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COMPARISON OF ONCE- OR TWICE-DAILY BIMATOPROST WITH TWICE-DAILY TIMOLOL IN PATIENTS WITH ELEVATED IOP

2002; Volume: 3; Issue: 1 Linguagem: Inglês

10.1097/00132578-200201000-00019

1536-4836

Ronald L. Fellman,

Corneal surgery and disorders

Brandt J, VanDenburgh A, Chen K, et al. Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP. Ophthalmology 2001;108:1023–1032. Original study reprint requests: James D. Brandt, Department of Ophthalmology, University of California Davis, 4860 Y Street, Suite 2400, Sacramento, CA 95817–2307. Research Objective To compare the safety, tolerability, and efficacy of bimatoprost 0.03% instilled once daily or twice daily with timolol 0.5% twice daily. Study Design A multicenter, randomized, double-masked, interventional comparison trial. Locations Thirty centers within the United States, Australia, and New Zealand. Funding Source Allergan, Inc., Irvine, CA. Relevant Methodology Five hundred ninety-six patients who were diagnosed with ocular hypertension or glaucoma received bimatoprost 0.03% ophthalmic solution one daily (8 PM, with vehicle control at 8 AM), bimatoprost 0.03% twice daily (8 AM; 8 PM), or timolol 0.5% twice daily (8 AM; 8 PM) in an uneven 2:2:1 randomization. Scheduled visits were at prestudy, baseline (day 0), and weeks 2 and 6, and month 3. Intraocular pressure (IOP) was measured at 8 AM (predose), 10 AM, and 4 PM. Outcome Measures The primary outcome measure was reduction in IOP in the eye with higher IOP at baseline. Secondary outcome measures included safety variables (adverse events, ophthalmoscopy, biomicroscopy, iris pigmentation, laser-flare meter, visual acuity, visual fields, heart rate, blood pressure, blood chemistry, hematology and urinalysis. Results At the third month, the mean reduction in IOP from baseline at 8 AM was 9.16 mm Hg (35.2%) with bimatoprost once daily, 7.78 mmHg (30.4%) with bimatoprost twice daily, and 6.74 mmHg (26.2%) with timolol twice daily. At all of the follow-up visits, mean IOP reductions were significantly greater in the bimatoprost once-daily group than in the timolol group at each time point (8 AM, 10 AM, and 4 PM;p < 0.001). Twice-daily dosing of bimatoprost also provided significantly greater mean reductions in IOP than timolol at most time points but was not as effective as one-daily dosing. Bimatoprost was associated with significantly more burning and stinging sensation in eyes. Overall, bimatoprost was well tolerated with few discontinuations because of adverse events. Conclusions Bimatoprost 0.03% once daily was safe and statistically superior to timolol 0.5% twice daily in lowering IOP in patients with ocular hypertension or glaucoma. Bimatoprost given once daily consistently provided IOP reductions approximately 2 to 3 mmHg greater than those provided by timolol. Once-daily dosing of bimatoprost, 0.03%, demonstrated greater IOP-lowering effect and better ocular tolerability than twice-daily dosing. Comment The prostaglandin analogues continue to be the most potent group of topical pressure-lowering medications, outdistancing the time-honored beta-adrenergic blocking agents while maintaining a favorable safety/tolerability profile. In this well-designed randomized multicenter study, evening application of bimatoprost 0.03%, a prostamide, reduced IOP significantly better than twice-daily timolol 0.5%. An important contribution of this study is the comparison of once- to twice-daily bimatoprost. Many physicians and patients are used to the old habit of twice daily instillation of antiglaucoma agents. A previous study by Brubaker et al. 1 demonstrated a 12% to 14%increase in both day and nighttime aqueous production with this compound. Excessive use of these compounds may exacerbate IOP control. In this study, the once-daily regimen of bimatoprost was more effective than twice daily. Sixty-two percent of patients using once-daily bimatoprost achieved an IOP less than or equal to 16 mmHg compared to only 39.5% with twice-daily therapy. Significantly more patients discontinued twice-daily therapy (11% versus 6%). Ophthalmologists must maintain extra vigilance concerning the proper usage of uveoscleral-enhancing outflow drugs, instructing patients that twice-daily dosage (with the exception of unoprostone) is detrimental to optimal IOP control. Either dose of bimatoprost 0.03% was still superior to timolol at all time points. Response rates for a target IOP of less than or equal to 15 mmHg were significantly better with once-daily bimatoprost than with timolol (45% versus 24%). The AGIS 2 clearly demonstrates that aggressive IOP reduction is necessary to preserve the visual field of patients with significant optic nerve damage. Ophthalmologists are fortunate to have the addition of this powerful IOP-reducing drug. Systemic side effects are minimal, and ocular side effects are expected to be comparable to other prostaglandin-type drugs including conjunctival hyperemia, hyperpigmentation, and eyelash growth. The authors suggest a new mechanism of IOP reduction with this prostamide. Further independent biochemical research will further elucidate the mechanism of IOP reduction compared to other uveoscleral outflow agents. This is only a 3-month study, and reports of ongoing data will be especially helpful regarding the important long-term effects of this new potent drug.