Original Article

Optical Coherence Tomography Angiography Findings
after Acute Intraocular Pressure Elevation in Patients

with Diabetes Mellitus versus Healthy Subjects

Maryam Ashraf Khorasani1, MD; Giancarlo A Garcia2, MD; Pasha Anvari1, MD, MPH; Abbas Habibi1, MD;
Shahriar Ghasemizadeh1, BS; Khalil Ghasemi Falavarjani1,3, MD

1Eye Research Center, The Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
2Byers Eye Institute at Stanford University, Palo Alto, CA, USA

3Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

ORCID:
Ashraf Khorasani: https://orcid.org/0000-0003-2046-5633

Khalil Ghasemi Falavarjani: https://orcid.org/0000-0001-5221-1844

Abstract

Purpose: To assess the changes in optic nerve head and macular microvascular
networks after acute intraocular pressure (IOP) rise in healthy eyes versus the
eyes of diabetic patients.
Methods: In this prospective, interventional, comparative study, 24 eyes of 24
adults including 12 eyes of healthy nondiabetic subjects and 12 eyes with mild
or moderate non-proliferative diabetic retinopathy (NPDR) were enrolled. IOP
elevation was induced by a suction cup attached to the conjunctiva. IOP and
optical coherence tomography angiographic (OCTA) images of the optic disc and
macula were obtained before and immediately after the IOP rise.
Results: Baseline and post-suction IOPs were not significantly different between
the two groups (all P > 0.05). The mean IOP elevation was 13.93 ± 3.41 mmHg
among all eyes and was statistically significant as compared to the baseline in
both groups (both P < 0.05). After IOP elevation, healthy eyes demonstrated a
reduction in the vessel density in the whole image deep and superficial capillary
plexuses and parafoveal deep capillary plexus (DCP) (all P < 0.05). In diabetic
retinopathy, foveal vessel density at DCP decreased significantly following IOP
rise (P = 0.003). In both groups, inside disc vessel density decreased significantly
after IOP rise (both P < 0.05), however, no significant change was observed in
peripapillary vessel density (both P > 0.05).
Conclusion: Acute rise of IOP may induce different levels of microvascular
changes in healthy and diabetic eyes. Optic disc microvasculature originating
from the posterior ciliary artery may be more susceptible to IOP elevation than
that of retinal microvasculature.

Keywords: Diabetic Retinopathy; Glaucoma; Intraocular Pressure; Macula; Ocular Blood
Flow; Ocular Perfusion; Optic Nerve; Optical Coherence Tomography Angiography; Retinal
Imaging; Vessel Density
This paper was presented in part in 7𝑡ℎ OCT and OCTA meeting, Rome, December 2019.

J Ophthalmic Vis Res 2022; 17 (3): 360–367

360 © 2022 Ashraf Khorasani et al. THIS IS AN OPEN ACCESS ARTICLE DISTRIBUTED UNDER THE CREATIVE COMMONS ATTRIBUTION LICENSE | PUBLISHED BY KNOWLEDGE E

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

INTRODUCTION

Glaucoma is a major cause of irreversible vision
loss and one of the leading causes of blindness
worldwide.[1, 2] Several studies have demonstrated
that structural changes that occur in the retina and
optic nerve in glaucoma are preceded by functional
disorders.[3–10]

The exact mechanism by which glaucoma
leads to structural changes has not yet been
well understood. Both mechanical and vascular
theories have been proposed to describe the
pathogenesis of glaucoma-induced structural
changes, though neither of these theories alone is
sufficient to fully explain the disease mechanism.
In both theories, however, increased intraocular
pressure (IOP) plays an important role.[11, 12]

The mechanical theory proposes that
increased IOP compresses intraocular structures
and attenuates axoplasmic flow leading to
glaucomatous changes. In the vascular theory,
it is believed that impaired blood supply leads
to structural damages.[12–14] The latter theory
is supported by findings that link systemic
hypotension to increased risk of glaucomatous
optic neuropathy.

Autoregulation is a mechanism that, despite
the changes in ocular perfusion pressure (OPP),
maintains a relatively constant level of ocular blood
flow (OBF) and provides sufficient oxygen and
nutrients for the cells.[15] OPP is expressed as the
difference between the arterial blood pressure and
the IOP. Accordingly, a reduction in blood pressure
or an increase in IOP leads to a reduction of OPP.
In normal eyes, autoregulation compensates for
these changes, and blood flow to the eye remains
constant. If, however, autoregulation is impaired,
or IOP surpasses a threshold and the eye is unable
to compensate, OBF becomes unstable; in this

Correspondence to:

Khalil Ghasemi Falavarjani, MD. Eye Research Center,
Rassoul Akram Hospital, Sattarkhan-Niaiesh St., Tehran
1449614535, Iran.
E-mail: drghasemi@yahoo.com
Received: 09-03-2021 Accepted: 28-12-2021

Access this article online

Website: https://knepublishing.com/index.php/JOVR

DOI: 10.18502/jovr.v17i3.11573

context, small changes in IOP lead to changes in
OBF that can induce glaucomatous changes.[16–19]

Dysfunctional ocular autoregulation that
plays an important role in the development
and progression of glaucoma occurs in diabetic
patients as well.[18, 19] The pathophysiology of
diabetes mellitus also involves dysfunctional
vascular regulation, where the disease is believed
to share an association with glaucoma, although a
definitive link has not been established.[18, 19]

Various modalities have been utilized
to asses OBF changes after acute IOP
rise, including Doppler sonography,[20, 21]
laser interferometry,[20, 22] and laser Doppler
flowmetry.[21, 22] However, these methods are
limited by their invasive nature and inability to
record all retinal vascular layers simultaneously.
Optical coherence tomography angiography
(OCTA), on the other hand, is a noninvasive
technology that enables the visualization of blood
vessels in different layers of the retina and choroid
without dye injection.[23] This modality employs
consecutive optical coherence tomography
(OCT) b-scans captured from the same location,
comparing the decorrelation signal between
scans to identify blood vessels and map blood
flow.[24] Previous studies have shown that OCTA
is a reliable imaging modality for the diagnosis
of different retinal, choroidal, and optic nerve
diseases.[25–27]

We herein utilized OCTA to assess changes in
the optic nerve head, the macular vasculature,
as well as retinal thickness following acute IOP
rise, and compared these changes in the eyes of
healthy versus diabetic subjects. To the best of our
knowledge, this is the first study assessing changes
in the optic nerve head and macular vasculature as
well as the retinal thickness around the optic disc
and in the macular area following the acute rise of
IOP in normal versus diabetic subjects.

This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

How to cite this article: Khorasani MA, Garcia GA, Anvari P,
Habibi A, Ghasemizadeh S, Falavarjani KG. Optical Coherence
Tomography Angiography Findings after Acute Intraocular
Pressure Elevation in Patients with Diabetes Mellitus versus
Healthy Subjects. J Ophthalmic Vis Res 2022;17:360–367.

JOURNAL OF OPHTHALMIC AND VISION RESEARCH Volume 17, Issue 3, July-September 2022 361

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

METHODS

This prospective interventional comparative study
was conducted at the Ophthalmology Clinic of the
Rassoul Akram Hospital, Iran University of Medical
Sciences. Participants were enrolled between
the periods of September and December 2018.
The Ethics Committee of the Iran University of
Medical Sciences approved the study protocol
(IR.IUMS.REC.1398.200). Informed consent was
obtained from the patients, and the study was
conducted in accordance with the tenets of the
Helsinki Declaration.

In this study, nondiabetic healthy subjects with
no ocular disorders and patients with mild or
moderate non-proliferative diabetic retinopathy
(NPDR group) were included. All participants
underwent a standard baseline comprehensive
ophthalmic examination that included the Snellen
best-corrected visual acuity (BCVA) measurements,
IOP measurements using a rebound tonometer
(Icare ic100, Icare®, Vantaa, Finland), slit-lamp
examination, and dilated fundus examination.

All included eyes had to have an IOP of
<22mmHg and spherical equivalent refraction
between –6 and +4 diopters. Healthy eyes
had a BCVA of 20/20 or better with normal
comprehensive ocular examinations. Inclusion
criteria for the NPDR group were type 2 diabetics
who were taking only oral antidiabetic medications,
with clinical evidence of mild or moderate NPDR
in both eyes according to the Early Treatment
of Diabetic Retinopathy Study (ETDRS) grading
criteria.[28]

Exclusion criteria were any media opacity
(e.g., cataract or vitreous hemorrhage) that might
interfere with imaging, eyes with an OCT scan
quality of <7, and a history of any ocular surgery or
ocular laser treatment.

Image Acquisition and Elevation of IOP

OCTA imaging was performed by a RTVue XR
Avanti device (Version 2017.1.0.151, Optovue,
Inc., Fremont, CA, USA). Baseline OCTA images
included macular (3× 3) and optic disc (4.5 × 4.5)
scans in the same session. IOP was recorded
using an Icare device at baseline. The procedure
for inducing IOP elevation has been described
elsewhere.[29] In brief, after achieving topical
anesthesia using tetracaine 0.5% ophthalmic

solution, the episcleral suction cup was attached
to the temporal conjunctiva to apply negative
pressure to the globe. Immediately after the
application of the suction cup, IOP was recorded
again while the suction cup was stable and the
imaging was repeated with the same macular
and optic disc protocols, with the suction cup in
place. A drop of artificial tears was administered
before post-suction measurements to avoid dry
eye-induced image distortion. A minimum increase
of 5 mmHg in IOP was needed to proceed to post-
suction image acquisition. If there was slippage of
the suction cup, all measurements were postponed
to another day.

The parameters extracted included retinal
vessel density at fovea and parafovea in the
deep capillary plexus (DCP) and at the superficial
capillary plexus (SCP) layers. The SCP en face
image was automatically segmented with an inner
boundary set at the internal limiting membrane
(ILM) and an outer boundary set at 9 µm above the
inner plexiform layer (IPL). The DCP en face image
was segmented with an inner boundary set at 9
µm above the IPL and an outer boundary at 9 µm
below the outer plexiform layer (OPL). Peripapillary
and inside disc vessel density measurements were
automatically recorded from the ILM to the lower
border of the nerve fiber layer. From the AngioDisc
images, the peripapillary retinal nerve fiber layer
(RNFL) thickness as well as the vessel density
of the peripapillary and inside disc regions were
recorded. “Inside disc vessel density” was defined
as the percentage of vessels inside the borders of
the optic disc that was automatically determined
by the OCTA software. Peripapillary vessel density
was calculated for the 750 µm wide ring-shaped
area that is located circumferentially around the
periphery of the optic disc margins.

Statistical Analysis

The SPSS software version 18.0 (SPSS, Inc.,
Chicago, IL, USA) and Medcalc software version
19 (MedcalcSoftware, Mariakerke, Belgium) were
utilized for statistical analysis. P-values < 0.05 were
considered statistically significant. All continuous
variables were expressed as mean ± standard
deviation (SD). Paired samples t-test was utilized
to compare variables before and after the IOP
rise. The general linear model was used to adjust
for differences in age and baseline vessel density
measurements.

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

Table 1. Baseline characteristics in the two groups.

Healthy eyes NPDR eyes 𝑃-value
Number of eyes 12 12

Age (Years) 40.00 ± 11.38 56.17 ± 12.11 0.03
Intraocular pressure (mmHg) 15.28 ± 2.95 17.34 ± 3.29 0.121
Whole image SCP vessel density (%) 47.47 ± 2.29 39.84 ± 5.38 <0.001
Foveal SCP vessel density (%) 18.22 ± 5.25 11.10 ± 5.09 0.003
Parafoveal SCP vessel density (%) 50.22 ± 2.50 41.97 ± 6.22 0.001
Whole image DCP vessel density (%) 49.50 ± 2.72 45.06 ± 5.02 0.016
Foveal DCP vessel density (%) 32.92 ± 6.53 25.21 ± 8.18 0.018
Parafoveal DCP vessel density (%) 51.32 ± 2.64 47.23 ±5.16 0.026
Whole image disc vessel density (%) 50.70± 1.22 48.46± 3.22 0.041
Peripapillary vessel density (%) 53.64 ± 1.27 51.03 ± 4.09 0.055
Inside disc vessel density (%) 49.97 ± 2.68 48.04 ± 3.48 0.142
Peripapillary RNFL thickness (µm) 114.92 ± 12.39 105.08 ± 12.59 0.067

The data is presented as mean ± SD.
SCP, superficial capillary plexus; DCP, deep capillary plexus; RNFL, retinal nerve fiber layer; DM, diabetes mellitus; NPDR, non-
proliferative diabetic retinopathy

Table 2. Baseline and post-suction values in healthy eyes.

Baseline Post-suction P-value

IOP (mmHg) 15.28 ± 2.95 28.52 ± 3.33 <0.001
Whole image SCP vessel density (%) 47.47 ± 2.29 45.86 ± 2.54 0.015
Foveal SCP vessel density 18.22 ± 5.25 17.67 ± 5.29 0.336
Parafoveal SCP vessel density (%) 50.22 ± 2.50 48.75 ± 2.54 0.050
Whole image DCP vessel density (%) 49.50 ± 2.72 47.22 ± 3.78 0.005
Foveal DCP vessel density 32.92 ± 6.53 33.06 ± 6.49 0.745
Parafoveal DCP vessel density (%) 51.32 ± 2.64 49.46 ± 3.70 0.010
Whole image disc density (%) 50.70± 1.22 49.67 ± 2.43 0.081
Peripapillary vessel density (%) 53.64 ± 1.27 53.12 ± 2.63 0.365
Inside disc vessel density (%) 49.97 ± 2.68 47.46 ± 4.15 0.017
Peripapillary RNFL thickness (µm) 114.92 ± 12.39 114.83 ± 11.91 0.862

IOP, intraocular pressure; SCP, superficial capillary plexus; DCP, deep capillary plexus; RNFL, retinal nerve fiber layer

RESULTS

In this study, 24 eyes (12 healthy eyes and 12 eyes
with NPDR) of 24 adult patients were included.
Baseline characteristics are shown in Table 1. The
mean age was 40.00 ± 11.38 and 56.17 ± 12.11 years
in healthy and NPDR eyes, respectively (P = 0.03).
The baseline IOP was 15.28 ± 2.95 mmHg and

17.34 ± 3.29 mmHg in healthy and NPDR eyes,
respectively (P = 0.121).

At baseline, the retinal vessel density for whole
image, foveal and parafoveal SCP and DCP
was significantly lower in the NPDR group as
compared to the healthy eyes (all P < 0.05).
While vascular density of the whole optic nerve
head was significantly lower in eyes with NPDR
as compared to the normal eyes (P = 0.041),

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

Table 3. Baseline and post-suction measurements in eyes with nonproliferative diabetic retinopathy.

Baseline Post-vacuum P-value

IOP (mmHg) 17.34 ± 3.29 31.96 ± 5.30 <0.001
Whole image SCP vessel density (%) 39.84 ± 5.38 38.64 ± 5.95 0.133
Foveal SCP vessel density 11.10 ± 5.09 10.52± 5.37 0.134
Parafoveal SCP vessel density (%) 41.97 ± 6.22 40.85 ± 6.79 0.179
Whole image DCP vessel density (%) 45.06 ± 5.02 43.87 ± 3.62 0.226
Foveal DCP vessel density 25.21 ± 8.18 24.25 ± 7.93 0.003
Parafoveal DCP vessel density (%) 47.23 ±5.16 46.28 ± 3.64 0.313
Whole image disc density (%) 48.46± 3.22 47.74 ± 2.66 0.233
Peripapillary vessel density (%) 51.03 ± 4.09 51.12 ± 3.01 0.901
Inside disc vessel density (%) 48.04 ± 3.48 44.35 ± 3.77 0.007
Peripapillary RNFL thickness (µm) 105.08 ± 12.59 103.33 ± 12.31 0.005

IOP, intraocular pressure; SCP, superficial capillary plexus; DCP, deep capillary plexus; RNFL, retinal nerve fiber layer

Table 4. Comparison of the measurement changes between healthy eyes and eyes with nonproliferative diabetic retinopathy
after acute rise of intraocular pressure after adjustment for age.

Group 1 (healthy eyes) Group 2 (NPDR) P-value∗

IOP (mmHg) 13.24 ± 3.97 14.62 ± 2.73 0.243
Whole image SCP vessel density (%) –1.62 ± 1.93 –1.20 ± 2.56 0.642
Foveal SCP vessel density –0.56 ± 1.92 –0.57 ± 1.23 0.774
Parafoveal SCP vessel density (%) –1.47 ± 2.31 –1.12 ± 2.71 0.767
Whole image DCP vessel density (%) –2.27 ± 2.22 –1.20 ± 3.24 0.332
Foveal DCP vessel density 0.14 ± 1.47 -0.96 ± 0.85 0.155
Parafoveal DCP vessel density (%) –1.87 ± 2.08 –0.95± 3.11 0.966
Whole image disc density (%) –1.03 ± 1.86 –0.72 ± 1.96 0.202
Peripapillary vessel density (%) 0.52 ± 1.92 0.08 ± 2.27 0.143
Inside disc vessel density (%) –2.51 ± 3.09 –3.69 ± 3.90 0.298
Peripapillary RNFL thickness (µm) –0.08 ± 1.62 –1.75 ± 1.71 0.011

SCP, superficial capillary plexus; DCP, deep capillary plexus; RNFL, retinal nerve fiber layer; DM, diabetes mellitus; NPDR, non-
proliferative diabetic retinopathy
∗P-value adjusted for age and baseline vessel density measurements using general linear model.

there were no statistically significant differences
in the peripapillary and inside disc vessel densitie
between the two groups.

The mean increase in IOP after scleral suction
was 13.24 mmHg in healthy eyes (range, 6.60–
19.40) and 14.62 mmHg in NPDR eyes (range, 11.0–
19.90), corresponding to a mean of 13.93 ± 3.41
mmHg among all eyes. A post-suction increase
of >9 mmHg was experienced by 90% of the
healthy eyes, and in 100% of the NPDR eyes.

Post-suction change in IOP had no statistically
significant differences between the two groups (P
= 0.243).

Tables 2–3 display OCTA measurements after
acute elevation in IOP. After the IOP rise in the
healthy eyes, vessel density in the whole image
of the SCP and DCP, and parafoveal DCP was
statistically significantly lower as compared to the
baseline (all P < 0.05). In addition, the inside disc

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

vessel density was significantly lower as compared
to baseline measurements (P = 0.017).

In the NPDR group, foveal vessel density at DCP,
inside disc vessel density, and peripapillary RNFL
thickness decreased significantly after IOP rise (P =
0.003, 0.007, and 0.005, respectively) [Table 3].

Comparison of the changes after acute IOP rise
between the two groups is presented in Table
4. Considering the differences between the mean
ages between the two groups, the comparison
was statistically adjusted for the age. None of
the measurement changes showed statistically
significant differences between the two groups
after adjusting for baseline age, except for the
peripapillary RNFL thickness (P = 0.011).

DISCUSSION

In this study, we evaluated the changes in macular
and optic disc microvasculature after acute IOP
elevation and compared the differences in the
eyes of patients without diabetes versus the eyes
of diabetics with NPDR. Statistically significant
changes in the SCP, DCP, and the inside disc
vascular density were observed after acute rise
of IOP in the healthy eyes. In the diabetic
eyes, however, inside disc vessel density and
foveal vessel density at DCP were the only
OCTA parameters that changed significantly after
IOP elevation. Peripapillary RNFL thickness also
decreased significantly in patients with diabetic
retinopathy following the IOP rise.

Our findings suggest that the optic disc
perfusion as shown by the inside disc vessel
density is impaired after an acute IOP elevation of
approximately 13 mmHg in healthy and diabetic
eyes. However, peripapillary vessel density did
not change significantly after an IOP rise. The
microvascular perfusion inside the optic disc
originates mainly from the posterior ciliary artery,
while the central retinal artery supplies the nerve
fiber layer.[27] This shows that the microvascular
perfusion originating from choriocapillaris may
be more susceptible to damage after acute
IOP elevation than the occurrence of retinal
microvasculature. We observed a decrease in
macular perfusion after an IOP rise that was more
prominent in the healthy eyes than in the eyes of
diabetics. Nagel and Vilser reported a paradoxical
response in the size of the veins and arteries
after acute elevation of IOP in the healthy eyes.[30]

The arterial diameter increased by +1.9% and the
venous vessel diameter decreased by –2.6%.
Therefore, the net consequence of these changes
in the vascular caliber may explain the decrease
in vessel density observed in our healthy eyes.
The vascular wall in diabetic patients is stiffer, and
thus less responsive to the acute rise of IOP.[31]
Our study findings correlate with the discoveries
of prior studies that suggest that dysfunctional
OBF autoregulation may be of importance in the
development and progression of glaucoma which
may also occur in diabetic individuals.[18, 19]

Our analyses were also notable for highlighting
variations in OCTA indices in eyes with and
without diabetic retinopathy before IOP elevation.
As expected, at baseline, eyes with NPDR tended
to demonstrate lower capillary density and flow in
many OCTA indices as compared to eyes without
retinopathy.[23, 32]

Several studies have evaluated the OCTA
measurements of the optic disc and/or macula
after IOP elevation. Zhang et al[33] did not observe
any statistically significant change in optic disc or
macular perfusion after moderate IOP elevation
(mean IOP rise of 9.6 ± 4.2 mmHg) induced by
the dark room prone provocative test (DRPPT) in
40 eyes who were suspected of acute primary
angle closure, suggesting efficacy of retinal blood
flow autoregulation in response to moderate IOP
rise. However, only individuals suspected of angle
closure who experienced IOP rise in response
to DRPPT were enrolled in this study, thus their
results may not be generalizable to other subjects.
Similarly, Ma and colleagues[34] found no significant
change in either the macular or papillary region
perfusion following laser peripheral iridectomy (LPI)
in subjects with a 10–20 mmHg IOP rise. However,
in people with IOP elevation >20 mmHg, optic disc
and macular perfusion decreased significantly,
suggesting a threshold at which autoregulatory
mechanisms fail to maintain retinal blood flow.
Their study was limited to a subgroup of subjects
with occludable angles. In addition, LPI might have
adversely affected the image quality and therefore
subsequent vessel density measurements.[35]
Wen et al[36] investigated optic disc perfusion
immediately after the administration of intravitreal
anti-VEGF injections and found a significant
reduction in optic disc vessel density. Similarly,
in a study by Barsash et al[37], both macular and
papillary vessel densities decreased following the
administration of intravitreal anti-VEGF injections.

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OCTA Findings after Acute IOP Elevation; Ashraf Khorasani et al

The superficial macular perfusion was affected
more severely as compared to the other regions.
In both of these studies, the occurrence of altered
image quality[35] after intravitreal injections and
including patients with different macular pathology
(diabetic macular edema or age-related macular
degeneration) were the major shortcomings. In
contrast to previously mentioned studies, our study
had the advantage of enrolling normal subjects as
well as diabetic patients with NPDR.

This study has several limitations. The sample
size was small, and Icare rebound tonometry was
used instead of applanation tonometry which is
considered gold standard for IOP measurements.
However, this limitation may have been mitigated
as the same standardized method was used to
measure IOP in all eyes both before and after
IOP elevation, as comparisons of IOP between
eyes were all drawn from measurements by the
same device. In addition, IOP elevation may
not be the same after repetition of the suction
procedure. Higher levels of IOP changes may
affect the microvascular network differently. We
also performed a single IOP measurement after
applying the suction and did not check the post-
suction IOP to determine probable IOP changes. It
is recommended that the clinical significance of the
observed changes in microvasculature and retinal
structure be explored further. Future analyses with
larger sample sizes are warranted.

In summary, the results of our study show that
retinal microvasculature in diabetics and healthy
eyes respond differently to the acute elevation of
IOP. This study provides preliminary insight into
changes in OCTA-measured indices after acute IOP
elevation, as well as into the potential disturbances
in autoregulation that may occur in eyes with and
without diabetic retinopathy. As glaucoma and
diabetes are highly prevalent causes of vision
loss worldwide and are commonly comorbid in
patients, a fundamental understanding of potential
pathophysiologic similarities is essential. Whether
these findings may be applicable to chronic
elevation of IOP, as is experienced in the majority of
subtypes of glaucoma, remains to be determined.

Financial Support and Sponsorship

None.

Conflicts of Interest

None declared.

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