Stratification-Based Investigation of Adjunctive Brimonidine or Timolol to a Prostaglandin Analogue in Japanese Patients with Normal-Tension Glaucoma

Abstract

Purpose

We previously investigated the efficacy and safety of adding 0.1% brimonidine (Brim) or 0.5% timolol (Tim) to prostaglandin analogue (PGA) monotherapy to treat patients with normal-tension glaucoma (NTG) with intraocular pressure (IOP) of ≤16 mmHg. Herein, we describe an additional post-hoc stratifying analysis of the possible differences in the effect of IOP-lowering and pulse rate (PR) after adjunctive Brim or Tim to PGA.

Patients and Methods

This study included 128 subjects. Patients with NTG treated with PGA were stratified based on their baseline IOP. The changes in IOP from baseline and the effect of patient factors on IOP changes were investigated. Patients were stratified by age for investigation of their PR and blood pressure (BP). The change and the effect of patient factors on PR and BP were investigated.

Results

After stratification analysis, in 52 eyes treated with Brim and 61 eyes with Tim with baseline IOP 12 ≤ IOP ≤ 16 mmHg, both eye drops lowered IOP significantly (P < 0.0001), and the IOP-lowering efficacy of Brim was non-inferior to that of Tim. However, in 9 Brim- and 6 Tim-treated eyes with baseline IOP of <12 mmHg, no statistically significant decrease in IOP was evident with either eye drop. In the Tim group, PR decreased significantly (P < 0.05) after stratification by age.

Conclusion

The IOP-lowering efficacy of Brim was non-inferior to that of Tim after stratification by baseline IOP (12 ≤ IOP ≤ 16 mmHg). The discrepancy in the IOP-lowering effects of Brim and Tim observed in the previous study was thought to be related to enrolled subjects with low baseline IOP. PR decreased significantly in the Tim group even after age stratification. PR should be considered when selecting β-blockers for glaucoma treatment.

Keywords:

• adjunctive therapy
• brimonidine
• intraocular pressure reduction
• post-hoc analysis
• pulse rate
• timolol

Data Sharing Statement

The datasets generated during the current study are available from the corresponding author on reasonable request.

Acknowledgments

The authors thank Motohiro Shirakashi, Akiyoshi Nitta, Shigeki Yamabayashi, Tairo Kimura, and Toshihiko Ueda for collecting data for this study.

Disclosure

Keiji Yoshikawa, Shiro Mizoue, Koji Nitta, and Shun Matsumoto have received personal fees and grants from Senju Pharmaceutical Co., Ltd. Keiji Yoshikawa also reports lecture fees from Santen Pharm. Co. Ltd., Crewt Medical, RE Medical, Ellex Co. Ltd., Otsuka Pharm. Co. Ltd., Kowa, Alcon, and Pfizer, during the conduct of the study. Shiro Mizoue also reports lecture fees from Santen Pharm. Co. Ltd., Otsuka Pharm. Co. Ltd., Ellex Co. Ltd., Kowa, and Novartis Pharma. Co. Ltd., during the conduct of the study. Koji Nitta also reports lecture fees from Santen Pharm. Co. Ltd., RE Medical, Ellex Co. Ltd., Otsuka Pharm. Co. Ltd., Kowa, Alcon, NIDEK Co. Ltd., and Novartis Pharma. Co. Ltd., during the conduct of the study. Ryuji Takeda has received personal fees from Senju Pharmaceutical Co., Ltd. Hiroshi Onishi, Masaharu Ikeda, Akemi Mizuno, Kaori Kawazoe, and Yoshiyuki Tamada are employees of Senju Pharmaceutical Co., Ltd. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Senju Pharmaceutical Co., Ltd.