Comparative Evaluation of the Efficacy of the Bimatoprost 0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide 2%, and Travoprost 0.004%/Timolol 0.5%-Fixed Combinations in Patients Affected by Open-Angle Glaucoma

doi:10.4236/ojoph.2012.24027

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http://dx.doi.org/10.4236/ojoph.2012.24027 Published Online November 2012 (http://www.SciRP.org/journal/ojoph)

Comparative Evalua tion of the Efficacy of the Bimatoprost

0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide

2%, and Travoprost 0.004%/Timolol 0.5%-Fixed

Combinations in Patients Affected by Open-Angle

Glaucoma*

Italo Giuffre

Department of Ophthalmology, Medical School, Catholic University of Rome, Rome, Italy.

Email: [email protected]

Received July 20th, 2012; revised September 22nd, 2012; accepted October 30th, 2012

ABSTRACT

Purpose: This is a retrospective, comparative, head-to-head, not commissioned study about the efficacy of bimatoprost

0.03%, brimonidine 0.2%, brinzolamide 1%, dorzolamide 2%, and travoprost 0.004%/timolol 0.5%-fixed combinations

in patients affected by naΐve open-angle glaucoma and IOP > 25 mmHg. Patients and Methods: Files from 70 patients

(35 M, 35 F, mean age 69.52 y, S.D. 11.56, range: 37 - 87 y) in our Glaucoma Service were retrospectively analyzed as

long as 12 months. Every subgroup, including 14 age- and sex-matched patients, was allocated to 1 of the 5 groups of

the fixed combinations monotherapy. Data recorded after 3 months follow-up were statistically analyzed by descriptive

and ANOVA statistics as percentage of IOP reduction from baseline. Results: All the fixed combinations were effective

in lowering IOP. The mean percentage reduction was: brimonidine/timolol 43.57%, dorzolamide/timolol 37.67%, bi-

matoprost/timolol 35.60%, travoprost/timolol 33.25% and brinzolamide/timolol 23.0%. The brimonidine/timolol fixed

combination showed to be statistically significant more effective only than brinzolamide/timolol fixed combination (p =

0.001). Setting the α error to 5%, the power of the study is 26%, phi: 0.842. Discussion: In all this cohort of patients the

target IOP was successfully achieved. All the fixed combinations used in this study had a very good profile of efficacy.

Brimonidine, dorzolamide, bimatoprost and travoprost/timolol fixed combinations statistically significantly reduced the

percentage of IOP from baseline (p = 0.001) more than brinzolamide/timolol fixed combination.

Keywords: Bimatoprost 0.03%; Brimonidine 0.2%; Brinzolamide 1%; Dorzolamide 2%, Travoprost 0.004%/Timolol

0.5% Fixed Combinations; Efficacy; IOP

1. Introduction

Glaucoma is a progressive, and potentially blinding, op-

tic neuropathy. The aetiology of glaucoma is multifacto-

rial, but, to date, reduction of intraocular pressure (IOP)

is the only evidence-based therapy for glaucoma. IOP

reduction is achieved by the use of topical medications

[1].

Fixed combinations of IOP-lowering medications have

been developed by combining different pharmacologic

classes of ocular hypotensive drugs commonly pre-

scribed for the treatment of elevated IOP in patients af-

fected by open-angle glaucoma or ocular hypertension.

Modern fixed combinations pair beta-adrenoceptor an-

tagonists (beta-blocker) with either prostaglandin analogs

or carbonic anhydrase inhibitors. Potential benefits of

fixed combinations include better compliance, reduction

in exposure to preservatives, and elimination of the wash-

out effect.

The first fixed combination was produced by Merck

Sharp & Dohme Inc. (White-House Station, NJ, USA):

2% dorzolamide-0.5% timolol (DTFC, Cosopt®). A new

fixed combination of the carbonic anhydrase inhibitor

brinzolamide 1% and timolol 0.5% (BRINTFC, Azarga®)

has been developed after 0.004% travoprost-0.5% ti-

molol (TRAVOTFC, Duotrav®) (Alcon Research, Ltd.,

Ft. Worth, Texas, USA). Other fixed combinations pro-

duced and commercialized by Allergan are 0.2% bri-

monidine-0.5% timolol (BRIMOTFC, Combigan®) and

0.03% bimatoprost-0.5% timolol (BIMATOFC, Ganfort®).

*Financial disclosure: The author has no proprietary or commercial

interest in any materials discussed in this article.

Comparative Evaluation of the Efficacy of the Bimatoprost 0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide

2%, and Travoprost 0.004%/Timolol 0.5%-Fixed Combinations in Patients Affected by Open-Angle Glaucoma

123

Different studies stress the efficacy and safety of

BRIMOTFC versus the unfixed components or another

fixed combination [2-9]. Other papers underline the effi-

cacy and safety of DTFC, even three times a day [10-18].

BRINTFC was recently compared to DTFC. Mostly 1%

brinzolamide-0.5% timolol ophthalmic suspension is

associated with a statistically significantly less ocular

discomfort profile than 2% dorzolamide-0.5% timolol

ophthalmic solution [19-22]. BIMATOFC was compared

to 0.03% bimatoprost [23]. The fixed combination pro-

vided an additional statistically significant reduction in

IOP [24,25]. TRAVOTFC and BIMATOFC were com-

pared to 0.005% latanoprost-0.5% timolol [26-29].

TRAVOTFC offers the potential benefits of increased

patient adherence, reduced exposure to preservatives (now

BAK-free), and reduced cost [30-38]. The aim of this

study is to compare the efficacy of these fixed combina-

tions.

2. Patients and Methods

This is a retrospective, comparative, head-to-head, not

commissioned study on Caucasian outpatients, affected

by naΐve open-angle glaucoma, who were assessed in our

Glaucoma Service in the last 12 months from 01-01-2011

till 12-31-2011. Inclusion criteria were: diagnosis of open-

angle glaucoma based on the European Glaucoma So-

ciety Guidelines criteria [39] with IOP > 25 mmHg, me-

dical therapy by only one fixed combination previously

cited in the worst eye. Exclusion criteria included: con-

traindications to β-blockers; closed or barely open ante-

rior chamber angles; ocular surgery or argon laser trabe-

culoplasty; ocular inflammation or infection; neovascular

patients; hypersensitivity to benzalkonium chloride (BAK)

or to any other fixed combination or any other component

of the solutions; any history of refractive surgery, preg-

nancy, breastfeeding, or childbearing potential without

adequate contraception. All patients included in their files:

uncorrected and corrected visual acuity, baseline IOP >

25 mmHg measured by Goldmann applanation tonometry,

adjusted by pachymetry, diurnal tonometric curve, fun-

dus oculi, 30-2 Sita standard Humphrey visual field ana-

lyzer including visual field index, HRT and OCT. Main

outcome of this paper is to measure the percentage of

IOP reduction at 10 am ± 1 hour due to each fixed com-

bination after three months from baseline. All data were

analyzed by descriptive and ANOVA statistical analysis.

3. Results

A total of 70 files from patients in the Glaucoma Service

(35 M, 35 F, mean age 69.52 years, S.D. 11.56, range: 37

- 87 years) (Table 1) matched the inclusion criteria and

were analyzed. These glaucoma patients were originally

naïve with IOP > 25 mmHg. We enrolled 14 patients

who were treated with one of the following fixed combi-

nations: bimatoprost 0.03% plus timolol 0.5% (Group A),

brimonidine 0.2% plus timolol 0.5% (Group B), brinzo-

lamide 1% plus timolol 0.5% (Group C), dorzolamide

2% plus timolol 0.5% (Group D), and travoprost 0.004%

plus timolol 0.5% (Group E) (Table 2). In all patients,

after three months follow-up, IOP was lower than 18

mmHg and no patient discontinued the therapy or needed

laser- or surgical therapy. Table 3 shows the mean per-

centage of IOP reduction from baseline due to any fixed

combination used: Group B (brimonidine 0.2% plus ti-

molol 0.5%, BRIMOTFC) 43.57%, Group D (DTFC)

37.67%, Group A (bimatoprost 0.03% plus timolol 0.5%,

BIMATOFC) 35.60%, Group E (travoprost 0.004% plus

timolol 0.5% (TRAVOTFC) 33.25%, and Group C

(brinzolamide 1% plus timolol 0.5%, BRINTFC) 23.0%.

The ANOVA test was not statistically significant be-

tween Group B and D (BRIMOTFC and DTFC) (p =

0.053), Group B and A (BRIMOTFC and BIMATOFC)

(p = 0.221), Group B and E (BRIMOTFC and TRAVOTFC)

(p = 0.167) but statistically significant between Group B

and C (BRIMOTFC and BRINTFC) (p = 0.001) (Table

4). Setting the α error to 5%, the power of this study is

26%, phi: 0.842.

4. Discussion

This is the first paper in the Literature to compare these

fixed combinations all together. All the data were age-

and sex-matched, so there is no gender difference in the

efficacy of drug combination. The results of this retro-

spective study clearly show the great efficacy of the fixed

combinations used, mostly brimonidine 0.2%-timolol

Table 1. Demographics.

PATIENTSMALEFEMALEMEAN AGE S.D.RANGE

70 35 35 69.52 y 11.5637 - 87 y

Table 2. Fixed combinations (Number of patients).

GROUP A BIMATOPROST 0.03%-TFC 14

GROUP B BRIMONIDINE 0.2%-TFC 14

GROUP C BRINZOLAMIDE 1%-TFC 14

GROUP D DTFC 14

GROUP E TRAVOPROST 0.004%-TFC 14

TOTAL 70

Legenda: DTFC: dorzolamide 2% timolol 0.5% fixed combination; TFC:

timolol 0.5% fixed combination.

Comparative Evaluation of the Efficacy of the Bimatoprost 0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide

2%, and Travoprost 0.004%/Timolol 0.5%-Fixed Combinations in Patients Affected by Open-Angle Glaucoma

124

Table 3. Results (% of IOP reduction).

BRIMONIDINE 0.2%-TFC (GROUP B) 43.57

DORZOLAMIDE 2%-TFC (GROUP D) 37.67

BIMATOPROST 0.03%-TFC (GROUP A) 35.60

TRAVOPROST 0.004%-TFC (GROUP E) 33.25

BRINZOLAMIDE 1%-TFC (GROUP C) 23.0

Legenda: TFC: timolol 0.5% fixed combination.

Table 4. Results.

BRIMONIDINE 0.2%-TFC

DORZOLAMIDE 2%-TFC

P = 0.053

BRIMONIDINE 0.2%-TFC

BIMATOPROST 0.003%-TFC

P = 0.221

BRIMONIDINE 0.2%-TFC

TRAVOPROST 0.004%-TFC

P = 0.167

BRIMONIDINE 0.2%-TFC

BRINZOLAMIDE 1%-TFC

P = 0.001

Legenda: TFC: timolol 0.5% fixed combination.

0.5% fixed combination (Table 4). All the mean per-

centage reduction after three months follow-up, due to

these drugs, was not statistically significant, apart from

brinzolamide 1%-timolol 0.5% fixed combination. This

fixed combination was commercialized later and it has a

good comfort profile in almost all the patients treated but,

maybe, less IOP-lowering efficacy. In conclusion all

these fixed combinations have a good profile of safety,

efficacy and tolerability. According to our experience, it

is mandatory to customize medical therapy to any glau-

coma patient, as in refractive surgery.

5. Acknowledgements

The Author thanks the staff of the Glaucoma Service of

the Department of Ophthalmology, Catholic University of

Rome, Rome, Italy, Europe.

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