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Lowering IOP With Medical Therapy in Patients With Glaucoma: First-Line Agents -- Prostaglandin Analogs


First-Line Agents -- Prostaglandin Analogs

Prostaglandins are the most commonly used first-line agents for IOP control. Other agents, including the beta-blockers (most commonly, timolol) and, less commonly used, the selective alpha-adrenergic agonist brimonidine and the topical anhydrase inhibitors brinzolamide and dorzolamide, are also approved for initial monotherapy. The beta-blockers in particular remain a cost-effective alternative with acceptable properties as initial therapy in selected patients. However, because these options are used less often than prostaglandins, we reserve our discussion of them for the second-line therapy discussion below.

Introduced in the United States in 1996, prostaglandins rapidly replaced topical beta-blockers as first-line IOP-lowering agents, mostly because of their potency, safe systemic side-effect profile, and once-daily dosing.[7-9] The 3 prostaglandins that are currently available in the United States are bimatoprost (0.03%), latanoprost (0.005%), and travoprost (0.004%). A reformulation of travoprost with a proprietary buffered ionic preservative system instead of benzalkonium chloride (BAK) has been introduced (Travatan Z; Alcon, Fort Worth, Texas).[10] A new formulation of bimatoprost 0.01% has been announced, but as of this writing, no data or clinical reports are available.

Prostaglandins reduce IOP by increasing outflow of aqueous humor mostly by enhancing the uveoscleral pathway. They have no effect on aqueous production. It is believed that prostaglandins improve the uveoscleral pathway by altering the ciliary body and scleral architecture, making it more amenable to aqueous egress through stimulation of collagenases and matrix metalloproteinases, and the relaxation of ciliary muscle bundles.[11,12] The exact mechanism of action, however, remains to be fully elucidated.

Strengths of Prostaglandins

Prostaglandins are the most potent topical agents for lowering IOP. In a recent meta-analysis of articles published up to 2003,[13] prostaglandins had the highest peak mean difference from baseline IOP compared with any other class of topical antiglaucoma agent. Their relative change from mean baseline at peak was 31% to 33% and at trough 28% to 29%; timolol peak and trough were 27% and 26%, respectively. Clinical trials comparing bimatoprost, latanoprost, and travoprost with timolol 0.5% used twice daily have been published.[7-9, 14] A 12-week trial comparing the prostaglandins themselves showed similar efficacy for all 3 agents.[15] Still, diversity in study design and patient population have made objective comparisons across studies difficult. As such, it is generally accepted that all 3 prostaglandins have similar efficacy, although some studies have shown small differences in IOP lowering.[16] Of note, individual patients may respond differently to drugs within this class.

Also, prostaglandins have not shown any significant measurable systemic side effects. Indeed, the lack of systemic side effects and the once-daily dosing, even more than the IOP potency, may be the main advantage of prostaglandins over topical beta-blockers in treating glaucoma.

Weaknesses of Prostaglandins

Although generally well tolerated, prostaglandins do have local side effects. The 3 agents share similar side effects, with variable frequencies, as reported in different studies.[15,16] Conjunctival hyperemia and irritation are the most common side effects, with bimatoprost and travoprost reported to have a slightly higher incidence of hyperemia than latanoprost. Newer formulations of bimatoprost (0.01%) and travoprost BAK-free may have a different incidence of topical side effects.

Prostaglandins can also cause noticeable changes in iris color, periocular skin pigmentation, and vellus hair growth and eyelashes. Iris color change is due to the increased melanin content of melanocytes with no other histopathologic changes. Although these changes are harmless and not a weakness per se, they should be discussed with patients upon initiation of treatment due to their aesthetic changes. The risk of developing uveitis with prostaglandins has been reported but remains low.[17] Studies[18,19] have not demonstrated an increase in cell or flare with chronic prostaglandin use, which should be reassuring to clinicians.

Table of Contents

  1. Introduction
  2. First-Line Agents -- Prostaglandin Analogs
  3. Concomitant Treatment of Glaucoma
  4. Fixed Combinations
  5. Conclusion
  • Print