Once a decision has been made to pursue medical therapy, the ophthalmologist must choose among the many medical options available. Prior to selecting a medication, the physician should review the patient's medical history, allergies, and experience with previous glaucoma medications. Documenting efficacy and side effects of medications previously used in a dedicated location in the medical record will reduce the likelihood of repeating unsuccessful therapeutic trials in the future.
Beta blockers are contraindicated in patients with asthma, chronic obstructive pulmonary disease (COPD) or bradycardia. Systemic CAIs should be avoided in patients with a history of calcific kidney stones or potential problems with metabolic acidosis. Systemic CAIs may be used with caution in patients with a sulfa allergy.50
Ocular conditions can also affect the choice of medications. Uveitis and cystoid macular edema (CME) are infrequently associated with prostaglandin analogs.51-55 Although rarely used, dipivefrin and epinephrine are associated with CME in aphakic patients. Echothiophate iodide is not used in phakic patients because of its cataractogenic properties, but it is a very effective treatment in pseudophakic and aphakic individuals. Miosis from any cholinergic agent can decrease visual function in patients with cataracts, especially central posterior subcapsular cataracts, and in patients with advanced glaucoma.
If there are no contraindications, one of the three available prostaglandin analogs (bimatoprost, latanoprost, and travoprost) is an excellent initial treatment choice. These medications are more efficacious than timolol in lowering IOP56-58 and require only once-daily dosing. Some studies have noted slight efficacy differences among these medications; however, these differences are of questionable practical clinical relevance from an initial treatment perspective.57'59'60 Additionally, there is increasing attention to IOP fluctuation as an independent, major risk factor for glaucoma progression.36,61 Since prostaglandin analogs appear to provide better diurnal pressure control than do other IOP-lowering medication classes,62,63 there is additional support for using prostaglandin analogs as first-line glaucoma therapy. In many cases, increasing medication cost and insurance-mandated formulary coverage will become the primary driver of which prostaglandin agent is initially chosen.
It is very important to review medication side effects with patients prior to beginning therapy. Iris color change, periorbital hyperpigmentation, and hyper-trichosis are unique to the prostaglandin class of drugs.64-66 Periorbital hyper-pigmentation and hypertrichosis may improve with medication stoppage. There is a tendency for less conjunctival hyperemia with latanoprost.60 Some patients who do not respond to latanoprost have shown an IOP lowering when switched to bimatoprost;67 therefore, if there is not an initial response to one prostaglandin agent, changing medication within this class may be a reasonable next step.
If there are no contraindications, a nonselective beta blocker may also be considered as initial therapy. Beta blockers function by reducing aqueous production. They have a long history of efficacy in lowering IOP in normal, ocular hypertensive, and glaucomatous patients.68 Patients have been maintained on these drugs for many years, and the side effect profile is well documented. These drugs are generally well tolerated. For patient adherence, timolol and levobunolol allow reliable once-daily dosing. In patients with abnormal lipid profiles, carteolol is a good choice because it has a less negative effect on serum lipids.69 Due to the availability of generic options, beta blockers may be an ideal choice when medication cost is a priority.
In a patient with a history of mild asthma or COPD, betaxolol provides a safer alternative. However, most studies have shown its efficacy in lowering IOP to be less than that of nonselective beta blockers.70 Furthermore, betaxolol has been associated with adverse pulmonary side effects in at-risk populations.71 Given the availability of alternate medications, the use of any beta blocker should be carefully considered in the presence of a relative contraindication.
Brimonidine, an alpha-2-selective agonist, can also be considered as initial treatment in select cases. Brimonidine reduces aqueous production and increases uveos-cleral outflow. The Brimonidine Study Group compared the IOP-lowering effect of brimonidine 0.2% with timolol 0.5%, each administered twice daily for 1 year.72 Both medications maintained a significant reduction in IOP from baseline throughout the study. At peak times, the IOP-lowering effect of brimonidine was greater than or equal to that of timolol. The IOP-lowering effect of timolol was greater than that of brimonidine for all follow-up visits at trough times. Additionally, timolol is used once or twice daily compared with brimonidine, which requires three-times-daily administration for complete coverage despite the fact that it is used twice daily in most cases. Brimonidine has been associated with dry mouth, ocular hyperemia, and ocular burning. From a cardiopulmonary perspective, brimonidine may be safer than beta blockers. Patients with cardiopulmonary disease may benefit from bri-monidine as initial treatment.
Topical CAIs, such as dorzolamide and brinzolamide, are useful because they lower IOP without the systemic problems of acetazolamide or methazolamide. Several studies highlight the IOP-lowering efficacy of both dorzolamide and brinzola-mide.73'74 These medications can also be considered as first-line treatment for glaucoma. However, when compared to beta blockers and latanoprost, which can often be used once daily, topical CAIs require twice-daily or three-times-daily dosing.
Cholinergic agonists, dipivefrin, epinephrine, apraclonidine, and systemic CAIs have become less popular early in the course of glaucoma management because of their side effect profiles and dosing intervals. Combination agents are not usually considered for initial therapy unless urgent, significant IOP reduction in needed.
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