The Effect of Fixed Combination of Brinzolamide 1% and Timolol 0.5% in Normal-Tension Glaucoma

Han Seok Park; Chul Young Choi; Jeong Hun Bae; Joon Mo Kim

doi:10.3341/jkos.2014.55.7.1056

Journal List > J Korean Ophthalmol Soc > v.55(7) > 1009729

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Park, Choi, Bae, and Kim: The Effect of Fixed Combination of Brinzolamide 1% and Timolol 0.5% in Normal-Tension Glaucoma

Original Article

J Korean Ophthalmol Soc 2014;55(7):1056-1063.

Published online: 30 August 2014

DOI: https://doi.org/10.3341/jkos.2014.55.7.1056

The Effect of Fixed Combination of Brinzolamide 1% and Timolol 0.5% in Normal-Tension Glaucoma

Han Seok Park, MD, Chul Young Choi, MD, Jeong Hun Bae, MD, Joon Mo Kim, MD

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

Address reprint requests to Joon Mo Kim, MD, Department of Ophthalmology, Kangbuk Samsung Hospital, #29 Saemunan-ro, Jongno-gu, Seoul 110-746, Korea, Tel: 82-2-2001-2250, Fax: 82-2-2001-2262 E-mail: kjoonmo1@gmail.com

Received 23 December 2013 Revised 16 April 2014 Accepted 24 June 2014

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

We conducted a study to evaluate the effects of brinzolamide/timolol fixed combination (BTFC) in normal-tension glaucoma (NTG) patients.

Methods

We reviewed the records of 33 normal-tension glaucoma patients treated with BTFC in the unilateral eye. We measured intraocular pressure (IOP) every 2 and 1/2 hours between 09:00 am and 04:30 pm. After using BTFC at 8:00 am and 8:00 pm for 6 months, we measured the IOP at the same time period. We analyzed and compared the IOP of eyes treated with BTFC and contralateral eyes.

Results

The mean reduction in IOP was −2.85 ± 1.43 mm Hg (-18.36 ± 8.58%) in the eyes treated with BTFC and −2.21 ± 1.73 mm Hg (-13.90 ± 10.66%) in the contralateral eyes. The IOP lowering effect was greater in the eyes treated with BTFC than in the contralateral eyes. After 6 months of BTFC instillation, the changes in IOP measurements were the lowest at 11:30 am and increased at each time point afterwards. The greatest reduction in IOP was observed at 1 month; however, significant IOP reduction was observed at 3 and 6 months in both BTFC and contralateral eyes. There was no serious adverse event causing ocular damage.

Conclusions

BTFC provided a significant IOP reduction in both BTFC and contralateral eyes in NTG patients.

Keywords: Brinzolamide, Fixed combination, Intraocular pressure, Normal-tension glaucoma, Timolol

References

1. Schulzer M. Intraocular pressure reduction in normal-tension glaucoma patients. The Normal Tension Glaucoma Study Group. Ophthalmology. 1992; 99:1468–70.

2. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002; 120:1268–79.

3. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002; 120:701–13. discussion 829-30.

4. Sacca SC, Rolando M, Marietta A, et al. Fluctuations of intraocular pressure during the day in open-angle glaucoma, normal-tension glaucoma and normal subjects. Ophthalmologica. 1998; 212:115–9.

5. De Vivero C, O'Brien C, Lanigan L, Hitchings R. Diurnal intraocular pressure variation in low-tension glaucoma. Eye (Lond). 1994; 8(Pt 5):521–3.

6. David R, Zangwill L, Briscoe D, et al. Diurnal intraocular pressure variations: an analysis of 690 diurnal curves. Br J Ophthalmol. 1992; 76:280–3.

7. Kano K, Kuwayama Y. Diurnal variation of intraocular pressure in normal-tension glaucoma. Nihon Ganka Gakkai Zasshi. 2003; 107:375–9.

8. Wilensky JT, Gieser DK, Dietsche ML, et al. Individual variability in the diurnal intraocular pressure curve. Ophthalmology. 1993; 100:940–4.

9. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001; 108:1943–53.

10. Bron A, Baudouin C, Denis P, et al. Satisfaction and compliance of ocular hypertensive and glaucoma patients topically treated with a combination therapy. J Fr Ophtalmol. 2008; 31:659–65.

11. Anderson DR, Drance SM, Schulzer M. Natural history of normal-tension glaucoma. Ophthalmology. 2001; 108:247–53.

12. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998; 126:487–97.

13. Cartwright MJ, Anderson DR. Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma). Arch Ophthalmol. 1988; 106:898–900.

14. Crichton A, Drance SM, Douglas GR, Schulzer M. Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma. Ophthalmology. 1989; 96:1312–4.

15. Kaback M, Scoper SV, Arzeno G, et al. Intraocular pressure-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination compared with brinzolamide 1% and timolol 0.5%. Ophthalmology. 2008; 115:1728–34. 34 e1-2.

16. Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzo- lamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2009; 18:293–300.

17. Oh JY, Park KH. The effect of latanoprost on intraocular pressure during 12 months of treatment for normal-tension glaucoma. Korean J Ophthalmol. 2005; 19:297–301.

18. Cho SW, Kim JM, Park KH, Choi CY. Effects of brimonidine 0.2%-timolol 0.5% fixed-combination therapy for glaucoma. Jpn J Ophthalmol. 2010; 54:407–13.

19. Suh MH, Park KH, Kim DM. Effect of travoprost on intraocular pressure during 12 months of treatment for normal-tension glaucoma. Jpn J Ophthalmol. 2009; 53:18–23.

20. Kim TW, Kim M, Lee EJ, et al. Intraocular Pressure-lowering Efficacy of Dorzolamide/Timolol Fixed Combination in Normal- tension Glaucoma. J Glaucoma. 2014; 23:329–32.

21. Kim NJ, Lee SM, Park KH, Kim DM. Factors associated with pro- gression of visual field defect in normal tension glaucoma. J Korean Ophthalmol Soc. 2003; 44:1351–5.

22. Han ES, Kim MJ, Park KH. The relationship between intraocular pressure and visual field defect progression in normal-tension glaucoma. J Korean Ophthalmol Soc. 2009; 50:1548–54.

23. Jonas JB, Budde W, Stroux A, et al. Single intraocular pressure measurements and diurnal intraocular pressure profiles. Am J Ophthalmol. 2005; 139:1136–7.

24. Zimmerman TJ, Kaufman HE. Timolol. A beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977; 95:601–4.

25. Drance SM. The uniocular therapeutic trial in the management of elevated intraocular pressure. Surv Ophthalmol. 1980; 25:203–5.

26. Kwitko GM, Shin DH, Ahn BH, Hong YJ. Bilateral effects of long-term monocular timolol therapy. Am J Ophthalmol. 1987; 104:591–4.

27. The Glaucoma Laser Trial: 4. Contralateral effects of timolol on the intraocular pressure of eyes treated with ALT. GLT Research Group. Ophthalmic Surg. 1991; 22:324–9.

28. Martin XD, Rabineau PA. Intraocular pressure effects of timolol after unilateral instillation. Ophthalmology. 1988; 95:1620–3.

29. Piltz J, Gross R, Shin DH, et al. Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study. Am J Ophthalmol. 2000; 130:441–53.

30. Bartels SP. Aqueous humor flow measured with fluorophotometry in timolol-treated primates. Invest Ophthalmol Vis Sci. 1988; 29:1498–504.

31. Dunham CN, Spaide RF, Dunham G. The contralateral reduction of intraocular pressure by timolol. Br J Ophthalmol. 1994; 78:38–40.

32. Huupponen R, Kaila T, Salminen L, Urtti A. The pharmacokinetics of ocularly applied timolol in rabbits. Acta Ophthalmol (Copenh). 1987; 65:63–6.

33. Lutjen-Drecoll E, Kaufman PL, Eichhorn M. Long-term timolol and epinephrine in monkeys. I. Functional morphology of the ciliary processes. Trans Ophthalmol Soc U K. 1986; 105(Pt 2):180–95.

34. Lutjen-Drecoll E, Kaufman PL. Long-term timolol and epinephrine in monkeys. II. Morphological alterations in trabecular meshwork and ciliary muscle. Trans Ophthalmol Soc U K. 1986; 105(Pt 2):196–207.

35. Saari KM, Ali-Melkkila T, Vuori ML, et al. Absorption of ocular timolol: drug concentrations and beta-receptor binding activity in the aqueous humour of the treated and contralateral eye. Acta Ophthalmol (Copenh). 1993; 71:671–6.

36. Radius RL, Diamond GR, Pollack IP, Langham ME. Timolol. A new drug for management of chronic simple glaucoma. Arch Ophthalmol. 1978; 96:1003–8.

37. Gibbens MV. The consensual ophthalmotonic reaction. Br J Ophthalmol. 1988; 72:746–9.

38. Sherwood MB, Craven ER, Chou C, et al. Twice-daily 0.2% brimo- nidine-0.5% timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial. Arch Ophthalmol. 2006; 124:1230–8.

Figure 1.

Diurnal intraocular pressure of Brinz/Tim eye and contralateral eye at baseline and month 6. Brinz/Tim = brinzolamide 1% + timolol 0.5% eye drops.

Figure 2.

Mean intraocular pressure of Brinz/Tim eye and contralateral eye at each visit point. Brinz/Tim = brinzolamide 1% + timolol 0.5% eye drops.

Table 1.

Mean baseline and month 6 IOP (mm Hg) in Brinz/Tim and contralateral eye

	Baseline	Month 6	Difference (%)	p-value^*
Brinz/Tim eye
Mean IOP	15.33 ± 2.22	12.48 ± 2.03	-2.85 ± 1.43 (-18.36 ± 8.58%)	<0.001
09:00 hour	15.42 ± 2.62	12.48 ± 2.64	-2.94 ± 1.95 (-18.66 ± 12.51%)	<0.001
11:30 hour	15.45 ± 2.15	12.36 ± 2.30	-3.09 ± 1.96 (-19.77 ± 11.67%)	<0.001
14:00 hour	15.09 ± 2.30	12.67 ± 2.15	-2.42 ± 1.68 (-15.69 ± 10.60%)	<0.001
16:30 hour	15.33 ± 2.27	12.39 ± 1.82	-2.94 ± 1.70 (-18.62 ± 9.16%)	<0.001
IOP maximum	16.21 ± 2.37	13.55 ± 2.36	-2.67 ± 1.71 (-16.22 ± 10.08%)	<0.001
IOP minimum	14.61 ± 2.41	11.52 ± 1.97	-3.09 ± 1.77 (-20.48 ± 10.82%)	<0.001
IOP fluctuation	1.61 ± 1.00	2.03 ± 1.13	+0.42 ± 1.42 (+48.44 ± 100.27%)	0.095
Contralateral eye
Mean IOP	15.23 ± 2.33	13.02 ± 2.05	-2.21 ± 1.73 (-13.90 ± 10.66%)	<0.001
09:00 hour	15.33 ± 2.83	13.15 ± 2.64	-2.18 ± 2.40 (-13.03 ± 15.75%)	<0.001
11:30 hour	15.45 ± 2.54	12.94 ± 2.41	-2.52 ± 2.33 (-15.42 ± 13.93%)	<0.001
14:00 hour	15.00 ± 2.40	13.03 ± 1.96	-1.97 ± 1.99 (-12.19 ± 12.40%)	<0.001
16:30 hour	15.15 ± 2.12	12.97 ± 1.94	-2.18 ± 1.72 (-13.87 ± 10.48%)	<0.001
IOP maximum	16.18 ± 2.44	14.12 ± 2.34	-2.06 ± 1.73 (-12.35 ± 10.22%)	<0.001
IOP minimum	14.36 ± 2.46	12.09 ± 2.08	-2.27 ± 2.28 (-14.52 ± 14.93%)	<0.001
IOP fluctuation	1.82 ± 1.31	2.03 ± 1.16	+0.21 ± 2.01 (+35.52 ± 114.40%)	0.549

Values are presented as mean ± SD.

IOP = intraocular pressure; Brinz/Tim = brinzolamide 1% + timolol 0.5% eye drops.

^* Paired t-test.

Table 2.

Mean IOP (mm Hg) changes according to the time interval from baseline to month 6

	Baseline-month 1	Baseline-month 3	Baseline-month 6
Brinz/Tim eye	-1.48 ± 1.84	-2.24 ± 2.53	-2.85 ± 1.43
p-value^*	<0.001	<0.001	<0.001
Contralateral eye	-0.93 ± 2.03	-1.57 ± 2.47	-2.21 ± 1.73
p-value^*	0.013	0.001	<0.001

Values are presented as mean ± SD.

IOP = intraocular pressure; Brinz/Tim = brinzolamide 1% + timolol 0.5% eye drops.

^* Paired t-test.

Table 3.

Mean IOP (mm Hg) of Brinz/Tim and contralateral eyes showing high correlation between fellow eyes

IOP	Baseline			Month 6
IOP	Brinz/Tim eye	Contralateral eye	r^2*	Brinz/Tim eye	Contralateral eye	r²
Mean	15.33 ± 2.22	15.23 ± 2.33	0.934	12.48 ± 2.03	13.02 ± 2.05	0.876
09:00 hr	15.42 ± 2.62	15.33 ± 2.83	0.912	12.48 ± 2.64	13.15 ± 2.64	0.806
11:30 hr	15.45 ± 2.15	15.45 ± 2.54	0.829	12.36 ± 2.30	12.94 ± 2.41	0.769
14:00 hr	15.09 ± 2.30	15.00 ± 2.40	0.888	12.67 ± 2.15	13.03 ± 1.96	0.813
16:30 hr	15.33 ± 2.73	15.15 ± 2.12	0.861	12.39 ± 1.82	12.97 ± 1.94	0.835
Maximum	16.21 ± 2.37	16.18 ± 2.44	0.831	13.55 ± 2.36	14.12 ± 2.34	0.827
Minimum	14.61 ± 2.41	14.36 ± 2.46	0.918	11.52 ± 1.97	12.09 ± 2.08	0.734

Values are presented as mean ± SD.

IOP = intraocular pressure; Brinz/Tim = brinzolamide 1% + timolol 0.5% eye drops.

^* Linear regression analysis.

TOOLS

Similar articles