Outcomes after Acute Central

Retinal Artery Occlusion

Robert G. Kowalski, MD, MS

Research Academy
July 18, 2019
Background

Central retinal artery occlusion (CRAO) is an neuro-

ophthalmologic emergency which frequently leads to
permanent unilateral blindness.

It is a precursor to secondary in-hospital acute ischemic

stroke in one-sixth of cases.1-3

Treatment of CRAO in the U.S. is variable,. Despite

encouraging recent results with thrombolysis,4 there
currently is no standard for therapy.5,6
Background

 CRAO annual incidence: 8.5 per 100,000

people.7
 Typically presents as a painless, acute monocular
visual vision loss.8
 The prognosis is poor, with approximately 80% of
patients experiencing permanent visual acuity of
20/400 or worse.5,9
CRAO is divided into four clinical categories:
1. Nonarteritic permanent CRAO (65%), involves occlusion
resulting from a fibrin embolus of atherosclerotic plaque
origin most commonly at the proximal internal carotid
artery
2. Nonarteritic CRAO with cilioretinal artery (20%), may
involve preservation of the macula and has an etiology
similar to nonarteritic CRAO
3. Nonarteritic transient CRAO (15%), has the best
prognosis and is either embolic or due to transient
vasospasm
4. Arteritic CRAO (5%), typically involving an underlying
vasculitis.5
CA, Corneal abrasion
AION, Anterior ischemic optic neuropathy
PION, Posterior ischemic optic neuropathy Front. Surg., 26 June 2017 |
https://doi.org/10.3389/fsurg.2017.00034
Established Risk Factors for CRAO Onset:

CRAO is associated with cardiovascular risk factors

that are similar to those for stroke, including:

 arterial hypertension
 ipsilateral carotid artery stenosis
 previous history of ischemic stroke

Modifiable risk factors include obesity and smoking.10

Current Treatment Options for CRAO

This study will evaluate treatment modalities applied and their

association with visual acuity and mortality in CRAO patients.

These treatment regiments include:

 ocular massage
 aspirin,
 Acetazolamide
 topical β-blockage
 anterior chamber paracentesis
 IV tPA
 hyperbaric oxygen
 IA tPA.4,6,11
 CRAO Outcomes Study

Summary:
The Central Retinal Artery Occlusion (CRAO) Outcomes
study, is an observational, multi-center, clinical investigation
of outcome in adult patients consecutively admitted to the
Henry Ford Hospital, and other participating medical centers,
with a diagnosis of acute CRAO.

Participating centers:
Henry Ford Hospital
Vanderbilt University
Brown University
University of Florida
Summary (continued):
The study will have two phases:

1. Retrospective review of data for patients treated for

CRAO at HFH for the past six years.
2. Prospective data collection for all patients newly admitted
for CRAO to HFH for a period of 5 years.

Data from both phases from HFH will be analyzed separately

and pooled with comparable data from other participating
institutions.
 Henry Ford Hospital CRAO Population

The study will include adult patients admitted to Henry Ford

Hospital (HFH) with a diagnosis of CRAO from 2013 to the
present (Phase 1, retrospective portion of study), and for a
period of 5 years after IRB approval of this study (Phase 2,
prospective portion of study).

Annual enrollment estimated at 100-110 patients,

The total population included in Phase 1 and Phase 2 is

expected to be approximately 1,100-1,200 patients.
Henry Ford Hospital Historical CRAO Population
108

106 107
106
104
104
102

100 101

98

96 97

94

92

2014 2015 2016 2017 2018

HFH CRAO Population – Monthly Variation
Primary Objective:
To identify factors that lead to prevention of blindness and restoration of
vision in CRAO.

Secondary Objectives:
To identify factors that predict stroke or MI following CRAO.
Hypothesis:
Information from a large multi-year, multi-center sample of
CRAO patients will provide a basis to develop better therapies
to restore vision in this condition, and to prevent secondary
ischemic stroke and myocardial infarction.
Aims:
Specific Aim 1: Characterization of patient and clinical
factors, and outcome at the time of hospital discharge. These
factors will be evaluated for associations and predictive effects
of study primary and secondary outcomes.

Specific Aim 2: Characterization of current treatment

regimens for CRAO at HFH and other participating medical
centers, including: ocular massage, anterior chamber
paracentesis, oxygen therapy and intravenous or intra-arterial
fibrinolysis. These therapies will be evaluated for association
and predictive effects on study primary and secondary
outcomes.
Study Measures:
I. Premorbid Data (prior to CRAO onset, retrospective
collection from medical records)

1. Demographics
2. Past medical/surgical history (including cardiovascular and
stroke history, blood pressure and cholesterol management.
3. Modifiable lifestyle factors including smoking history and illicit
drugs/EtOH use.
Study Measures:
II. History of Present Illness

1. Time of onset of symptoms (when the patient was last able to

see at their baseline level)
2. Time of initial contact with a medical provider (including phone
call to an office, office visit, EMS contact, arrival in ER, etc)
3. Time of initial therapy (if no acute treatment given, time of
arrival in the ER; if multiple therapies given, the time for each)
Study Measures:
III. Hospital Course Data

1. Type of all acute treatments employed

2. Visual acuity on arrival, at 24 hours after onset
3. Acute stroke (any stroke on imaging, whether or not it is
symptomatic, confirmed by MRI or CT findings) inflammatory
markers, hypertensive crisis, etc.
4. Fundoscopic exam findings on all patients (including how often
emboli are visible). Fluorescein angiography findings should be
included when available.
5. Vascular risk factor screening and results of screening tests (including
screening for carotid artery disease and echocardiography)
6. Hospital length of stay
7. Brain imaging findings
8. Acute surgical intervention required
9. Medication regimen change as a result of the evaluation
Study Measures:
IV. Outcome Data
Outcome will be assessed at the time of hospital discharge, and at 90
days, 1 year and 2 years after discharge, when data is available in the
patient medical record from subsequent hospital or clinic visits.

1. Visual acuity
2. Mortality
3. Acute ischemic stroke
4. Acute MI
Future CRAO Outcomes Study Directions:

1. Data from participating centers will be pooled for multi-center analysis of risk
factors and treatment associations and predictive effects on outcome.

2. Pooled data will be used as pilot data for preparation of R21 grant to support
a pilot study of IA tPA for CRAO, potentially leading to a full-scale RCT.
Study investigators
Robert G. Kowalski, MD, MS (Principal Investigator)
Alex Abou-Chebl, MD (Co-Investigator)
Panayiotis Mitsias, MD (Co-investigator)
Angelos Katramados, MD (Co-investigator)
Daniel Miller, MD (Co-investigator)
Shaneela Malik, MD (Co-investigator)
Riad Ahmad Ramadan, MD
Bradley N. Howell, MD (Co-investigator)
Hebah M. Hefzy, MD
Nilushi Karunamuni (Medical student – WSU)
Ian Clark, BS (Research volunteer - MSU)
Marta Sholobetska (Neurology research student – UM)
Summary of Knowledge to be Gained
Knowledge gained could have potential societal benefits through
new insights into the diagnosis, prognosis and treatment of
central retinal artery occlusion, and secondary ischemic stroke
and myocardial infarction. These benefits may include:

 Preservation or restoration of visual function

 Reduced incidence of secondary stroke
 Reduced incidence of secondary MI
 Further understanding of the pathophysiological basis of CRAO
 New treatment modalities
 Better allocation of hospital resources in this patient population, and
guidance for public policy decisions
References
1. Avery MB, Magal I, Kherani A, Mitha AP. Risk of Stroke in Patients With Ocular Arterial Occlusive Disorders: A
Retrospective Canadian Study. J Am Heart Assoc. 2019;8(3):e010509.
2. Leisser C, Findl O. Rate of strokes 1 year after retinal artery occlusion with analysis of risk groups. Eur J Ophthalmol.
2019:1120672119830925.
3. Mir TA, Arham AZ, Fang W, et al. Acute Vascular Ischemic Events in Patients with Central Retinal Artery Occlusion in
the United States: A Nationwide Study 2003-2014. Am J Ophthalmol. 2019.
4. Schrag M,Youn T, Schindler J, Kirshner H, Greer D. Intravenous Fibrinolytic Therapy in Central Retinal Artery
Occlusion: A Patient-Level Meta-analysis. JAMA Neurol. 2015;72(10):1148-1154.
5. Limaye K, Wall M, Uwaydat S, et al. Is Management of Central Retinal Artery Occlusion the Next Frontier in
Cerebrovascular Diseases? J Stroke Cerebrovasc Dis. 2018;27(10):2781-2791.
6. Youn TS, Lavin P, Patrylo M, et al. Current treatment of central retinal artery occlusion: a national survey. J Neurol.
2018;265(2):330-335.
7. Schumacher M, Schmidt D, Jurklies B, et al. Central retinal artery occlusion: local intra-arterial fibrinolysis versus
conservative treatment, a multicenter randomized trial. Ophthalmology. 2010;117(7):1367-1375 e1361.
8. Nowak RJ, Amin H, Robeson K, Schindler JL. Acute central retinal artery occlusion treated with intravenous
recombinant tissue plasminogen activator. J Stroke Cerebrovasc Dis. 2012;21(8):913 e915-918.
9. Varma DD, Cugati S, Lee AW, Chen CS. A review of central retinal artery occlusion: clinical presentation and
management. Eye (Lond). 2013;27(6):688-697.
10. Callizo J, Feltgen N, Pantenburg S, et al. Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a
Prospective and Standardized Medical Examination. Ophthalmology. 2015;122(9):1881-1888.
11. Page PS, Khattar NK, White AC, et al. Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A
Systematic Review and Meta-Analysis. Front Neurol. 2018;9:76.
Cover photo. Central retinal vein occlusion
(CRAO) with cherry red spot. Mehul A. Shah,
MD. Retina Image Bank 2014; Image 19815.
©American Society of Retina Specialists.
Thank you