JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS

Volume 26, Number 2, 2010

© Mary Ann Liebert, Inc.
DOI: 10.1089/jop.2009.0124

Meta-Analysis of 24-h Intraocular Pressure Fluctuation Studies

and the Efficacy of Glaucoma Medicines

William C. Stewart,1 Anastasios G.P. Konstas,2 Bonnie Kruft,3 Heather M. Mathis,3 and Jeanette A. Stewart1

Abstract
Purpose: To compare the change in 24-h fluctuation of the intraocular pressure (IOP) from various medical
therapies in patients with ocular hypertension, primary open-angle (POAG), or exfoliative glaucoma (XFG).
Methods: A meta-analysis of published studies that were controlled, prospective, and comparative trials. Based
on study requirements for an objective fluctuation analysis, only studies from the authors’ work met the criteria
for this analysis and contained: ≥4-week treatment period, ≥20 patients per treatment arm, and ≥6 time points
measured with Goldmann applanation over 24 h, not spaced >5 h apart. Fluctuations were defined by the mean
of the difference between the highest and lowest measured IOP for each individual patient (Σ[maximum − mini-
mum IOP]/number of patients).
Results: Thirteen articles were included evaluating 28 treatment arms in 1,017 patients. Among all individual
treatments, bimatoprost demonstrated the greatest reduction in fluctuation (P = 0.03, 3.4 mm Hg). In contrast,
2-drug therapy did not reduce fluctuations from monotherapy (P = 0.09). Among prostaglandin therapies, no sta-
tistical difference existed between evening and morning dosing (P = 0.20). In XFG, a greater reduction in fluctua-
tions was observed progressing from 1 to 2 medicines (P = 0.01), but not increasing from 2 to 3 drug therapy (P =
0.14). In general, XFG patients demonstrated a greater decrease in fluctuations than POAG patients (P = 0.003).
Conclusions: In POAG differences exist in fluctuations among monotherapy treatments with bimatoprost show-
ing the greatest effect. However, POAG patients generally demonstrate less decrease in fluctuations with treat-
ment than compared with XFG.

Introduction

T he practice of glaucoma has been assisted greatly

over the past several years by a number of well-con-
trolled, prospective trials demonstrating the importance of
mean intraocular pressure (IOP) reduction in preventing
the progression of glaucoma and ocular hypertension.1–5
Unfortunately, despite the lowering of IOP some patients
still suffer glaucomatous progression. Other factors may
exist, at least in some patients, which allow them to progress
despite ocular hypotensive therapy.
Several previous studies have suggested that patients with a
higher standard deviation of the IOP (or peak pressure) during
the daytime, or a greater fluctuation in the pressure over the
24-h day, may be at more risk for glaucomatous progression.2,6,7
These findings have led to a greater interest in the effect of
glaucoma therapy on the fluctuation of the pressure.
Accordingly, most new medications have been evaluated
over a 24-h time period in post-marketing trials by several
groups of investigators. Specifically, the work of Konstas,
Stewart, and associates has used an average range of pres-
sure (the mean of the highest minus the lowest IOP for each
individual patient over 6 time points during the 24-h day)
to measure the pressure fluctuation of glaucoma medicines.8
However, little effort has been made to summarize the find-
ings of 24-h fluctuation curves.
The purpose of this study was to compare the change in
fluctuation of various medical therapies by a meta-analysis
of studies that contained an evaluation of 24-h fluctuation
of the IOP in patients with ocular hypertension or primary
open-angle (POAG) or exfoliative glaucoma (XFG).

1
PRN Pharmaceutical Research Network LLC, 3Charleston Research Company, LLC, North Charleston, South Carolina.
2
Glaucoma Unit, 1st University Department of Ophthalmology, AHEPA Hospital, Thessaloniki, Greece.

175

J Ocul Pharmacol Ther 2010;26(2):175-80 THIS MATERIAL MAY BE

2010051682 PROTECTED BY COPYRIGHT
LAW (17 USC)
176
Methods
Procedures
Articles included in this meta-analysis were found
through the Pubmed database (www.pubmed.gov) from
its inception (1966) to February 2007. Search terms were:
“glaucoma, ocular hypertension, exfoliation, fluctuation,
24-h treatment” and specific glaucoma medicines includ-
ing: “betaxolol, timolol, timolol gel forming solution, dorzol-
amide, brinzolamide, brimonidine, latanoprost, bimatoprost,
and travoprost.” Both the brand and generic names of single
agent preparations, and these medicines combined into fixed
combinations, were used as search terms.
Each article was reviewed by 2 of the authors (B.K.,
H.M.M.) to determine if the study met the further inclusion
criteria of: prospective, crossover or parallel, comparative
trial with a treatment period of at least 4 weeks. Studies
must have consisted of patients with common open-angle
forms of elevated pressure including: ocular hypertension,
primary open-angle, exfoliative or pigment dispersion glau-
coma. In each treatment, arm therapy was advanced by one
medicine from baseline.
Intraocular pressures must have been measured with
Goldmann applanation tonometry in the sitting posi-
tion during waking hours. No more than 5 h should have
separated any 2 measurements and at least 6 time points
must have been collected over the 24-h period. Although
other applanation techniques in other positions have been
assessed in prior research, fluctuations have not been calcu-
lated and consequently could not be used in this report.9,10
Based on the study requirements for an objective 24-h fluc-
tuation analysis, only studies from the authors’ work met
the criteria for this analysis.
The fluctuation of the IOP (range of pressure) must have
been evaluated in the article by taking the mean of the dif-
ference between the highest and lowest measured pressure
for each individual patient (Σ[maximum − minimum pres-
sure]/number of patients).
Potential articles were further evaluated by 2 of the
authors (B.K. and H.M.M.) for quality according to the
Delphi criteria.11 These measures helped assure the quality
of an article used for a meta-analysis and are summarized
in Table 1. However, each included article did not meet all
criteria. None of the articles specified an intent-to-treat anal-
ysis. This was because each study included matched pairs
that demanded that each patient complete all measures in
Table 1. Delphi Criteria not Met in This Analysis
Delphi criteria
Delphi 1
Dates of starting and ending accession?
Delphi 2
Treatment allocation:
Was a method of randomization performed?
Was the treatment allocation blinded?
Was the outcome accessor blinded?
Does the analysis include an intent-to-treat
analysis?
STEWART ET AL.
the treatment period although some individual data points
could have been missing. If a patient had discontinued in
treatment Period 1, or prior to the 24-h evaluation in treat-
ment Period 2, then the matched treatment pairwise com-
parison was not possible, negating the usefulness of the
patient’s data. Consequently, a per-protocol analysis was
typical of these studies. Also, few articles had the dates of
the beginning or the end of the trial. However, we did not
judge that this information was necessary for an adequately
performed trial. Also, none of the articles specified if the
outcome assessor was masked in the methods section and
3 were not randomized or masked. In these studies only
one medicine was used and the treatment groups varied.
Therefore, masking or randomizations were not needed
(Table 1). Based on the Delphi criteria, no additional articles
were excluded, beyond that derived from the exclusion cri-
teria of this meta-analysis.11
Since the research was performed at a limited number of
research centers in Greece, over time and potentially on dif-
ferent medicines, a patient may have been included in sev-
eral studies. Since the published manuscripts do not indicate
name, any potential repeated patients were not known to the
authors.
Statistics
Between group statistical comparisons for 24-h fluctua-
tion from each study (Σ[maximum − minimum pressure
for each patient]/number of patients) were compared with
a random effects model. This model evaluated differences
in the reductions of fluctuations from nontreatment baseline
between treatment groups.
The 24-h mean fluctuations were based on one 24-h diur-
nal curve of the pressure for baseline and each active treat-
ment in a study. This method has the advantage in that it
takes into account the range of 24-h pressure per individual
subject and not just a range or standard deviation of mean
fluctuations of whole study populations. In addition, this
method accounts for the peak pressure the patient suffers
throughout the 24-h day. Six individual time points were
utilized in the meta-analysis to describe mean changes in
pressure over the 24-h curve. For all studies that met the
inclusion criteria, the time points used were at 02:00, 06:00,
10:00, 14:00, 18:00, and 22:00.
Fluctuations for ocular hypertension and POAG were
evaluated apart from XFG because the latter form of the
References
Refs. 8,16–19,21,24 did not include the data
Refs. 12,13,22,23 were not randomized
Refs. 12,13,22,23 were not masked
None
None
INTRAOCULAR PRESSURE FLUCTUATION STUDIES 177

disease has been shown to demonstrate higher untreated Results

and treated pressures.12,13 For POAG, fixed and unfixed com-
binations were evaluated together, and for prostaglandin
therapy specifically, morning dosing was analyzed apart
from evening dosing. Further, individual treatments were
evaluated among monotherapies.
For exfoliation glaucoma, all monotherapy, 2-drug and
3-drug therapy regimens were compared. Also, fluctuations
were compared between all treated exfoliation and POAG
patients.
All evaluations were 2-way (fluctuations could have
increased or decreased with treatment) and a P value of
0.05 used to declare significance. Fluctuation values were
weighed in analyzing the means by the sample size of the
study. Further, a test for heterogeneity was performed sepa-
rately for exfoliative and POAG treatment arms to assure the
appropriateness of the pooled data.14
Included articles
In total, 16 studies that measured 24-h IOP curves were
initially chosen for this meta-analysis. Upon further review,
3 articles were rejected for the following reasons: because
1 did not meet the inclusion criteria and 2 did not evaluate
fluctuations.
The review process left 13 articles, with 28 treatment arms
including 1,017 patients, which were included in this analy-
sis that met the inclusion/exclusion criteria.8,12,13,15–24 These
articles are detailed in Table 2. Of these, 772 had POAG or
ocular hypertension of which 451 were on monotherapy,
152 fixed combination therapy, and 169 unfixed combina-
tion therapy. There were 245 patients with XFG, of which 118
were on monotherapy, 61 unfixed combination therapy, and
66 multiple drug therapy.

Table 2. Studies Used in This Meta-Analysis

References Diagnosis Treatment Patients Fluctuation

Konstas et al.8 Primary open-angle glaucoma Latanoprost 42 4.0 ± 1.6

Bimatoprost 42 3.5 ± 1.5
Konstas et al.12 Exfoliative glaucoma Timolol 38 7.0 ± 3.2
Primary open-angle glaucoma Timolol 38 5.6 ± 2.4
Konstas et al.13 Exfoliative glaucoma Latanoprost 40 4.3 ± 1.9
Travoprost 40 3.9 ± 1.7
Konstas et al.15 Primary open-angle glaucoma Latanoprost AM 34 5.7 ± 2.4
Latanoprost PM 34 4.4 ± 1.8
Timolol 34 4.3 ± 1.6
Konstas et al.16 Primary open-angle glaucoma Timolol 36 5.7 ± 1.6
Latanoprost and 36 4.4 ± 1.6
timolol AM
Latanoprost and 36 3.6 ± 1.6
timolol PM
Konstas et al.17 Primary open-angle glaucoma Latanoprost 33 4.4 ± 1.8
LTFC 33 3.9 ± 1.3
Konstas et al.18 Primary open-angle glaucoma Latanoprost 33 4.8 ± 1.8
DTFC 33 4.6 ± 1.8
Konstas et al.19 Primary open-angle glaucoma Latanoprost 53 3.5 ± 1.5
DTFC 53 3.7 ± 1.7
Konstas et al.20 Primary open-angle glaucoma Timolol 34 4.4 ± 1.8
LTFC 33 3.2 ± 1.1
Konstas et al.21 Exfoliative glaucoma Latanoprost and 33 4.3 ± 2.0
DTFC
Pilocarpine and 33 4.5 ± 1.7
DTFC
Konstas et al.22 Exfoliative glaucoma Dorzolamide 31 6.1 ± 4.1
and timolol
Primary open-angle glaucoma Dorzolamide 31 3.8 ± 2.2
and timolol
Konstas et al.23 Exfoliative glaucoma Apraclonidine 30 6.6 ± 4.5
and timolol
Primary open-angle glaucoma Apraclonidine 30 4.9 ± 2.5
and timolol
Konstas et al.24 Primary open-angle glaucoma Travoprost AM 33 4.0 ± 1.5
Travoprost PM 33 3.2 ± 1.0

Mean ± standard deviation (mm Hg).

Abbreviations: SD, standard deviation; LTFC, latanoprost/timolol fixed combination; DTFC,
dorzolamide/timolol fixed combination.
178 STEWART ET AL.

Table 3. Primary Open-Angle Glaucoma Mean Fluctuation Levels

Reduction in Treatment
Comparison Treatment fluctuation arms P value

Between individual monotherapies Latanoprost 1.5 ± 0.6 13 0.03

Timolol 0.4 ± 1.0
Bimatoprosta 3.4
Travoprost 2.2 ± 1.0
Between individual fixed and unfixed LTFC 0.6 ± 0.6 8 0.5
combinations Apraclonidine and 2.0
timolola
DTFC 0.7 ± 0.8
Latanoprost and 1.6 ± 0.1
timolol
All monotherapies versus all fixed and unfixed All combinations 0.3 ± 1.2 8 1.0
combinations

Mean ± standard deviation (mm Hg).

a
No standard deviation is available since there is only one treatment group.
Abbreviations: LTFC, latanoprost/timolol fixed combination; DTFC, dorzolamide/timolol fixed combination.

Intraocular pressure fl uctuation, primary open-angle
glaucoma
The results of the meta-analysis for the IOP fluctua-
tions are shown in Table 3. The results demonstrated that
there was a statistical difference in the reduction of fluc-
tuations from no treatment among all individual mono-
therapy treatments with bimatoprost demonstrating the
greatest reduction of all 4 treatments compared together
(P = 0.03). In contrast, there was no further decrease in
fluctuations with 2-drug treatment from monotherapy
(P = 1.0). In addition, there was no statistical difference in
the change in fluctuations between monotherapy among
fixed and unfixed combinations (P = 0.5). The test for
heterogeneity was negative among treatment arms includ-
ing POAG patients (P = 0.6).
Among prostaglandin therapies specifically, including
monotherapy and fixed as well as unfixed combination
therapies, evening and morning dosing provided statisti-
cally equivalent changes in fluctuations from prior therapy
(P = 0.20, Table 4).
Intraocular pressure fl uctuation, exfoliation glaucoma
The results including exfoliative patients are seen
in Table 5. Adding a second medicine to monotherapy
decreased fluctuations from monotherapy (P = 0.01) but a
further reduction was not noted by adding a third medicine

Table 4. Morning Versus Evening Mean Fluctuation Levels

Comparison Treatment Fluctuation Treatment arms P value

Morning versus evening Latanoprost morning 1.0 ± 2.4 6 0.20

Latanoprost evening 0.3 ± 1.8
Latanoprost and timolol morning 0.5 ± 1.6
Latanoprost and timolol evening 1.1 ± 1.6
Travoprost morning 0.7 ± 1.5
Travoprost evening 0.9 ± 1.0

Mean ± standard deviation (mm Hg).

Table 5. Exfoliative Glaucoma Mean Fluctuation Levels

Comparison Treatment Fluctuation Treatment arms P value

All monotherapies versus all fixed/unfixed All monotherapies 4.9 ± 0.9 3 NA

combinations and all ≥3 drug therapy All combinations 2.5 ± 0.5 2 0.01
All 3-drug therapy 1.7 ± 0.1 2 0.14
All POAG therapies to all XFG therapies All POAG therapies 1.8 ± 1.2 28 0.003
All XFG therapies 2.6 ± 0.8

Mean ± standard deviation (mm Hg).

Abbreviations: POAG, primary open-angle glaucoma; XFG, exfoliative glaucoma.
INTRAOCULAR PRESSURE FLUCTUATION STUDIES 179

(P = 0.014). The reduction in fluctuations with monotherapy may not allow for a further decrease in fluctuation. However,
was not evaluable because only one study was available to additional medications beyond 2-drug therapy (which was
evaluate this therapeutic step. evaluated partially in only one of the included studies in
In addition, for all studies adding a medicine in exfolia- this analysis) might conceivably further lower fluctuation
tive patients demonstrated statistically greater reduction in beyond the level of monotherapy, but this needs further
fluctuations versus in POAG (P = 0.003). The test for het- study.17
erogeneity was negative among exfoliative treatment arms In contrast, POAG patients generally demonstrated
(P = 0.3). less reduction in fluctuations than exfoliation patients.
Further, adding a second medicine to monotherapy in
XFG decreased fluctuations from monotherapy but a fur-
Discussion ther reduction was not noted by adding a third medicine.
The reduction in fluctuations with monotherapy was not
Despite the recent interest in evaluation of the 24-h IOP
evaluable because only one study was available to evalu-
curve, the amount of available data that links fluctuation of
ate this therapeutic step. However, the decrease in fluc-
this measure to progression is limited. Three lines of evidence
tuations with monotherapy was significant in the original
can be used to assert the importance of IOP fluctuation. First,
article.13
in a retrospective, 5-year outcomes study, Konstas, Stewart
The finding of a greater reduction in fluctuation in exfo-
and colleagues showed that fluctuation of the daytime IOP
liative, than in POAG patients, was not a surprise because
was an independent risk factor for glaucomatous progres-
previous studies have noted that this form of glaucoma,
sion.15 However, not all studies by these authors have dem-
as in our own studies, demonstrates higher untreated and
onstrated such a finding.16 Second, the Advanced Glaucoma
treated pressures and fluctuations.13,27 This higher pressure
Intervention Study investigators noted patients with peak
most likely results from greater outflow obstruction owing
pressures of ≤18 mm Hg, associated with a mean pressure
to the exfoliation material within the trabecular mesh-
of 12.8 mm Hg, had very little evidence of progression over 5
work.27 Further, these patients may require more therapy to
years.2 In addition, the Early Manifest Glaucoma Trial study,
control the mean IOP than patients with POAG.13,27 Possibly,
as well as an additional study by Bengtsson and Heijl, has
the higher non-treated fluctuations in XFG allowed for the
showed that there was no association with fluctuation and
greater statistical reduction with additional drug therapy
progression over time.3,4 Third, in a 24-h, prospective study
not observed in POAG that is generally associated with the
Asrani and coworkers showed that patients who had 24-h
lower fluctuations.
IOPs taken in the clinic or at home over 5 days had elevated
This study suggests that in POAG differences exist in
fluctuations as an independent risk factor for progression.6
fluctuations among monotherapy treatments with bimato-
In addition, even if fluctuations are important several
prost showing the greatest effect. However, POAG patients
other problems exist before using this parameter in rou-
demonstrate generally less decrease in fluctuations with
tine practice, first, we do not yet understand which times
treatment than in exfoliation glaucoma.
during the 24-h day are necessary to measure the IOP to ac-
Monotherapy reduces fluctuations from no treatment
curately assess this parameter. Possibly, in the future, sur-
with bimatoprost showing the greatest effect. However,
rogate times points during the day could be described that
these patients demonstrate generally less decrease in fluc-
reflect pressures found at night so that physicians in routine
tuation with treatment than in treated XFG.
clinical practice could assess this parameter. Second, a clin-
This meta-analysis did not evaluate all monother-
ically measurable target pressure, for fluctuation, in a sim-
apy and fixed combination therapies available. In addi-
ilar fashion as for mean pressures to prevent glaucomatous
tion, the number of XFG patients evaluated was limited.
progression needs to be identified and last, no method cur-
Consequently, a number of useful comparisons were not
rently is available that guarantees an accurate pressure read-
able to be performed in this meta-analysis. In addition, this
ing during the nighttime when the patient usually is supine,
analysis did not include only randomized studies that might
and asleep.
have led to differences in baseline values between trials.
The purpose of this study was to compare the change in
Consequently other factors may have influenced the extent
fluctuation of various medical therapies by a meta-analysis
of pressure reductions apart from the medicine that were
of studies that contained an evaluation of 24-h fluctuation
not apparent by our results. Further, fluctuations still need
of the IOP in patients with ocular hypertension or primary
to be assessed in the supine position as well as their extent
open-angle glaucoma or XFG.
based on the mean level of IOP. In addition, the fluctuation of
This meta-analysis showed of all monotherapies evalu-
the IOP as an independent risk factor needs to be confirmed.
ated, bimatoprost, followed by travoprost, demonstrated to
Additionally, target pressures for fluctuation that assist in
be the 2 most effective medicines in reducing the fluctuations
preventing glaucomatous progression, and daytime time
among all monotherapies compared together. This finding is
points that simulate 24-h fluctuations, need to be described
not surprising since several prior trials indicate they may be
to make using this parameter practical in routine clinical
the most effective monotherapy agents available, although
practice.
this finding is not consistent.25–27
In contrast, there was no further decrease in fluctua-
tions with 2 or more drug treatments from monotherapy.
Author Disclosure Statement
In addition, there was no statistical difference in the change
in fluctuations from monotherapy among various fixed and The authors have no competing interests to declare. This
unfixed combinations. This finding indicates that adding a meta-analysis was not supported by any public or private
second medicine, either as a fixed or unfixed combination, funding agency.
180
References
1. Gordon, M.O., Beiser, J.A., Brandt, J.D., et al. The Ocular
Hypertension Treatment Study: baseline factors that predict
the onset of primary open-angle glaucoma. Arch. Ophthalmol.
120:714 –20; discussion 829, 2002.
2. The AGIS Investigators. The Advanced Glaucoma Intervention
Study (AGIS): 7. The relationship between control of intraocu-
lar pressure and visual field deterioration. Am. J. Ophthalmol.
130:429– 440, 2000.
3. Bengtsson, B., Leske, M.C., Hyman, L., et al.; Early Manifest
Glaucoma Trial Group. Fluctuation of intraocular pressure and
glaucoma progression in the early manifest glaucoma trial.
Ophthalmology. 114:205 –209, 2007.
4. Heijl, A., Leske, M.C., Bengtsson, B., et al.; Early Manifest
Glaucoma Trial Group. Reduction of intraocular pressure
and glaucoma progression: results from the Early Manifest
Glaucoma Trial. Arch. Ophthalmol. 120:1268 –1279, 2002.
5. Collaborative Normal-Tension Glaucoma Study Group. The
effectiveness of intraocular pressure reduction in the treatment
of normal-tension glaucoma. Am. J. Ophthalmol. 126:498 – 505,
1998.
6. Asrani, S., Zeimer, R., Wilensky, J., et al. Large diurnal fluctua-
tions in intraocular pressure are an independent risk factor in
patients with glaucoma. J. Glaucoma. 9:134 –142, 2000.
7. Stewart, W.C., Chorak, R.P., Hunt, H.H., et al. Factors associ-
ated with visual loss in patients with advanced glaucomatous
changes in the optic nerve head. Am. J. Ophthalmol. 116:176 –181,
1993.
8. Konstas, A.G., Katsimbris, J.M., Lallos, N., et al. Latanoprost
0.005% versus bimatoprost 0.03% in primary open-angle glau-
coma patients. Ophthalmology. 112:262–266, 2005.
9. Liu, J.H., Sit, A.J., and Weinreb, R.N. Variation of 24-hour
intraocular pressure in healthy individuals: right eye versus left
eye. Ophthalmology. 112:1670 –1675, 2005.
10. Orzalesi, N., Rossetti, L., Invernizzi, T., et al. Effect of timolol,
latanoprost, and dorzolamide on circadian IOP in glaucoma or
ocular hypertension. Invest. Ophthalmol. Vis. Sci. 41:2566 –2573,
2000.
11. Verhagen, A.P., de Vet, H.C., de Bie, R.A., et al. The Delphi list: a
criteria list for quality assessment of randomized clinical trials
for conducting systematic reviews developed by Delphi con-
sensus. J. Clin. Epidemiol. 51:1235 –1241, 1998.
12. Konstas, A.G., Mantziris, D.A., and Stewart, W.C. Diurnal
intraocular pressure in untreated exfoliation and primary
open-angle glaucoma. Arch. Ophthalmol. 115:182–185, 1997.
13. Konstas, A.G., Mantziris, D.A., Cate, E.A., et al. Effect of timolol
on the diurnal intraocular pressure in exfoliation and primary
open-angle glaucoma. Arch. Ophthalmol. 115:975 –979, 1997.
14. Wolf, F.M. Meta-Analysis: Quantitative Methods for Research
Synthesis. Newbury Park: Sage, 1986.
15. Konstas, A.G., Maltezos, A.C., Gandi, S., et al. Comparison of
24-hour intraocular pressure reduction with two dosing regi-
mens of latanoprost and timolol maleate in patients with pri-
mary open-angle glaucoma. Am. J. Ophthalmol. 128:15 –20, 1999.
16. Konstas, A.G., Nakos, E., Tersis, I., et al. A comparison of once-
daily morning vs evening dosing of concomitant latanoprost/
timolol. Am. J. Ophthalmol. 133:753 –757, 2002.
STEWART ET AL.
17. Konstas, A.G., Boboridis, K., Tzetzi, D., et al. Twenty-four-hour
control with latanoprost-timolol-fixed combination therapy vs
latanoprost therapy. Arch. Ophthalmol. 123:898 –902, 2005.
18. Konstas, A.G., Papapanos, P., Tersis, I., et al. Twenty-four-hour
diurnal curve comparison of commercially available latano-
prost 0.005% versus the timolol and dorzolamide fixed combi-
nation. Ophthalmology. 110:1357–1360, 2003.
19. Konstas, A.G., Kozobolis, V.P., Tsironi, S., et al. Comparison
of the 24-hour intraocular pressure-lowering effects of
latanoprost and dorzolamide/timolol fixed combination
after 2 and 6 months of treatment. Ophthalmology. 115:99–103,
2008.
20. Konstas, A.G., Lake, S., Economou, A.I., et al. 24-Hour control
with a latanoprost-timolol fixed combination vs timolol alone.
Arch. Ophthalmol. 124:1553 –1557, 2006.
21. Konstas, A.G., Lake, S., Maltezos, A.C., et al. Twenty-four hour
intraocular pressure reduction with latanoprost compared with
pilocarpine as third-line therapy in exfoliation glaucoma. Eye
(Lond). 15:59– 62, 2001.
22. Konstas, A.G., Maltezos, A., Bufidis, T., et al. Twenty-four hour
control of intraocular pressure with dorzolamide and timolol
maleate in exfoliation and primary open-angle glaucoma. Eye
(Lond). 14 (Pt 1):73 –77, 2000.
23. Konstas, A.G., Maltezos, A., Mantziris, D.A., et al. The compara-
tive ocular hypotensive effect of apraclonidine with timolol
maleate in exfoliation versus primary open-angle glaucoma
patients. Eye (Lond). 13 (Pt 3a):314 –318, 1999.
24. Konstas, A.G., Mikropoulos, D., Kaltsos, K., et al. 24-hour
intraocular pressure control obtained with evening- versus
morning-dosed travoprost in primary open-angle glaucoma.
Ophthalmology. 113:446 – 450, 2006.
25. Noecker, R.S., Dirks, M.S., Choplin, N.T., et al.; Bimatoprost/
Latanoprost Study Group. A six-month randomized
clinical trial comparing the intraocular pressure-lowering
efficacy of bimatoprost and latanoprost in patients with
ocular hypertension or glaucoma. Am. J. Ophthalmol. 135:55 – 63,
2003.
26. Netland, P.A., Landry, T., Sullivan, E.K., et al.; Travoprost Study
Group. Travoprost compared with latanoprost and timolol in
patients with open-angle glaucoma or ocular hypertension. Am.
J. Ophthalmol. 132:472– 484, 2001.
27. Parrish, R.K., Palmberg, P., and Sheu, W.P.; XLT Study Group.
A comparison of latanoprost, bimatoprost, and travoprost in
patients with elevated intraocular pressure: a 12-week, random-
ized, masked-evaluator multicenter study. Am. J. Ophthalmol.
135:688 –703, 2003.
Received: November 10, 2009
Accepted: February 9, 2010
Address correspondence to:
Dr. William C. Stewart
6296 Rivers Avenue
Suite 309
North Charleston, SC 29406
E-mail: info@prnorb.com