Chapter 62. Glaucoma

Glaucoma is a progressive eye disease. It affects three million Americans and is the second leading cause of blindness in the United States. There are two major types of glaucoma: primary open angle glaucoma (POAG) and angle closure glaucoma. The most common type, POAG, will be the focus of this discussion. Angle closure glaucoma, though less common, is considered a medical emergency. Angle closure glaucoma may result in sudden loss or blurring of vision, significantly elevated eye pressures, nausea and vomiting. Both types of glaucoma may result in optic nerve damage and permanent blindness if not treated. Glaucoma does not cause symptoms in the majority of patients. It is important for pharmacists to counsel patients about routine eye examinations and glaucoma screenings for early detection. There are several risk factors associated with the development of glaucoma. These include age >40 years, African American or Asian race, diabetes, hypertension, elevated intraocular pressure, myopia, and family history in a first-degree relative. Treatment is aimed at reduction in intraocular pressure. Eye drops and surgery are the most common treatments. The most potent eye drops are the prostaglandin analogs. The pharmacist's role in the care of patients with glaucoma includes disease and medication counseling, review of eye drop administration technique, eye drop adherence evaluations, and recommendations for routine eye examinations.1,2

Diagnosis and Clinical Presentation

Patients with glaucoma usually do not report symptoms until substantial visual field destruction occurs. Visual field loss occurs in 8% to 20% of patients despite reaching therapy goals. Eighty percent of patients without treatment will develop bilateral blindness. Patients with glaucoma may be involved in a motor vehicle accident because they have blind spots related to peripheral vision field defects. Elderly patients with long-standing glaucoma often experience declining vision, headaches, and eye pain.3 Some elderly patients continue to use eye drops even after blindness develops to decrease the incidence of eye pain. Glaucoma can be distinguished from other eye diseases, affecting the optic nerve, by performing a dilated eye examination. Ophthalmologists may note during examination that the rim of the optic nerve is thinning. This thinning is caused by loss of retinal nerve cells. The pink color of the eye fields will remain. Other neuropathies of the optic nerve are characterized by loss of the pink color. Optic nerve thinning results in an enlarged cup-to-disc ratio, which is a hallmark visual finding during examination of the eye. The optic disc is the anatomical location where the optic nerve and blood vessels enter the retina. The optic disc can be flat or it can have a certain amount of normal cupping. In glaucoma, increased pressures cause pathological cupping of the optic disc. The pink disc contains nerve fibers. The white cup is a pit with no nerve fibers. As glaucoma advances, the cup enlarges to cover most of the disc. A normal value for the cup-to-disc ratio is 0.3. A greater value indicates glaucoma. Intraocular pressure (IOP) is often elevated. A normal IOP value is between 10 and 21 mm Hg. Elevated IOP in the absence of optic nerve changes may be diagnosed as ocular hypertension. Some patients with glaucoma have normal intraocular pressures.2,3

Gonioscopy, perimetry, and tonometry testing provide the ophthalmologist with additional information for the diagnosis of glaucoma. Gonioscopy measures the anterior chamber angle between the iris and cornea and is used to diagnose the type of glaucoma. Automated perimetry testing is used to identify loss of visual fields. Tonometry is also an important assessment tool. Tonometry is the measure of IOP. Applanation tonometry is measured using a small probe to determine the force required to flatten the cornea. This test requires the use of anesthetic eye drops because the small probe is inserted directly onto the eye. Applanation tonometry is very accurate and is used after a simple screening test, such as pneumotonometry or air-puff tonometry, and has indicated an increased IOP. Pneumotonometry does not touch the eye but uses a puff of air to flatten the cornea. This is a more convenient test. It is not as accurate but is used routinely as a screening method.3

Eye Physiology

The angle formed by the iris and cornea is measured to define the type of glaucoma present. The most common glaucoma type, POAG, is diagnosed when the angle is not obstructed. Aqueous humor is the fluid that bathes the eye and supplies nutrients.

Aqueous humor, produced by the ciliary body, circulates throughout the anterior chamber of the eye and drains into the eye filter, also known as the trabecular meshwork. Filtration through the meshwork depends on pressure gradients and so blood pressure and IOP changes affect aqueous humor production. The trabecular meshwork may become scarred or clogged with a resultant increase in intraocular pressure. Intraocular pressure elevations may also occur because of reduced aqueous outflow from the trabecular meshwork. The increased pressure results in damage to the ganglion-cell axons that make up the optic nerve. This is a progressive disorder that can lead to blindness. The goal of treatment is to decrease the intraocular pressures to slow the damage caused to the optic nerve.1-4

Glaucoma can also be caused or worsened by certain classes of medications. Pharmacist should review medication regimens and recommend alternatives to improve outcomes for patients with glaucoma. Table 62-1 summarizes medications known to worsen glaucoma.5

The major goals of glaucoma treatment are to preserve vision and decrease intraocular pressure. Medications, the most common treatment, are often used first line to decrease the intraocular pressure. Medication therapy is administered topically using eye drops. Eye drops are absorbed quickly into the eye. This increases efficacy and decreases the incidence of systemic side effects. Oral medications are a second-line option. Surgery is also a treatment option. Medications utilize several different mechanisms to accomplish this goal. For instance, prostaglandin analogs increase uveoscleral outflow. Beta-blockers decrease aqueous humor production and improve aqueous humor outflow. Carbonic anhydrase inhibitors decrease aqueous humor production by inhibiting the enzyme carbonic anhydrase. The two most effective classes of medications are the prostaglandin analogs and the beta-blockers. Each class of medications has their own unique side effects to consider. The most common side effects of these medications are listed in Table 62-2. The incidence of systemic side effects can be significantly decreased by teaching appropriate eye drop administration techniques.3,4

Adherence and Persistence

There are several studies addressing the issues of adherence and persistence in the treatment of glaucoma.6-8 Adherence has been shown to sharply rise 1 week prior to the doctor's appointment. Persistence evaluates the rate of treatment adherence over time. Rates of persistence are generally below 50% at 1 year.6 The pharmacists should recommend the most effective and least side-effect prone medications. Patients need to be educated about side effects. In most instances, minor eye irritations caused by eye drops improve over time. Patients are more likely to continue treatment despite minor side effects if they understand that the side effects will decrease over time. Patients should be educated about the different classes of eye drops. This would help them understand that other options are available if side effects occur. Prostaglandin analogs are the most commonly prescribed drops for glaucoma. They are the most effective class of eye drops and have few serious side effects. Table 62-2 summarizes the differences in dosing, efficacy, and side effects among the various classes of eye drops. Pharmacists can also monitor refill dates to help monitor and promote adherence.

Eye Drop Administration Technique

Patients should be instructed to wash their hands prior to eye drop administration. They should also avoid touching the tip of the medication bottle to the eye or any other surface to avoid contamination and eye infections. Some eye drops are suspensions, such as brinzolamide (Azopt), betaxolol (Betoptic-S), timolol and dorzolamide combination product (Cozopt), and timolol gel-forming solution (Timoptic XE). These suspensions should be shaken before use. Table 62-3 summarizes the steps for appropriate eye drop technique.3

Beta-Blockers

Beta-blockers are very effective options for the treatment of POAG and are considered an appropriate first line of therapy. There are once daily formulations to promote adherence. However, they are not the most commonly prescribed first-line option because side effects may limit their tolerability. Stinging, dry eyes, blurred vision, and blepharitis are common local side effects. Systemic side effects are also very common and include decreased blood pressure, decreased heart rate, and bronchospasm. Systemic side effects are problematic for patients with diabetes, congestive heart failure, heart block, or severe chronic obstructive pulmonary disease. Nasolacrimal occlusion (NLO) helps decrease the frequency of systemic side effects.2-3

Prostaglandin Analogs

Prostaglandin analogs have become the most commonly prescribed first-line therapy for POAG. They are extremely effective in lowering IOP and they have a very favorable side effect profile. They can decrease IOP as much as 36%. These medications are also among the first class to demonstrate a diurnal IOP-lowering effect. This means that they are very effective at lowering IOP even at night during sleep when IOP readings are the highest. The most common side effects include hyperpigmentation of the iris and hypertrichosis of the eyelashes. It is believed that these effects are only harmful from a cosmetic point of view. Someone with mixed hazel-brown eyes will probably have more brown color apparent between 3 to 12 months of use. These eye drops are usually dosed once daily at bedtime.9-15

Alpha-2 Agonist

Alpha-2 agonists decrease intraocular pressure by decreasing the production of aqueous humor. They lower IOP 15% and are often combined with other agents. The unique use of alpha-2 agonists is after cataract or laser surgery. They have a rapid onset of effect. They are usually dosed two to three times daily. Side effects include lid edema, foreign body sensation, itching, and hyperemia. Systemic side effects include dizziness, fatigue, and dry mouth. NLO helps decrease the incidence of systemic side effects.2,3

Sympathomimetics and Parasympathomimetics

Sympathomimetics and parasympathomimetics are older agents that are used last line due to local and systemic side effects. They decrease IOP 25%. They are usually dosed two to four times daily. Side effects include tearing, blurred vision, brow-ache, and hyperemia. Systemic side effects include headache, increased blood pressure, tachycardia, tremor, and anxiety.2,3

Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors inhibit secretion of sodium and bicarbonate by enzyme inhibition. They lower intraocular pressure 10% to 26%.They are usually dosed two to three times daily. Local side effects include stinging, blurred vision, and conjunctivitis. Systemic side effects include acidosis, nausea, weight loss, diaphoresis, and myopia. Oral therapy is a last-line option when eye drops are not effective or when eye drop technique is difficult, such as in patients with mental disabilities. However, close monitoring is required due to the risk of serious systemic side effects.2,3

Combination Therapy

Combination therapies such as Cosopt and Combigan help improve compliance and decrease eye drop burden. The combinations are more effective than the individual agents alone. Side effects are a culmination of the two individual agents.3

• Glaucoma is a progressive eye disease. It affects three million people and is a leading cause of blindness in the United States.
• Early detection and treatment of glaucoma are important for preservation of vision.
• The two major types of glaucoma are primary open angle glaucoma (POAG) and angle closure glaucoma. POAG is the most common type.
• Topical medications are the first choice for treatment of primary open angle glaucoma.
• Prostaglandin analogs and beta-blockers are first-line medication choices. Current prescribing trends favor the prostaglandin analogs.
• Therapy must be individualized. Drug of choice is based on concomitant disease states and medication side effects.
• Carbonic anhydrase inhibitors contain a sulfa moiety. Patients allergic to sulfa should not receive a carbonic anhydrase inhibitor.
• Older agents, such as alpha-2 agonist, sympathomimetics, and pilocarpine cause significant side effects. These agents are last line in the treatment of glaucoma.
• Teaching eye drop administration technique and utilizing nasolacrimal occlusion improves medication efficacy and decreases the risk of systemic absorption and side effects.
• Education about glaucoma and the medications used to treat it, review of eye drop administration technique. and evaluation of medication adherence are all important goals for pharmacists to help patients prevent blindness associated with glaucoma.