PRIMARY OPEN ANGLE GLAUCOMA (POAG)

  SIGNS AND SYMPTOMS
Although early POAG patients are virtually asymptomatic, there are at least three definitive signs: elevated intraocular pressure (approximately 21mm Hg or more), enlargement of the optic cup and repeatable field loss. Other possible signs include nerve fiber layer dropout, notching of the neuroretinal rim at the inferior or superior poles, and splinter hemorrhages adjacent to the optic disc.

PATHOPHYSIOLOGY
Despite decades of research and over two million diagnosed cases of open angle glaucoma in the U.S. alone, much remains unknown about this disease. Elevated intraocular pressure almost certainly plays a significant role, but the process is poorly understood. According to the mechanical theory of POAG, chronically elevated IOP crimps the axons of retinal ganglion cells as they pass through the lamina cribrosa, eventually killing the cells. The vascular theory suggests that, with elevated IOP, reduced blood flow to the optic nerve starves the cells of oxygen and nutrients.

New research presented in 1996 offers another possible mechanism of ganglion cell death. Studies show that some glaucoma patients exhibit elevated levels of the neurotransmitter glutamate within the vitreous. Ganglion cells contain protein receptors that, when activated by glutamate, increase intracellular calcium to toxic levels, killing the cells.

MANAGEMENT
Although several new IOP lowering drugs have been released in the past few years, beta-blockers continue to be the mainstay of glaucoma therapy. The typical management plan is to set a target IOP at least 25 percent below pre-treatment levels, and prescribe your beta-blocker of choice two or three times per day until the target is reached.

The 19-year-old timolol (Timoptic) is the most commonly prescribed beta-blocker available, but others are also noteworthy. Betimol from Ciba Vision Ophthalmics is a new, low-cost formulation of timolol that, unlike Timoptic, cannot be surreptitiously replaced with a generic by the pharmacist.

A familiar but often overlooked beta-blocker that is gaining in prominence is betaxolol (Betoptic). This drug selectively blocks beta-1 receptors, largely sparing beta-2 receptors in the lungs and thereby making it a safer option for patients with some pulmonary conditions. Betoptic also has less likelihood of reducing blood flow (and may, in fact, increase perfusion) to the optic nerve than other beta-blockers, has less propensity to reduce the levels of HDL cholesterol in blood, and preserves the visual field equally or better than other beta-blockers, even though its IOP reduction tends to be somewhat less. Finally, new research also shows that betaxolol provides ganglion cells with at least some protection from calcium toxicity caused by glutamate binding.

Other unique beta-blockers include carteolol, which, like betaxolol, has less propensity to reduce HDL cholesterol levels, and Timoptic-XE, which allows for once-a-day therapy.

New medications such as the prostaglandin analog latanoprost (Xalatan) and the topical carbonic anhydrase inhibitor dorzolamide (Trusopt) offer alternative therapies, but beta-blockers have been the gold standard against which all new pressure lowering medications are measured, and this is unlikely to change. In all likelihood, beta-blockers will remain the first-line therapy of choice in POAG, and prostaglandin analogs will supplant older second-line therapies. Xalatan is comparable in IOP lowering effect to Timoptic; its main side effect is darkening of the pigment in light-colored irises.

Another new IOP lowering drug, the alpha-2 adrenergic agonist brimonidine (Alphagan), has not been proven clinically superior to apraclonidine (Iopidine) although it is approved for chronic use whereas Iopidine 1% is intended to control post-surgical pressure spikes and angle closure attacks. A lower concentration, Iopidine 0.5%, has been developed and approved for chronic care of POAG patients. It is likely that Alphagan and Iopidine will equally share the alpha-2 adrenergic agonist market.

CLINICAL PEARLS
Prostaglandin analogs reduce IOP by increasing aqueous outflow through the uveoscleral pathway by dilating the spaces between ciliary muscle bundles. However, miotics such as pilocarpine tighten these bundles by contracting the iris dilator muscle, so these two medications are counter-effective. Discontinue any miotics prior to adding Xalatan to the regimen.

To improve compliance for patients on multiple medications, it is helpful to identify the cap colors of each drug being used (e.g., "Remember to use the one with the yellow cap twice a day and the blue one four times a day.")