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Published in final edited form as:

Semin Ophthalmol. 2018 ; 33(4): 517–524. doi:10.1080/08820538.2017.1324039.

The Water-Drinking Test Revisited: An Analysis of Test Results

in Subjects with Glaucoma
M. Reza Razeghinejad1,2,ID, Zahra Tajbakhsh1, M. Hossein Nowroozzadeh1, Shane J.
Havens2, Deepta Ghate2, and Vikas Gulati2
1Poostchi Eye Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA
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Abstract
Purpose—The Water-Drinking Test (WDT) has been shown to predict the diurnal IOP change.
This study evaluates the factors that may affect the WDT results.

Methods—This study was conducted on 203 glaucoma patients who had undergone
trabeculectomy (53) or tube surgery (31), or had a medically controlled open-angle (82) or closed-
angle (37) glaucoma. IOP was measured at baseline and then every 15 minutes over a one-hour
period after drinking water. The main outcome measures were IOP change (increase in IOP from
baseline) at all measurement time points, IOP peak (highest IOP after drinking water), IOP
fluctuation (difference between IOP peak and baseline), and assessing the association of these
IOPs with a patient’s demographic and management modalities.
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Results—The mean age of the participants was 54±18 years, and 113 (56%) were male. Female
patients showed greater IOP fluctuation than males (7.28 vs. 5.92 mm Hg; P=0.016), and a greater
IOP peak (22.7 vs. 20.1 mm Hg; P=0.001). The observed associations between gender and IOP
changes were only significant in <50 years. IOP at 60 minutes was greater in tube than
trabeculectomy (5.6 vs. 3.1 mm Hg; P=0.007). The number of topical medications showed a direct
independent association with IOP changes (P<0.001). Compared to other classes of topical
medications, latanoprost showed lower WDT-IOP profile (P=0.0003).

Conclusions—WDT-IOP change was diminished in subjects on latanoprost, and was greater in

females <50 years, and those on greater number of medications.

Keywords
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Glaucoma; trabeculectomy; tube surgery; water-drinking test

Correspondence: M. Reza Razeghinejad, Truhlsen Eye Institute, 3902 Leavenworth Street, Omaha, NE 68105, USA.
razeghinejad@yahoo.com.
ORCID
M. Reza Razeghinejad http://orcid.org/0000-0001-7961-8425
DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
 Razeghinejad et al. Page 2

INTRODUCTION
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The goal of glaucoma management is to lower intraocular pressure (IOP) below the level
that is likely to cause further damage to the optic nerve, thus preventing progressive visual
field loss. This safe range of eye pressure is called the target IOP, and is typically determined
with data collected from isolated clinical measurements during usual office working hours.
In a subset of patients, visual field loss continues in spite of normal in-office IOP readings.1
This could be explained by undetected IOP fluctuation during the day or could be the result
of pressure peaks outside of usual office hours.2,3 Studies that evaluate 24-hour IOP in
glaucoma patients found that about 75% of them exhibit their highest IOP values outside of
regular clinic hours.4,5

It would be ideal to measure 24-hour IOP in all patients with glaucoma. A modified diurnal
tension curve (IOP is tested every three hours over an 8–10 hour period) and home
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tonometry have also been explored as a way to identify IOP fluctuation.6,7 However, the cost
and labor involved in 24-hour IOP monitoring make the process difficult. Additionally, these
simplified evaluations can miss up to 70% of IOP spikes, because most of the highest IOP
levels occur in the early morning hours with the individual in the supine position.8 Sleep
laboratory serial IOP measurement has proven cumbersome and expensive.-9 A contact lens
censor for continuous 24-hour monitoring of IOP had shown fair to good reproducibility
without severe side-effects.10 However, this instrument is not always available commercially
and has not yet gained wide popularity outside of highly specialized centers, and cost
remains prohibitive.

In the 1960s, the water-drinking test (WDT) was described as a diagnostic test for glaucoma
and to predict which ocular hypertensive patient is more prone to visual field loss, but now it
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is regarded as a stress test to assess the capacitance of aqueous outflow and to predict the
IOP peak of the diurnal tension curve.11–13 Also, the WDT has been used to assess the
effectiveness of treatments in controlling IOP, including medications14 and trabeculectomy
patency.15 There are reports on the reproducibility of WDT for evaluating the IOP
fluctuation; however, there are no reports on the variables that may affect the results. This
study evaluates the effect of patients’ demographic and management modalities on the WDT
results.

MATERIAL AND METHODS

Study Population
This interventional case series was conducted after approval by the local ethics committee.
Written informed consent was obtained from all study subjects. Study subjects at or below
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target IOP based on isolated office readings after prior surgery (trabeculectomy or tube
shunt) and/or topical anti-glaucoma medications were prospectively and consecutively
recruited. IOPs were measured in all visits with both a Goldmann applanation tonometer and
a non-contact tonometer (CT80; Topcon Co., Tokyo, Japan), at a tertiary eye care hospital.
All surgical procedures were performed by one surgeon (MRR). The trabeculectomy group
(Trab) had undergone standard trabeculectomy with adjunctive Mitomycin-C (0.2 mg/ml for
two minutes) and were followed for at least six months after surgery with IOPs at or below

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target with or without IOP-lowering medications. The tube shunt group (Tube) had
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undergone Ahmed Glaucoma Valve (FP7, New World Medical, Rancho Cucamonga, LA,
USA) implantation at least six months before study enrollment and their IOPs were at or
below target with or without IOP lowering medications. The Medically Controlled Closed
Angle Glaucoma Group (MCCAG) had laser iridotomy and an IOP at or below target with
IOP-lowering medications. The Medically Controlled Open Angle Glaucoma Group
(MCOAG) also had IOP at or below target with IOP-lowering medications but no prior
surgical intervention.

All patients underwent a complete ophthalmic examination, which included Snellen visual
acuity, IOP measurement, and a dilated stereoscopic fundus examination to assess the
amount of optic nerve head damage using the Disc Damage Likelihood Scale.16 The average
thickness of the peripapillary retinal nerve fiber layer on optical coherent tomography was
also recorded. Subjects were excluded if they had a history of refractive surgery, current
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ocular infection, pregnancy, cardiac or renal diseases, history of urinary retention, any
corneal abnormalities preventing reliable IOP measurements, previous argon laser or
selective laser trabeculoplasty, more than one trabeculectomy or shunt surgery, follow-up of
less than six months after trabeculectomy, shunt surgery, or laser iridotomy, and a target IOP
greater than 22 mm Hg.

Water-Drinking Test
Subjects were instructed to refrain from food and fluid intake for three hours preceding the
WDT. After checking the baseline IOP, patients were instructed to drink one liter of bottled
water (15 mL/kg in those below 16 years) in five minutes. IOP was then measured every 15
minutes for one hour. Five IOP measurements was performed (baseline and then at 15
minutes, 30 minutes, 45 minutes, and 60 minutes after water consumption). One examiner
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measured the IOPs with a non-contact tonometer (CT80; Topcon Co., Tokyo, Japan). In a
recent meta-analysis on all available tonometers compared with Goldmann applanation
tonometer, the least amount of variability in IOP measurement (mean difference of 0.2 mm
Hg) was seen with non-contact tonometers.17 The average of three measurements was
recorded and the measurement was repeated if the difference between three measurements
was greater than 3 mm Hg.

Outcome Measures
IOP change (increase in IOP from baseline) at all measurement time points, IOP peak
(highest IOP after drinking water), IOP mean (the mean of the four IOPs after drinking
water), IOP fluctuation (difference between IOP peak and baseline) were assessed and
analyzed. Association between WDT results and the patient’s demographic and management
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modalities were also evaluated.

Statistical Analysis
IOP was measured in both eyes, if both eyes met the eligibility criteria; one eye was
randomly selected for inclusion in the study. All data were recorded and analyzed using IBM
SPSS Statistics software version 21 (SPSS Inc., Chicago, IL) and MedCalc version 12.2.1
(MedCalc Software, Mariakerke, Belgium). Repeated-measures analysis of variance, linear

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 Razeghinejad et al. Page 4

regression analysis, and linear mixed models (LMM) were used for statistical analysis. The
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tested variables included age, sex, surgery vs. medication, trabeculectomy vs. tube, OAG vs.
CAG, number of topical medications, class of topical medications (Latanoprost vs. others, β-
blockers vs. others, carbonic anhydrase inhibitors vs. others, and α2-agonists vs. others),
weight, height, body mass index, spherical equivalent of refraction, astigmatism, lens status
(phakic vs. pseudophakic, vs. aphakic), Disc Damage Likelihood Scale, visual field mean
and pattern standard deviation, average retinal nerve fiber layer thickness, and IOP baseline.
A P value of < 0.05 was considered statistically significant.

RESULTS
The data from 203 eyes of 203 patients were analyzed. Fifty-three eyes were in the Trab
group, 31 in the Tube group, 82 with MCOAG, and 37 with MCCAG. Demographic and
baseline characteristics of participants are presented in Table 1. Considering all 203 eyes, the
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mean IOP increased from 14.8 mm Hg at baseline to 17.8 mm Hg at 15 minutes after WDT
(P < 0.001), then to 19.3 mm Hg at 30 minutes (P < 0.001) and remained stable afterwards.
An IOP of 30–40 mm Hg was detected at 15, 30, 45, and 60 minutes in 2 (1.0%), 7 (3.4%),
12 (5.9%), and 11 (5.4%) patients, respectively. The results of the WDT in the four groups
are given in Table 2 and Figure 1.

Table 3 lists different IOP parameters after WDT in all patients and within each group. The
IOP peak occurred at 15 minutes in 34 patients (16.7%), at 30 minutes in 55 (27.1%), at 45
minutes in 56 (27.6%), and at 60 minutes in 43 (21.2%) cases. The highest frequency of IOP
peak in the Trab group was observed at 45 minutes (30.2%), which did not differ from the
Tube group (32.3% at 30 minutes), MCOAG (27% at 30 minutes), or MCCAG subjects
(30.5% at 45 minutes). The frequency of different time-slots for the IOP peaks did not differ
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significantly in the four groups (P = 0.53).

Table 4 summarizes the possible association of several demographic and ocular variables to
the IOP fluctuation. Female patients showed more prominent IOP change compared to males
(Figure 2A). The averages of the IOP peak were 22.7 ± 5.8 mm Hg in females vs. 20.1 ± 5.4
mm Hg in males (P = 0.001). IOP fluctuation was significantly greater in females than males
(7.2 ± 4.5 vs. 5.9 ± 3.6, P = 0.016). Females under 50 years had greater IOP changes after
WDT than those over 50 (Figure 2B), and the observed associations between gender and
IOP fluctuation after WDT were only significant for patients <50 years of age (Figure 2C).
Comparing the Tube vs. Trab groups, greater IOP change was observed in the Tube group.
IOP change at 60 minutes after WDT was significantly greater in the Tube group than the
Trab group (5.6 ± 3.6 vs. 3.1± 4.3; P = 0.007; Figure 3).
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The number of topical medications showed a direct independent association with IOP
changes after WDT (Figure 4A and B). Compared to other classes of topical medications,
Latanoprost showed lower IOP profile after WDT (Figure 4C).

DISCUSSION
In this study, many factors were found to have a statistically significant effect on the results
of the WDT, but only the following factors were found to have significant associations in

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 Razeghinejad et al. Page 5

multiple regression analysis with IOP change after WDT: female sex, type of surgery,
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number of medications, Latanoprost use, and IOP baseline.

The exact mechanism of IOP rise after WDT is yet to be determined. Brucculeri et al.18
found no variation in hematocrit, total plasma osmolality, or plasma colloid osmotic pressure
and therefore concluded that neither vitreous hydration nor increased aqueous ultrafiltration
could explain the IOP increase. The Diestelhorst and Krieglstein19 study showed an increase
in episcleral venous pressure (from average of 8.2 mm Hg to 18.2 mm Hg) 60 minutes after
drinking water. This increased episcleral venous pressure would reduce the conventional
outflow via the trabecular meshwork. Although the physiology is not completely
understood, recent studies have suggested an expansion of choroidal volume to contribute to
the increase in IOP.20 Whatever the mechanism, after WDT, there is an increase in the IOP.
The ability of the eye to recover from this IOP elevation depends on its outflow facility.21
Brubaker,12 in a computer simulation, proposed that the WDT could be used as an indirect
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tool to measure outflow facility. However, due to the limitations of currently available
techniques to assess trabecular or uveoscleral outflow, it is difficult to directly and
objectively determine whether the WDT is measuring specifically trabecular or uveoscleral
outflow.

The number of topical medications demonstrated an independent association with IOP

changes after WDT. The association can be explained as follows: a greater inherent
resistance in the outflow pathway manifests as a higher unmedicated IOP, thus requiring
more medications to maintain IOP at target level. In other words, the greater number of
medications required to maintain target IOP may be an indirect measure for increased
resistance in the outflow system. Although medications lower the IOP and reduce diurnal
IOP changes, they are not able to compensate for decreased outflow facility in glaucoma
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patients after a challenge of 1000 ml of water ingestion, as in the WDT.

There was an independent association for IOP fluctuation and latanoprost. Currently, the five
classes of drugs commonly used for treating glaucoma are β-blockers, prostaglandin
analogues, α2-adrenergic agonists, carbonic anhydrase inhibitors, and cholinergic agents.
The prostaglandin analogues reduce IOP primarily by increasing aqueous flow via the
uveoscleral pathway.22 The major mechanism for other classes of medications except
cholinergic agents, which are less commonly used these days, is decreasing aqueous
production. Because latanoprost reduces overall aqueous outflow resistance, it follows that it
would have the greatest effect on the WDT, as the only commonly used IOP-lowering
medication that enhances overall aqueous outflow.23–25 When outflow facility is enhanced,
the eye is capable of handling an increase in volume more efficiently and the IOP changes in
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response to the WDT would be blunted. This finding has been corroborated in other studies.
In a study of a total of 280 primary OAG patients on IOP-lowering medications, 40 patients
per group for each of the tested medications (timolol, dorzolamide, brinzolamide, travoprost,
latanoprost, bimatoprost, and brimonidine) underwent the WDT. The prostaglandins gave
the best results in controlling IOP during the WDT in terms of IOP mean rise, IOP mean
peak, and IOP mean percentage increase.26 It has been shown that the latanoprost effect on
IOP resulted in less fluctuation throughout the circadian cycle compared with timolol and
with dorzolamide.27 In a study comparing IOP fluctuation in response to the WDT in

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patients using latanoprost vs. unoprostone, the mean ±SD of IOP fluctuation of WDT was
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5.2± 2.6 mm Hg in the unoprostone group and 3.7± 2.3 mm Hg in latanoprost group (P =
0.006).28

There are mixed results about the effect of estrogen on IOP, but several studies have
demonstrated that testosterone is associated with an increase in IOP.29 The greater IOP
change in women observed in this study may not be due entirely to a hormonal effect on the
eye. Different male vs. female hormonal effects on body fat composition and water retention
may play a role in the load of water influx into the eye and subsequently distinct responses
to WDT. Aging, which is accompanied by diminished sex hormones in both sexes, may
reduce the observed differences compared with younger individuals.

A study on WDT and choroidal thickness in 30 patients with primary OAG revealed that
IOP peaks occurred 15 minutes after the increase in choroidal thickness was observed.20 An
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increase in volume posteriorly in the choroid would be accommodated by fluid exit from the
anterior chamber to compensate for the gradient pressures generated from volume dynamics
within the globe. Therefore, the amount of change in choroidal volume and IOP could be
dependent on the combination of choroidal thickness change and outflow facility. A study on
72 healthy reproductive-age and 72 post-menopausal women showed that the choroid was
significantly thinner in the post-menopausal group (271.3 ± 65.6 µm) compared to pre-
menopausal group (325.4 ± 65.7 µm; P = 0.005).30 Li et al.31 investigated subfoveal
choroidal thickness in 1323 children aged 11 to 12 years. They found that choroidal
thickness in girls increased with body height and sexual maturation, whereas height or
puberty had no effect on boy’s measurements. The difference in choroidal thickness and the
effect of female sex hormones on it may explain the differences in IOP profiles after WDT
in women less than 50 years of age.
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IOP baseline had an independent association with IOP peak (r = 0.51, P < 0.001), IOP range
(r = 0.06, P< 0.001), and IOP mean (r = 0.56, P < 0.001). These results agree with previous
reports showing that higher IOP baseline was associated with greater 24-hour IOP changes
measured in the seated position.-32,33 The Early Manifest Glaucoma Treatment Trial showed
that lowering IOP halved the rate of optic nerve damage and visual field progression in
patients with newly diagnosed open-angle glaucoma. For each 1-mm Hg reduction in IOP
over the course of the study, the risk of glaucoma progression was reduced by 10%. One of
the baseline risk factors for worsening visual field was higher IOP.34 The response to WDT
was also considered a risk factor for the development of visual field defect progression in
OAG.35 Yoshikawa et al.36 evaluated the clinical tests that could predict the progression of
visual field loss in normal tension glaucoma. The WDT was considered the main predictive
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test for glaucomatous progression in the study group. Therefore, when the IOP baseline is
lower, the possibility of diurnal IOP changes might be reduced, which seems to be a
contributing factor in progressive visual field loss.37

Although the WDT is an inexpensive and feasible test, coexisting systemic diseases,
including cardiac or renal disease, or history of urinary retention, are contraindications to
this test. The majority of glaucoma patients are elderly, thus increasing the likelihood of a
coexisting comorbidity that may preclude performing WDT. After drinking the water, the

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 Razeghinejad et al. Page 7

kidney is the primary organ to handle the ingested water load via diuresis.38 For these
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reasons, patients with cardiovascular or renal disease and males with urinary retention
should not undergo this test.

One of the potential limitations of this study includes the use of non-contact tonometry for
IOP measurement. Non-contact tonometry was used in this large sample size study as an
alternative to Goldmann applanation tonometer because it has been shown to closely
correspond with Goldmann IOP readings, with a mean difference of 0.2 mm Hg.17 To
control for potential differences, all IOP measurements were performed by one examiner and
the average of three measurements was recorded. Measurements were repeated if the
difference between three measurements was greater than 3 mm Hg in effort to increase the
accuracy of IOP measurement.

In conclusion, this study showed that females under 50 years of age, subjects with higher
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IOP baseline and greater number of medications experienced higher IOP changes during the
WDT. In contrast, those on latanoprost had fewer IOP changes.

Acknowledgments
FUNDING

Vikas Gulati received financial support from the National Eye Institute (K23EY02366).

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FIGURE 1.
Mean difference of IOP in four groups at each timeslot: MCCAG, medically controlled
closed angle glaucoma; MCOAG, medically controlled open angle glaucoma; Trab,
trabeculectomy; Tube, tube-shunt surgery.
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 Razeghinejad et al. Page 11
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FIGURE 2.
(A) Higher IOP profile in females (P=0.047, LMM controlling for IOP baseline and number
of medications); (B) IOP change in females over and under 50 years; (C) comparison of IOP
fluctuation in males vs. females categorized by age groups.
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FIGURE 3.
Greater IOP change in the Tube compared to the Trabeculectomy group (P=0.03 for surgery
× time interaction on LMM).
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FIGURE 4.
(A) Greater IOP change with greater number of medications (P<0.0001, LMM after
controlling for baseline IOP); (B) higher IOP fluctuation with higher number of topical
medications (P<0.0001 in univariate analysis); (C) lower IOP profile in those on latanoprost
(P=0.0003, LMM after controlling for baseline and number of meds).
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TABLE 1

Demographic and baseline characteristics of participants.

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Number 203
Age, years Mean (SD): 54 (18)
Range: 7 to 88
Gender (Male/Female) 113/90
Eye (Right/Left) 97/106
Weight, kg Mean (SD): 67 (15)
Range: 21 to 106
Height, cm Mean (SD): 161 (11)
Range: 122 to 194
Body Mass Index, kg/m2 Mean (SD): 25.7 (5.0)
Range: 14.1 to 40.6
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Spherical Equivalent, Diopters Mean (SD): −0.8 (2.8)

Range: −12.5 to 12.0
Astigmatism, Diopters Mean (SD): −1.2 (1.1)
Range: −5.0 to 0
Optic Nerve Head Damage (DDLS) Mean (SD): 6.8 (1.8)
Range: 1 to 9
Mean Deviation of Humphery Visual Field Mean (SD): −9.8 (9.0)
Range: −30.1 to 0.8
Pattern Standard Deviation Mean (SD): 6.2 (4.2)
Range: 1.1 to 17.4
Average Retinal Nerve Fiber Layer Thickness in Optical Coherent Tomography, µm Mean (SD): 68 (20)
Range: 34 to 122
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Intraocular Pressure Baseline, mm Hg Mean (SD): 14.8 (3.4)

Range: 6.5 to 22
Primary glaucoma diagnosis, n (%) Primary open angle: 103 (50.7)
Primary closed angle: 40 (19.7)
Pseudoexfoliative: 24 (11.8)
Congenital: 8 (3.9)
Others: 28 (13.8)
Lens status, n (%) Phakic:141 (69.5)
Pseudophakic: 57 (28.1)
Aphakic: 5 (2.5)
Glaucoma medications, n (%) None: 24 (11.8)
1: 26 (12.8)
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2: 50 (24.6)
≥3: 103 (50.7)
Group, n (%) Trab Group: 53 (26.1)
Tube Group: 31 (15.3)
MCOAG Group: 82 (40.4)

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Number 203
MCCAG Group: 37 (18.2)
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MCOAG: Medically Controlled Open Angle Glaucoma; MCCAG: Medically Controlled Closed Angle Glaucoma; SD: Standard Deviation; DDLS:
Disc Damage Likelihood Scale.
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TABLE 2

Intraocular pressure measurements at baseline and after water-drinking test in four groups.

Intraocular Pressure, mm Hga

Baseline 15 minutes 30 minutes 45 minutes 60 minutes P valueb

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Trab Group 14.1±3.2 16.9±5.4cc 17.9±5.3c 17.6±5.2c 17.3±5.6c <0.001

Tube Group 14.3±3.9 17.3±5.6c 19.0±5.6c, d 19.4±5.8c 19.9±6.0c <0.001

MCOAG Group 14.9±.3.1 18.2±4.2c 20.1±5.1c, d 20.0±5.8c 19.8±5.6c <0.001

MCCAG Group 15.8±3.6 18.7±4.2c 19.9±5.0c 20.4±5.8c 19.9±6.1c <0.001

a
Presented as Mean ± SD.
b
Calculated using repeated-measures ANOVA with pairwise comparison using Bonferroni correction.
c
Indicates that the measurement is statistically different from the baseline measurement of the same group.
d
Indicates that the measurement is statistically different from the previous measurement of the same group.

MCCAG: Medically Controlled Closed Angle Glaucoma; MCOAG: Medically Controlled Open Angle Glaucoma; Trab: Ttrabeculectomy; Tube: Tube-Shunt Surgery.

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TABLE 3

Comparison of IOP parameters in four groups.

IOP parametersa All Cases Trab Group Tube Group MCOAG Group MCCAG Group

IOP peak, mm Hg 21.2±5.7 19.6±6.0 21.1±5.8 21.8±5.3 22.3±5.8

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IOP mean, mm Hg 18.9±5.0 17.4±4.9 18.9±5.4 19.5±4.7 19.7±4.8

IOP fluctuation, mm Hg 6.5±4.1 5.5±4.4 6.8±3.4 6.9±4.0 6.5±4.3
IOP change at 60 minutes, mm Hg 4.4±4.4 3.1±4.3 5.6±3.6 4.9±4.6 4.1±4.5

a
Presented as Mean ± SD.

MCCAG: Medically Controlled Closed Angle Glaucoma; IOP: intraocular pressure; MCOAG: Medically Controlled Open Angle Glaucoma.

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TABLE 4

Effect of selected covariates on the IOP fluctuation after water-drinking test.

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IOP Fluctuation (Mean±

Variable Number Standard Deviation) P value
Gender Female 113 7.28 ± 4.44
Male 90 5.92 ± 3.65 0.02
Group Trab 53 5.48 ± 4.38
Tube 31 6.84 ± 3.36
MCOAG 37 6.62 ± 4.13
MCCAG 82 7.02 ± 4.01 0.16
Trab vs. Tube Trab 53 5.48 ± 4.38
Tube 31 6.84 ± 3.36 0.13
Latanoprost Yes 79 6.12 ± 4.17
No 124 6.78 ± 3.99 0.26
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Number of medications 0 24 4.21 ± 3.41

1 26 5.50 ± 4.80
2 50 6.43 ± 3.26
3 75 6.86 ± 4.05
4 25 8.26 ± 4.09
5 3 12.67 ± 1.53 <0.0001
Females Under 50 31 8.37 ± 4.70
Over 50 59 6.71 ± 4.22 0.096
Surgery (Trab or Tube) yes 84 5.98 ± 4.07
no 119 6.91 ± 4.04 0.11
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