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

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.

Full text

Open Journal of Ophthalmology, 2012, 2, 122-126
http://dx.doi.org/10.4236/ojoph.2012.24027 Published Online November 2012 (http://www.SciRP.org/journal/ojoph)
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*
Italo Giuffre
Department of Ophthalmology, Medical School, Catholic University of Rome, Rome, Italy.
Email: italogiuffre@libero.it
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.
Copyright © 2012 SciRes. OJOph

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.
PATIENTS MALE FEMALE MEAN AGE S.D. RANGE
70 35 35 69.52 y 11.56 37 - 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.
Copyright © 2012 SciRes. OJOph

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
vs
DORZOLAMIDE 2%-TFC
P = 0.053
BRIMONIDINE 0.2%-TFC
vs
BIMATOPROST 0.003%-TFC
P = 0.221
BRIMONIDINE 0.2%-TFC
vs
TRAVOPROST 0.004%-TFC
P = 0.167
BRIMONIDINE 0.2%-TFC
vs
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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