase the risk of visual loss. If the patient is not taking medication regularly, it is essential that he or she admit this to the physician. Otherwise, the doctor may increase the dosage, thereby precipitating unwelcome side effects.

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. For example, the combination of pilocarpine with latanoprost is most effective when pilocarpine is taken four times a day and when the bedtime dose is administered an hour after latanoprost.
  • Some patients may be candidates for single medications that combine two agents, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice day. Patients who need additional glaucoma drugs, however, will need to take these two agents separately.
  • When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss reducing the dosage or trying other drugs with the physician.

Administering Eye Drops

A common reason for the failure of medication is improper administration. It is useful for patients to 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 a patient is taking both ointments and eyedrops, the eye drops should be administered first.
  • To reduce widespread side effects, a patient should be lying down while applying the drugs, administering one drop every five minutes.
  • The head should be tilted back and the lower eyelid pulled down to form a cup.
  • After each drop has been instilled, the patient should press the index finger firmly against the nasal corner of the eye. Gently move the lower lid upward until the eye is closed.
  • Continue pressing lightly against the corner of the closed eye for one to two minutes. This maneuver blocks drainage into the nose, and helps minimize the amount of drug that gets into the bloodstream.

Drug Therapy for Acute Closed-Angle Glaucoma

In this emergency situation, ophthalmologists 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, physicians may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.

Therapies for Less Common Glaucomas

Most rare forms of glaucoma respond to the same medications and surgery used for open angle glaucoma. Irido corneal endothelial syndrome (ICE) is difficult to treat and if surgery is required, filtering surgery is the best choice. Neovascular glaucoma is also very hard to treat; researchers are investigating drainage implants for this disorder.


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