Original Article

Intraocular Pressure Changes after Water Drinking Test
in Surgically Treated Primary Congenital Glaucoma

Reza Razeghinejad, MD1, 2; Zahra Tajbakhsh, MS2; Masoumeh Beigom Masoumpour, MD2

M. Hossein Nowroozzadeh, MD2

1Glaucoma Service, Wills Eye Hospital, Philadelphia, PA, USA
2Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

ORCID:
M. Hossein Nowroozzadeh: https://orcid.org/0000-0002-7412-1900

Reza Razeghinejad: https://orcid.org/0000-0001-7961-8425

Abstract
Purpose: To assess intraocular pressure (IOP) changes after the water drinking test
(WDT) in patients with primary congenital glaucoma (PCG).
Methods: In this prospective interventional study, 20 eyes of 20 patients with PCG were
included. All patients had undergone trabeculotomy. Six out of twenty eyes had received
a glaucoma drainage device (GDD) implantation. IOP was measured using an air-puff
tonometer at baseline, and 15, 30, 45, and 60 min after WDT. The repeated-measures
analysis of variance test was used to compare the mean IOPs at different time points.
Results: The mean (± standard deviation) of participants’ age was 9.9 ± 2.7 years (range,
6 to 16 years), and 8 (40%) participants were male. The mean IOPs at baseline and 15,
30, 45, and 60 minutes after the WDT were 15.8 ± 3.7, 18.6 ± 3.4, 19.0 ± 3.8, 17.9 ± 3.8,
and 16.9 ± 3.5 mmHg, respectively (P < 0.001). Pairwise comparisons revealed that the
mean IOPs after 15 and 30 min were significantly greater than the baseline IOP (P < 0.001
and P = 0.002, respectively); however, the difference in mean IOPs after 45 and 60 min
were not statistically significant from the baseline IOP. The averages of IOP peak and
IOP fluctuation after the WDT were 20.0 ± 3.5 and 4.2 ± 2.9 mmHg, respectively. IOP
fluctuation in those who underwent trabeculotomy alone was twice that of those with
GDDs, but the difference was not statistically significant (5.0 vs 2.5 mmHg; P = 0.08).
Conclusions: In patients with PCG, WDT induced significant IOP elevation 15 and 30 min
after the test, which returned to pre-test values after 45 min.

Keywords: Glaucoma Drainage Device; Intraocular Pressure; Primary Congenital Glaucoma;
Trabeculotomy; Water Drinking Test

J Ophthalmic Vis Res 2020; 15 (3): 318–325

Correspondence to:

M. Hossein Nowroozzadeh, MD. Poostchi
Ophthalmology Research Center, Poostchi Clinic,
Zand St., Shiraz 713499, Iran.
Email: nowroozzadeh@hotmail.com
Received: 14-04-2019 Accepted: 03-04-2020

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DOI:
10.18502/jovr.v15i3.7450

INTRODUCTION

Primary congenital glaucoma (PCG) is the
most common hereditary type of glaucoma in

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How to cite this article: Razeghinejad R, Tajbakhsh Z, Masoumpour MB,
Nowroozzadeh MH. Intraocular Pressure Changes after Water Drinking Test
in Surgically Treated Primary Congenital Glaucoma. J Ophthalmic Vis Res
2020;15:318–325.

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Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

childhood.[1] Several mechanisms have been
suggested for the development of PCG, which
result in angle dysgenesis and compromise outflow
through the trabecular meshwork. Goniotomy and
trabeculotomy have been recommended as the
initial procedures to improve outflow by removing
the abnormal trabecular tissue and making a
direct connection between the anterior chamber
and the Schlemm’s canal. Trabeculectomy and
glaucoma drainage device (GDD) implantation are
employed if the intraocular pressure (IOP) cannot
be controlled with the aforementioned procedures
or glaucoma medications.[2] The goal of glaucoma
medical and surgical interventions is to keep the
IOP at a specific level in order to halt or slow down
glaucoma progression.[3]

IOP is a dynamic parameter with an individual
circadian rhythm. Currently, management of
glaucoma include IOP measurements during clinic
hours performed a few times a year. A diurnal curve
may be used to evaluate glaucoma progression in a
patient when the office IOP is within an acceptable
range. The most common methods for assessing
the diurnal curve in glaucoma patients are IOP
readings at different time points during clinic hours
and hospitalization in a sleep laboratory; both are
cumbersome and costly. The Water Drinking Test
(WDT) has been suggested as a practical and easy-
to-perform test to estimate the diurnal IOP profile
in a more feasible and controlled fashion.[4, 5]

IOP changes after WDT have been evaluated in
adult patients with various types of glaucoma,[6, 7]
but not in children with PCG. Previous studies
also evaluated the WDT-IOP profile of adult
glaucoma patients who were taking glaucoma
medications or had undergone trabeculectomy,
deep sclerectomy, and GDD implantation.[8–11]
However, there is no study in patients
with PCG with prior trabeculotomy or GDD
implantation.

The main objective of the present study was to
evaluate the IOP changes after WDT in patients
with PCG and to compare the IOP changes in
those with the history of trabeculotomy and those
who underwent trabeculotomy followed by GDD
surgery.

METHODS

This prospective interventional study was
conducted in a tertiary eye care hospital
after getting approval from the local Ethics
Committee. The study followed the principles of
the Declaration of Helsinki, and informed consent
was obtained from the parents of all participants.

All enrolled patients underwent a complete
ophthalmological examination, which included
checking visual acuity, IOP measurement, and a
dilated stereoscopic fundus examination to assess
the amount of optic nerve head damage using Disc
Damage Likelihood Scale.[12] Subsequently, those
who met the eligibility criteria were included. The
average thickness of the peripapillary retinal nerve
fiber layer (using optical coherent tomography)
and the central corneal thickness were also
recorded.

At our center, all congenital glaucoma patients
undergo trabeculotomy at the superonasal and
inferotemporal sites in one session, and if the
IOP cannot be controlled using medications,
Ahmed Glaucoma Valve (FP7, New World Medical,
Rancho Cucamonga, LA, USA) is implanted
in the superotemporal quadrant. We do not
perform trabeculectomy because of the high
chance of failure. Therefore, all patients in the
current study had the history of trabeculotomy
procedure as the first line treatment. The
inclusion criterion was having a controlled PCG
with office IOP equal to or under 22 mmHg
with or without medication. The exclusion
criteria were the presence of ocular infection,
corneal opacity, or scar preventing reliable IOP
measurements; active heart or renal diseases; and
refusal of parents to enroll their children in the
study.

Water drinking test

Subjects were instructed to refrain from food and
fluid intake 3 hours preceding the WDT. After
checking the baseline IOP, patients drank 15 mL/kg
of bottled water in five minutes. Subsequently,
IOP was measured every 15 min for 1 hour.
The IOP was measured five times (baseline, 15,
30, 45, and 60 min after drinking water). One
examiner measured the IOP using a non-contact
tonometer (CT80; Topcon Co., Tokyo, Japan). The
average of three measurements was recorded
and the measurements were repeated if the
differences between the three measurements were
greater than 3 mmHg. The following parameters
were assessed: IOP trough (lowest IOP after
drinking water), IOP peak (highest IOP after
drinking water), IOP mean (the mean of the
four IOPs after drinking water), IOP fluctuation
(difference between peak IOP and baseline),
IOP range (difference between peak IOP and
lowest IOP reading after drinking water), and
end-pressure difference (IOP at 60 min versus
baseline).

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Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

Statistical analysis

The IOP of both eyes was measured, but one
eye was randomly selected (using a randomization
chart generated by a randomization software) for
inclusion in the study. All data were analyzed using
IBM SPSS Statistics software version 21 (SPSS Inc.,
Chicago, IL) and MedCalc version 12.2.1 (MedCalc
Software, Mariakerke, Belgium). Descriptive results
were presented as the mean ± standard deviation
(SD). A P-value < 0.05 was considered to be
statistically significant.

RESULTS

Patients’ baseline characteristics are presented
in Table 1. Of the 20 studied patients, 17 (85%)
had no associated systemic disease. Cardiac
disease (repaired ventricular septal defect),
phenylketonuria, and glucose-6-phosphate
dehydrogenase deficiency were each found in
one patient. However, no subject was on systemic
medications, and no patient was prohibited from
undergoing the WDT by the pediatrician.

The mean IOPs at baseline, and 15, 30, 45, and
60 min after WDT were 15.8 ± 3.7, 18.6 ± 3.4, 19.0 ±
3.8, 17.9 ± 3.8, and 16.9 ± 3.5 mm Hg, respectively
(P < 0.001, repeated-measures analysis of variance
(ANOVA); Figure 1). Pairwise comparisons using
Bonferroni correction revealed that the mean IOPs
15 and 30 min after WDT were significantly greater
than the baseline IOP (P < 0.001 and P = 0.002,
respectively), however, the mean IOPs after 45 and
60 min were not (P = 0.062 and P = 1, respectively).
The IOP after 60 min was significantly lower than
the IOP after 30 min (P = 0.03).

The values of different WDT-IOP parameters
were as following: IOP trough, 16.2 ± 3.2 (range,
10.0 to 22.0) mm Hg; IOP peak, 20.0 ± 3.5 (13.0
to 25.0); IOP mean, 18.1 ± 3.3 (12.0 to 23.3); IOP
fluctuation, 4.2 ± 2.9 (0.0 to 11.0); IOP range, 3.8
± 1.8 (1.0 to 7.0); and end-pressure difference, 1.1 ±
3.1 (–4.0 to 7.0). The first time-point to show an IOP
peak was 15 min in nine patients (45%), 30 min in six
(30%) patients, 45 min in three (15%) patients, and
60 min in two (10%) patients.

Linear regression analysis revealed the IOP
baseline to be the only statistically significant
determinant of the IOP peak (R2 = 0.463; P =
0.001; Figure 2A). The use of a higher number
of topical medications was also associated with a
trend toward higher IOP peak values (R2 = 0.170; P =
0.071). IOP fluctuation was significantly associated
with the IOP baseline (R2 = 0.216; P = 0.039; Figure
2B); and it was lower in the GDD group compared

with the trabeculotomy group (R2 = 0.158; P =
0.082).

Figure 2C and Table 2 summarize the results
of WDT in the GDD group and trabeculotomy
alone group. The repeated measures analysis of
covariance (assuming age, gender, body mass
index (BMI), and number of topical medications
as possible covariates) revealed no significant
difference in WDT-IOP changes between the two
surgical groups (P = 0.46; Figure 2C). Similarly,
with the exception of the IOP fluctuation, which
was marginally greater in the trabeculotomy alone
group than in the GDD group (5.0 vs 2.5 mm Hg;
P = 0.08; Table 2), the WDT-IOP parameters were
not significantly different. However, because of the
small sample size of the groups, the possibility
of a type 2 error should be considered while
interpreting the insignificant P-values.

Figure 2D shows the WDT-IOP changes in eyes
that underwent trabeculotomy with and without
adjunctive topical antiglaucoma medications.

DISCUSSION

Previous studies evaluated the WDT response
in medically treated glaucoma and in adults
who underwent trabeculectomy or GDD
implantation.[9, 11] In our study involving PCG
patients, the mean IOPs 15 and 30 min, but not 45
and 60 min, after WDT were significantly greater
than the baseline IOP. The highest mean IOP was
observed after 30 min. In the study by Martinez
et al,[11] comparing the results of the WDT in 40
eyes of 34 primary open angle glaucoma (POAG)
patients who underwent trabeculectomy or GDD
implantation, the highest mean IOP in both groups
was observed 30 min after WDT. Similarly, 20 eyes
from 20 POAG or ocular hypertension patients had
the highest mean IOP after WDT 30 min following
selective laser trabeculoplasty; however, before
the laser procedure the highest mean IOP was
observed after 45 min.[13] In the study by Mansouri
et al[14] involving normal subjects, the highest
mean IOP was detected 15 min after the WDT. The
ability of the outflow pathway to handle the load
after WDT may have affected the time at which
the highest mean IOP was detected. In normal
adults with normal outflow facility, the highest
IOP was observed after 15 min; however, in adult
patients who underwent trabeculectomy or GDD
implantation and in our patients, the highest IOP
was observed after 30 min.[11, 14]

In our study the IOP fluctuation in all patients
(GDD plus trabeculectomy), and in each of the
trabeculectomy, and GDD groups were 4.2, 5.0,

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Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

Table 1. Baseline characteristics of patients with primary congenital glaucoma

Characteristic Value

Age, year(s) 9.9 ± 2.7 (6 to 16)𝑎

Gender, (Male/Female) 8/12
Eye, (Right/Left) 12/8
Weight, kg 30.3 ± 12.2 (14 to 53)𝑎

Height, cm 134 ± 17 (104 to 169)𝑎

Body Mass Index, kg/m2 16.1 ± 3.4 (12.9 to 23.0)𝑎

Spherical Equivalent Refraction, Diopter(s) –2.7 ± 4.7 (–17.5 to +1.3)𝑎

Astigmatism, Diopter(s) –1.1 ± 1.1 (–4.5 to 0.0)𝑎

Central Corneal Thickness, μm 582 ± 47 (488 to 653)𝑎

Cup-to-Disc ratio, % 48 ± 24 (10 to 80)𝑎

Average Retinal Nerve Fiber Layer Thickness, μm 92 ± 23 (51 to 140)𝑎

Number of Topical Medications 1.4 ± 1.1 (0 to 3)𝑎

Lens status, n (%) Phakic: 20 (100)
Operation, n (%) Trabeculotomy only: 14 (70) GDD 6 (30)
Baseline Intraocular Pressure, mm Hg 15.8 ± 3.7 (8.5 to 21.0)𝑎

𝑎Scalar data are presented as mean ± standard deviation (range)

Table 2. Comparison of WDT-IOP parameters between the GDD (n = 6) and the trabeculotomy (n = 14) group

Parameter (mmHg) Operation P-value𝑏

Trabeculotomy𝑎 GDD𝑎

IOP Trough 16.0 ± 2.9 16.7 ± 4.1 0.66
IOP Peak 20.1 ± 3.4 19.6 ± 4.1 0.75
IOP Mean 18.0 ± 3.2 18.3 ± 3.9 0.86
IOP Fluctuation 5.0 ± 2.6 2.5 ± 3.1 0.08
IOP Range 4.2 ± 1.8 2.9 ± 1.6 0.14
End Pressure Difference 1.5 ± 3.1 0.3 ± 2.9 0.41

𝑎All data are presented as mean ± standard deviation; 𝑏Calculated with Independent Samples T-test; all measurements passed
the Shapiro–Wilk test of normality
IOP, intraocular pressure; GDD, glaucoma drainage device; WDT, water drinking test

and 2.5 mmHg, respectively. The reported IOP
fluctuation in adult glaucoma patients managed
medically ranged from 4.3 to 8.4 mmHg.[8–10, 15, 16]
The reported IOP fluctuations in eyes that
underwent trabeculectomy ranged from 1.6 to
3.95 (Table 3).[8, 10, 11]

A study on GDDs reported an IOP fluctuation
of 3.6 mmHg.[11] The IOP fluctuation in our
trabeculotomy group (4.2 mmHg) was greater
than the values reported in trabeculectomy (3.95
mmHg) and GDD (3.6 mmHg) groups in previous
studies. However, the IOP fluctuation in our GDD
group (2.5 mmHg) was lower than the value in
POAG patients with GDD (3.6 mmHg).[11]

Several studies have suggested that IOP
fluctuation is an important contributor to the
risk of glaucoma progression.[8, 17] The Early
Manifest Glaucoma Trial showed that even a 1
mmHg increase in IOP was associated with an
11% increase in the hazard ratio for glaucoma
progression.[18] The Advanced Glaucoma
Intervention Study Group suggested that IOP
peaks should be below 18 mmHg to prevent visual-
field deterioration in patients with moderate-
or advanced-stage glaucoma.[19] As glaucoma
progression is correlated with IOP peaks and
fluctuations,[20] accurate identification of at-risk
patients has become imperative as the first step

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Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

Table 3. The results of the water drinking test in normal subjects, primary open angle glaucoma, ocular hypertension, and
pseudoexfoliation syndrome

Authors Diagnosis Management of
glaucoma

Average
age of
patients
(years)

IOP
baseline
(mmHg)

IOP peak
(mmHg)

IOP
fluctuation
(mmHg)

Ozyol et al[15] XFS (34) No treatment 16.3 18.1 1.8
XFG(30) Medical therapy 65.6 19.7 26.9 7.2

De Moraes et al[16] POAG (22) Medical therapy 54.3 12.4 20.00 7.6
Danesh-Meyers et al[29] POAG Trabeculectomy 70 10.4 11.7 1.3

Medical therapy 68 11.4 17.3 5.9
Mansouri et al[8] POAG Trabeculectomy 67.1 10.1 12.5 2.4

Deep Sclerectomy 72.5 13.8 17.6 3.8
Latanoprost 71.2 15.9 21.1 5.2

Mansouri et al[14] Normal subjects (25) No treatment 35.6 14.9 16.8 1.9
Guedes RA et al[10] Normal subjects (20) No treatment 58.9 13.9 15.8 1.9

Glaucoma subjects (21) No treatment 17.5 26 8.4
Glaucoma subjects (21) Dorzolamide-timolol 14.2 18.6 4.3
Glaucoma subjects (15) Deep sclerectomy 12.3 14.1 1.7
Glaucoma subjects (21) Trabeculectomy 10 11.6 1.6

Kocabeyoglu et al[30] Normal subjects (20) No treatment 64.4 14 15.5 1.5
XFS (20) No treatment 66.1 15 17.2 2.2

Kerr et al[13] POAG and OHTN Before SLT 73 16.9 21 4.1
After SLT 14.2 16.5 2.3

Martinez et al[11] POAG Trabeculectomy (20) 67.9 12.3 16.25 3.95
GDD (20) 66.2 12.5 16.15 3.6

XFS, pseudoexfoliation syndrome; XFG, pseudoexfoliative glaucoma; POAG, primary open angle glaucoma; OHTN, ocular
hypertension; SLT, selective laser trabeculoplasty

in preventing further irreversible glaucomatous
damage.[21] It has been shown that, in two-thirds
of glaucoma patients, the highest IOP values
occur outside regular clinic hours, frequently
during the nocturnal/sleep period.[22] Therefore,
significant IOP fluctuation may be missed if relying
only on clinic IOP measurements. Twenty-four
hour IOP monitoring and provocative tests such
as WDT were suggested as viable options for
identifying a greater number of patients with
poorly controlled glaucoma. A group of normal
tension glaucoma patients underwent several
clinical tests for predicting the progression of
visual field loss, and the WDT was the most useful
clinical predictor for visual field progression.[5]
The IOP peak occurred during home tonometry
in approximately 30% of patients with progressive
visual field loss while it occurred during home
tonometry in 5% of patients with stable visual
fields.[23] After drinking water, the ability of the

outflow system to modulate the stress of an IOP
rise is the only mechanism that can control the
IOP. Interventions that improve outflow facility can
be expected to induce fewer changes in the IOP
after WDT.

The smoother WDT-IOP profile in our GDD
group may have a protective effect on the
damaged optic nerve. It is plausible that
trabeculotomy increases aqueous outflow, but
not as effective as GDD surgery, which bypasses
the congenitally abnormal aqueous drainage
pathway in PCG. The IOP fluctuation in the
trabeculotomy group was two times greater than
that in the GDD group (5.0 vs 2.5 mmHg; P =
0.08).

The IOP profile in the trabeculotomy group
on glaucoma medications was greater, though
not statistically significant, compared to the
trabeculotomy group who were not on medication

322 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 3, JULY-SEPTEMBER 2020



Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

Figure 1. The average intraocular pressure at baseline and at each time-point after the water drinking test in patients with
congenital glaucoma.

(Figure 2D). A trend toward a greater IOP
peak was observed as the number of topical
medications increased (R2 = 0.170; P = 0.071).
The use of glaucoma medications following the
surgical procedure indicates insufficient IOP
control and suggests the existence of increased
resistance to the outflow. In other words, the
higher number of medications may be an indirect
measure of the increased resistance in the outflow
pathway.

The baseline IOP was the only significant
determinant of the IOP peak (R2 = 0.463; P = 0.001).
This is in line with the findings of previous studies
in adult patients demonstrating that a higher IOP
at baseline is associated with greater 24-hour IOP
changes when measured in the seated position.[24]
The rate of aqueous production is steady and the
outflow facility is the only determinant factor of
IOP. When the baseline IOP is low, the possibility
of IOP fluctuation might be reduced because the
outflow pathway can handle the load and vice
versa.

IOP variation over time may be divided into
diurnal, short-term, and long-term fluctuations. It
is often difficult to get a true picture of a patient’s
IOP profile when it is measured only several times
a year. The current method of IOP measurements

is simply a snapshot of the real IOP over time and
does not represent the actual IOP profile. The
WDT is utilized as a provocative test to evaluate
outflow capacitance and the effect of medical or
surgical glaucoma treatments on the IOP peak
and fluctuation.[19] Studies have shown that the
WDT-IOP peak strongly correlates with the peak
of shortened diurnal curves and the long-term IOP
profile.[6, 16] The exact mechanism that underlies
IOP elevation after water ingestion remains
unclear. The proposed mechanisms include
choroidal expansion, plasma hypo-osmolality-
enhanced aqueous ultrafiltration, autonomic
nervous system stimulation, and increased
episcleral venous pressure.[7, 19] Compared
to the 24-hour IOP curve measurement that
requires the patient to stay in the hospital and
involves the measurement of IOPs at night,
the WDT could be an inexpensive and feasible
alternative.

This study has several limitations including
the small number of patients, especially in
the GDD group, and the fact that the IOP was
measured using an air-puff tonometer. In most
studies that involved performing WDT in adult
glaucoma patients, the number of participants was
around 20–30 patients, and in some studies both

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Water Drinking Test in Congenital Glaucoma; Razeghinejad et al

Figure 2. (A) The scatter diagram and regression line showing direct association between IOP baseline and IOP peak. (B) The
scatter diagram and regression line showing reverse association between IOP baseline and IOP fluctuation. (C) The IOP profile
after the water drinking test in the trabeculotomy and glaucoma drainage device implantation groups. (D) The IOP profile after
the water drinking test in eyes that underwent trabeculotomy with and without adjunctive topical antiglaucoma medications.

eyes were included (Table 3). In this study, we
included one eye from each patient. The global
prevalence of glaucoma for the population aged
40–80 years is 3.54%, which is much greater
than that for PCG (0.01–0.001%).[25, 26] The rarity
of this disease makes recruiting PCG patients
challenging. With respect to cooperation for IOP
measurement, non-Goldmann tonometer are
usually used for IOP measurement in pediatric
patients. It has been shown that, in PCG patients,
IOP values obtained using an air-puff tonometer
are similar to those obtained using a Goldmann
tonometer.[27] Additionally, in a recent meta-
analysis that compared all available tonometers
with the Goldmann applanation tonometer, air-
puff tonometers yielded the least amount of
variability in IOP values (mean difference of 0.2
mm Hg).[28]

In conclusion, the WDT induced significant
IOP elevation 15 and 30 min after the test
in patients with PCG. This increased IOP
returned to pre-test values after 45 min. In eyes
previously treated with trabeculotomy, the IOP
fluctuation was greater, though not statistically
significant.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

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