Effect of Antiplatelet Anticoagulant Use On.98326 PDF

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Effect of Antiplatelet/Anticoagulant use on Glaucoma Progression in Eyes with Optic Disc
Hemorrhage
Jiyun Lee, Kyung Rim Sung, Junki Kwon, Joong Won Shin
Department of Ophthalmology, College of Medicine, University of Ulsan, Asan Medical Center,
Seoul, South Korea
The authors have no proprietary or competing interests in or financial support for the
development or marketing of instruments or equipment mentioned in this article.
Corresponding Author: Kyung Rim Sung
Department of Ophthalmology, University of Ulsan

College of Medicine, Asan Medical Center
388–1 Pungnap-2-dong, Songpa-gu, Seoul, Korea 138–736
Tel: +82–2-3010–3680; Fax: +82–2-470–6440; E-mail: sungeye@gmail.com
Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of the article is prohibited.
ABSTRACT
Purpose: To assess whether the use of antiplatelets (APs)/anticoagulants (ACs) affects

glaucoma progression in eyes with optic disc hemorrhage (DH)
Methods: One hundred and nineteen eyes from 119 patients with primary open angle glaucoma
in whom a DH was observed at least once during the follow-up period (mean follow-up duration:
6.2 years) were included in this retrospective observational study. Cox proportional hazard
models were used to identify the association between putative factors, including AP/AC use, and
glaucoma progression. Glaucoma progression was assessed on the basis of changes noted on
serial optic disc and retinal nerve fiber layer photographs or changes in the visual field.
Results: Nineteen of the 119 patients took AP/AC drugs daily (AP/AC use group [AG]), while
the others did not (no use group [NG]). The follow-up period to progression was significantly
different between the two groups (61.2  23.5 months for the AG and 47.6  22.0 months for the
NG; P=0.016). Kaplan-Meier analysis revealed a greater cumulative probability of glaucoma
progression in the NG than in the AG, with borderline statistical significance (P=0.081). Higher
mean intraocular pressure during the follow-up period was a risk factor for glaucoma
progression (hazard ratio [HR], 1.107; P=0.014), while AP/AC drug use protected against
glaucoma progression (HR, 0.576; P=0.046).
Conclusions: According to our result, use of AP/ AC drugs was associated with lower risk of
glaucoma progression in eyes with DH.
Key words; Glaucoma, Disc hemorrhage, Progression, Antiplatlet, Anticoagulant
Disclosure: The authors declare no conflict of interest.
INTRODUCTION
Glaucoma is an optic neuropathy that is characterized by characteristic structural damage to the
optic nerve head accompanied by functional visual loss, i.e., defects in the visual field (VF).
Previous studies have identified various risk factors for glaucoma development, including high
intraocular pressure (IOP),1 old age,2 family history,3,4 and myopia.5 Numerous studies have
shown that optic disc hemorrhage (DH) is related to a rapid progression of glaucomatous
structural changes and functional deficits.6-11 In other words, progression of neuroretinal rim
notching or thinning and widening of the retinal nerve fiber layer (RNFL) defect are observed
after DH occurrence.6,7 Other studies have reported accelerated deterioration of the VF and
development of new VF defects as a consequence of DH.8,9 DH is a complex phenomenon that
stems from diverse factors such as mechanical disruption of the RNFL, vascular disturbances,
and other causes.12 Furthermore, DH is more frequently observed in normal tension glaucoma
(NTG) than high tension glaucoma (HTG) which is a dominant form of primary open angle
glaucoma (POAG) in east Asian countries like Korea or Japan. 11 However, the cause of the DH
observed in cases of glaucoma has not been fully elucidated.
As glaucoma frequently develops in old age and older patients are at a high risk for
chronic systemic vascular diseases such as hypertension, ischemic heart disease, and diabetic
mellitus, a considerable proportion of patients with glaucoma take anticoagulant or antiplatelet
(AP/AC) drugs. Because these drugs can alter optic disc hemodynamics, DHs are sometimes
observed in patients taking such medications, and even in non-glaucomatous patients taking
such medications.13-15 Indeed, a positive relationship between the use of AP drugs and the
frequency of DH occurrence has been observed.16,17 Thus, in this study, we aimed to compare
the longitudinal clinical course of POAG accompanied by DH in patients taking AP/AC
medications and in those not taking these medications. We also aimed to assess the effect of
AP/AC use on glaucoma progression.
METHODS
Data were collected from the ongoing Asan Glaucoma Progression Study (APGS). A
retrospective review of the medical records of 296 eyes of 296 patients with POAG who
developed a DH at least once between March 2007 and April 2017 and were examined by a
single glaucoma specialist (KRS) was performed. Patients who met the below-mentioned
inclusion criteria were selected for further analysis. The Institutional Review Board of Asan
Medical Center approved this study, and the study was carried out in accordance with the
principles of the Declaration of Helsinki.
All subjects underwent a comprehensive ophthalmologic examination, comprising a
review of systemic diseases and the patient’s medical history, including the use of
anticoagulant/antiplatelet medications such as aspirin, clopidogrel, warfarin, and cilostazol, as
well as the duration and number of medications used; best-corrected visual acuity (BCVA)
measurement; a refraction test; slit-lamp biomicroscopy; Goldmann applanation tonometry;
gonioscopy; central corneal thickness measurement (DGH-550;DGH Technology, Inc., Exton,
PA, USA); fundoscopic examination; stereoscopic optic disc and red-free RNFL photography
(AFC-210; Nidek, Aichi, Japan); ganglion cell inner plexiform layer (GCIPL) and RNFL
imaging (Cirrus HD-OCT; Carl Zeiss Meditec); and standard automated perimetry (Humphrey
Field analyzer with Swedish Interactive Threshold Algorithm standard 24–2 test; Carl Zeiss
Meditec). Baseline IOP was defined as the IOP measured before starting glaucoma medication,
and reduction in IOP was defined as baseline IOP minus the average of follow-up IOPs
measured during the course of treatment. Patients were followed up every 6 to 9 months with
OCT and VF examinations, optic disc and RNFL photography, and IOP measurements. Patients
included in the present study were those with POAG who had been followed up for greater than
36 months in whom a DH was observed during at least one follow-up visit and for whom the
results of at least five reliable OCT and VF examinations performed at different times were
available. Glaucoma was diagnosed on the basis of presence of retinal nerve fiber layer (RNFL)
defects or glaucomatous optic disc changes (neuroretinal rim thinning, disc excavation, and DH)
and corresponding visual field (VF) defects as confirmed by at least 2 reliable VF examinations.
Only reliable VF test results (i.e., false-positive errors < 15%, false-negative errors < 15%, and
fixation loss < 20%) were considered. Glaucomatous VF defects were defined as a cluster of 3
or more non-edged contiguous points on a pattern deviation plot with P<0.05 (with at least one
point having a P value of less than 0.01) as confirmed by at least 2 consecutive examinations, a
pattern standard deviation with P<0.05, or glaucoma hemifield test results outside normal limits.
Those eyes with all IOP measurements lower than 21 mmHg including baseline measurement
were considered NTG. If both eyes of a patient were eligible, one eye was selected at random
and included in the study. Patients with any ophthalmic or neurologic disease known to affect
the optic nerve head or VF were excluded. If surgical or laser treatment was performed during
the follow-up period, only data obtained in the period before that treatment, which had to exceed
36 months, were analyzed.
Assessment of optic disc hemorrhage
All stereoscopic optic disc/RNFL photographs were independently and carefully
reviewed by two glaucoma specialists (KRS and JYL). All DHs were evaluated and their
locations and shapes were recorded on a chart. We defined a DH as an isolated flame or splinter
hemorrhage on the optic disc, or that crossing the disc border, or that in the peripapillary area. A
non-recurrent DH was defined as a DH that occurred in an eye that had no other episodes of DH
in the follow-up period, while a recurrent DH was defined as the enlargement of an earlier DH
or the development of a new DH elsewhere. The total number of DHs was the sum of non-
recurrent and recurrent DHs.
Definition of glaucoma progression
Glaucoma progression was evaluated from both structural and functional aspects.
Structural progression was assessed by observing changes in the optic disc and RNFL, either by
comparing serial optic disc/RNFL photographs, or by using guided progression analysis (GPA)
provided by a Cirrus spectral-domain OCT system.18 The criteria for progression included
changes in notching or thinning of the neuroretinal rim, changes in the vessel contour of the
optic disc, and an increase in the cup-to-disc ratio, as seen on optic disc photographs, as well as
increments in the depth or width of existing RNFL defects or the appearance of newly occurring
defects on RNFL photographs. The progression of the optic disc and RNFL defects were
determined by evaluating a whole series of the stereoscopic optic disc and red-free RNFL
photographs, which were displayed on a liquid crystal display monitor. Two glaucoma experts
(JK and JWS), who were unaware of each other’s assessments and were blind to all clinical and
VF information, independently assessed all photographs to estimate glaucoma progression. Each
grader classified each glaucomatous eye as either stable or progressing. If the opinions of the
two graders differed, the third examiner (KRS) made the final decision.
RNFL thickness was measured using the optic disc cube protocol of a Cirrus OCT
system running version 6.0 software (Cirrus OCT; Carl Zeiss Meditec, Inc., Dublin, CA).
Images exhibiting involuntary saccade, misalignment, or blinking artifacts and those with a
signal strength of <6 were discarded. Images featuring algorithm segmentation failure were also
excluded after careful visual inspection. Glaucomatous progression in RNFL thickness was
determined by Cirrus OCT GPA.
VF progression was evaluated by either trend- or event-based analysis using GPA. In
trend-based linear regression analysis using the visual field index, a significantly negative slope
(P<0.05) indicated VF progression. In event-based analysis, progression was defined as a
significant deterioration from the baseline pattern deviation at three or more of the same test
points on three consecutive examinations.19
Statistical Analysis
We used the independent t-test or Mann-Whitney U test for continuous variables and the
chi- square test or Fishers’ exact test for categorical factors, according to the normality of the
data, to compare demographic and progression-related parameters between the AP/AC use group
(AG) and the no use group (NG). Cox proportional hazard models were used to identify putative
risk factors including AP/AC use as covariates for glaucoma progression. Univariate and
multivariate Cox analyses were carried out, and adjusted hazard ratios (HRs) were calculated.
Variables with a P value less than 0.2 in the univariate analysis were included in the multivariate
analysis. Kaplan-Meier survival analyses with the log rank test were used to compare glaucoma
progression between the AG and NG. All statistical analyses were performed with SPSS version
15.0 (SPSS Inc., Chicago, IL, USA), and P < 0.05 was considered statistically significant.
RESULTS
Of the 296 patient charts reviewed for inclusion, 119 met the inclusion criteria. One
hundred and seventy-seven charts were excluded for the following reasons: the patient had
undergone glaucoma surgery previously with a follow-up period of less than 36 months (n=96),
the patient had undergone refractive surgery previously (n=32), systemic medical information
was lacking (n=20), examinations taken less than five times including the VF test, OCT, and
optic disc photographs and red-free fundus photographs (n=29). Among 96 patients excluded by
previous glaucoma surgery, 17 patients were taking AP/ACs (17.7%) while 79 patients (82.3%)
were not.
A total of 119 eyes of 119 patients, consisting of 19 patients in the AG and 100 in the NG,
were included in the final analysis. Among 119 eyes, 15 eyes were HTG, while 104 eyes were
NTG. Four eyes in the AG (21.1%) and the 11 eyes in the NG (11%) were HTG.
The 19 patients in the AG had been taking AP/AC drugs daily for a mean duration of
96.3  53.1 months when reviewed at baseline. In terms of combinations of AP or AC drugs, 10
patients used only AP drugs; 2, only AC drugs; and 7, both AP and AC drugs. The most
commonly used drugs were aspirin (52.6%), clopidogrel (21.1%), warfarin (15.8%), and
cilostazol (10.5%).
Of the 119 subjects, 61 were men and 58 were women, and the mean age of the
subjects was 59.6  11.2 years. Table 1 summarizes the demographic and clinical characteristics
of the participants. The follow-up period was 74.8  22.0 months for all patients, and the follow-
up period to glaucoma progression was 49.8  22.7 months. The follow-up period to glaucoma
progression was significantly different between the two groups (61.2  23.5 months for the AG
and 47.6  22.0 months for the NG; P=0.016). However, total follow up period was not different
between two groups (77.2  19.9 (AG) vs 74.4 22.4 months, p=0.606).
Regarding optic disc/RNFL photographic assessment, two experts showed the same
opinion in all 119 eyes (100%) for the DH assessment. However, in terms of the progression
determination, two experts agreed in 105 eyes (88.2%), hence the third examiner made the final
decision for remained 14 eyes.
Overall, 16 eyes in the AG (84.2%) and the 84 eyes in the NG (84%) showed
progression by one of three progression criteria during the follow up period. By VF criterion, 8
eyes (42.1%) of AG and 20 eyes (20%) of NG patients progressed. According to the optic
disc/RNFL criterion, 12 eyes (63.2%) of AG and 79 eyes (79%) of NG progressed. By OCT
criterion, 9 eyes (47.4%) of AG and 37 eyes (37%) of NG progressed, respectively. Presence of
family history of glaucoma was more frequent in the NG than in the AG (P<0.001), while
presence of systemic diseases such as hypertension, diabetes mellitus, and dyslipidemia was
more frequent in the AG than in the NG (P=0.003, P=0.001, P=0.007, respectively). The mean
number of optic disc/RNFL photographs examined per eye was 10.2  2.6, and was not
significantly different between the two groups (AG, 1.8  0.9; NG, 1.6  1.0; P=0.601).
However, the reduction in IOP during follow-up was greater in the NG than in the AG (AG, 0.2
 3.1; NG, 2.2  3.4 mmHg; P=0.022), and VF pattern standard deviation (PSD) was higher in
the NG than in the AG (AG, 2.9  2.7; NG, 4.6  4.0; P=0.022).
According to a Cox proportional hazard analysis, in the univariate analysis of all
patients, mean follow up IOP, total number of DH occurrence, and AP/AC use were likely
associated with glaucoma progression. In the multivariate analysis, higher mean follow-up IOP
(HR=1.1, P=0.014) was associated with glaucoma progression, while AP/AC use was protective
against glaucoma progression (HR=0.6, P= 0.046; Table 2). Kaplan-Meier analysis revealed a
greater cumulative probability of glaucoma progression in the NG than in the AG, but only a
borderline statistical significance was noted (P=0.081; Figure 1).
Meanwhile, subgroup analysis of the AG revealed that greater average RNFL thickness
and worse VF mean deviation (MD) were associated with glaucoma progression in the
multivariate Cox analysis (Table 3), while a smaller reduction in mean follow-up IOP and
greater total number of disc hemorrhage occurrence, were marginally associated with glaucoma
progression in the NG (P= 0.075, P= 0.064, respectively) (Table 4).
Figure 2 illustrates the location of disc hemorrhages in each group. In both groups, the
inferior region of the optic disc had the greatest number of hemorrhages. Hemorrhages in the
superior region of the disc were more common in the AG than in the NG. DH recurrence rates
were 52.6% (10 of 19 eyes) in the AG and 39% (39 of 100 eyes) in the NG, but the difference
was not significant (P=0.268).
DISCUSSION
In this study, we found that a higher mean IOP was a risk factor for glaucoma
progression, whereas AP/AC drug use reduced the likelihood of progression in Cox proportional
analysis in the glaucomatous eyes that showed DH during follow-up. Kaplan-Meier analysis
also revealed that the NG had a greater cumulative probability of progression, though this
finding was of borderline statistical significance.
Disc hemorrhage (DH) is widely considered to be a significant risk factor for the
development and progression of glaucoma.20 However, the pathogenesis of DH is unclear, and
there is an ongoing debate regarding the relationship between DH and glaucoma progression.
According to previous studies,19,21 DH is an independent risk factor for VF progression, and
recently Kim et al22 reported that DH was associated with a 2.4-fold higher probability of
progression of normal tension glaucoma. These findings suggested that IOP reduction is not able
to completely prevent glaucoma deterioration, and that other factors also contribute to glaucoma
progression.2016,23-25 Use of aspirin16 is a risk factor for DH occurrence. Kim et al found a
marginal association between use of aspirin and DH (P=0.079), and Grodum et al26 reported a
positive association between these two factors.
DH can be originated from ischemic micro-infarctions in the optic disc, as well as from
mechanical rupture of small blood vessels due to structural changes in the lamina cribrosa.23,27
Because aspirin prevents thromboxane A2 production by inhibiting cyclooxygenase, thereby
interfering with platelet aggregation, use of aspirin could boost the risk of developing DH. In
addition, owing to the DH mechanism, as described above, patients taking aspirin tend to have
vascular diseases that may eventually result in a DH.13,14
Therefore, we decided to examine whether use of AP/AC drugs affected glaucoma
progression and to establish its true influence on the disease. Since, in our cohort, there were
only few patients on AP drugs only, we included them in the same group as patients using AC
drugs such as warfarin, clopidogrel, or cilostazol. Although their pharmacological dynamics and
mechanisms are different, all these medications increase bleeding tendency. According to the
results of the multivariate analysis, the use of AP/AC drugs was protective against glaucoma
progression. These observations suggest that the use of AP/AC drugs may increase the
frequency of occurrence of DHs or hamper the absorption of DHs, but that these effects are not
related to glaucoma progression because they may not be caused solely by glaucomatous
structural change. Another possible explanation would be that AP /AC use itself can reduce the
risk of glaucomatous progression by benefitting the cardiovascular aspect. In the subgroup
analysis of the AG, average RNFL thickness and VF MD were associated with glaucoma
progression, which were in line with the findings of previous studies.1,28-32 Meanwhile, in the
NG, the higher number of DH occurrence and smaller reduction in IOP were weakly associated
with progression. In both groups, the inferior region of the optic disc had the greatest number of
hemorrhages. As reported by previous study, inferior region of the optic disc is the most
frequently affected in glaucoma.33 The observation that hemorrhages in the superior region of
the disc were more common in the AG than in the NG could be explained that some of those
DHs were related to non-glaucomatous cause. However, this is a speculation which needs to be
confirmed in the forthcoming study.
The present study had several limitations. First, there was an imbalance between the
numbers of patients in the two groups; the fact that there were more patients in the NG and
relatively fewer in the AG might have affected the result of statistical analysis. However, other
variables including total follow-up period and number of optic disc/RNFL photographs analyzed
did not differ significantly. Second, there were patients who took systemic medications other
than AP or AC drugs. The effect of those medications on systemic diseases such as hypertension
and diabetes mellitus can affect the progression of glaucoma, and it is impossible to rule out the
effects of these systemic medications on hemodynamic changes in the optic disc. Further studies
that address these limitations are needed.
To the best of our knowledge, this study is the first to assess the effect of use of AC/AP
drugs on glaucoma progression in eyes that developed DH during follow-up. We conclude that
in patients with POAG who developed DH, use of AP/AC drugs does not aggravate
glaucomatous changes, but was rather associated with a less probability of progression
compared with those not taking AP/AC medications. DH occurred in patients with POAG who
were taking AP/AC drugs; thus, DH may be more related to the result of a greater bleeding
tendency rather than due to glaucoma. Otherwise, AP/AC medication would be helpful for
slowing glaucomatous progression by improving systemic circulation.
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FIGURE 1. Kaplan-Meier analysis of the probability of no glaucoma progression in
patients in the no use group (NG) and the antiplatelet/anticoagulant use group (AG). Log
rank tests comparing the probability of no glaucoma progression between the control group and
the antiplatelet/anticoagulant use group showed borderline significant differences (P=0.081).
FIGURE 2. Locations of disc hemorrhages including recurrent hemorrhages in both
groups
Table 1. Demographic and clinical characteristics of the antiplatelet/anticoagulant use
group (AG) and the no use group (NG).
Total AG NG P
value*
(n = 119) (n=19) (n=100)
Total follow-up period 74.8  22.0 77.2  19.9 74.4 22.4 .606
(month)
Follow-up period to 49.8  22.7 61.2  23.5 47.6  22.0 .016
Progression (month)
Age (year) 59.6  11.2 66.2  10.8 58.3  10.9 .004
Laterality (OD/OS) (n) 58 / 61 11 / 8 47 / 53 .428
Sex (M/F) (n) 61 / 58 14 / 5 47 / 53 .040
Previous op. history (n) 14 (11.76%) 4 (21.1%) 10 (10.0%) .170
Number of glaucoma 1.12  0.63 1.26  0.73 1.09  0.61 .276
medications at the last
follow-up visit (n)
Family history of 7 (5.88%) 0 (0%) 7 (7.0%) <.001
glaucoma (n)
Hypertension (n) 39 (32.77%) 12 (63.2%) 27 (27.0%) .003
Diabetes (n) 23 (19.33%) 9 (56.3%) 14 (14.0%) .001
Hypercholesterolemia (n) 23 (19.33%) 8 (42.1%) 15 (15.0%) .007
BCVA 0.96  0.15 0.91  0.17 0.96  0.15 .228
SE (diopters) -1.93  3.05 -1.47  2.95 -2.01  3.07 .501
Baseline IOP (mmHg) 15.95  3.46 14.74  2.98 16.18  3.51 .095
Mean IOP (mmHg) 14.08  2.80 14.50  2.54 14.01  2.85 .482
Reduction in IOP (mmHg) 1.87  3.39 0.24  3.12 2.18  3.37 .022
CCT (㎛) 524.83  28.23 527.18  24.95 524.50  28.80 .770
VF MD (dB) -3.21  4.19 -2.79  4.23 -3.29  4.20 .637
VF PSD (dB) 4.35  3.86 2.87  2.69 4.63  3.99 .022
Number of optic disc 10.20  2.63 10.68  3.09 10.11  2.55 .386
photographs per eye
Number of disc 1.62  0.91 1.78  0.86 1.66  1.01 .601
hemorrhage (n)
occurrence
Average RNFL thickness 80.02  10.37 78.21  9.15 80.36  10.60 .411
(㎛)
Average C/D ratio 0.74  0.08 0.74  0.05 0.73  0.09 .860
Vertical C/D ratio 0.73  0.08 0.72  0.07 0.74  0.08 .455
Rim area 0.86  0.19 0.89  0.18 0.85  0.19 .409
BCVA, best-correct visual acuity; SE, spherical equivalent; IOP, intraocular pressure; CCT,
central corneal thickness; VF, visual field; MD, mean difference; PSD, pattern standard
deviation; C/D ratio, cup-to-disc ratio; RNFL, retinal nerve fiber layer
*Mann-Whitney U test
For categorical analysis, Fisher’s exact test was performed.
Table 2. Univariate and multivariate cox-proportional hazards models assessing the association between
different parameters and glaucoma progression in all patients
Univariate Multivariate
Factor Exp (B) P value Exp (B) P value
Age (year) .990 .285
Sex (male,as control) .958 .830
SE (diopters) .989 .736
Baseline IOP(mmHg) 1.011 .650
Mean follow up IOP (mmHg) 1.104 .018 1.107 .014
Reduction in IOP (mmHg) .967 .221
Mean RNFL thickness (㎛) 1.011 .290
Number of DH occurrence (n) 1.152 .188 1.139 .223
CCT (㎛) 1.003 .526
VF MD (dB) .982 .430
Use of antiplatelet or anticoagulant drugs .597 .061 .576 .046
SE, spherical equivalent; IOP, intraocular pressure; CCT, central corneal thickness; VF MD, visual field mean
deviation; DH, disc hemorrhage; RNFL, retinal nerve fiber layer
Table 3. Univariate and multivariate cox-proportional hazards models assessing the association between
parameters and glaucoma progression in the antiplatelet/anticoagulant use group (AG)
Age (year) 1.051 .083 1.057 .097
Sex 1.157 .807
(male, as control)
SE (diopters) 1.240 .141 1.101 .666
Baseline IOP (mmHg) 1.125 .199 1.205 .276
Mean IOP (mmHg) 1.239 .072 .907 .659
Reduction in IOP 1.004 .965
(mmHg)
Mean RNFL thickness 1.054 .176 1.165 .008
(㎛)
Number of DH 1.028 .944
occurrence (n)
CCT (㎛) 1.016 .416
VF MD (dB) .861 .098 .672 .003
SE, spherical equivalent; IOP, intraocular pressure; CCT, central corneal thickness; VF MD, visual field mean
deviation ; DH, disc hemorrhage; RNFL, retinal nerve fiber layer
Table 4. Univariable and multivariable cox-proportional hazards models assessing the association between
parameters and glaucoma progression in the no use group (NG)
Age (year) .980 .130 .982 .077
Sex (male, as control) .858 .483
SE (diopters) .972 .445
Baseline IOP (mmHg) .985 .619
Mean IOP (mmHg) 1.086 .054 1.060 .223
Reduction in IOP (mmHg) .934 .070 .937 .075
Mean RNFL thickness (㎛) 1.007 .545
Number of DH occurrence (n) 1.167 .163 1.244 .064
CCT (㎛) 1.002 .636
VF MD (dB) .999 .975
IOP, intraocular pressure; CCT, central corneal thickness; VF MD, visual field mean deviation; DH, disc
hemorrhage; RNFL, retinal nerve fiber layer; SE, spherical equivalent

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Journal of Glaucoma Publish Ahead of Print

Effect of Antiplatelet/Anticoagulant use on Glaucoma Progression in Eyes with Optic Disc

Department of Ophthalmology, College of Medicine, University of Ulsan, Asan Medical Center,

Seoul, South Korea

development or marketing of instruments or equipment mentioned in this article.

Corresponding Author: Kyung Rim Sung

Department of Ophthalmology, University of Ulsan

Purpose: To assess whether the use of antiplatelets (APs)/anticoagulants (ACs) affects

Key words; Glaucoma, Disc hemorrhage, Progression, Antiplatlet, Anticoagulant

Disclosure: The authors declare no conflict of interest.

Glaucoma is an optic neuropathy that is characterized by characteristic structural damage to the

development of new VF defects as a consequence of DH.8,9 DH is a complex phenomenon that

observed in cases of glaucoma has not been fully elucidated.

mellitus, a considerable proportion of patients with glaucoma take anticoagulant or antiplatelet

the longitudinal clinical course of POAG accompanied by DH in patients taking AP/AC

AP/AC use on glaucoma progression.

principles of the Declaration of Helsinki.

All subjects underwent a comprehensive ophthalmologic examination, comprising a

anticoagulant/antiplatelet medications such as aspirin, clopidogrel, warfarin, and cilostazol, as

measurement; a refraction test; slit-lamp biomicroscopy; Goldmann applanation tonometry;

36 months, were analyzed.

Assessment of optic disc hemorrhage

All stereoscopic optic disc/RNFL photographs were independently and carefully

recurrent and recurrent DHs.

Definition of glaucoma progression

VF information, independently assessed all photographs to estimate glaucoma progression. Each

determined by Cirrus OCT GPA.

(P<0.05) indicated VF progression. In event-based analysis, progression was defined as a

points on three consecutive examinations.19

96.3  53.1 months when reviewed at baseline. In terms of combinations of AP or AC drugs, 10

decision for remained 14 eyes.

disc/RNFL criterion, 12 eyes (63.2%) of AG and 79 eyes (79%) of NG progressed. By OCT

criterion, 9 eyes (47.4%) of AG and 37 eyes (37%) of NG progressed, respectively. Presence of

According to a Cox proportional hazard analysis, in the univariate analysis of all

borderline statistical significance was noted (P=0.081; Figure 1).

progression in the NG (P= 0.075, P= 0.064, respectively) (Table 4).

was not significant (P=0.268).

finding was of borderline statistical significance.

development and progression of glaucoma.20 However, the pathogenesis of DH is unclear, and

According to previous studies,19,21 DH is an independent risk factor for VF progression, and

progression.2016,23-25 Use of aspirin16 is a risk factor for DH occurrence. Kim et al found a

positive association between these two factors.

Because aspirin prevents thromboxane A2 production by inhibiting cyclooxygenase, thereby

vascular diseases that may eventually result in a DH.13,14

Therefore, we decided to examine whether use of AP/AC drugs affected glaucoma

risk of glaucomatous progression by benefitting the cardiovascular aspect. In the subgroup

confirmed in the forthcoming study.

prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. Jama.

(Chicago, Ill : 1960). 1994;112(1):69-73.

risk of primary open-angle glaucoma. Population-based familial aggregation study.

Archives of ophthalmology (Chicago, Ill : 1960). 1998;116(12):1640-1645.

myopia: the Blue Mountains Eye Study. Ophthalmology. 1999;106(10):2010-2015.

disk hemorrhage cases. American journal of ophthalmology. 2002;134(6):920-922.

7. Ishida K, Yamamoto T, Sugiyama K, Kitazawa Y. Disk hemorrhage is a significantly

negative prognostic factor in normal-tension glaucoma. American journal of

The British journal of ophthalmology. 2014;98(11):1555-1559.

ophthalmology & visual science. 2009;50(10):4727-4733.

Glaucoma as Determined by Two Different Criteria. Korean J Ophthalmol.

glaucomatous disc hemorrhage. Prog Retin Eye Res. 2017;60:20-43.

Function and Disc Hemorrhage in Patients With Normal-Tension Glaucoma: A

Prospective Cross-Sectional Study. American journal of ophthalmology.

Journal canadien d'ophtalmologie. 2015;50(2):155-158.

ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle