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Comparison of the 24-h efficacy and safety of fixed combination carteolol/latanoprost and timolol/latanoprost in patients with primary open-angle glaucoma and ocular hypertension: a prospective crossover study



To evaluate the 24-h efficacy and safety of fixed combination carteolol/latanoprost (LCFC) and timolol/latanoprost (LTFC) in patients with primary open-angle glaucoma and ocular hypertension.

Study design

Prospective, randomized, crossover study


Twenty-two patients pretreated with a prostaglandin analog at baseline were randomly assigned at a 1:1 ratio to either LCFC or LTFC treatment. The patients received the assigned study drug in both eyes daily in the evening (20:00). Each treatment group crossed over after a 2-month treatment period. The 24-h curves of intraocular pressure (IOP), pulse rate, and blood pressure were evaluated. Safety was also assessed.


The changes in mean daytime IOP from baseline at the end of the 2-month treatment period in the LCFC and LTFC groups were  – 0.93 and  – 1.15 mmHg, respectively. The changes in peak IOP in the 2 groups were  – 0.91 and  – 0.68 mmHg, respectively. The nighttime pulse rate in the LCFC group increased; that in the LTFC group was lower at all time points. The changes in pulse rate from baseline at 22:00, 2:00, 4:00, and 6:00 differed statistically between the 2 groups. No differences in changes from baseline in systolic and diastolic blood pressures were found between the groups.


The 24-h IOP curve of patients in the LCFC group was similar to that of the LTFC group, but on the basis of the pulse rate findings, the effect of LCFC on the cardiovascular system over 24 h was less than that of LTFC.

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This study was funded by Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan. We thank Dr Tetsuji Asao (SunFlare Co., Ltd., Tokyo, Japan) for medical writing services. We also appreciate Mr Hidetoshi Uenaka for statistical analysis services, Mr Taishi Okamoto for EDC system development, and Ms Fumiko Okamoto—all of intellim Corporation Co., Ltd., Tokyo, Japan—for statistical analysis programing. The services provided by all of the aforementioned individuals were funded by Otsuka Pharmaceutical Co., Ltd.

Author information




M. Aihara, N. Kishimoto, and Y. Shibasaki developed the study concept and design. N. Kishimoto, and Y. Shibasaki wrote the protocol with supervision from M. Aihara and Y. Saito. Y. Saito as principal investigator, J. Kizaki, and Y. Wada enrolled the patients and conducted the study. N. Kishimoto supervised the monitoring activities performed by intellim Corporation Co., Ltd. Y. Shibasaki interpreted the data. All the authors critically reviewed the drafts and approved the final manuscript.

Corresponding author

Correspondence to Yuta Saito.

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Conflicts of interest

Y. Saito, Grant (Otsuka); J. Kizaki, Grant (Otsuka); Y. Wada, Grant (Otsuka); Y. Shibasaki, Employee (Otsuka); N. Kishimoto, Employee (Otsuka); M. Aihara, Grant (Otsuka).

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Corresponding Author: Yuta Saito

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Saito, Y., Kizaki, J., Wada, Y. et al. Comparison of the 24-h efficacy and safety of fixed combination carteolol/latanoprost and timolol/latanoprost in patients with primary open-angle glaucoma and ocular hypertension: a prospective crossover study. Jpn J Ophthalmol 65, 598–607 (2021).

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  • Carteolol/latanoprost
  • Cardiovascular effect
  • Fixed combination
  • Primary open-angle glaucoma
  • Timolol/latanoprost