Content uploaded by Sebastião Cronemberger
Author content
All content in this area was uploaded by Sebastião Cronemberger on Sep 10, 2021
Content may be subject to copyright.
https://doi.org/10.1177/1120672120957584
European Journal of Ophthalmology
1 –8
© The Author(s) 2020
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/1120672120957584
journals.sagepub.com/home/ejo
EJO European
Journal of
Ophthalmology
Introduction
Primary open-angle glaucoma (POAG) is a multifacto-
rial disease in which elevated IOP is the main and only
treatable risk factor for onset and progression. Thus,
despite technological advances, the early diagnosis of
POAG and the detection of disease progression still
remain great challenges.
Optical coherence tomography (OCT) is a noninvasive
imaging technique that can obtain images that can be used
to evaluate the morphology and retinal nerve fiber layer
(RNFL) thickness, optic disc and macula with micrometer
resolution.1 Several studies have documented that reliable
measurements of RNFL thickness can be made from OCT
images.1–5 Diniz-Filho et al. investigated the association
between average intraocular pressure (IOP) and rates of
Correlation between retinal nerve fiber
layer thickness and IOP variation in
glaucoma suspects and patients with
primary open-angle glaucoma
Sebastião Cronemberger1, Artur W Veloso1,2 , Christy Veiga1,
Gustavo Scarpelli1, Yara C Sasso1 and Rafael V Merola1
Abstract
Purpose: To analyze the relationship between retinal nerve fiber layer thickness (RNFLT) and intraocular pressure
(IOP) variation in glaucoma suspects (GS) and patients with primary open-angle glaucoma (POAG).
Methods: Thirty-one GS and 34 POAG patients underwent ophthalmologic examination and 24-h IOP measurements.
GS had IOPs ranging from 19 to 24 mmHg and/or suspicious appearance of the optic nerve. POAG patients had
reproducible abnormal visual fields. We only included patients who presented with short-term IOP fluctuation >6 mm
Hg (∆IOP). Only one eye per patient was included through a randomized process. Peripapillary RNFLT was assessed by
spectral-domain optical coherence tomography. We correlated RNFLT with IOP parameters.
Results: Mean IOP was similar between GS and POAG groups (15.6 ± 3.47 vs 15.6 ± 2.83 mmHg, p = 0.90) as was IOP
peak at 6 AM (21.7 ± 3.85 vs 21.3 ± 3.80 mmHg, p = 0.68). Statistically significant negative correlations were found in
POAG group between IOP at 6 AM and RNFLT in global (rs = −0.543; p < 0.001), inferior (rs = −0.540; p < 0.001), superior
(rs = −0.405; p = 0.009), and nasal quadrants (rs = −0.561; p < 0.001). Negative correlations were also found between ∆IOP
and RNFLT in global (rs = −0.591; p < 0.001), and all other sectors (p < 0.05). In GS IOP at 6 AM correlated only with
inferior quadrant (rs = −0.307; p = 0.047).
Conclusion: IOP at 6 AM and ∆IOP had negative correlations with RNFLT quadrants in POAG. In GS this correlation
occurred between IOP at 6 AM and inferior quadrant. These findings may indicate potential risk factors for glaucoma
progression.
Keywords
Spectral domain OCT, POAG, IOP peak, glaucoma suspect
Date received: 19 April 2020; accepted: 14 August 2020
1 Visual Sciences Laboratory, Department of Ophthalmology and
Otorhinolaryngology of the Federal University of Minas Gerais, Belo
Horizonte, Minas Gerais, Brazil
2
Minas Gerais Research Foundation (FAPEMIG), Belo Horizonte, Minas
Gerais, Brazil
Corresponding author:
Sebastião Cronemberger, Federal University of Minas Gerais, Av. Prof.
Alfredo Balena, 190, Room 199, Belo Horizonte, MG 30130100, Brazil.
Email: secronem@gmail.com
957584EJO0010.1177/1120672120957584European Journal of OphthalmologyCronemberger et al.
research-article2020
Original research article
2 European Journal of Ophthalmology 00(0)
RNFLT change.2 These authors found that higher levels of
IOP during follow-up were associated with faster rates of
RNFL thickness loss over time, as measured by spectral
domain (SD) OCT. However, the authors emphasized that
although average IOP has been consistently established as
a risk factor for the development and progression of glau-
coma, other IOP parameters, such as 24-h IOP peaks and
fluctuations, potentially related to glaucomatous damage
have not yet been investigated.2 Miki et al. reported that
the rate of global RNFL thickness loss in glaucoma sus-
pects who developed a visual field defect (VFD) was more
than twice as fast when compared with eyes that did not
develop a VFD.3 A joint longitudinal survival model
showed that a 1-µm/year faster rate of RNFL thickness
loss corresponded to a 2.05-times higher risk of develop-
ing a VFD.3 The authors suggested that “measuring the
rate of SD-OCT RNFL loss may be a useful tool to help
identify patients who are at a high risk of developing
visual field loss.”3 Despite this finding, appropriate
investigation of IOP through 24-h IOP measurements,
also known as the daily curve of intraocular pressure
(DCPo), is not performed by most ophthalmologists
around the world because of expense and inconvenience.
Therefore, it is necessary to understand the role of 24-h
IOP measurements in the risk of developing glaucoma
and visual field loss. In our Glaucoma Service, 24-h IOP
measurements are routinely performed in glaucoma sus-
pects and in patients with glaucoma to detect early
changes or progression.6,7
Thus, the purpose of this study was to determine the
relationship between the RNFL thickness and the IOP
peak, mean and fluctuation.
Materials and methods
In this prospective, observational, case series study, glau-
coma suspects (GS), and POAG patients were evaluated.
The participants were identified at the Glaucoma Service
of São Geraldo Hospital from October 2013 to October
2016. Written informed consent was obtained from all
patients, and the investigation adhered to the tenets of
Declaration of Helsinki and started after approval of proto-
col by the Ethics Committee of the Federal University of
Minas Gerais.
All participants underwent ophthalmologic examina-
tions by a single glaucoma specialist (SC), including best-
corrected visual acuity (BCVA), slit-lamp examination of
the anterior ocular segment, Goldmann applanation
tonometry, 24-h IOP (DCPo) assessment,6,7 central corneal
thickness (CCT), gonioscopy, dilated fundus examination,
and standard automated perimetry. Vertical cup-disc (C/D)
assessment was performed by the same glaucoma special-
ist using a 78 Volk diopter lens, and a factor of correction
(×1.1) was applied to define the exact measurement. A
standard automated perimetry (SAP) was performed by an
experienced full-time operator in both eyes using a
Humphrey Field Analyzer (24-2 full-threshold test pro-
gram; Carl Zeiss Meditec, Dublin, Calif).
Inclusion criteria
GS were patients presenting with IOP values ranging from
19 to 24 mmHg in isolated measurements, considering
that 18 mmHg is the normal upper limit of IOP in Brazil,6,7
and/or a C/D ratio ⩾ 0.7 in one or both eyes, and/or asym-
metry of the C/D ratio ⩾ 0.3, and a visual field without
characteristic loss from glaucoma. POAG patients pre-
sented with a mean deviation (MD) < −2 decibels (dB)
and a consistent glaucomatous VFD comprising three
major patterns: (1) a Glaucoma Hemifield Test outside the
normal limits on at least two fields, (2) a cluster of three
or more non-edge points in a location typical for glau-
coma, two of which are depressed on the pattern deviation
plot at a p value of less than 5%, and one of which is
depressed at a p value of less than 1% on two consecutive
fields, or (3) a pattern standard deviation (PSD) that
occurs in less than 5% of normal fields on two consecu-
tive fields.8 Taking into account the between-eye correla-
tion in the individual, we included only one eye per patient
through a randomized process using computer software
(Research Randomizer, Version 4.0).9,10 Patients with sec-
ondary glaucoma and eyes with known ocular diseases,
such as the presence of a staphyloma, optic disc anoma-
lies or prior refractive surgery, were excluded.
Twenty-four-hour intraocular pressure
evaluation
All patients underwent a 24-h IOP with five IOP measure-
ments at 9 and 12 AM and 6 and 10 PM with a Goldmann
applanation tonometer and on the following day at 6 AM,
in a supine position in bed and in darkness, with a hand-
held Goldmann applanation tonometer (Perkins tonome-
ter) before the patient stood up. The DCPo was done for
early diagnosis in GS and for treatment assessment in
POAG. Only patients who presented with an abnormal
short-term IOP fluctuation (difference between highest
and lowest IOP value [ΔIOP] > 6 mmHg) were
included.6,7,11–19 All patients who met the inclusion criteria
had peripapillary RNFL thickness imaging by a Spectralis
SD-OCT (Heidelberg Engineering GmbH, Heidelberg,
Germany). The RNFL thickness were correlated with the
IOP at different time points.
RNFL imaging
The RNFLT was measured with the SD-OCT peripapil-
lary circle scan (Spectralis HRA+OCT; Heidelberg
Engineering Inc., Heidelberg, Germany). The basic princi-
ples of the SD-OCT technique have been described in the
Cronemberger et al. 3
literature.20 All SD-OCT images were acquired by a single,
well-trained technician who was blinded to the subjects’
clinical information. The examiner used the built-in scan
acquisition function called “circular” to acquire peripapil-
lary B-scans (high speed mode with automatic real time set
at 16 frames to improve image quality and optimize the
images with noise reduction, covering 30°) in a circular
(128 [approximately 3.4 mm] in diameter) pattern centered
at the optic disc. Only scans with a signal strength quality
⩾15, proper centration and the retina completely included
in image frame were included.
Statistical analysis
Statistical analysis was performed with the Statistical
Package for Social Sciences version 19.0 (SPSS Inc,
Chicago, IL) for Windows using Student t-tests, chi-square
tests, and Spearman’s rho correlations with a level of sig-
nificance <5% (p < 0.05).
Results
A total of 65 subjects (31 GS and 34 POAG, 65 eyes) were
enrolled in this study. Table 1 summarizes the demographic
characteristics, RNFL thickness, and CCT values of
patients in both groups. In patients with POAG, the mean
RNFL thickness was statistically significantly lower than
that in GS patients in the global and sectorial quadrants
(Table 1) except for the temporal quadrant (p = 0.79).
Figure 1 illustrates cases of RNFL thickness measured by
SD-OCT in the GS and POAG groups.
In the POAG group, 15 patients (44.1%) were using
only one glaucoma medication, 9 (26.5%) were using
two, 9 (26.5%) were using three, and 1 (2.9%) was using
four medications. A prostaglandin analogue was being
used alone by 29.4% of the patients and combined with
another glaucoma medication by 32.3% of the patients.
The remaining 38.3% of the patients were using one of
the following medications (alone or in combination):
timolol maleate, brimonidine tartrate, dorzolamide ace-
tate, brinzolamide or pilocarpine. All patients had
BCVA ⩾ 20/30, open-angle on the gonioscopy and nor-
mal anterior segment. The IOP peak (ΔIOP > 6 mmHg)
occurred at 6 AM in both groups, and there was no statis-
tically significant difference between groups. Table 2
summarizes the results of the statistical analysis of the
24-h IOP measurements, cup-to-disc ratio, MD, and PSD
of both groups.
In the POAG group, the IOP at 6 AM correlated signifi-
cantly with the RNFL thickness in the global (Spearman’s
rho correlation coefficient rs = −0.543, p < 0.001), inferior
(rs = −0.540, p < 0.001), superior (rs = −0.405, p = 0.009),
and nasal parameters (rs = −0.561, p < 0.001; Table 3).
Nevertheless, such correlations were not found to the same
degree in GS patients, with only the inferior parameter
reaching significance (rs = −0.307, p = 0.047).
Additionally, in the POAG group, the IOP at 10 PM sig-
nificantly correlated with the RNFLT in the global
(Spearman’s rho correlation coefficient rs = −0.321,
p = 0.032), inferior (rs = −0.348, p = 0.022), superior
(rs = −0.389, p = 0.012), and nasal parameters (rs = −0.403,
p = 0.009; Table 4). Again, in GS, only the inferior quad-
rant was significant (rs = −0.340, p = 0.031).
Analyzing the variation, the ∆IOP in POAG correlated
negatively with the RNFL thickness in all sectors: global
(rs = −0.591; p < 0.001), superior (rs = −0.321; p = 0.039),
inferior (rs = −0.429; p = 0.008), nasal (rs = −0.456;
p = 0.005), and temporal (rs = −0.566; p < 0.001). Figure 2
illustrates the relationship between the ∆IOP and RNFL
thickness across quadrants.
When considering the IOP measurements only during
office hours (9 AM, 11 AM, 6 PM), the mean IOP did not
show the same strength of correlation as the ∆IOP in the
POAG patients (Table 5).
Table 1. Subject demographic data, RNFL thickness and CCT (n = 65).
Variables GS, n = 31 eyes POAG, n = 34 eyes p value
Mean ± SD or n (%)
Age (years) 62.2 ± 15.6 64.6 ± 12.0 0.50
Sex M 11 (35.5) 12 (35.3) 0.98
F 20 (64.5) 22 (64.7)
CCT (µm) 530 ± 36.4 533 ± 30.3 0.68
RNFL thickness (µm) G 94.2 ± 16.1 84.5 ± 17.3 0.02**
I 122 ± 26.2 108 ± 26.6 0.03**
S 117 ± 23.2 104 ± 25.0 0.03**
N 72.7 ± 16.1 63.0 ± 15.3 0.01**
T 63.5 ± 14.9 63.4 ± 18.3 0.79
RNFL: retinal nerve fiber layer; CCT: central corneal thickness; GS: glaucoma suspects; POAG: primary open-angle glaucoma; n: number of eyes;
G: global; I: inferior; S: superior; N: nasal; T: temporal; M: male; F: female.
**Statistically significant.
4 European Journal of Ophthalmology 00(0)
Table 2. DCPo, MD, PSD, and C/D ratio of study subjects (n = 65).
Variables GS, n = 31 eyes POAG, n = 34 eyes p value
Mean ± SD
DCPo (mmHg) 6 AM 21.7 ± 3.85 21.3 ± 3.80 0.68
9 AM 15.0 ± 4.21 14.4 ± 3.21 0.54
11 AM 14.6 ± 3.47 14.3 ± 2.84 0.71
6 PM 13.9 ± 3.73 13.8 ± 3.22 0.92
10 PM 13.1 ± 3.94 13.9 ± 3.65 0.37
Mean 15.6 ± 3.47 15.6 ± 2.83 0.90
SD 3.72 ± 0.97 3.67 ± 0.97 0.85
C/D ratio 0.62 ± 0.14 0.66 ± 0.17 0.40
MD 0.41 ± 1.33 −3.09 ± 3.23 <0.001**
PSD 2.66 ± 1.09 9.23 ± 6.83 0.005**
DCPo: daily curve of IOP; MD: mean deviation; PSD: pattern standard deviation; C/D: cup-to-disc; GS: glaucoma suspects; n: number of eyes; SD:
standard deviation; POAG: primary open-angle glaucoma.
**Statistically significant.
Table 3. Correlation between intraocular pressure at 6 AM and retinal nerve fiber layer (RNFL) thickness in glaucoma suspects
(GS) and primary open angle glaucoma (POAG).
GS POAG
rs value* p value rs value* p value
RNFL thickness (µm)
Global −0.219 0.122 −0.543 <0.001**
Inferior −0.307 0.047** −0.540 <0.001**
Superior −0.157 0.199 −0.405 0.009**
Temporal −0.167 0.189 −0.285 0.05
Nasal −0.169 0.182 −0.561 <0.001**
*Spearman’s rho correlation coefficient.
**Statistically significant.
Figure 1. Examples of spectral domain optical coherence tomography in glaucoma suspect (GS) and primary open angle glaucoma
(POAG) groups. (a) Right eye of a 67-year-old GS patient with an intraocular pressure (IOP) peak of 21 mmHg at 6 AM and a retinal
nerve fiber layer (RNFL) thickness within normal limits; (b) Left eye of a 53-year-old POAG patient with an IOP peak of 25 mmHg
at 6 AM and an RNFL thickness outside normal limits in the global, nasal superior and temporal superior quadrants.
Cronemberger et al. 5
Using paired Student t-tests, the short-term IOP fluctua-
tion was also different when comparing 24-h IOP with the
measurements taken only during office hours (9.06 ± 2.38
vs 2.76 ± 1.68 mmHg, respectively; p < 0.001) in POAG
and GS (9.42 ± 2.41 vs 2.61 ± 1.72 mmHg, respectively;
p < 0.001).
Discussion
Elevated IOP has been consistently established as a prin-
cipal risk factor for the development and progression of
glaucoma. However, no consensus exists about what is
more important between the IOP peak and the IOP fluc-
tuation.21–23 It is necessary to emphasize that, from our
point of view, the IOP presents with normal fluctuation
in normal patients or might present as abnormal fluctua-
tion in glaucoma patients over 24 h. It is well-known that
the same normal or abnormal fluctuation may occur in
arterial blood pressure, glycemia, and other blood fea-
tures.24–27 Therefore, the IOP peak only reflects an
abnormal IOP fluctuation in POAG patients if it occurs
more often in early morning hours (6 AM in bed and in
darkness). This IOP peak is certainly an important risk
factor for the development and progression of glaucoma
in a great percentage of patients.6,11–19 Thomas et al.
found that the mean short-term IOP fluctuation was
8.6 mmHg in an ocular hypertensive population that
eventually progressed to POAG over 5 years of follow-
up compared to a mean of less than 6 mmHg in the group
that did not progress.16 Gonzalez et al. found similar
findings in their study in which 64% of cases with a
short-term fluctuation higher than 5 mmHg developed
visual field defects within a 4 year period.15 In a previous
study, we also reported that short-term fluctuations
higher than 6 mmHg with IOP peaks at 6 AM were
related to the diagnosis of pre-perimetric glaucoma in
64.3% of GS.6
There is substantial evidence that elevated or uncon-
trolled IOP even with medication develops into irrevers-
ible optic neuropathy and glaucoma progression, and
normalization of IOP is currently the only possible treat-
ment.21,28 We know that SD-OCT is a very important tool
for detecting RNFL thickness loss and its progression
during the moderate phase of glaucoma, but it is unable
to help with early glaucoma diagnosis and to follow
glaucoma progression in the final phase. Therefore, the
findings of this paper highlight that adequate investiga-
tion of 24-h IOP is paramount in the investigation of
glaucoma suspects and of uncontrolled glaucoma
patients. To the best of our knowledge, this study is the
Table 4. Correlation between intraocular pressure at 10 PM and retinal nerve fiber layer (RNFL) thickness in glaucoma suspects
(GS) and primary open angle glaucoma (POAG).
GS POAG
rs value* p value rs value* p value
RNFL thickness (µm)
Global −0.186 0.163 −0.321 0.032**
Inferior −0.340 0.031** −0.348 0.022**
Superior −0.138 0.230 −0.389 0.012**
Temporal −0.070 0.356 −0.020 0.455
Nasal −0.087 0.321 −0.403 0.009**
*Spearman’s rho correlation coefficient.
**Statistically significant.
Table 5. Correlations between retinal nerve fiber layer (RNFL) thickness and mean office-hours intraocular pressure (IOP −
office) and short-term intraocular pressure fluctuation (∆IOP) in primary open angle glaucoma.
IOP office ∆IOP
rs value* p value rs value* p value
RNFL thickness (µm)
Global −0.165 0.176 −0.591 <0.001**
Inferior −0.302 0.041** −0.429 0.008**
Superior −0.050 0.390 −0.321 0.039**
Temporal −0.011 0.475 −0.566 <0.001**
Nasal −0.278 0.056 −0.456 0.005**
*Spearman’s rho correlation coefficient.
**Statistically significant.
6 European Journal of Ophthalmology 00(0)
first study to investigate RNFL thickness by SD-OCT in
GS and POAG patients receiving treatment who had an
IOP peak (with a difference between the higher and the
lesser IOP value > 6 mmHg) at 6 AM over the course of
the 24-h IOP measurements.
As was expected, in our study, RNFL thickness was
lower in the global and sectorial quadrants of POAG
patients under treatment compared to GS patients (except
for the temporal quadrant). It is worth mentioning that the
mean IOP was 15.6 ± 3.47 and 15.6 ± 2.83 in the GS and
POAG groups, respectively (p = 0.90), and these values
would be lower if we were to exclude the measurements of
IOP at 6 AM (21.7 ± 3.85 in GS and 21.3 ± 3.80 in POAG,
p = 0.68). We found that the IOP at 6 AM significantly and
negatively correlated with global RNFL and most sectors
of RNFL thickness parameters in POAG patients, but we
only found this negative correlation to a lesser degree in
the inferior quadrant of the GS group. The IOP at 10 PM
also correlates negatively with the RNFL thickness in the
same quadrants as the IOP at 6 AM for the POAG patients,
and such significance was found only in the inferior quad-
rant for the GS patients. Previous studies with OCT have
identified the average and inferior RNFL thickness as the
best parameters to discriminate between healthy and glau-
comatous eyes.29–34 One study found that inferior RNFL
location had the highest accuracy for distinguishing GS
from control eyes.35 Possibly, elevated IOP as a risk factor
may have some influence on the values of RNFL, with the
inferior quadrant apparently manifesting these changes
earlier in GS. Also, IOP value at 10 PM, despite being one
of the lowest measured, correlated with the inferior quad-
rant in GS group. Increase in IOP at this time could poten-
tially lead to glaucoma progression by direct elevation of
IOP, or by reduced ocular perfusion associated with lower
blood pressure at night.36 However, a longitudinal study
would be necessary to evaluate those hypotheses.
The ∆IOP also correlated negatively with all sectors of
the RNFL thickness in the POAG patients, especially the
temporal sector (rs = −0.566, p < 0.001), which was not
found for other parameters.
It is worth mentioning that the mean IOP taken during
office-hours had a weaker correlation with RNFL thick-
ness than the ∆IOP, with only a significant relation in the
inferior quadrant of the POAG patients (rs = −0.302;
p = 0.041). These findings may indicate that if the IOP
peak is not adequately reversed, SD-OCT might show
Figure 2. Scatterplots demonstrating the relationship between RNFL thickness and ∆IOP in primary open angle glaucoma.
RNFL: retinal nerve fiber layer; ∆IOP: (highest intraocular pressure − lowest intraocular pressure) over 24 h.
Cronemberger et al. 7
RNFL thickness changes over time, since higher levels of
IOP are associated with faster rates of RNFL thickness
loss.2,6,23 Thus, it is necessary in further studies to use
SD-OCT to determine the role of short-term and long-term
IOP peak in the evaluation and progression of GS and
POAG patients.
To avoid SD-OCT changes, we prescribed one drop of
2% pilocarpine at 10 PM for glaucoma suspects who pre-
sented with an abnormal DCPo associated with an IOP
peak at 6 AM with good results in the reversion of the IOP
peak.37 For the POAG patients under treatment who pre-
sented with an IOP peak at 6 AM, we changed the anti-
glaucomatous medication, and will repeat the 24-h IOP
measurements to examine its efficacy.
The limitations of this study were the relatively small
number of patients and ethical issues of a longitudinal
OCT follow-up of GS without medication. Further investi-
gations are warranted for measuring the longitudinal rates
of RNFL thickness loss with the purpose of identifying
patients who are at a high risk of developing visual field
defects because of their IOP peak (ΔIOP > 6 mmHg).
Conclusion
In the POAG group, the IOP at 6 AM and 10 PM and the
∆IOP correlated negatively with the RNFL thickness
quadrants, while in GS IOP at 6 AM and 10 PM correla-
tions were only seen in the inferior quadrant. Further stud-
ies are needed to establish if these findings are potential
risk factors for glaucoma progression.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iDs
Sebastião Cronemberger https://orcid.org/0000-0003-1466
-9963
Artur W Veloso https://orcid.org/0000-0003-2771-3556
Rafael V Merola https://orcid.org/0000-0002-8846-3610
References
1. Lin SC, Singh K, Jampel HD, et al. Optic nerve head and
retinal nerve fiber layer analysis: a report by the American
Academy of Ophthalmology. Ophthalmology 2007;
114(10): 1937–1949.
2. Diniz-Filho A, Abe RY, Zangwill LM, et al. Association
between intraocular pressure and rates of retinal nerve fiber
layer loss measured by optical coherence tomography.
Ophthalmology 2016; 123(10): 2058–2065.
3. Miki A, Medeiros FA, Weinreb RN, et al. Rates of reti-
nal nerve fiber layer thinning in glaucoma suspect eyes.
Ophthalmology 2014; 121(7): 1350–1358.
4. Cronemberger S, Veiga C, Lobato MH, et al. Spectral-
domain OCT and 24-hour intraocular pressure in glaucoma
suspects and glaucoma patients. Invest Ophthalmol Vis Sci
2016; 57(12): 6457–6457.
5. Hood DC and Raza AS. On improving the use of OCT imag-
ing for detecting glaucomatous damage. Br J Ophthalmol
2014; 98(Suppl. 2): ii1–ii9.
6. Cronemberger S, Silva AC and Calixto N. Importance of
intraocular pressure measurement at 6:00 a.m. in bed and in
darkness in suspected and glaucomatous patients. Arq Bras
Oftalmol 2010; 73(4): 346–349.
7. Calixto NC. Intraocular pressure, daily curve of intraocu-
lar pressure, sclera rigidity and tonographic coefficients
(means, of normality in different age-groups). PhD Thesis,
Federal University of Minas Gerais, Brazil, 1967.
8. Anderson DR and Patella VM. Interpretation of a single
field. In: Automated static perimetry. 2nd ed. St. Louis:
Mosby, 1999, pp. 151–153.
9. Murdoch IE, Morris SS and Cousens SN. People and eyes:
statistical approaches in ophthalmology. Br J Ophthalmol
1998; 82(8): 971–973.
10. Ray WA and O’Day DM. Statistical analysis of multi-eye
data in ophthalmic research. Invest Ophthalmol Vis Sci
1985; 26(8): 1186–1188.
11. Cioffi GA, Durcan FJ and Girkin CA. American Academy of
Ophthalmology, basic and clinical science course (BCSC)
section 10: glaucoma. San Francisco, CA: American
Academy of Ophthalmology, 2010, pp. 17–31.
12. Sakata R, Aihara M, Murata H, et al. Intraocular pres-
sure change over a habitual 24-hour period after changing
posture or drinking water and related factors in normal
tension glaucoma. Invest Ophthalmol Vis Sci 2013; 54(8):
5313–5320.
13. Sacca SC, Rolando M, Marletta A, et al. Fluctuations of
intraocular pressure during the day in open-angle glau-
coma, normal-tension glaucoma and normal subjects.
Ophthalmologica 1998; 212: 115–119.
14. Fogagnolo P, Orzalesi N, Centofanti M, et al. Short- and
long-term phasing of intraocular pressure in stable and pro-
gressive glaucoma. Ophthalmologica 2013; 230(2): 87–92.
15. Gonzalez I, Pablo LE, Pueyo M, et al. Assessment of diurnal
tensional curve in early glaucoma damage. Int Ophthalmol
1996; 20(1–3): 113–115.
16. Thomas R, Parikh R, George R, et al. Five-year risk of
progression of ocular hypertension to primary open angle
glaucoma. A population-based study. Indian J Ophthalmol
2003; 51: 329–333.
17. Tajunisah I, Reddy SC and Fathilah J. Diurnal variation
of intraocular pressure in suspected glaucoma patients and
their outcome. Graefes Arch Clin Exp Ophthalmol 2007;
245(12): 1851–1857.
18. Jonas JB, Budde WM, Stroux A, et al. Diurnal intraocular
pressure profiles and progression of chronic open-angle
glaucoma. Eye (Lond) 2007; 21(7): 948–951.
19. 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 2000; 9(2): 134–142.
8 European Journal of Ophthalmology 00(0)
20. van Velthoven ME, Faber DJ, Verbraak FD, et al. Recent
developments in optical coherence tomography for imaging
the retina. Prog Retin Eye Res 2007; 26(1): 57–77.
21. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular
hypertension treatment study: a randomized trial deter-
mines that topical ocular hypotensive medication delays or
prevents the onset of primary open-angle glaucoma. Arch
Ophthalmol 2002; 120(6): 701–713; discussion 829–730.
22. Leidl MC, Choi CJ, Syed ZA, et al. Intraocular pressure
fluctuation and glaucoma progression: what do we know?
Br J Ophthalmol 2014; 98(1): 1315–1319.
23. Gautam N, Kaur S, Kaushik S, et al. Postural and diurnal
fluctuations in intraocular pressure across the spectrum of
glaucoma. Br J Ophthalmol 2016; 100(4): 537–541.
24. Troisi RJ, Cowie CC and Harris MI. Diurnal variation in
fasting plasma glucose: implications for diagnosis of dia-
betes in patients examined in the afternoon. JAMA 2000;
284(24): 3157–3159.
25. Pimentel LG, Gracitelli CP, da Silva LS, et al. Association
between glucose levels and intraocular pressure: pre- and
postprandial analysis in diabetic and nondiabetic patients. J
Ophthalmol 2015; 2015: 1–5.
26. Kim YK, Oh WH, Park KH, et al. Circadian blood pressure
and intraocular pressure patterns in normal tension glau-
coma patients with undisturbed sleep. Korean J Ophthalmol
2010; 24(1): 23–28.
27. Fijorek K, Puskulluoglu M and Polak S. Circadian models
of serum potassium, sodium, and calcium concentrations in
healthy individuals and their application to cardiac electro-
physiology simulations at individual level. Comput Math
Methods Med 2013; 2013: 1–8.
28. Appropriateness of Treating Glaucoma Suspects RAND
Study Group. For which glaucoma suspects is it appropriate
to initiate treatment? Ophthalmology 2009; 116(4): 710–
716, 716.e711–782.
29. Gyatsho J, Kaushik S, Gupta A, et al. Retinal nerve fiber
layer thickness in normal, ocular hypertensive, and glau-
comatous Indian eyes: an optical coherence tomography
study. J Glaucoma 2008; 17(2): 122–127.
30. Leung CK, Chan WM, Yung WH, et al. Comparison of
macular and peripapillary measurements for the detec-
tion of glaucoma: an optical coherence tomography study.
Ophthalmology 2005; 112(3): 391–400.
31. Medeiros FA, Zangwill LM, Bowd C, et al. Evaluation
of retinal nerve fiber layer, optic nerve head, and macu-
lar thickness measurements for glaucoma detection using
optical coherence tomography. Am J Ophthalmol 2005;
139(1): 44–55.
32. Shin HJ and Cho BJ. Comparison of retinal nerve fiber layer
thickness between Stratus and Spectralis OCT. Korean J
Ophthalmol 2011; 25(3): 166–173.
33. Mwanza JC, Durbin MK, Budenz DL, et al. Glaucoma
diagnostic accuracy of ganglion cell-inner plexiform layer
thickness: comparison with nerve fiber layer and optic nerve
head. Ophthalmology 2012; 119(6): 1151–1158.
34. Mwanza JC, Oakley JD, Budenz DL, et al. Ability of cirrus
HD-OCT optic nerve head parameters to discriminate nor-
mal from glaucomatous eyes. Ophthalmology 2011; 118(2):
241–248.e241.
35. Liu S, Wang B, Yin B, et al. Retinal nerve fiber layer reflec-
tance for early glaucoma diagnosis. J Glaucoma 2014;
23(1): e45–e52.
36. Moon Y, Kwon J, Jeong DW, et al. Circadian patterns of
intraocular pressure fluctuation among normal-tension
glaucoma optic disc phenotypes. PLoS One 2016; 11(12):
e0168030, 1–17.
37. Moraes MN, Cronemberger S, Lana PC, et al. Efficacy of
one drop of 2% pilocarpine on the control of the peak of
the intraocular pressure at 6 a.m. in glaucoma. Vis Pan Am
2012; 11(13): 14–16.
