Risk Factors

The major risk factors for POAG are the following:

Of these, elevated IOP is most important. Please note, however, that glaucomatous optic nerve damage can develop even when IOP is normal (i.e., below 20 mm Hg). Furthermore, some individuals can have very high IOP (e.g., 30 mm Hg) with no associated injury to the optic nerve. These individuals are said to have ocular hypertension—not glaucoma.

Screening

Because POAG has no symptoms (until significant and irreversible optic nerve injury has occurred), regular testing for early POAG is important among individuals at high risk. With early detection and treatment, blindness can usually be prevented.

Management

Treatment of POAG is directed at reducing elevated IOP, the only risk factor we can modify. Although POAG has no cure, reduction of IOP can slow or even stop disease progression. Management is usually initiated by specialists; however, primary care providers often play a role in ongoing monitoring and follow-up of patients taking these medications.

The principal method for reducing IOP is chronic therapy with drugs. Drugs lower IOP by either (1) facilitating aqueous humor outflow or (2) reducing aqueous humor production. As indicated in Table 84.1, the first-line drugs for glaucoma belong to three classes: beta-adrenergic blocking agents (beta blockers), alpha₂-adrenergic agonists, and prostaglandin analogs. Other options—cholinergic drugs and carbonic anhydrase inhibitors—are considered second-line choices. All of the antiglaucoma drugs are available for topical administration, which is the preferred route. For more than 25 years, the beta blockers (e.g., timolol) have been considered drugs of first choice. However, the alpha₂ agonists (e.g., brimonidine) and prostaglandin analogs (e.g., latanoprost) are just as effective as the beta blockers and have a more desirable side-effect profile. Accordingly, these drugs have joined the beta blockers as first-choice agents. Because drugs in different classes lower IOP by different mechanisms, combined therapy can be more effective than monotherapy. Because all of these drugs are applied topically, systemic effects are relatively uncommon. Nonetheless, serious systemic reactions can occur if sufficient absorption takes place.

If drugs are unable to reduce IOP to an acceptable level, surgical intervention to promote outflow of aqueous humor is indicated. Options include trabeculectomy and laser trabeculoplasty.

Systemic.

Beta blockers can be absorbed in amounts sufficient to cause systemic effects. For example, instilling 1 drop of 0.5% timolol in each eye can produce the same blood level as taking 10 mg of timolol by mouth (the usual starting dose for hypertension). Effects on the heart and lungs are of greatest concern.

Blockade of cardiac beta₁ receptors can produce bradycardia and atrioventricular (AV) heart block. Pulse rate should be monitored. Because of their ability to depress cardiac function, beta blockers are contraindicated for patients with AV heart block, sinus bradycardia, and cardiogenic shock. In addition, they should be used with caution in patients with heart failure.

Blockade of beta₂ receptors in the lung can cause bronchospasm. Constriction of the bronchi can occur with beta₁-selective antagonists as well as with “nonselective” beta-adrenergic blockers—although the risk is greatest with the nonselective agents. Only one ophthalmic beta blocker—betaxolol—is beta₁ selective. This drug is preferred to other beta blockers for patients with asthma or chronic obstructive pulmonary disease.

Latanoprost

Latanoprost [Xalatan], an analog of prostaglandin F₂ alpha, was the first prostaglandin approved for glaucoma and will serve as our prototype for the group. The drug is applied topically to lower IOP in patients with open-angle glaucoma and ocular hypertension. Latanoprost lowers IOP by facilitating aqueous humor outflow, in part by relaxing the ciliary muscle. The recommended dosage is 1 drop (0.005% solution) applied once daily in the evening. At this dosage, latanoprost produces the same reduction in IOP as does timolol twice daily.

Latanoprost is generally well tolerated, and systemic reactions are rare. The most significant side effect is a harmless heightened brown pigmentation of the iris, which is most noticeable in patients whose irides are green-brown, yellow-brown, or blue/gray-brown. The effect is rare in patients whose irides are blue, green, or blue-green. Heightened pigmentation stops progressing when latanoprost is discontinued but does not usually regress. Topical latanoprost may also increase pigmentation of the eyelid and may increase the length, thickness, and pigmentation of the eyelashes. Other side effects include blurred vision, burning, stinging, conjunctival hyperemia, and punctate keratopathy. Rarely, latanoprost may cause migraine.

Other Prostaglandin Analogs

In addition to latanoprost, three other topical prostaglandins are approved for topical therapy of glaucoma. Like latanoprost, these drugs—travoprost [Travatan], bimatoprost [Lumigan], and tafluprost [Zioptan]—reduce IOP by increasing aqueous humor outflow. In clinical trials, these agents were at least as effective as timolol, a representative beta blocker. Interestingly, one drug—travoprost—was more effective in blacks than in nonblacks. Like latanoprost, these prostaglandins can cause a gradual increase in brown pigmentation of the iris, which may be irreversible. In addition, these drugs can increase pigmentation of the eyelid and growth of the eyelashes. In fact, bimatoprost, marketed as Latisse, is used for the specific purpose of increasing eyelash length, darkness, and thickness. With prostaglandins used to treat glaucoma, the most common adverse effect is ocular hyperemia (engorgement of ocular blood vessels). Less commonly, these drugs cause blurred vision, eye discomfort, ocular pruritus, conjunctivitis, dry eye, light intolerance, and tearing.

Brimonidine

Brimonidine [Alphagan P, Alphagan ] is the first and only topical alpha₂-adrenergic agonist approved for long-term reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. Effects on IOP are similar to those achieved with timolol. The drug lowers IOP by reducing aqueous humor production and perhaps by increasing outflow. In addition to lowering IOP, brimonidine may delay optic nerve degeneration and may protect retinal neurons from death. This possibility arises from the ability of alpha₂ agonists to protect neurons from injury caused by ischemia. The most common adverse effects are dry mouth, ocular hyperemia, local burning and stinging, headache, blurred vision, foreign body sensation, and ocular itching. In contrast to apraclonidine (see later), brimonidine can cross the blood-brain barrier and hence can cause drowsiness, fatigue, and hypotension. (Recall from Chapter 13 that activation of alpha₂ receptors in the brain decreases sympathetic outflow to blood vessels, and thereby lowers blood pressure.) Brimonidine can be absorbed onto soft contact lenses. Accordingly, at least 15 minutes should elapse between drug administration and lens installation.