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Ophthalmology Volume 115, Number 1, January 2008

DTFC dosed twice daily in patients with POAG or ocular During the assessment of the 24-hour diurnal curve, the inves-
hypertension in a sample larger than those studied previ- tigator who performed the IOP measurements was masked to the
ously. treatment regimen. The same investigator at each site used the
same calibrated instruments (Goldmann applanation tonometer) to
determine diurnal curves of the IOP. Patients were admitted to the
Materials and Methods hospital in the morning, and measurements were recorded at 10
AM,2 PM,6 PM, 10 PM,2 AM, and 6 AM. At the 10 PM measurement,
Patients patients were awake at bed rest. The 2 AM and 6 AM IOP sitting
measurements were performed immediately after wakening. Pa-
Patients selected for this prospective study were recruited consec- tients were encouraged to carry out a normal life as much as
utively from the glaucoma clinic of the First University Depart- possible within the hospital boundaries.
ment of Ophthalmology, AHEPA Hospital, Thessaloniki, and the Masking was performed by placing a label with the patient
outpatient clinic of the Department of Ophthalmology, Democritus number over the study medicine bottle that was purchased from the
University of Thrace. We enrolled patients of either gender, older manufacturer. The relabeled medicine bottle was then placed in an
than 39 years, who demonstrated IOP 24 mmHg at 10 PM after opaque medicine bottle. The patients were instructed not to show
6 weeks without treatment. Patients had open normal-appearing the medicine bottle to any study personnel or physician (except a
angles and either ocular hypertension or POAG. The latter group designated dosing coordinator).
demonstrated typical glaucomatous visual field (VF) loss (nasal Patients were instructed regarding correct medication instilla-
step or arcuate, paracentral, or Seidel’s scotoma), as determined by tion and compliance. In this study, all patients were advised to
automated static threshold perimetry, and glaucomatous optic perform nasolacrimal occlusion for 1 minute after instillation of
nerve head cupping (neural rim notching, thinning, or sauceriza- each study eyedrop. At each visit, local and systemic side effects
tion). All patients in this study who were previously treated with that occurred during the treatment period were recorded.
latanoprost or the DTFC were on the therapy for more than 6
months and demonstrated an adequate therapeutic response to it. Statistics
Patients were excluded from this study if they demonstrated a
history of ocular surgery/trauma, previous use of ocular cortico- Statistical analyses comparing the IOP responses with the drug
steroids, contact lens use, dry eyes, corneal abnormality, or any regimens for the primary efficacy variable, mean 24-hour IOP (the
condition that prevented reliable applanation tonometry. Also ex- average of the 6 individual time points for each patient), were
cluded were patients with systemic use of -blockers, evidence of performed using repeated measures of analysis.
ocular infection, advanced cataract, ocular inflammation, or a In addition, the secondary efficacy variables were analyzed by
history of renal or hepatic impairment. Only patients who did not a paired t test including the reduction in the mean 24-hour pressure
have a contraindication for topical use of -blockers (bradycardia, IOP at month 6; comparison between treatments for the 24-hour
decompensated heart failure, or reactive airway disease) were IOP at month 2; and, for each individual treatment, change in
selected for this study. In a patient with bilateral elevated pressure, pressures between months 2 and 6 for the 24-hour curve.
although both eyes were treated, only one eye was randomly A paired t test was also used to evaluate the mean maximum,
selected at the time of enrollment to be analyzed in this study. minimum, and fluctuation of 24-hour pressure (average of the
Patients with an allergy to sulfonamides also were excluded from highest lowest pressure over the 24-hour period for each indi-
this trial. vidual patient). 8 –11
The significance level was set at 5%, and a 2-way analysis was
Procedures used for all tests. This study had at least an 80% power to identify
a 1.2-mmHg difference between mean diurnal pressures, assuming
The procedures for the present study were similar to those de- a standard deviation of 2.8 mmHg between treatments. 13–17 Only
scribed previously. 11,12 All patients signed an institutional review one eye was randomly chosen to be included in the analysis.
board–approved informed consent agreement before any proce- Adverse events were evaluated by a McNemar test. 18
dures were performed. At the screening visit (visit 1), all patients
had ocular and systemic histories taken, and dilated optic disc
examination and VF testing (Humphrey 24-2, Humphrey Field Results
Analyzer, Humphrey Instruments, San Leandro, CA) were per-
formed. At the screening visit and each subsequent visit, patients Patients
also had slit-lamp biomicroscopy, Goldmann applanation tonom-
etry (one measure for each time point at each visit), and Snellen Fifty-three patients completed this study, and 58 were enrolled.
visual acuity performed or determined. Qualified patients then Two additional patients were screened for the study but failed to
spent 6 weeks free of glaucoma medicine before treatment with the qualify due to IOP inclusion requirements. Of these patients, all
study medication. were Caucasian and ethnic Greek. Thirty-nine patients had POAG
At the baseline visit (visit 2), patients who continued to qualify and 14 had ocular hypertension. Additional patient characteristics
were randomly assigned to receive either latanoprost 0.005% are shown in Table 1. Five patients were treated with latanoprost
(Pfizer Hellas, Athens, Greece) once every evening (8 PM) and a before the study, with a baseline IOP of 28.8 2.5 mmHg, and 9
placebo in the morning (8 AM) or the dorzolamide/timolol maleate were treated with the DTFC before the study, with an IOP of
fixed combination (Vianex SA/MSD, Athens, Greece) twice daily 26.0 1.9 mmHg. There were 29 right and 24 left eyes randomly
(8 am and 8 pm) for the first 6-month treatment period, and then selected in this study.
they were crossed over to the second treatment period.
Also, at baseline (visit 2), month 2 (visits 3 and 5), and month Intraocular Pressure
6 (visits 4 and 6) of each treatment period patients underwent
24-hour assessment of their IOP. The 6-month treatment period The absolute IOP results for months 2 and 6 are shown in Tables
was chosen to reflect a midterm-length investigation of the med- 2 and 3 (available at http://aaojournal.org), respectively. The IOP
ication effect. No washout period separated the treatment periods. results at the 6-month visit are diagramed in Figure 1.

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