The Effect of a Fixed Combination of 0.0015% Tafluprost-0.5% Timolol in Normal Tension Glaucoma Patients

Dae Hwan Shin; Jeong Hun Bae; Joon Mo Kim

doi:10.3341/jkos.2018.59.8.752

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Shin, Bae, and Kim: The Effect of a Fixed Combination of 0.0015% Tafluprost-0.5% Timolol in Normal Tension Glaucoma Patients

Original Article

J Korean Ophthalmol Soc 2018;59(8):752-759.

Published online: 25 September 2018

DOI: https://doi.org/10.3341/jkos.2018.59.8.752

The Effect of a Fixed Combination of 0.0015% Tafluprost-0.5% Timolol in Normal Tension Glaucoma Patients

Dae Hwan Shin, MD, Jeong Hun Bae, MD, PhD, Joon Mo Kim, MD, PhD

Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Address reprint requests to Joon Mo Kim, MD, PhD Department of Ophthalmology, Kangbuk Samsung Hospital, #29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea Tel: 82-2-2001-2250, Fax: 82-2-2001-2262 E-mail: kjoonmo1@gmail.com

Received 12 April 2018 Revised 28 May 2018 Accepted 27 July 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

This study evaluated the effect of a fixed combination of 0.0015% tafluprost-0.5% timolol (Tapcom^®, Santen, Osaka, Japan) in glaucoma patients.

Methods

This study included 23 patients who were diagnosed with normal tension glaucoma and treated with a fixed combination of 0.0015% tafluprost-0.5% timolol as the first therapy. Diurnal intraocular pressure (IOP) was measured every 2 and 0.5 hours between 9:00 am and 4:30 pm. The IOP change with respect to body position (positional IOP) was measured at baseline and at 6 months after eye-drop instillations. IOP fluctuation was defined as the standard deviation of IOP measurements. Throughout the study, all side effects were recorded and monitored by the investigators.

Results

The mean reduction in IOP in the 0.0015% tafluprost-0.5% timolol fixed combination-treated eyes was −3.37 ± 2.39 mmHg (−19.70 ± 13.97%) for the right eye and −3.22 ± 2.27 mmHg (−18.81 ± 13.28%) for the left eye (paired t-test, p < 0.001). The mean positional IOP measured at 4 pm at 6 months after 0.0015% tafluprost-0.5% timolol fixed combination instillation showed statistically significant reduction from the mean positional IOP at baseline. There was a significant difference in the number of patients with ≤3 mmHg IOP variation over four time points between baseline and at 6 months in the 0.0015% tafluprost-0.5% timolol fixed combination-treated eyes (McNemar test, p < 0.001). There was no serious adverse event causing ocular damage.

Conclusions

Use of 0.0015% tafluprost-0.5% timolol fixed combination was effective and well tolerated in reducing IOP and in maintaining its effectiveness in glaucoma patients.

Keywords: Fixed combination, Glaucoma, Tafluprost, Timolol

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Figure 1.

Mean intraocular pressure changes after 0.0015% ta-fluprost-0.5% timolol fixed combination instillation according to the time interval from baseline to month 6. The mean intraocular pressure at 1, 3, 6 months after 0.0015% tafluprost-0.5% timolol fixed combination instillation showed statistically significant reduction from the mean intraocular pressure at baseline.

Table 1.

Profile and demographics of the patients (n = 23)

Number of final patients used TTFC	Value
Mean age (years)	57.30 ± 12.09
Sex (male:female) (n, %)	18 (78.26):5 (21.74)
DM (n, %)	4 (17.39)
HTN (n, %)	8 (34.78)

Values are presented as mean ± standard deviation or n (%) unless otherwise indicated.

TTFC= tafluprost 0.0015%/timolol 0.5% fixed combination; DM = diabetes mellitus; HTN = hypertension.

Table 2.

Intraocular pressure (IOP) changes at 6 months after 0.0015% tafluprost-0.5% timolol fixed combination instillation from baseline

Diurnal IOP	IOP (mmHg)		Measured IOP chan (mmHg)	p-value^*
Diurnal IOP	At baseline	At 6 months after eye-drop instillation	Measured IOP chan (mmHg)	p-value^*
Right eye (n = 23)
9:00 am	17.65 ± 2.53	13.91 ± 2.64	3.74 (20.48%)	<0.001
11:30 am	17.39 ± 2.92	13.87 ± 2.65	3.52 (19.49%)	<0.001
2:00 pm	17.09 ± 2.73	13.43 ± 1.80	3.65 (19.68%)	<0.001
4:30 pm	16.30 ± 3.02	13.70 ± 1.79	2.61 (13.13%)	0.002
Mean	17.11 ± 2.42	13.74 ± 1.89	3.37 (19.70%)	<0.001
IOP fluctuation (Highest IOP-Lowest IOP)	3.30 ± 1.79	2.65 ± 1.47	–	0.203
Left eye (n = 23)
9:00 am	17.83 ± 2.50	14.30 ± 2.05	3.52 (18.44%)	<0.001
11:30 am	17.04 ± 2.75	14.17 ± 2.29	2.87 (15.78%)	<0.001
2:00 pm	17.13 ± 2.28	13.61 ± 1.70	3.52 (19.40%)	<0.001
4:30 pm	16.48 ± 2.97	13.74 ± 2.00	2.74 (14.49%)	<0.001
Mean	17.12 ± 2.21	13.90 ± 1.73	3.22 (18.81%)	<0.001
IOP fluctuation (Highest IOP-Lowest IOP)	3.39 ± 1.78	2.39 ± 1.50	–	0.070

Values are presented as mean ± standard deviation or n (%) unless otherwise indicated.

% = percentage changes from baseline.

^* Analyzed with the paired t-test.

Table 3.

Positional intraocular pressure (IOP) changes at 6 months after 0.0015% tafluprost-0.5% timolol fixed combination instillation from baseline (at 4:30 pm)

Position	IOP (mmHg)		Measured IOP change (mmHg)	p-value^*
Position	At baseline	At 6 months after eye-drop instillation	Measured IOP change (mmHg)	p-value^*
Right eye (n = 14)
Sitting	16.75 ± 1.40	13.36 ± 1.78	3.29 (18.81%)	0.001
Supine	18.64 ± 2.06	15.14 ± 2.45	3.20 (16.14%)	0.002
Right decubitus	19.41 ± 2.16	15.86 ± 2.74	3.13 (15.51%)	0.001
Left decubitus	17.91 ± 2.22	13.79 ± 1.76	3.87 (20.63%)	<0.001
Mean	18.18. ± 2.29	14.54 ± 2.39	3.39 (18.06%)	<0.001
Left eye (n = 14)
Sitting	17.06 ± 2.22	13.36 ± 1.60	3.77 (21.20%)	<0.001
Supine	18.50 ± 2.52	15.43 ± 2.68	3.05 (15.26%)	0.004
Right decubitus	17.88 ± 2.34	13.93 ± 2.06	3.88 (21.10%)	<0.001
Left decubitus	19.44 ± 2.44	16.29 ± 2.16	2.92 (14.74%)	0.006
Mean	18.22 ± 2.49	14.75 ± 2.41	3.47 (17.85%)	<0.001

Values are presented as mean ± standard deviation or n (%) unless otherwise indicated.

% = percentage changes from baseline.

^* Analyzed with the paired t-test.

Table 4.

Intraocular pressure (IOP) fluctuation change after 0.0015% tafluprost-0.5% timolol fixed combination instillation from baseline to month 6

Instilled eye (n = 46) IOP fluctuation	Baseline (n)	Month 6 (n)	p-value <0.001^*
≤3 mmHg	24	39
>3 mmHg	22	7

^* Analyzed with McNemar test.

Table 5.

Mean intraocular pressure (IOP) changes after 0.0015% tafluprost-0.5% timolol fixed combination instillation according to the time interval from baseline to month 6

	Baseline– Month 1	Month 1– Month 3	Month 3– Month 6	Month 1– Month 6
Right eye (n = 15)	−3.62 ± 0.85	0.53 ± 0.67	−0.13 ± 0.67	0.40 ± 0.41
p-value^*	0.001^*	0.438	0.846	0.341
Left eye (n = 15) p-value^*	−3.53 ± 0.80 0.001^*	0.27 ± 0.42 0.535	−0.06 ± 0.53 0.906	0.20 ± 0.49 0.683

Values are presented as mean ± standard deviation unless otherwise indicated.

^* Analyzed with the paired t-test, Bonferroni corrected.

Table 6.

Frequency and incidence of patients with adverse drug reactions

Patients with adverse drug reactions^*	Value
Pruritis	1 (4.35)
Burning sensation	1 (4.35)
Ocular hyperemia	2 (8.70)
Total	4 (17.39)

Values are presented as n (%).

^* ‘Adverse drug reaction’ means ‘treatment-related adverse event’.

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