Characteristics and Outcomes of Retinal Artery Occlusion

Nationally Representative Data

Emily M. Schorr, MD; Kyle C. Rossi, MD; Laura K. Stein, MD; Brian L. Park, MD;
Stanley Tuhrim, MD; Mandip S. Dhamoon, MD, DrPH

Background and Purpose—There are few large studies examining comorbidities, outcomes, and acute interventions for
patients with retinal artery occlusion (RAO). RAO shares pathophysiology with acute ischemic stroke (AIS); direct
comparison may inform emergent treatment, evaluation, and secondary prevention.
Methods—The National Readmissions Database contains data on ≈50% of US hospitalizations from 2013 to 2015.
We used International Classification of Diseases, Ninth Revision, codes to identify and compare index RAO and
AIS admissions, comorbidities, and interventions and Clinical Comorbidity Software codes to identify readmissions
causes, using survey-weighted methods when possible. Cumulative risk of all-cause readmission after RAO ≤1 year
was estimated by Kaplan-Meier analysis.
Results—Among 4871 RAO and 1 239 963 AIS admissions, patients with RAO were less likely (P<0.0001) than patients
with AIS to have diabetes mellitus (RAO, 24.3% versus AIS, 36.8%), congestive heart failure (9.1% versus 14.8%), atrial
fibrillation (15.5% versus 25.2%), or hypertension (62.2% versus 67.6%) but more likely to have valvular disease (13.3%
versus 10.5%) and tobacco usage (38.6% versus 32.9%). In RAO admissions, thrombolysis was administered in 2.9%
(5.8% in central RAO subgroup, versus 8.0% of AIS), therapeutic anterior chamber paracentesis in 1.0%, thrombectomy
in none; 1.4% received carotid endarterectomy during index admission, 1.6% within 30 days. Nearly 1 in 10 patients
with RAO were readmitted within 30 days and were more than twice as likely as patients with AIS to be readmitted for
dysrhythmia or endocarditis. Readmission for stroke after RAO was the highest within the first 150 days after index
admission, and risk was higher in central RAO than in branch RAO.
Conclusions—Patients with RAO had high prevalence of many stroke risk factors, particularly valvular disease and
smoking, which can be addressed to minimize subsequent risk. Despite less baseline atrial fibrillation, RAO patients
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were more likely to be readmitted for atrial fibrillation/dysrhythmias. A variety of interventions was administered. AIS
risk is the highest shortly after RAO, emphasizing the importance of urgent, thorough neurovascular evaluation.   (Stroke.
2020;51:800-807. DOI: 10.1161/STROKEAHA.119.027034.)
Key Words: brain infarction ◼ humans ◼ retinal artery occlusion ◼ risk factors ◼ tobacco

R etinal artery occlusion (RAO) is an ophthalmological

emergency and an important cause of acute vision loss
with an incidence of 1 to 2 cases per 100 000 per year.1 RAO is
most commonly caused by embolus, thrombosis, or arteritis.
It can cause partial or complete visual loss.2 Without interven-
tion, <20% of patients will have significant visual recovery,3
and the majority will have visual acuity of 20/400 or worse
in the affected eye.2 Furthermore, RAO is associated with an
increased risk of subsequent stroke particularly in the few
weeks after RAO.4–6
The pathophysiology of RAO is similar to cerebral stroke,
with the majority of cases thought to be due to cardioembolic
or artery-artery embolism, often the ipsilateral carotid ar-
tery.7,8 A small percent of RAO is due to other causes such as
vasculitis, primarily giant cell arteritis (GCA).2,9 Acute treat-
ment remains controversial.9 Traditional interventions such
as anterior chamber paracentesis or ocular massage have no
proven benefit10,11 and may actually be harmful; cases that
receive these treatments have been associated with recovery
rates less than half of cases that receive no intervention at all3
but are still often performed.12 A 2015 study found that intra-
venous thrombolysis was associated with more than a 2-fold
likelihood of recovery if given within 4.5 hours of onset,3
and intra-arterial fibrinolysis has shown mixed but promising
results especially when given within 4 to 6 hours of onset.13–15
Given the relative lack of consistent evidence-based data
about this complex disease, only 20% of academic centers
have a formal RAO treatment protocol, and there is often lack

Received July 16, 2019; final revision received November 7, 2019; accepted December 2, 2019.
From the Department of Neurology (E.M.S., L.K.S., S.T., M.S.D.) and Department of Pediatrics (B.L.P.), Icahn School of Medicine at Mount Sinai, New
York, NY; and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (K.C.R.).
Guest Editor for this article was Emmanuel Touzé, PhD.
Presented in part at the American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4–10, 2019.
Correspondence to Mandip S. Dhamoon, MD, DrPH, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, Annenberg 301B, New York, NY
10029. Email mandip.dhamoon@mssm.edu
© 2020 American Heart Association, Inc.
Stroke is available at https://www.ahajournals.org/journal/str DOI: 10.1161/STROKEAHA.119.027034

800
 Schorr et al   Characteristics and Outcomes of RAO   801
of consensus even within a department.12 A sizable portion of
those who treat RAO do not routinely assess vascular risk fac-
tors, and management varies when an ophthalmologist or neu-
rologist is the primary physician.12
There are few studies examining RAO with larger than
several hundred cases, and few directly compare RAO to acute
ischemic stroke (AIS). We sought to assess nationwide RAO
demographics, comorbidities, acute treatments provided,
readmissions, and subsequent stroke risk, compared with AIS.
Methods
We utilized the Nationwide Readmissions Database (NRD), released
by the Healthcare Cost and Utilization Project (HCUP), analyzing
data from January 1, 2013, to September 30, 2015. The NRD contains
nationwide data on US admissions for all payers and the uninsured;
it includes data from almost half of all US hospitalizations, excluding
rehabilitation and long-term acute-care hospitalizations. Each in-
dividual in the NRD has an anonymized, verified linkage identifier
that allows for analysis of readmissions. A variable is also provided
that allows calculation of days between admissions for an individual.
The Mount Sinai Hospital Institutional Review Board reviewed and
approved this project, and all analyses comply with the HCUP data
use agreement. Because HCUP data are publicly available, we will
not provide the data, analytic methods, and study materials; the
authors are further limited to release data by the data use agreement.
We identified RAO by International Classification of Diseases,
Ninth Revision (ICD-9), Clinical Modification codes 362.31 (central
RAO [CRAO]), 362.32 (retinal artery branch occlusion [BRAO]),
362.33 (partial BRAO), and 362.34 (transient RAO). Limited data are
available about validation of ICD-9 coding for this diagnosis, so we
included all potentially relevant ICD-9 codes. We identified index AIS
admissions using ICD-9 codes previously validated in the literature
(433.x1, 434.x1, 436), which have a sensitivity of 74%, specificity of
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95%, and positive predictive value of 88% when used in the primary
diagnosis position.16,17 We used standard ICD-9 codes to identify risk
factors and comorbidities, such as diabetes mellitus, tobacco usage,
hypertension, and others as listed in the Table. Endovascular throm-
bectomy cases were identified by ICD-9 procedure code 39.74 and
thrombolysis administration by code 99.10. Other procedures were
identified by the ICD-9 code listed in the figures.
We described characteristics of the index hospitalization as de-
fined by HCUP, including hospital bed size (small, medium, or large),
teaching hospital status (metropolitan nonteaching, metropolitan
teaching, and nonmetropolitan hospital), income quartile of patient’s
zip code, and National Center for Health Statistics urban-rural lo-
cation classification (central counties of metro areas of ≥1 million
population, fringe counties of metro areas of ≥1 million population,
counties in metro areas of 250 000–999 999 population, counties in
metro areas of 50 000–249 999 population, micropolitan counties
of 10 000–49 999 population, and not metropolitan or micropol-
itan counties). Patients in the NRD are categorized into All Patient
Refined Diagnosis Related Groups using 3M Health Information
Systems software, which classifies patients into 25 major diagnostic
categories. Patients are further subdivided into 4 severity of illness
subclasses according to degree of loss of function (minor, mod-
erate, major, and extreme) and 4 risk of mortality subclasses (minor,
moderate, major, and extreme); these 2 subclasses are calculated
independently. The All Patient Refined Diagnosis Related Groups
mortality score is correlated with mortality rates.18,19 HCUP catego-
rizes discharge disposition as routine; transfer to short-term hospital;
transfer to skilled nursing facility, intermediate care facility, or other
facility, home health care; against medical advice; died, or discharged
alive, destination unknown.
Statistical Analysis
We calculated baseline characteristics at the time of index admis-
sion and presented results by type of index admission (RAO versus
AIS). We calculated means and SDs for continuous variables and
frequencies and percentages for categorical variables. To test for sig-
nificant differences between cohorts (RAO versus AIS), we used t
tests for continuous variables, and χ2 for categorical variables, using
population weights and survey procedures in SAS, and reported P for
differences. For RAO and AIS separately, we calculated the propor-
tion of index admissions in which thrombolysis was given, by year
and in total.
We examined causes for readmissions within 30 days after dis-
charge from index admissions using the primary diagnosis ICD-9
codes. We ranked the top causes for 30-day readmission, stratified by
type of index admission (RAO versus AIS). For each index admission
and 30-day readmission, we summarized the most common vascular
procedures, identified using ICD-9 procedure codes, and stratified by
index admission type (RAO versus AIS).
We calculated 30-day all-cause readmission rates using weights
provided by HCUP and survey-weighted procedures as recom-
mended by HCUP.
We then created Kaplan-Meier curves of the cumulative risk of
ischemic stroke readmission after RAO. For this analysis, we used
all available follow-up data and measured time from discharge from
the index hospitalization to readmission. Because only the month of
admission and not the exact date is available in the NRD, for those
without the event of interest, we calculated the maximum observed
follow-up period as the number of days from the midpoint of the
month of index admission to the last day of the year. For this analysis,
we assumed full capturing of mortality and no loss to follow-up.
In secondary analysis, we repeated all analyses described above
for CRAO (ICD-9 code 362.31) BRAO (codes 362.32 and 362.33),
and transient RAO (code 362.34) separately. Analyses were per-
formed in SAS, version 9.4.
Results
Using weighted frequencies, there were a total of 4871 RAO
and 1 239 963 AIS index admissions. Baseline RAO and AIS
characteristics are summarized in the Table. Mean age was
slightly lower in RAO admissions (66.8 years) compared with
AIS admissions (70.8 years). Several comorbidities were doc-
umented more often with RAO index admissions compared
with AIS admissions, including tobacco usage (38.6% versus
32.9%), valvular disease (13.3% versus 10.5%), and rheuma-
toid arthritis/collagen vascular disease (4.6% versus 2.8%).
Other vascular risk factors were documented less often dur-
ing RAO index admissions compared with AIS admissions:
diabetes mellitus (24.3% in RAO versus 36.8% in AIS),
atrial fibrillation (AF)/atrial flutter (15.6% versus 25.2%),
hypertension (62.2% versus 67.6%), congestive heart failure
(9.1% versus 14.8%), and obesity (9.1% versus 12.0%).
Hypercholesterolemia prevalence was similar. Compared with
AIS index admissions, RAO admissions occurred more often
at larger, teaching, metropolitan hospitals (Table). Length of
stay was shorter for RAO cases.
In secondary analysis of RAO subgroups, there were sev-
eral relevant differences. Among RAO admissions, 2163 were
CRAO (44.4%), 642 BRAO/partial CRAO (13.2%), and 2066
transient RAO (42.5%). There was a higher prevalence of val-
vular disease with CRAO (13.9%) and BRAO (15.1%) com-
pared with AIS (10.5%). Variables that were less common in
RAO versus AIS and largely similar across RAO subgroups
include diabetes mellitus (DM), AF, congestive heart failure
(CHF), and rheumatoid arthritis/collagen vascular disease.
Hypertension was similar when comparing CRAO and AIS
but was less common than AIS with BRAO (57.5%) and
transient RAO (61.5%). Hypercholesterolemia prevalence
was similar across all subgroups and similar to AIS. BRAO
 802  Stroke  March 2020

Table. Baseline Characteristics of Index Ischemic Stroke Admission Group Table. Continued

RAO, n (%) AIS, n (%) P Value RAO, n (%) AIS, n (%) P Value
Total 4871 1 239 963 …  Transfer to SNF, ICF, or 163 (3.3) 420 027 (33.9)
other facility
Demographics at index admission
 HHC 479 (9.8) 229 884 (18.6)
Mean age, y 66.8 70.8 <0.0001
 AMA 69 (1.4) 10 394 (0.8)
Women 2371 (48.7) 633 001 (51.1) 0.043
 Died <10 (0.1) 59 101 (4.8)
Tobacco use 1882 (38.6) 407 989 (32.9) <0.0001
Hospital bed size
Diabetes mellitus 1184 (24.3) 455 986 (36.8) <0.0001
 Small 422 (8.7) 160 994 (13.0) <0.0001
Hypertension 3028 (62.2) 837 737 (67.6) <0.0001
 Medium 1026 (21.1) 327 490 (26.4)
Hypercholesterolemia 2906 (59.7) 727 332 (58.7) 0.38
 Large 3423 (70.3) 751 479 (60.6)
Atrial fibrillation/flutter 761 (15.6) 312 309 (25.2) <0.0001
Hospital urban-rural designation <0.0001
Congestive heart failure 442 (9.1) 182 891 (14.8) <0.0001
 Large metro area >1 million 3158 (64.8) 645 668 (52.1)
Cardiac valvular disease 649 (13.3) 130 022 (10.5) <0.0001
residents
Obesity 441 (9.1) 148 851 (12.0) <0.0001
 Small metro areas <1 1516 (31.1) 467 553 (37.7)
Hypothyroidism 621 (12.8) 175 091 (14.1) 0.10 million residents
Alcohol abuse 158 (3.2) 58 708 (4.7) 0.0052  Micropolitan areas 168 (3.5) 92 461 (7.5)
Drug abuse 142 (2.9) 36 884 (3.0) 0.89  Not metropolitan or 28 (0.6) 34 281 (2.8)
Rheumatoid arthritis or 223 (4.6) 34 089 (2.8) <0.0001 micropolitan
collagen vascular disease Teaching status of hospital <0.0001
Peripheral vascular disease 580 (11.9) 127 489 (10.3) 0.0246  Nonmetropolitan 197 (4.0) 126 742 (10.2)
Intracranial hemorrhage <10 42 935 (3.5) <0.0001  Metropolitan teaching 3596 (73.8) 731 837 (59.0)
Received intravenous 140 (2.9) 98 976 (8.0) <0.0001  Metropolitan nonteaching 1078 (22.1) 381 383 (30.8)
thrombolysis
Primary expected payer <0.0001
Received thrombectomy 0 (0) 19 856 (1.6) NA
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 Medicare 2983 (61.4) 838 535 (67.7)

Length of stay, d 2.6 6.8 <0.0001
 Medicaid 393 (8.1) 95 815 (7.7)
Total charges, $ 30 290 55 293 <0.0001
 Private insurance 1145 (23.6) 215 038 (17.4)
Patient ZIP code income quartile <0.0001
 Self-pay 204 (4.2) 51 233 (4.1)
 0–25th percentile 1238 (25.8) 365 208 (29.9)
 No charge 30 (0.6) 6601 (0.5)
 26th–50th percentile 1138 (24.7) 328 141 (26.9)
 Other 103 (2.1) 31 312 (2.5)
 51st–75th percentile 1166 (24.3) 288 746 (23.7)
Baseline characteristics of ischemic stroke population at the time of index
 76th–100th percentile 1204 (25.1) 238 567 (19.5) admission; included are the characteristics of the index admissions themselves
and hospital characteristics. AIS indicates acute ischemic stroke; AMA, against
APR-DRG mortality <0.0001
medical advice; APR-DRG, All Patient Refined Diagnosis Related Group; HHC,
 1: minor likelihood of dying 2929 (60.1) 369 262 (29.8) home health care; ICF, intermediate care facility; NA, not applicable; RAO,
 2: moderate likelihood of 1534 (31.5) 528 816 (42.7) retinal artery occlusion; and SNF, skilled nursing facility.
dying
patients were more likely than AIS to come from the highest
 3: major likelihood of dying 390 (8.0) 236 187 (19.1)
quartile ZIP code (30.3%).
 4: extreme likelihood of dying 17 (0.4) 105 588 (8.5) There were several differences in the treatments received.
APR-DRG severity <0.0001 As shown in Figure 1, thrombolysis was given to 2.9% of RAO
 1: minor (or no) loss of 1302 (26.7) 163 597 (13.2) patients in 2013, 1.7% in 2014, and 3.2% in 2015. Among
function the CRAO-only cohort, 5.8% received thrombolysis, similar
 2: moderate loss of function 2828 (58.1) 601 418 (48.5) to AIS. Endovascular thrombectomy was administered to no
RAO patients and 1.6% of AIS patients.
 3: major loss of function 719 (14.8) 369 770 (29.8)
The 30-day all-cause readmission rate after RAO index ad-
 4: extreme loss of function 23 (0.5) 105 069 (8.5) mission was 0.089 (95% CI, 0.075–0.104) and 0.122 (95% CI,
Disposition <0.0001 0.121–0.123) after AIS. After RAO index admission, 18.5%
 Routine: home or self-care 4140 (85.0) 498 840 (40.3) of patients had at least 1 readmission ≤1 year after index ad-
mission (range, 0–9) versus 24.2% after AIS (range, 0–17).
 Transfer to short-term 14 (0.3) 19 998 (1.6)
hospital
Top reasons for 30-day readmissions (Figure 2) included ce-
rebrovascular disease: occlusion and stenosis of carotid artery
(Continued )
without mention of cerebral infarct (20.8% in RAO and 4.5%
 Schorr et al   Characteristics and Outcomes of RAO   803
in AIS), occlusion and stenosis of carotid artery with cerebral
infarct (0 in RAO and 1.8% in AIS), cerebral artery occlusion
with cerebral infarct (4.0% in RAO and 12.6% in AIS), and
transient ischemic attack (1.0% in RAO and 2.1% in AIS).
GCA comprised 2.0% of readmissions after RAO (all of which
were from the transient RAO subgroup, 4.4% of all transient
RAO readmissions), versus 0.02% after AIS. Infections were a
more common cause for readmission after AIS compared with
RAO. Readmission for cardiac dysrhythmia or AF in RAO
(5.0%) was equivalent between CRAO (5.5%) and transient
RAO (5.5%), compared with 2.1% in patients with AIS (2.1%).
Long-term risk (≤1 year) of ischemic stroke after RAO
(Figure 3) accelerated soon after discharge from the index ad-
mission and plateaued at approximately day 140. Cumulative
risk was 0.0075 at day 50, 0.0100 at day 100, and 0.0124 at
day 150. In secondary analysis, cumulative risk of AIS after
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BRAO (0.004 at 300 days) was lower than CRAO and tran-
sient RAO (around 0.015 at 300 days).
Figure 2. Reasons for 30-d readmission. AIS indicates acute ischemic stroke; RAO, retinal artery occlusion; and unspec., unspecified.
Figure 1. Thrombolysis by year. AIS indicates
acute ischemic stroke; and RAO, retinal artery
occlusion.
In RAO, procedures performed included biopsy of blood
vessel (7.0% during index admission for RAO overall, 8.6%
for CRAO, 5.7% for BRAO, and 5.1% for transient RAO;
and 1.3% during 30-day readmissions after RAO), hyperbaric
oxygenation (1.8% during index admission), and diagnostic
or therapeutic aspiration of anterior eye chamber (0.8% and
1.0%, respectively, during index admission). Endovascular
procedures other than thrombectomy occurred at similar fre-
quencies overall in RAO versus AIS admissions at baseline
and readmissions. These procedures include arteriography
of cerebral arteries (5.0% in RAO, 5.3% in AIS), insertion
of vascular stent (≤0.5% on initial admission and readmis-
sion), percutaneous angioplasty of extracranial vessels (0.4%
in RAO versus 0.7% in AIS on index admission), and per-
cutaneous insertion of carotid artery stent (≤0.5% in index
and baseline admissions for both groups). The exception
was head or neck endarterectomy, which occurred with sim-
ilar frequency on index admission (1.4% versus 1.5%) but
 804  Stroke  March 2020
slightly more frequently on readmission in the RAO cohort
(1.6% versus 0.6%).
Discussion
Using nationally representative US data from 2013 to 2015,
with 4871 patients, this study is one of the largest RAO cohorts
in the literature, as well as one of the largest to directly com-
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pare RAO to AIS. Baseline demographics and comorbidities
were generally similar between RAO and AIS, emphasizing
their close relationship. Secondary analysis, although limited
by unknown specificity of differences among these diagnostic
codes, revealed some notable differences between CRAO,
BRAO, and transient RAO. The wide-ranging inpatient treat-
ments given for RAO may reflect the lack of a standardized
approach. The reasons for readmission and the risk of stroke
after a RAO event emphasize the need for appropriate neuro-
vascular evaluation and excellent preventative care.
There are discordant findings in the literature regarding
RAO demographics and comorbidities, likely because most
studies have small cohorts often with <200 patients or regional
populations. Mean RAO cohort age was 66.8 years, similar to
previous data.5,20–22 Patients with RAO were likelier to have
private insurance than patients with AIS, and less likely to
have Medicare, although this may be because of the slightly
younger average age of RAO patients. The RAO group was
more likely to be from the highest quartile income zip code
(25.1% versus 19.5%), particularly in the BRAO subgroup.
There are little data about the impact of socioeconomic status
on timely, accurate RAO diagnosis or likelihood of inpatient
admission for RAO workup; this warrants further investiga-
tion. We found similar and high prevalence of hyperlipidemia
between RAO and AIS, greater prevalence of DM, hyperten-
sion, AF/atrial flutter, CHF in AIS, and greater prevalence of
valvular disease and tobacco use in RAO.
Although patients with AIS more often had hypertension
and CHF, patients with RAO more often had documented
valvular disease (13.3% versus 10.5%), more pronounced
Figure 3. Kaplan-Meier cumulative risk of
ischemic stroke after central retinal artery
occlusion.
among CRAO and BRAO subgroups. Perhaps RAO is more
likely than AIS to have a cardioembolic mechanism. Some
valvular disease in RAO may be related to endocarditis, as
suggested by the higher rate of RAO readmission for en-
docarditis (3% of all readmissions versus 1.2% in AIS). A
2010 study found an abnormality on echocardiogram in 61%
of patients with RAO, compared with 20% in retinal vein
occlusion patients.23 Despite the high pretest probability of
an abnormality, a 2018 nationwide survey of academic hos-
pital department leaders revealed that only 62% reported that
echocardiogram was part of their standard RAO diagnostic
investigation, and only 89% reported that vascular risk factor
assessment was done routinely.12
AF was diagnosed much more often in AIS (25.2%) than
in RAO (15.6%), although the prevalence in RAO is signif-
icantly greater than in the general adult population where it
has been reported as about 4 percent in adults over 60.24 The
prevalence of AF in RAO that we found is higher than that
from some prior studies (eg, 21.4%,6 9%,4 13% arrhythmia in
a 38-patient study).23 Possibly, those with RAO are less likely
than patients with AIS to receive adequate cardiac monitor-
ing and thereby have uncaptured AF. A recent study on 103
patients with RAO found AF in only 10.6% of patients by
either history or new diagnosis; but of 34 screened, 3 addi-
tional cases of AF were found.20 We found that readmissions
for patients with RAO were >2× as likely to be for AF or
cardiac dysrhythmia than the AIS group (about 5% versus
2%), although BRAO patients had no readmissions for these
diagnoses. Perhaps cardiac monitoring and treatment of dys-
rhythmias such as AF in the index admission for RAO could
decrease 30-day readmissions.
DM was less common with RAO than AIS (24.3% versus
36.8%), but as with AF was notably higher than the national
DM prevalence of 9.4%.25 Prior studies have shown vary-
ing prevalence of DM with RAO (eg, 36%,6 10.5%).23 A
Taiwanese nationwide database study found that patients with
DM had a comorbidity-adjusted RAO incidence of 0.89, over
 Schorr et al   Characteristics and Outcomes of RAO   805
twice as high as non-DM patients at 0.39.26 The notably high
prevalence of tobacco usage in RAO, even higher than that in
AIS, highlights this modifiable atherosclerotic risk factor.
Both 1-year and 30-day readmissions after RAO are
only slightly less frequent than after AIS, which is per-
haps surprising given the AIS cohort’s overall higher rate
of diagnosed serious comorbidities and the often disabling
symptoms of cerebral stroke that predispose to further com-
plications. Overall, despite lower baseline frequencies of
CHF, AF, and hypertension, patients with RAO were more
likely than patients with AIS to be readmitted within 30 days
for several neurological or cardiovascular reasons (Figure 2).
This could be related to inadequate recognition and manage-
ment of modifiable neurovascular risk factors during index
admission compared with AIS patients.
Patients with RAO were more likely than patients with
AIS to be readmitted within 30 days for GCA (2.0% versus
0.02%). This is consistent with the slightly higher rate of
collagen vascular disease in RAO patients (4.6% versus
2.8% in AIS patients), which in turn may be related to the
role of vessel dissection and RAO. All readmissions, al-
though small in number, for GCA were in the transient RAO
subgroup—a reminder that transient RAO symptoms war-
rant proper GCA evaluation.
Just over one-fifth of readmissions after RAO were for
stenosis/occlusion of precerebral arteries, and almost 2% of
30-day RAO readmissions included endarterectomy. Some
30-day readmissions after RAO, particularly those for occlu-
sion/stenosis of carotid artery, were likely for planned carotid
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endarterectomy. Seven percent of RAO readmissions were
for cerebral infarct, as compared with a total of 17.5% of AIS
readmissions. Similar to prior studies,6,27,28 we found the high-
est risk of readmission for stroke shortly after RAO; the risk
plateaued around day 150 (Figure 4).
Recent studies have found significantly elevated stroke
risk after RAO4,6; one reported a 1.7% incidence of cerebro-
vascular accident within 15 days after RAO.5 Another study
found that in the 3 years after RAO, there was a 20% inci-
dence of stroke or transient ischemic attack, versus 10% in
general population.29 A study of 401 patients with RAO found
that 15% had a cerebral stroke within 10 years, versus 8.0%
in a risk factor–matched group.4 Another study found that
Figure 4. Vascular procedures during index admission and during 30-d readmissions. AIS indicates acute ischemic stroke; and RAO, retinal artery occlusion.
patients with RAO had a similar risk of stroke, MI, and death
as did patients with high-risk transient ischemic attack and
higher than all transient ischemic attacks.20 Specifying which
risk factors are present is crucial: a 2017 study found that
RAO patients with large artery atherosclerosis had ≈4× higher
risk of vascular events compared with those RAO patients
without.28 The current study further confirms the high fre-
quency of neurovascular risk factors and risk of AIS in RAO
patients, but unfortunately, the practice of referring RAO
patients for acute neurovascular assessment is not universal.12
Other studies also emphasize the urgency of this evaluation;
for example, of 103 CRAO patients, inpatient workup led to a
medication change in 93%.27
Our results reflect a broad range of treatment approaches,
with 1% to 2% receiving anterior chamber paracentesis, ≈2%
receiving hyperbaric oxygenation, and ≈3% receiving throm-
bolysis. Thus practices with no clear evidence of benefit and
even potentially harmful outcomes3,10 continue and are given
about as commonly as thrombolysis.
Of the survey respondents from the 2018 study on aca-
demic department leaders, ocular massage was considered
first-line RAO treatment by 19%, and anterior chamber para-
centesis was first line by 14% (and offered at least sometimes
in 42%; offered over 3× more commonly by ophthalmologists
than neurologists). Fifty-three percent of survey respondents
reported offering thrombolysis to select patients in 53%, and
only 36% considered it first line. Of those who did offer tPA
(tissue-type plasminogen activator), the majority gave it with
similar selection criteria and dosing used for cerebral infarct.12
Our data are consistent with a low rate of tPA administration
for RAO; 2.9% of cases between 2013 and 2015, versus 8.0%
in AIS; when we examined CRAO specifically in secondary
analysis, 5.8% were treated with thrombolysis. Notably, our
data are from before 2015 when one of the most compelling
studies in favor of tPA for RAO was published.
We found similar rates of endarterectomy between RAO and
AIS on index admission (1.4%–1.5%) and higher rates of endar-
terectomy in RAO on 30-day readmission than AIS. No inpatient
thrombectomy occurred for any RAO cases, and using standard
ICD-9 coding (39.74, which is generally coding used to code
thrombectomy, and when coded along with 99.10 thromboly-
sis often indicates intra-arterial thrombolysis), this also suggests
 806  Stroke  March 2020
no intra-arterial thrombolysis was documented as being admin-
istered. Data analysis ending in 2015 may not capture rapidly
emerging changes in current endovascular management. The
role of intra-arterial fibrinolysis remains uncertain. Several prior
studies have shown its benefits.30,31 Others have shown no clear
benefit,32 such as a 2010 randomized trial with intra-arterial fibri-
nolysis versus conservative treatment (including heparin) did not
demonstrate a difference in visual acuity recovery.33
Strengths of this study include the large nationally rep-
resentative population of RAO patients, the wide variety
of variables assessed, and the direct comparison with AIS
patients. Limitations of this study include the lack of valida-
tion of administrative coding for RAO; some experts believe
retinal artery ischemia is overdiagnosed as a cause of transient
monocular vision loss in many large studies.34 Given this, we
are particularly cautious in interpreting data about differences
among CRAO/BRAO/transient RAO; the accuracy of distinc-
tion among these nuanced diagnoses has not been validated,
but prior studies suggest there are differences among these
subgroups.26 Since our data collection categorized patient ad-
mission by primary diagnosis, those admitted with both AIS
and RAO may be over or underrepresented in either group,
and this may include a significant number of patients. Prior
studies have shown that between 37.3%6 to about 25%28 of
admitted RAO patients had coincident acute stroke. We also
did not capture data from RAO patients who were not admit-
ted, and this outpatient-only cohort may represent a sizable
group. Importantly, patients with RAO who are not admitted
may be even less likely to receive a thorough evaluation.
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Whether certain comorbidities, such as AF, are truly less
common in RAO or are simply underrecognized warrants fur-
ther investigation. The high rates of multiple neurovascular
comorbidities, notably valvular disease and tobacco use, and
high rates of readmissions for endocarditis and arrhythmia/
AF in RAO, in addition to the high incidence of AIS shortly
after RAO, all demonstrate the importance of urgent neuro-
vascular and cardiac evaluation. Patients with RAO still re-
ceive treatments with poor evidence such as anterior chamber
paracentesis. Only a small percent of RAO cases received
thrombolysis, although limited literature suggests appropri-
ately timed intravenous or intra-arterial thrombolysis may be
a beneficial acute treatment. Close communication between
colleagues in many specialties including ophthalmology,
emergency medicine, interventional radiology, and neurology
is critical for further research to improve and standardize man-
agement of this complex, potentially devastating entity.
Disclosures
None.
References
1. Leavitt JA, Larson TA, Hodge DO, Gullerud RE. The incidence of central
retinal artery occlusion in olmsted county, minnesota. Am J Ophthalmol.
2011;152:820–3.e2. doi: 10.1016/j.ajo.2011.05.005
2. Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual
outcome. Am J Ophthalmol. 2005;140:376–391. doi: 10.1016/j.ajo.
2005.03.038
3. Schrag M, Youn T, Schindler J, Kirshner H, Greer D. Intravenous fibri-
nolytic therapy in central retinal artery occlusion: a patient-level meta-
analysis. JAMA Neurol. 2015;72:1148–1154. doi: 10.1001/jamaneurol.
2015.1578
4. Rim TH, Han J, Choi YS, Hwang SS, Lee CS, Lee SC, et al. Retinal artery
occlusion and the risk of stroke development: twelve-Year Nationwide
Cohort Study. Stroke. 2016;47:376–382. doi: 10.1161/STROKEAHA.
115.010828
5. Chodnicki KD, Pulido JS, Hodge DO, Klaas JP, Chen JJ. Stroke risk be-
fore and after central retinal artery occlusion in a US cohort. Mayo Clin
Proc. 2019;94:236–241. doi: 10.1016/j.mayocp.2018.10.018
6. French DD, Margo CE, Greenberg PB. Ischemic stroke risk in medi-
care beneficiaries with central retinal artery occlusion: a retrospective
cohort study. Ophthalmol Ther. 2018;7:125–131. doi: 10.1007/s40123-
018-0126-x
7. Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion:
associated systemic and ophthalmic abnormalities. Ophthalmology.
2009;116:1928–1936. doi: 10.1016/j.ophtha.2009.03.006
8. Sharma S, Sharma SM, Cruess AF, Brown GC. Transthoracic echocardi-
ography in young patients with acute retinal arterial obstruction. RECO
Study Group. Retinal emboli of cardiac origin group. Can J Ophthalmol.
1997;32:38–41.
9. Limaye K, Adams HP Jr. Is management of central retinal artery occlu-
sion the next frontier in cerebrovascular diseases? J Stroke Cerebrovasc
Dis. 2019;28:521. doi: 10.1016/j.jstrokecerebrovasdis.2018.09.042
10. Fraser SG, Adams W. Interventions for acute non-arteritic central retinal
artery occlusion. Cochrane Database Syst Rev. 2009:CD001989. doi:
10.1002/14651858.CD001989.pub2
11. Fieß A, Cal Ö, Kehrein S, Halstenberg S, Frisch I, Steinhorst UH. Anterior
chamber paracentesis after central retinal artery occlusion: a tenable
therapy? BMC Ophthalmol. 2014;14:28. doi: 10.1186/1471-2415-14-28
12. Youn TS, Lavin P, Patrylo M, Schindler J, Kirshner H, Greer DM, et al.
Current treatment of central retinal artery occlusion: a national survey. J
Neurol. 2018;265:330–335. doi: 10.1007/s00415-017-8702-x
13. Aldrich EM, Lee AW, Chen CS, Gottesman RF, Bahouth MN, Gailloud P, et
al. Local intraarterial fibrinolysis administered in aliquots for the treatment
of central retinal artery occlusion: the Johns Hopkins Hospital experience.
Stroke. 2008;39:1746–1750. doi: 10.1161/STROKEAHA.107.505404
14. Chen CS, Lee AW, Campbell B, Lee T, Paine M, Fraser C, et al. Efficacy
of intravenous tissue-type plasminogen activator in central retinal ar-
tery occlusion: report from a randomized, controlled trial. Stroke.
2011;42:2229–2234. doi: 10.1161/STROKEAHA.111.613653
15. Agarwal N, Gala NB, Karimi RJ, Turbin RE, Gandhi CD,
Prestigiacomo CJ. Current endovascular treatment options for central
retinal arterial occlusion: a review. Neurosurg Focus. 2014;36:E7. doi:
10.3171/2013.11.FOCUS13331
16. Roumie CL, Mitchel E, Gideon PS, Varas-Lorenzo C, Castellsague J,
Griffin MR. Validation of ICD-9 codes with a high positive predictive value
for incident strokes resulting in hospitalization using Medicaid health data.
Pharmacoepidemiol Drug Saf. 2008;17:20–26. doi: 10.1002/pds.1518
17. Tirschwell DL, Longstreth WT Jr. Validating administrative data in
stroke research. Stroke. 2002;33:2465–2470. doi: 10.1161/01.str.
0000032240.28636.bd
18. Shen Y. Applying the 3M all patient refined diagnosis related groups
grouper to measure inpatient severity in the VA. Med Care. 2003;41(6
suppl):II103–II110. doi: 10.1097/01.MLR.0000068423.39715.CE
19. Baram D, Daroowalla F, Garcia R, Zhang G, Chen JJ, Healy E, et al. Use
of the All Patient Refined-Diagnosis Related Group (APR-DRG) risk of
mortality score as a severity adjustor in the medical ICU. Clin Med Circ
Respirat Pulm Med. 2008;2:19–25. doi: 10.4137/ccrpm.s544
20. Lavin P, Patrylo M, Hollar M, Espaillat KB, Kirshner H, Schrag M. Stroke
risk and risk factors in patients with central retinal artery occlusion. Am
J Ophthalmol. 2019;200:271–272. doi: 10.1016/j.ajo.2019.01.021
21. Christiansen CB, Torp-Pedersen C, Olesen JB, Gislason G, Lamberts M,
Carlson N, et al. Risk of incident atrial fibrillation in patients presenting
with retinal artery or vein occlusion: a nationwide cohort study. BMC
Cardiovasc Disord. 2018;18:91. doi: 10.1186/s12872-018-0825-1
22. Leisser C, Findl O. Rate of strokes 1 year after retinal artery occlusion
with analysis of risk groups [published online February 19, 2019]. Eur J
Ophthalmol. 2019. doi: 10.1177/1120672119830925
23. Klatt C, Purtskhvanidze K, Hasselbach H, Treumer F, Hillenkamp J,
Roider J. [Retrospective case analysis of ophthalmological and systemic
risk factors in patients with retinal vascular occlusion]. Ophthalmologe.
2010;107:446–451. doi: 10.1007/s00347-009-2018-x
24. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV,
et al. Prevalence of diagnosed atrial fibrillation in adults: national
implications for rhythm management and stroke prevention: the
Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study.
JAMA. 2001;285:2370–2375. doi: 10.1001/jama.285.18.2370
 Schorr et al   Characteristics and Outcomes of RAO   807
25. CDC report: Estimates of Diabetes and Its Burden in the United States.
National Diabetes Statistics Report. Atlanta, GA: Centers for Disease
Control; 2017.
26. Chang YS, Ho CH, Chu CC, Wang JJ, Tseng SH, Jan RL. Risk of retinal
artery occlusion in patients with diabetes mellitus: a retrospective large-
scale cohort study. PLoS One. 2018;13:e0201627. doi: 10.1371/journal.
pone.0201627
27. Lavin P, Patrylo M, Hollar M, Espaillat KB, Kirshner H, Schrag M. Stroke
risk and risk factors in patients with central retinal artery occlusion. Am
J Ophthalmol. 2018;196:96–100. doi: 10.1016/j.ajo.2018.08.027
28. Hong JH, Sohn SI, Kwak J, Yoo J, Ahn SJ, Woo SJ, et al. Retinal artery
occlusion and associated recurrent vascular risk with underlying etiolo-
gies. PLoS One. 2017;12:e0177663. doi: 10.1371/journal.pone.0177663
29. Chang YS, Jan RL, Weng SF, Wang JJ, Chio CC, Wei FT, et al. Retinal
artery occlusion and the 3-year risk of stroke in Taiwan: a nationwide
population-based study. Am J Ophthalmol. 2012;154:645–652.e1. doi:
10.1016/j.ajo.2012.03.046
Downloaded from http://ahajournals.org by on February 2, 2024
30. Mercier J, Kastler A, Jean B, Souteyrand G, Chabert E, Claise B, et
al. Interest of local intra-arterial fibrinolysis in acute central retinal
artery occlusion: clinical experience in 16 patients. J Neuroradiol.
2015;42:229–235. doi: 10.1016/j.neurad.2014.02.007
31. Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlu-
sion of the central retinal artery: a meta-analysis of the published data.
Br J Ophthalmol. 2000;84:914–916. doi: 10.1136/bjo.84.8.914
32. Ahn SJ, Kim JM, Hong JH, Woo SJ, Ahn J, Park KH, et al. Efficacy and
safety of intra-arterial thrombolysis in central retinal artery occlusion. Invest
Ophthalmol Vis Sci. 2013;54:7746–7755. doi: 10.1167/iovs.13-12952
33. Schumacher M, Schmidt D, Jurklies B, Gall C, Wanke I, Schmoor C, et al;
EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial
fibrinolysis versus conservative treatment, a multicenter randomized trial.
Ophthalmology. 2010;117:1367–75.e1. doi: 10.1016/j.ophtha.2010.03.061
34. Biousse V, Nahab F, Newman NJ. Management of acute retinal is-
chemia: follow the guidelines! Ophthalmology. 2018;125:1597–1607.
doi: 10.1016/j.ophtha.2018.03.054