Comparison of Intraocular Pressure-Lowering Effect of Every Night Versus Every Other Night Dosing of Bimatoprost 0.03%

Introduction

Glaucoma is the second leading cause of vision loss worldwide, ¹ affecting >2 million persons in the United States. ² Reduction of elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. Bimatoprost 0.03% (Lumigan^®; Allergan, Inc., Irvine, CA) is one of the prostaglandin analogs that are commonly used to reduce IOP.^3,4 It reduces the IOP by 6.5–8.9 mm Hg in patients with open-angle glaucoma or ocular hypertension when used once at night.^5–7 In a head-to-head randomized comparison of all 3 major prostanoid agents used for 6 months, Noecker and co-workers found a statistically significant advantage for bimatoprost over both latanoprost and travoprost. ⁸ Studies showed that there is a higher incidence of hyperemia with bimatoprost and travoprost than latanoprost ⁹ ; it also appears that a somewhat larger percentage of patients have troublesome local side effects with bimatoprost compared with latanoprost. ¹⁰ Conjunctival hyperemia is the most frequent adverse event of bimatoprost, affecting 45% of patients and accounting for discontinuation of therapy in 3% of patients. ¹¹

The authors switched patients who experienced troublesome side effects such as conjunctival hyperemia on bimatoprost 0.03% from every night (QHS) to every other night (QOD-HS) regimen as an alternative to discontinuation of the drop, switching the patient to a different medication and/or doing laser trabeculoplasty. In many instances, patients presented to the authors forgetting to use their bimatoprost the night before the visit without effect on the IOPs. This observation encouraged us to switch patients who complained about the bimatoprost-induced conjunctival hyperemia or irritation to QOD-HS regimen.

The aim of this study was to compare IOP reduction profiles of bimatoprost 0.03% administered every other night (QOD-HS) versus every night (QHS) in patients with primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG).

Methods

This is a retrospective chart review study that included all patients who were switched from QHS bimatoprost 0.03% to QOD-HS due to self-reported poor tolerance to the bimatoprost-related side effects between May 2002 and May 2005.

The poor tolerance to QHS bimatoprost 0.03% was due to troublesome side effects such as conjunctival hyperemia, ocular irritation, and/or periorbital discoloration.

Morning (AM) and afternoon (PM) IOPs were measured in patients on daily (QHS) bimatoprost, and were compared with the IOPs measured in the morning (AM) and afternoon (PM) of the day after administration (day 1) and the day after (day 2) on QOD-HS regimen. Each eye served as its own control. AM and PM IOPs on QOD-HS were measured 4–6 weeks after switching from bimatoprost QHS to QOD-HS.

Inclusion criteria included being treated with bimatoprost QHS for POAG or PXFG. Patients were excluded if they required a change in any of their other ocular hypotensive medications or had an intraocular surgery done during the follow-up period. Patients who reported noncompliance on were also excluded from the study.

The statistical analysis was performed using the Statistical Program for the Social Sciences Version 10.0 (SPSS, Inc., Chicago, IL).

Student's t-test was performed to compare the IOP at corresponding points of time (AM to AM and PM to PM) on bimatoprost 0.03% administered every other night (QOD-HS) versus every night (QHS).

The differences between the different groups were considered statistically significant if the P value was <0.05.

Institutional review board approval was not required for this study.

Results

The age and sex of the 45 patients were consistent with a glaucomatous population (Table 1).

Mean duration of using bimatoprost QHS was 552.2±473.9 days. The mean number of glaucoma medications used was 2±0.65. Eleven eyes were on bimatoprost monotherapy.

Mean IOPs on QHS bimatoprost were 15.9±3.4 mm Hg in the AM and 15.5±2.7 mm Hg in the PM, whereas mean IOPs on QOD-HS were 14±2 mm Hg (AM) and 14.2±2.5 mm Hg (PM) on day 1, and 14.7±2.6 mm Hg (AM) and 14.4±2.4 mm Hg (PM) on day 2 after administration.

The mean diurnal IOP on QHS bimatoprost was 15.7±2.7 mm Hg, whereas on QOD-HS it was 14.1±2.2 mm Hg day 1 (P=0.0001) and 14.6±2.3 mm Hg day 2 (P=0.04) after administration (Fig. 1).

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FIG. 1.

Intraocular pressure (IOP) on every night (QHS) versus every other night (QOD-HS) regimens at days 1 and 2 after administration. *Statistically significant lower IOP compared with the QHS regimen.

IOP in the AM after QOD-HS therapy was lower than the IOP in the AM after QHS by 2.18±2.9 mm Hg (P=0.00001), and on day 2 was lower in the AM by (1.3±3.2 mm Hg at P=0.01). PM IOP on QOD-HS regimen was lower than PM IOP on QHS by (1.5±3.3 mm Hg at P=0.004) in the day 1 and in the PM of the day 2 IOP was lower by (1±3.2 at P=0.04).

Difference between IOP fluctuation on QHS and QOD-HS days 1 and 2, respectively, were not significant (P=0.87 and 0.94).

Accordingly, there was a statistically significant difference between QHS and QOD-HS in favor of QOD-HS in the AM and PM of days 1 and 2 after administration.

All patients subjectively reported better tolerance to bimatoprost-induced hyperemia on QOD-HS regimen compared with QHS.

Discussion

Prostaglandin analogs are widely used as a first line of medical treatment for glaucoma and ocular hypertension because of their safety and efficacy, in addition to the convenience of using them once a day.

Review of literature showed that travoprost lowers the IOP significantly for up to 60 h after the last dose. ¹² From our daily clinical observations, we noticed that bimatoprost has an extended duration of action beyond 24 h. In many instances, patients presented to the authors forgetting to use their bimatoprost the night before the visit without effect on the IOPs. These observations encouraged us to switch patients who complained about the bimatoprost-induced conjunctival hyperemia or irritation to QOD-HS regimen.

This study demonstrated that patients switched from bimatoprost 0.03% QHS to QOD-HS regimen had statistically lower IOPs throughout days 1 and 2, without any significant difference in the diurnal IOP fluctuations on the 2 regimens.

Unlike most ocular hypotensive medications, more of prostaglandin analogs is not better. Prostaglandin analogs once daily dosage appears to be superior to twice daily.^13–15 A very recent study by Katz et al. showed that bimatoprost 0.01% was equivalent to bimatoprost 0.03% in lowering IOP and demonstrated improved tolerability, including less frequent and less severe conjunctival hyperemia, suggesting that 0.03% bimatoprost was probably toward the high end of the concentration curve required to achieve the therapeutic response. ¹⁶

Similarly, our study demonstrates that every other night bimatoprost 0.03% is more effective than every night bimatoprost 0.03%. This suggests that a lower dosage of bimatoprost can be as effective as or even more effective than the currently recommended daily dosage.

Conclusion

In this select group of patients with POAG and PXFG who had troublesome side effects on bimatoprost 0.03% QHS regimen, every other night dosing (QOD-HS) of bimatoprost 0.03% was effective in controlling IOP, and may be considered as an alternative to everyday treatment.

The small sample and the nonrandomized nature of the comparison are the main limitations of this study. Further work needs to be directed toward comparing lower doses of bimatoprost, for example, bimatoprost 0.01% daily versus bimatoprost 0.03% every other night.