Risk of Normal Tension Glaucoma Progression
From Automated Baseline Retinal-Vessel
Caliber Analysis: A Prospective Cohort Study
TIMOTHY P.H. LIN, HERBERT Y.H. HUI, ANNIE LING, POEMEN P. CHAN, RUYUE SHEN, MANDY O.M. WONG,
NOEL C.Y. CHAN, DEXTER Y.L. LEUNG, DEJIANG XU, MONG LI LEE, WYNNE HSU, TIEN YIN WONG,
CLEMENT C. THAM, AND CAROL Y. CHEUNG
• PURPOSE: To determine the relationship between base-
line retinal-vessel calibers computed by a deep-learning
system and the risk of normal tension glaucoma (NTG)
progression.
• DESIGN: Prospective cohort study.
• METHODS: Three hundred and ninety eyes from 197
patients with NTG were followed up for at least 24
months. Retinal-vessel calibers (central retinal arteriolar
equivalent [CRAE] and central retinal venular equiva-
lent [CRVE]) were computed from fundus photographs
at baseline using a previously validated deep-learning sys-
tem. Retinal nerve fiber layer (RNFL) thickness and vi-
sual field (VF) were evaluated semiannually. The Cox
proportional-hazards model was used to evaluate the re-
lationship of baseline retinal-vessel calibers to the risk of
glaucoma progression.
• RESULTS: Over a mean follow-up period of 34.36 ±
5.88 months, 69 NTG eyes (17.69%) developed progres-
sive RNFL thinning and 22 eyes (5.64%) developed VF
deterioration. In the multivariable Cox regression analy-
sis adjusting for age, gender, intraocular pressure, mean
ocular perfusion pressure, systolic blood pressure, ax-
ial length, standard automated perimetry mean deviation,
and RNFL thickness, narrower baseline CRAE (hazard
Supplemental Material available at AJO.com.
Clement C. Tham and Carol Y. Cheung contributed equally as senior au-
thors and co-correspondence authors.
Accepted for publication September 23, 2022.
From the Department of Ophthalmology and Visual Sciences, the Chi-
nese University of Hong Kong (T.P.H.L., H.Y.H.H., A.L., P.P.C., R.S.,
M.O.M.W., N.C.Y.C., D.Y.L.L., C.C.T., C.Y.C.), Hong Kong, China;
Hong Kong Eye Hospital, Hong Kong, China; Lam Kin Chung, Jet King-
Shing Ho Glaucoma Treatment and Research Centre, the Chinese Uni-
versity of Hong Kong(P.P.C., C.C.T., C.Y.C.), Hong Kong, China; De-
partment of Ophthalmology and Visual Sciences, Prince of Wales Hospi-
tal (N.C.Y.C.), Hong Kong, China; Department of Ophthalmology, Hong
Kong Sanatorium and Hospital (D.Y.L.L.), Hong Kong, China; School of
Computing, National University of Singapore (D.X., M.L.L., W.H.), Sin-
gapore; Singapore Eye Research Institute, Singapore National Eye Cen-
tre (T.Y.W.), Singapore; Ophthalmology and Visual Sciences Academic
Clinical Programme, Duke-NUS Medical School (T.Y.W.), Singapore; Ts-
inghua Medicine, Tsinghua University (T.Y.W.), Beijing, China
Inquiries to Clement C. Tham and Carol Y. Cheung, Department of
Ophthalmology and Visual Sciences, the Chinese University of Hong
Kong, Kowloon, Hong Kong, China.; e-mail: clemtham@cuhk.edu.hk,
carolcheung@cuhk.edu.hk
0002-9394/$36.00 © 2022 ELSEVIER INC. ALL RIGHTS RESERVED.
https://doi.org/10.1016/j.ajo.2022.09.015
ratio per SD decrease [95% confidence interval], 1.36
[1.01-1.82]) and CRVE (1.35 [1.01-1.80]) were associ-
ated with progressive RNFL thinning and narrower base-
line CRAE (1.98 [1.17-3.35]) was associated with VF
deterioration.
• CONCLUSION: In this study, each SD decrease in the
baseline CRAE or CRVE was associated with a more
than 30% increase in the risk of progressive RNFL thin-
ning and a more than 90% increase in the risk of VF
deterioration during the follow-up period. Baseline at-
tenuation of retinal vasculature in NTG eyes was as-
sociated with subsequent glaucoma progression. High-
throughput deep-learning–based retinal vasculature anal-
ysis demonstrated its clinical utility for NTG risk as-
sessment. (Am J Ophthalmol 2023;247: 111–120. ©
2022 Elsevier Inc. All rights reserved.)
N
ormal tension glaucoma (NTG) is a
common subgroup of primary open-angle glau-
coma in which the development and progression
of the disease occur in the absence of elevated intraoc-
ular pressure (IOP).1 , 2 Hence, clinical risk assessment
and management are particularly challenging because
the current glaucoma management is centered on IOP
reduction.3 , 4 NTG patients with higher risk of progression
may be identified by risk factors calculation.5 Nonetheless,
the strategy of identifying this group of patients for close
monitoring and aggressive treatment remains theoretical
and controversial. Furthermore, the pathogenesis of NTG
remains unclear. Currently, evidence suggests a role of
the “vascular theory” of glaucoma, which postulates that
circulatory insufficiency and ocular ischemia culminate in
retinal ganglion cell degeneration and glaucomatous visual
field (VF) loss, in the pathogenic processes of NTG.6-8 In
support of this theory were observations that NTG eyes
had a higher prevalence of disc hemorrhage compared with
other glaucoma subtypes, and patients with NTG were
more likely to suffer from systemic vascular diseases1 , 3 , 9 , 10
and microvascular dysregulation.11 , 12
One potential method for the assessment of the vascu-
lar risk of an eye is to examine the state of the retinal
vasculature. We have previously demonstrated in a cross-
111
sectional study that diffuse retinal-vessel caliber narrow-
ing was more significant in NTG eyes as compared with
healthy eyes, and narrowed retinal vessels in NTG were as-
sociated with worse glaucomatous structural and functional
measurements.13 Other studies have also revealed impaired
ocular blood flow in NTG eyes.14-17 However, the designs of
existing studies that have evaluated retinal vasculature and
ocular hemodynamics in NTG are all cross-sectional in na-
ture.13-17 This limits their ability to ascertain a temporal re-
lationship of degeneration of retinal vasculature and ocular
perfusion impairment at baseline to the progression of glau-
comatous measures over time. Further evidence to support
the vascular theory in NTG6-8 and the clinical utility of a
retinal vascular assessment in NTG are highly warranted.
Previous studies analyzing the retinal vasculature were
based on semiautomated computer programs that required
significant human input and were highly labor inten-
sive,13 , 18 , 19 with variable intra- and intergrader agreement
of measurements despite highly standardized protocols were
used.18-23 Artificial intelligence, in particular deep-learning
(DL), is of great interest to the medical community and is
specifically useful for medical image analysis.24 Our group
has recently developed and validated a fully automated DL
system (DLS) for the analysis of retinal-vessel calibers from
fundus photographs.19 This new strategy of retinal vascu-
lature analysis addresses a significant gap in the clinical
adoption of retinal vasculature analysis for the evaluation
and correlation of diseases and their retinal vascular status,
which can be applied in the risk assessment of NTG pro-
gression.
In this prospective cohort study, we determined the rela-
tionship between baseline retinal-vessel measurements (ar-
teriolar and venular calibers) computed by the DLS to the
subsequent risk of progression in a cohort of patients with
NTG. We hypothesized that baseline narrowing of retinal-
vessel calibers is an independent prognostic factor for NTG
progression. We further examined whether baseline retinal-
vessel calibers provided value in the prediction of the risk of
glaucoma progression, compared with previously reported
risk factors. The findings in this study could provide evi-
dence to support the vascular theory of glaucoma6-8 and the
clinical application of DL-based retinal vasculature analysis
in the risk assessment of NTG.
METHODS
• STUDY POPULATION: This prospective cohort study was
conducted in a tertiary referral center. A total of 197 pa-
tients with NTG were consecutively recruited from the
CUHK Eye Centre of the Chinese University of Hong
Kong and the Hong Kong Eye Hospital from 2016 to 2021.
All subjects had a follow-up period of at least 24 months
and attended follow-up visits semiannually. For inclusion
in this study, participants had to be diagnosed with NTG
112 AMERICAN JOURNAL OF OPHTHALMOLOGY
according to the definition provided below and of 18 years
of age or above. Exclusion criteria included the past med-
ical history of diabetes mellitus, maculopathy, other op-
tic neuropathies, history of ocular surgery (except cataract
surgery), neurologic diseases, or major systemic illnesses.
One or both eyes of a subject could be enrolled. The study
was conducted in accordance with the 1964 Declaration of
Helsinki and approved by the Research Ethics Committee
(Kowloon Central/Kowloon East) of the Hospital Author-
ity (Ref: KC/KE-17-0099/ER-3). Written informed consent
was obtained from all participants.
• CLINICAL EXAMINATION: All participants underwent a
comprehensive ophthalmic examination at baseline and
semiannually during follow-up, including measurements
of best-corrected visual acuity, refractive error by an au-
torefractor (ARK-510A; Nidek Co, Ltd), axial length
(AL) (IOL Master; Carl Zeiss Meditec), IOP by Gold-
mann applanation tonometry, central corneal thickness
by a noncontact tonopachymeter (TONOPACHY 530P;
Nidek Co, Ltd), slit-lamp biomicroscopy examination of
the optic disc and retina, dilated fundus examination, si-
multaneous stereophotography of the optic disc, and stan-
dard automated perimetry (SAP, Humphrey Field Analyzer;
24-2 Swedish interactive threshold algorithm; Carl Zeiss
Meditec Inc) were performed. Peripapillary retinal nerve
fiber layer (RNFL) thickness was measured with Cirrus HD-
OCT (Carl Zeiss Meditec Inc). Systolic and diastolic blood
pressure (SBP and DBP) and pulse rate were measured
twice according to the scientific statement from the Amer-
ican Heart Association on the measurement of BP in hu-
mans with an automatic blood pressure instrument (Omron
Avant 2120; Nonin Medical, Inc),25 and the mean value
was used in the analysis. Mean ocular perfusion pressure
(MOPP) was calculated as 2/3 × (DBP + 1/3 × (SBP –
DBP)) – IOP.26
• STANDARD AUTOMATED PERIMETRY: All participants
underwent VF testing at baseline and every 6 months using
the 24-2 pattern Swedish interactive threshold algorithm
on the Humphrey Field Analyzer (Carl Zeiss Meditec Inc).
Only reliable tests (≤33% fixation losses and false nega-
tives, and ≤15% false positives) were included. The quality
of VF tests was reviewed by study investigators to identify
and exclude VFs with evidence of inattention or inappro-
priate fixation, artefacts such as eyelid and lens rim arte-
facts, fatigue effects, and abnormal results caused by diseases
other than glaucoma.
• MEASUREMENT OF RNFL WITH HD-OCT: Cirrus HD-
OCT (software version 9.5; Carl Zeiss Meditec) was used
to measure the average RNFL thicknesses from the optic
disc cube scan (200 × 200 pixels), generating the RNFL
thickness map at the peripapillary region (6 mm × 6 mm)
at baseline and each follow-up visit. OCT images with poor
image quality or significant image artifacts were excluded,
MARCH 2023
including (1) signal strength of less than 6, (2) motion arti-
facts, (3) blurry images, and signal loss (eg, due to eye blink-
ing).
• DEFINITION OF NTG: NTG was diagnosed based on: (1)
6 median untreated IOP readings consistently less than 21
mm Hg, with no more than 1 reading equal to 23 or 24
mm Hg, and no single measurement more than 24 mm Hg,
as per the Collaborative NTG study.27 At least 2 readings
were obtained at different times of the day from the rest. (2)
Anterior chamber angle of Shaffer grade II or above on dark
room gonioscopy. (3) Glaucomatous optic disc cupping and
loss of neuroretinal rim. (4) VF defect according to the Col-
laborative NTG study.27 (5) Glaucoma hemifield test being
“outside normal limits.” (6) Pattern standard deviation with
a P value of <.05. (7) A cluster of 3 points or more in the
pattern deviation plot in a single hemifield with a P value
of <.05, one of which must have a P value of <.01. Any
one of these criteria, if repeatable, was considered to be suf-
ficient evidence of a glaucomatous VF defect. (8) Absence
of secondary causes for the glaucomatous optic neuropathy
(eg, previous trauma, use of steroids, and uveitis).
• DEFINITION OF GLAUCOMA PROGRESSION: In this
study, both structural and functional glaucoma progres-
sion were evaluated. Structural glaucoma progression was
defined as progressive RNFL thinning measured by Cirrus
HD-OCT that was determined by Guided Progression
Analysis (GPA) (Carl Zeiss Meditec)—an event-based
algorithm that has been used in previous studies for detec-
tion of progressive RNFL thinning in glaucoma and widely
adopted in the clinical setting for identification of patients
with glaucoma progression.28 , 29 Functional glaucoma pro-
gression was defined as VF deterioration determined by
GPA of the Humphrey Field Analyzer. VF progression was
defined as the presence of “likely progression” on GPA.30 , 31
All participants had 3 or more visits during the 24-month
follow-up period for detection of glaucoma progression on
GPA.
• DEEP-LEARNING–BASED RETINAL-VESSEL CALIBER
MEASUREMENT: Optic disc–centered fundus photographs
were obtained from all participants using a nonmydriatic
retinal camera (TRC 50DX; Topcon Inc) after pharma-
cologic pupil dilation. A validated DLS for retinal-vessel
caliber analysis (SIVA-DLS; National University of Singa-
pore, Singapore)19 was used to estimate retinal arteriolar
and venular calibers from the disc-centered fundus pho-
tographs in a region from 0.5 to 2.0 disc diameters away
from the disc margin. For the overall assessment of the
retinal-vessel calibers, summary data of the arteriolar and
venular measurements, which were referred to as central
retinal arteriolar equivalent (CRAE) and central retinal
venular equivalent (CRVE), respectively, as described
previously,13 were generated in the output of SIVA-DLS.
The heat maps in the Figure illustrate the boundaries of the
VOL. 247 RISK OF NORMAL TENSION GLAUCOMA PROGRESSION
arterioles and venules. SIVA-DLS focused on to calibrate
the CRAE and CRVE predictions. The agreement in
retinal-vessel caliber measurements between SIVA-DLS
and human was assessed in a subgroup of 168 eyes within
our cohort, with the intraclass correlation coefficients of
CRAE and CRVE being 0.865 and 0.897, respectively
(Supplemental Table 1).
• STATISTICAL ANALYSIS: In this study, each eligible eye
was regarded as a unit of analysis. Statistical analysis was
performed using SPSS version 25 (SPSS, Inc) and R soft-
ware version 3.6.3 (R Foundation for Statistical Comput-
ing). The Cox proportional-hazards model was used to ex-
amine the relationship between baseline retinal-vessel cal-
ibers and the risk of glaucoma progression in the NTG co-
hort, adjusting for previously reported risk factors (age,32 , 33
gender,34 IOP,35 MOPP,36 SBP,37 AL,38 SAP mean devia-
tion [MD],33 and RNFL thickness39 ). A shared frailty model
after a γ distribution was used to adjust for intereye correla-
tion.40 Schoenfeld’s global test was used to confirm that the
proportional-hazards assumption was not violated.41 Haz-
ard ratios (HRs) and their 95% confidence intervals (CIs)
were also calculated.
We further examined the incremental value of adding
the retinal-vessel caliber measurements for the predictive
discrimination of glaucoma progression. The C-statistic for
the Cox regression model proposed by Steyerberg and as-
sociates41 in terms of quantifying the predictive discrimi-
nation power was calculated to compare the performance
between the prediction models. A C-statistic of 0.5 indi-
cates no discriminative power, and a C-statistic close to 1
indicates perfect discrimination. The likelihood ratio test
was used for model comparisons. To assess the overall per-
formance including calibration and to compare the influ-
ence of individual components on predictive ability, we also
computed the integrated Brier score at 48-month follow-up
to assess the calibration of the prediction models using the
R package “pec.”42 A P value of less than .05 was considered
statistically significant.
RESULTS
After excluding poor-quality fundus photographs (4 eyes),
390 eyes from 197 patients with NTG were included in the
final analysis. The baseline demographics of the included
study subjects are shown in Table 1. Over a mean follow-up
period of 34.36 ± 5.88 months, 69 eyes (17.69%) devel-
oped glaucoma progression detected as progressive RNFL
thinning, whereas 22 eyes (5.64%) developed VF deterio-
ration (Supplemental Figure 1). There were no significant
differences in age, gender, follow-up duration, IOP, central
corneal thickness, spherical errors, AL, SAP MD, SAP pat-
tern standard deviation, SAP visual field index, and aver-
age RNFL thickness between the groups with and without
113
 114

TABLE 1. Baseline Demographics of Eyes With and Without Normal Tension Glaucoma Progression

Variables Progressive RNFL Thinning Without Progressive RNFL Thinning P Value VF Deterioration Without VF Deterioration P Value
AMERICAN JOURNAL OF OPHTHALMOLOGY

Subjects (n) 61 189 — 21 195 —

Eyes (n) 69 321 — 22 368 —
Age at recruitment (y), mean (SD) 58.2 (12.27) 59.83 (11.40) .299 55.64 (11.52) 59.78 (11.54) .102
Gender (male/female) 36/33 155/166 .573 13/9 178/190 .328
Follow-up (mo), mean (SD) 34.28 (5.73) 34.38 (5.92) .886 36.09 (6.83) 34.26 (5.81) .263
IOP (mm Hg), mean (SD) 15.70 (2.79) 15.35 (3.05) .272 15.66 (2.77) 15.40 (3.02) .833
MOPP (mm Hg), mean (SD) 52.98 (7.51) 54.89 (7.65) .049 49.54 (6.13) 54.85 (7.64) .001
SBP (mm Hg), mean (SD) 130.20 (18.64) 134.06 (18.54) .130 124.00 (15.87) 133.93 (18.61) .017
DBP (mm Hg), mean (SD) 77.67 (10.38) 79.50 (10.24) .164 72.95 (7.44) 79.55 (10.31) <.001
CCT (μm), mean (SD) 536.29 (64.93) 540.96 (50.40) .689 527.82 (27.78) 540.87 (54.27) .131
Spherical errors (diopters), mean (SD) −4.16 (4.84) −3.82 (4.16) .513 −4.55 (4.21) −3.82 (4.30) .418
Axial length (mm), mean (SD) 25.96 (1.97) 25.55 (1.87) .124 26.07 (1.89) 25.60 (1.89) .189
SAP MD (dB), mean (SD) −4.99 (4.70) −5.72 (5.80) .258 −6.54 (5.19) −5.53 (5.65) .443
SAP VFI (%), mean (SD) 88.22 (12.75) 85.7 (17.38) .174 84.32 (13.92) 86.25 (16.83) .371
Average RNFL thickness (μm), mean (SD) 75.94 (10.67) 74.37 (11.66) .284 72.55 (10.94) 74.77 (11.52) .368
CRAE (μm) 141.38 (19.42) 147.51 (19.99) .026 138.73 (21.50) 146.89 (19.85) .065
CRVE (μm) 226.23 (35.93) 237.79 (39.81) .036 228.39 (52.19) 236.19 (38.51) .536

CCT = central corneal thickness, CRAE = central retinal arteriolar equivalent, CRVE = central retinal venular equivalent, DBP = diastolic blood pressure, IOP = intraocular pressure, MD = mean
deviation, MOPP = mean ocular perfusion pressure, RNFL = retinal nerve fiber layer, SAP = standard automated perimetry, SBP = systolic blood pressure, VFI = visual field index.
MARCH 2023
FIGURE. Automated estimation of central retinal arteriolar caliber (CRAE) and central retinal venular caliber (CRVE) using
a deep-learning system (SIVA-DLS). The original retinal photograph captured by a 45° digital retinal camera (A). The color of
retinal arterioles is generally lighter, and the width of retinal arterioles is generally smaller than that of retinal venules. SIVA-DLS
automatically generates heat maps based on the features of the retinal vessels for prediction and estimation of CRAE (B) and CRVE
(C).

glaucoma progression (all Ps > .05). In comparison with the
group without progressive RNFL thinning, the group with
progressive RNFL thinning had lower MOPP (52.98 mm
Hg vs 54.89 mm Hg, P = .049) and smaller CRAE (141.38
μm vs 147.51 μm) and CRVE (226.23 μm vs 237.79 μm)
(P = .026 and P = .036, respectively) at baseline. In com-
parison with the group without VF deterioration, the group
with VF deterioration had lower MOPP (49.54 mm Hg vs
54.85 mm Hg, P = .001), lower SBP (124.00 mm Hg vs
133.93 mm Hg) and DBP (72.95 mm Hg vs 79.55 mm
Hg) (P = .001, P = .017 and P < .001, respectively),
and smaller CRAE (138.73 μm vs 146.89 μm) and CRVE
(228.39 μm vs 236.19 μm) at baseline, although the latter
did not reach a statistically significant level (both Ps > .05).
Supplemental Figure 2 demonstrates baseline retinal-vessel
calibers computed by SIVA-DLS and baseline demograph-
ics between 2 eyes with and without glaucoma progression,
respectively.
The relationships between baseline retinal-vessel cal-
ibers and NTG progression are summarized in Table 2. In
the multivariable Cox regression analysis, narrower base-
line CRAE (HR [95% CI], 2.95 [1.20-7.23], first quartile
vs fourth quartile; HR per SD decrease, 1.36 [1.01-1.82])
and narrower baseline CRVE (HR per SD decrease, 1.35
[1.01-1.80]) were independently associated with progressive
RNFL thinning, after adjusting for age, gender, IOP, MOPP,
SBP, AL, SAP MD, and RNFL thickness. Similarly, nar-
rower baseline CRAE (HR, 5.57 [1.13-27.49], first quartile
vs fourth quartile; HR, 7.57 [1.56-36.73], second quartile
vs fourth quartile; HR, 3.93 [1.03-14.98], third quartile vs
fourth quartile; HR per SD decrease, 1.98 [1.17-3.35]) was
associated with VF deterioration, but there were no statis-
tically significant associations between baseline CRVE and
VF deterioration.
The clinical predictive value of baseline retinal-vessel
calibers for glaucoma progression was further evaluated.
Table 3 shows the C-statistic for Cox regression models pre-
dicting glaucoma progression, comparing the model based
on baseline retinal-vessel calibers, age, gender, IOP, MOPP,
and SBP alone with the model based on all previously re-
ported risk factors. Models with inclusion of CRAE (C-
statistic, 0.702 vs 0.701, P = .595), CRVE (C-statistic,
0.700 vs 0.701, P = .726), or both CRAE and CRVE (C-
statistic, 0.703 vs 0.701, P = .242) showed comparable and
noninferior predictive discrimination for progressive RNFL
thinning, compared with the model based on all previ-
ously reported risk factors. Similar results were observed in
the model with inclusion of both CRAE and CRVE (C-
statistic, 0.85 vs 0.819, P = .026) for VF deterioration,
compared with the model based on all previously reported
risk factors. As shown in Supplemental Table 2, we further
compared the models with inclusion of baseline retinal-
vessel calibers and all previously reported risk factors with
the model based on all the previously reported risk factors
alone. The results were in line with those in Table 3, in
which models with inclusion of baseline retinal-vessel cal-
ibers demonstrate statistically superior predictive discrimi-
nation for NTG progression to the model based on previ-
ously reported risk factors (Supplemental Table 2).
Supplemental Figure 3 shows the prediction error curves
of Cox regression models predicting glaucoma progression
determined by the presence of progressive RNFL thinning
and VF deterioration. The integrated Brier scores of these
models at 48-month follow-up were calculated. Cox re-
gression models for NTG progression with inclusion of
previously reported risk factors and retinal-vessel calibers
(CRAE, CRVE, or both CRAE and CRVE) all had lower
Brier scores (progressive RNFL thinning: 0.100; VF deterio-
ration: 0.029), indicating better calibration compared with
the model that included previously reported risk factors
only (progressive RNFL thinning: 0.102; VF deterioration:
0.030) and the model that included only baseline retinal-

VOL. 247 RISK OF NORMAL TENSION GLAUCOMA PROGRESSION 115

 TABLE 2. Relationships of Baseline Central Retinal Arteriolar Equivalent (CRAE) and
Central Retinal Venular Equivalent (CRVE) as Measured by a Deep-Learning System
(SIVA-DLS) to Risk of Glaucoma Progression in a Cohort of Normal Tension Glaucoma

Model 1 Model 2

HR (95% CI) P Value HR (95% CI) P Value

Outcome: progressive RNFL thinning

CRAE
First quartile 2.95 (1.37-6.34) .006 2.95 (1.20-7.23) .018
Second quartile 1.13 (0.64-2.01) .670 1.10 (0.55-2.22) .790
Third quartile 1.84 (0.95-3.57) .069 2.06 (0.98-4.35) .058
Four th quar tile Reference Reference
Per SD decrease 1.31 (1.05-1.63) .018a 1.36 (1.01-1.82) .043a
CRVE
First quartile 1.62 (0.76-3.42) .210 1.53 (0.64-3.67) .340
Second quartile 1.25 (0.61-2.55) .540 1.09 (0.50-2.39) .830
Third quartile 0.60 (0.33-1.10) .099 0.61 (0.31-1.22) .160
Four th quar tile Reference Reference
Per SD decrease 1.33 (1.03-1.72) .027a 1.35 (1.01-1.80) .042a
Outcome: VF deterioration
CRAE
First quartile 4.71 (1.29-17.20) .019 5.57 (1.13-27.49) .035
Second quartile 3.97 (1.09-14.47) .037 7.57 (1.56-36.73) .012
Third quartile 2.34 (0.80-6.81) .120 3.93 (1.03-14.98) .045
Four th quar tile Reference Reference
Per SD decrease 1.63 (1.15-2.31) .006a 1.98 (1.17-3.35) .011a
CRVE
First quartile 1.84 (0.52-6.49) .34 1.63 (0.39-6.74) .500
Second quartile 3.39 (0.67-17.15) .14 4.35 (0.77-24.69) .097
Third quartile 0.67 (0.24-1.86) .44 0.76 (0.24-2.40) .640
Four th quar tile Reference Reference
Per SD decrease 1.49 (0.92-2.40) .100a 1.52 (0.84-2.73) .160a

CI = confidence interval, HR = hazard ratio, RNFL = retinal nerve fiber layer, VF = visual field.
Model 1 was unadjusted. Model 2 was adjusted for age, gender, intraocular pressure, mean ocular
perfusion pressure, systolic blood pressure, central corneal thickness, axial length, mean deviation,
and average RNFL thickness. Unless otherwise indicated, P values were determined on the basis
of caliber measures entered as a categorical variable (quartiles) and compared with the reference
quartile.
a
P values were determined on the basis of caliber measures entered as a continuous variable.

vessel calibers, age, gender, IOP, MOPP, and SBP (progres-
sive RNFL thinning: 0.103; VF deterioration: 0.031).
DISCUSSION
In the current cohort study, baseline retinal-vessel calibers
computed by a DLS were significantly associated with the
risk of glaucoma progression in NTG eyes, independent
of previously reported risk factors, such as age,32 , 33 gen-
der,34 MOPP,36 SBP,37 AL,38 SAP MD,33 and RNFL thick-
ness39 at baseline. Furthermore, models based on baseline
retinal-vessel calibers demonstrated comparable or superior
predictive discrimination of glaucoma progression to the
model based on previously reported risk factors only. These
findings revealed that baseline assessment of retinal-vessel
calibers provides significant prognostic information for the
evaluation of the risk of NTG progression. In addition, the
results provided evidence to support the clinical application
of a DLS for high-throughput fundus photography analysis
in NTG risk assessment.
In this study, we found that each SD decrease in the
baseline CRAE or CRVE was associated with a more than
30% increase in the risk of progressive RNFL thinning
and a more than 90% increase in the risk of VF de-
terioration during the follow-up period. To the best of
our knowledge, this is the first longitudinal study evalu-
ating the association between baseline retinal-vessel cal-
iber measurements computed by a DLS and the subse-
quent risk of glaucoma progression in a cohort of patients
with NTG. Previously, evidence pinpointed an association

116 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH 2023

 TABLE 3. Predictive Discrimination for Glaucoma Progression With Baseline Retinal-Vessel Calibers in the Cox Regression Models in
Comparison With the Models Based on Previously Reported Risk Factors

C-Statistic

Outcomes Current Model Current Previously Reported Change in C-Statistic P Value

Model Risk Factorsa (%)

Progressive RNFL thinning CRAE + Age + Gender + IOP + MOPP + SBP 0.702 0.701 +0.001 (+0.143) .595
Progressive RNFL thinning CRVE + Age + Gender + IOP + MOPP + SBP 0.700 0.701 −0.001 (−0.143) .726
Progressive RNFL thinning CRAE + CRVE + Age + Gender + IOP + MOPP + SBP 0.703 0.701 +0.002 (+0.285) .242
VF deterioration CRAE + Age + Gender + IOP + MOPP + SBP 0.848 0.819 +0.029 (+3.54) .085
VF deterioration CRVE + Age + Gender + IOP + MOPP + SBP 0.829 0.819 +0.01 (+1.22) .827
VF deterioration CRAE + CRVE + Age + Gender + IOP + MOPP + SBP 0.85 0.819 +0.031 (+3.79) .026

AL = axial length, CRAE = central retinal arteriolar caliber, CRVE = central retinal venular caliber, IOP = intraocular pressure, MOPP = mean
ocular perfusion pressure, RNFL = retinal nerve fiber layer, SAP = standard automated perimetry, SBP = systolic blood pressure, VF = visual
field.
a
Model with previously reported risk factors consisted of baseline age, gender, IOP, MOPP, SBP, AL, SAP mean deviation (MD), and RNFL
thickness.

between altered ocular hemodynamics and the incidence
of glaucoma.13 , 43 , 44 In the population-based Blue Moun-
tains Eye study, glaucoma eyes were reported to be at least
2 times more likely to have retinal arteriolar narrowing
than healthy eyes,22 and similar associations between glau-
coma and worse geometric measurements of the retinal vas-
culature including decreased retinal-vessel tortuosity and
branching angle were also demonstrated in the Singapore
Malay Eye study.18 The attenuations of retinal-vessel pa-
rameters were further shown to be associated with worse
structural and functional glaucomatous measurements.13 , 45
In these population-based studies, it was observed that glau-
coma were associated with both narrowing in retinal arte-
rioles and venules,20 , 22 , 46 and our current findings of the
associations between baseline attenuation in CRAE and
CRVE and glaucoma progression in NTG were largely cor-
roborative with earlier observations in the literature. These
findings on alterations in retinal vasculature in glaucoma
from fundus photography were in line with earlier ocular
perfusion studies on Doppler imaging and fluorescein an-
giography14-17 and recent studies on retinal capillary net-
works using optical coherence tomography angiography
(OCTA),13 , 43 , 44 , 47 which all underlined the relationship
between retinal circulatory insufficiency and glaucoma.
In the past, studies on retinal vasculature and glaucoma
were of largely cross-sectional design, and hence unable to
ascertain the temporal and causal relationships between de-
generation in retinal vasculature and glaucoma develop-
ment. Findings from our longitudinal study provide novel
and additional evidence to the elucidation of the vascular
theory6-8 in glaucoma development by demonstrating that
degeneration in retinal vasculature heralds the advent of
glaucoma progression in NTG. Our current findings also
corroborate with the longitudinal results from OCTA re-
ported in a recent study by Moghimi and associates,48 which
revealed that reduced optic nerve head and macular vessel
density at baseline were associated with progressive RNFL
thinning, both supporting a clinically significant role of vas-
cular insufficiency in glaucoma development and progres-
sion.
In this study, we also evaluated the application of DL-
based retinal-vessel analysis in the clinical risk assessment
of NTG. Previously, the evaluation of the retinal vascula-
ture in glaucoma remains to be of limited utility in clini-
cal settings as evidence regarding the role of vascular pa-
rameters in risk assessment, prognosis, and management of
glaucoma is lacking. Furthermore, computer programs de-
veloped for the analysis of fundus photographs or OCTA
images were highly labor intensive, time consuming, and
could be susceptible to human errors as substantial hu-
man input was involved.18-23 The implications of our re-
sults were 2-fold. First, we demonstrated that baseline reti-
nal vasculature measurements obtained from SIVA-DLS,
when combined with basic demographical data (age, gen-
der, IOP, MOPP, and SBP), yielded statistically compara-
ble and noninferior outcomes for the prediction of NTG
progression, compared with the prediction model based on
all previously reported risk factors obtained from exten-
sive ophthalmic investigations (Table 3). Moreover, when
such baseline retinal vasculature measurements were added
into the prediction model based on all previously reported
risk factors, it further improved the predictive accuracy of
NTG progression (Supplemental Table 2). This provided
evidence to support the use of fully automated and highly ef-
ficient DL-based image analysis technology to compute reti-
nal vascular parameters for glaucoma risk assessment from
fundus photographs. These findings are of particular clin-
ical interest as fundus photography is a readily available
ophthalmic assessment, and by virtue of DL-based image
analysis, this universal clinical assessment can yield signif-
icant prognostic information about the risk of progression
in NTG to navigate ophthalmologists in identification of

VOL. 247 RISK OF NORMAL TENSION GLAUCOMA PROGRESSION 117

high-risk patients for close monitoring and aggressive treat-
ments, meanwhile sparing the necessity of extensive oph-
thalmic investigations in resource-limited settings.
It should be recognized that despite that the prediction
models with the addition of baseline retinal-vessel calibers
enhanced the predictive discrimination of NTG progres-
sion, compared with models based on previously reported
risk factors alone, such improvements remained modest.
Lin and associates49 recently reported that glaucoma eyes
with high myopia were more susceptible to a rapid decrease
in macular vessel density on OCTA, compared with glau-
coma eyes without high myopia. Vascular abnormalities
may be of a dominant role in glaucoma development and
progression in this special subset of patients. Further stud-
ies would be warranted to identify specific glaucoma patient
subgroups who may benefit from early retinal vascular as-
sessment for stratification of risk of progression. In addition,
future studies that apply the prediction models to indepen-
dent samples for validation of the performance of the mod-
els would also provide valuable information regarding the
prognostic value of such prediction models.
It is noteworthy that there was an apparent discordance
in progressive RNFL thinning and VF deterioration in
which 15 eyes with detectable VF deterioration did not
demonstrate statistically significant progressive RNFL thin-
ning (Supplemental Figure 1). It is believed that structural
defects precede functional deficits in the development and
progression of glaucoma. In postmortem studies, significant
VF defects only occurred after 25% to 35% of retinal gan-
glion cell loss.50 , 51 Alasil and associates52 showed that sub-
stantial RNFL thinning occurred before initially detectable
VF defects in glaucoma, and Yu and associates53 reported
that progressive RNFL thinning determined by GPA was
predictive of VF progression in glaucoma. Hood and asso-
ciates54 have accounted for such apparent discordance in
structural and functional measurements by modeling and
showed that such observation did not suggest the occur-
rence of VF defects in the absence of underlying RNFL
thinning. On the contrary, it only reflected that the RNFL
thinning in such eyes did not reach a statistically significant
level to be detected by the GPA algorithm.54 It is plausi-
ble that due to the floor effect of RNFL thinning,55 eyes
with preceding RNFL thinning would demonstrate no sta-
tistically significant progressive RNFL thinning by the time
significant VF deterioration occurred.
Funding/Support: This work was supported by Health and Medical Research Fund, Hong Kong (Ref. No. 05162836 to C.C.T.), and General Research
Fund, Hong Kong (Ref. No. 14107516 to C.C.T.). The funding organization had no role in the design or conduct of this research.
Financial Disclosures: The authors declare no conflict of interest. All authors attest that they meet the current ICMJE criteria for authorship.
REFERENCES
1. Lee JWY, Chan PP, Zhang X, et al. Latest developments in
normal-pressure glaucoma: diagnosis, epidemiology, genetics,
118 AMERICAN JOURNAL OF OPHTHALMOLOGY
The strength of our study was the prospective study de-
sign and longitudinal follow-up, which enabled the evalua-
tion of the temporal relationship between the altered reti-
nal vasculature at baseline and the subsequent glaucoma
progression. Furthermore, we included a large cohort of pa-
tients with NTG in which glaucoma developed and pro-
gressed in the absence of elevated IOP, and vascular factors
have been postulated to be of role in the underlying patho-
genesis.6-8 Our findings supported a linkage between altered
retinal vasculature and glaucoma progression, and further
provided novel evidence for the clinical application of DL-
based retinal-vessel analysis in the risk assessment of NTG.
We acknowledge the limitations of our study. The follow-up
period of our study was relatively short, and there were only
a small group of eyes with demonstrable glaucoma progres-
sion as NTG is a slowly progressing disease; further studies
to evaluate if baseline abnormalities in retinal vasculature
can be extrapolated to predict glaucoma progression in the
long term are warranted. In addition, our cohort comprised
mainly NTG eyes with mild-to-moderate glaucoma, and
our findings may not be generalized to eyes with advanced
glaucoma. This, however, may render the model more suit-
able in the evaluation and risk assessment of patients with
early-stage glaucoma before the occurrence of symptomatic
vision loss. In this regard, our cohort also lacked preperi-
metric cases. Further studies to evaluate the clinical utility
of baseline retinal vascular assessment in this group would
also be warranted. Finally, we adjusted for MOPP in our
multivariable Cox regression analysis and prediction model
(Tables 2 and 3). Recently, Stodtmeister and associates56
have reported a new method for the measurement of reti-
nal venous pressure (RVP), and that RVP may not equate
with IOP and an elevated RVP could result in impaired op-
tic nerve head perfusion and be associated with glaucoma.57
Nonetheless, RVP has not been studied in the literature for
its association with glaucoma progression. It would be of
interest to determine its relationship with glaucoma pro-
gression and adjust for RVP in analysis related to glaucoma
progression in future studies.
In conclusion, narrowing of retinal-vessel calibers com-
puted by a DLS at baseline was associated with an increased
risk of NTG progression. These findings provide new in-
sights about the vascular theory of glaucoma and support a
prognostic role of retinal vasculature analysis in the clinical
risk assessment of NTG.
etiology, causes and mechanisms to management. Asia Pac J
Ophthalmol (Phila). 2019;8(6):457–468.
2. Weinreb RN, Aung T, Medeiros FA. The pathophys-
iology and treatment of glaucoma: a review. JAMA.
2014;311(18):1901–1911.
MARCH 2023
 3. Mallick J, Devi L, Malik PK, Mallick J. Update on normal
tension glaucoma. J Ophthalmic Vis Res. 2016;11(2):204–208.
4. Kaufman PL, Mohr ME, Riccomini SP, Rasmussen CA. Glau-
coma drugs in the pipeline. Asia Pac J Ophthalmol (Phila).
2018;7(5):345–351.
5. Leung DY, Iliev ME, Chan P, et al. Pressure-cornea-vascu-
lar index (PCVI) for predicting disease progression in normal
tension glaucoma. Br J Ophthalmol. 2011;95(8):1106–1110.
6. Hwang JC, Konduru R, Zhang X, et al. Relationship among
visual field, blood flow, and neural structure measurements in
glaucoma. Invest Ophthalmol Vis Sci. 2012;53(6):3020–3026.
7. Flammer J, Mozaffarieh M. Autoregulation, a balanc-
ing act between supply and demand. Can J Ophthalmol.
2008;43(3):317–321.
8. Galassi F, Giambene B, Varriale R. Systemic vascular dysregu-
lation and retrobulbar hemodynamics in normal-tension glau-
coma. Invest Ophthalmol Vis Sci. 2011;52(7):4467–4471.
9. Leighton DA, Phillips CI. Systemic blood pressure in
open-angle glaucoma, low tension glaucoma, and the normal
eye. Br J Ophthalmol. 1972;56(6):447–453.
10. Kim C, Kim TW. Comparison of risk factors for bilateral and
unilateral eye involvement in normal-tension glaucoma. In-
vest Ophthalmol Vis Sci. 2009;50(3):1215–1220.
11. Flammer J, Konieczka K, Flammer AJ. The primary vascular
dysregulation syndrome: implications for eye diseases. EPMA
J. 2013;4(1):14.
12. Gasser P, Flammer J. Blood-cell velocity in the nailfold capil-
laries of patients with normal-tension and high-tension glau-
coma. Am J Ophthalmol. 1991;111(5):585–588.
13. Lin TPH, Wang YM, Ho K, et al. Global assessment of arterio-
lar, venular and capillary changes in normal tension glaucoma.
Sci Rep. 2020;10(1):19222.
14. Butt Z, O’Brien C, McKillop G, et al. Color Doppler imaging
in untreated high- and normal-pressure open-angle glaucoma.
Invest Ophthalmol Vis Sci. 1997;38(3):690–696.
15. Plange N, Remky A, Arend O. Colour Doppler imaging and
fluorescein filling defects of the optic disc in normal tension
glaucoma. Br J Ophthalmol. 2003;87(6):731–736.
16. Plange N, Kaup M, Remky A, Arend KO. Prolonged retinal
arteriovenous passage time is correlated to ocular perfusion
pressure in normal tension glaucoma. Graefes Arch Clin Exp
Ophthalmol. 2008;246(8):1147–1152.
17. Akarsu C, Bilgili MYK. Color Doppler imaging in ocular hy-
pertension and open-angle glaucoma. Graefes Arch Clin Exp
Ophthalmol. 2004;242(2):125–129.
18. Wu R, Cheung CY, Saw SM, et al. Retinal vascular geometry
and glaucoma: the Singapore Malay Eye study. Ophthalmology.
2013;120(1):77–83.
19. Cheung CY, Xu D, Cheng CY, et al. A deep-learning sys-
tem for the assessment of cardiovascular disease risk via
the measurement of retinal-vessel calibre. Nat Biomed Eng.
2020;5(6):498–508.
20. Amerasinghe N, Aung T, Cheung N, et al. Evidence of retinal
vascular narrowing in glaucomatous eyes in an Asian popula-
tion. Invest Ophthalmol Vis Sci. 2008;49(12):5397 -4402.
21. Sherry LM, Wang JJ, Rochtchina E, et al. Reliability of com-
puter-assisted retinal vessel measurement in a population. Clin
Exp Ophthalmol. 2002;30(3):179–182.
22. Mitchell P, Leung H, Wang JJ, et al. Retinal vessel diame-
ter and open-angle glaucoma: the Blue Mountains Eye study.
Ophthalmology. 2005;112(2):245–250.
VOL. 247 RISK OF NORMAL TENSION GLAUCOMA PROGRESSION
23. Huang F, Dashtbozorg B, Zhang J, et al. Reliability of
using retinal vascular fractal dimension as a biomarker
in the diabetic retinopathy detection. J Ophthalmol.
2016;2016:6259047.
24. Rajkomar A, Dean J, Kohane I. Machine Learning in
medicine. N Engl J Med. 2019;380(14):1347–1358.
25. Muntner P, Shimbo D, Carey RM, et al. Measurement
of blood pressure in humans: a scientific statement
from the American Heart Association. Hypertension.
2019;73(5):e35–e66.
26. Leske MC. Ocular perfusion pressure and glaucoma: clini-
cal trial and epidemiologic findings. Curr Opin Ophthalmol.
2009;20(2):73–78.
27. The effectiveness of intraocular pressure reduction in the
treatment of normal-tension glaucoma. Collaborative Nor-
mal-Tension Glaucoma Study Group. Am J Ophthalmol.
1998;126(4):498–505.
28. Hou HW, Lin C, Leung CK. Integrating macular ganglion
cell inner plexiform layer and parapapillary retinal nerve fiber
layer measurements to detect glaucoma progression. Ophthal-
mology. 2018;125(6):822–831.
29. Leung CK, Cheung CY, Weinreb RN, et al. Evaluation of reti-
nal nerve fiber layer progression in glaucoma: a study on opti-
cal coherence tomography guided progression analysis. Invest
Ophthalmol Vis Sci. 2010;51(1):217–222.
30. Tanna AP, Desai RU. Evaluation of visual field progression in
glaucoma. Curr Ophthalmol Rep. 2014;2(2):75–79.
31. Artes PH, O’Leary N, Nicolela MT, et al. Visual field progres-
sion in glaucoma: what is the specificity of the Guided Pro-
gression Analysis? Ophthalmology. 2014;121(10):2023–2027.
32. Chan TCW, Bala C, Siu A, et al. Risk factors for
rapid glaucoma disease progression. Am J Ophthalmol.
2017;180:151–157.
33. Zhang X, Parrish RK, Greenfield DS, et al. Predictive factors
for the rate of visual field progression in the Advanced Imag-
ing for Glaucoma Study. Am J Ophthalmol. 2019;202:62–71.
34. Chauhan BC, Mikelberg FS, Balaszi AG, et al. Cana-
dian Glaucoma Study: 2. Risk factors for the pro-
gression of open-angle glaucoma. Arch Ophthalmol.
2008;126(8):1030–1036.
35. Heijl A, Leske MC, Bengtsson B, et al. Reduction of in-
traocular pressure and glaucoma progression: results from
the Early Manifest Glaucoma Trial. Arch Ophthalmol.
2002;120(10):1268–1279.
36. Gherghel D, Orgul S, Gugleta K, et al. Relationship between
ocular perfusion pressure and retrobulbar blood flow in pa-
tients with glaucoma with progressive damage. Am J Ophthal-
mol. 2000;130(5):597–605.
37. Lee K, Yang H, Kim JY, et al. Risk factors associated with
structural progression in normal-tension glaucoma: intraocu-
lar pressure, systemic blood pressure, and myopia. Invest Oph-
thalmol Vis Sci. 2020;61(8):35.
38. Qiu C, Qian S, Sun X, et al. Axial myopia is associated with
visual field prognosis of primary open-angle glaucoma. PLoS
One. 2015;10(7):e0133189.
39. Sehi M, Bhardwaj N, Chung YS, et al. Evaluation of baseline
structural factors for predicting glaucomatous visual-field pro-
gression using optical coherence tomography, scanning laser
polarimetry and confocal scanning laser ophthalmoscopy. Eye
(Lond). 2012;26(12):1527–1535.
119
40. Abbring JH, Van den Berg GJ. The unobserved het-
erogeneity distribution in duration analysis. Biometrika.
2007;94(1):87–99.
41. Steyerberg EW, Harrell FE, Borsboom GJJM, et al. In-
ternal validation of predictive models: efficiency of some
procedures for logistic regression analysis. J Clin Epidemiol.
2001;54(8):774–781.
42. Gerds TA, Schumacher M. Efron-type measures of pre-
diction error for survival analysis. Biometrics. 2007;63(4):
1283–1287.
43. Moghimi S, Hou H, Rao H, Weinreb RN. Optical coher-
ence tomography angiography and glaucoma: a brief review.
Asia Pac J Ophthalmol (Phila). 2019 Published online April 4.
doi:10.22608/APO.201914.
44. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Peri-
papillary and macular vessel density in patients with glau-
coma and single-hemifield visual field defect. Ophthalmology.
2017;124(5):709–719.
45. Tham YC, Cheng CY, Zheng Y, et al. Relationship between
retinal vascular geometry with retinal nerve fiber layer and
ganglion cell-inner plexiform layer in nonglaucomatous eyes.
Invest Ophthalmol Vis Sci. 2013;54(12):7309–7316.
46. Gao J, Liang Y, Wang F, et al. Retinal vessels change in pri-
mary angle-closure glaucoma: the Handan Eye study. Sci Rep.
2015;5:9585.
47. Jia Y, Wei E, Wang X, et al. Optical coherence tomography
angiography of optic disc perfusion in glaucoma. Ophthalmol-
ogy. 2014;121(7):1322–1332.
48. Moghimi S, Zangwill LM, Penteado RC, et al. Macu-
lar and optic nerve head vessel density and progressive
retinal nerve fiber layer loss in glaucoma. Ophthalmology.
2018;125(11):1720–1728.
120 AMERICAN JOURNAL OF OPHTHALMOLOGY
49. Lin F, Li F, Gao K, et al. Longitudinal changes in macular
optical coherence tomography angiography metrics in primary
open-angle glaucoma with high myopia: a prospective study.
Invest Ophthalmol Vis Sci. 2021;62(1):30.
50. Kerrigan-Baumrind LA, Quigley HA, Pease ME, et al. Num-
ber of ganglion cells in glaucoma eyes compared with thresh-
old visual field tests in the same persons. Invest Ophthalmol Vis
Sci. 2000;41(3):741–748.
51. Harwerth RS, Crawford ML, Frishman LJ, et al. Visual field
defects and neural losses from experimental glaucoma. Prog
Retin Eye Res. 2002;21(1):91–125.
52. Alasil T, Wang K, Yu F, et al. Correlation of retinal nerve
fiber layer thickness and visual fields in glaucoma: a broken
stick model. Am J Ophthalmol. 2014;157(5):953–959.
53. Yu M, Lin C, Weinreb RN, et al. Risk of visual field pro-
gression in glaucoma patients with progressive retinal nerve
fiber layer thinning: a 5-year prospective study. Ophthalmology.
2016;123(6):1201–1210.
54. Hood DC, Kardon RH. A framework for comparing structural
and functional measures of glaucomatous damage. Prog Retin
Eye Res. 2007;26(6):688–710.
55. Hood DC, Anderson SC, Wall M, Kardon RH. Structure ver-
sus function in glaucoma: an application of a linear model.
Invest Ophthalmol Vis Sci. 2007;48(8):3662–3668.
56. Stodtmeister R, Wetzk E, Herber R, et al. Measurement
of the retinal venous pressure with a new instrument
in healthy subjects. Graefes Arch Clin Exp Ophthalmol.
2022;260(4):1237–1244.
57. Stodtmeister R, Koch W, Georgii S, et al. The distribution
of retinal venous pressure and intraocular pressure differs sig-
nificantly in patients with primary open-angle glaucoma. Klin
Monbl Augenheilkd. 2022;239(3):319–325.
MARCH 2023