s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1

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Major review

Central retinal artery occlusiondA new,

provisional treatment approach

Argyrios Chronopoulos, MDa,b,*, James S. Schutz, MDb

a
Department of Ophthalmology, Hospital of Ludwigshafen, Teaching Hospital of the University of Johannes
Gutenberg-University Mainz, Mainz, Germany
b
Department of Ophthalmology, University Hospitals and School of Medicine, Geneva, Switzerland

article info abstract

Article history: The retinal ganglion cells infarcted in central retinal artery occlusion (CRAO) are the
Received 3 September 2018 somata of the optic nerve axons, part of the central nervous system. Consequently, CRAO
Received in revised form 13 January with inner retinal infarction is a small vessel stroke, usually with the devastating conse-
2019 quence of severe visual loss in the affected eye. At present, there is no generally accepted,
Accepted 17 January 2019 evidence-based therapy of nonarteritic CRAO in contrast to ischemic cerebral stroke that
Available online 30 January 2019 has well-accepted treatment protocols. Widely divergent and controversial therapeutic
options for CRAO reflect the desperation of treating physicians and disparate conflicting
Keywords: studies. We examine reasons why treatment of nonarteritic CRAO remains problematic
central retinal artery occlusion and then suggest a provisional new approach to treatment based on updated under-
retinal infarction standing of CRAO pathophysiology and analysis of current therapeutic options and their
retinal stroke rationales.
cherry red spot ª 2019 Elsevier Inc. All rights reserved.
anterior chamber paracentesis

1. Introduction ischemic cerebral stroke which has well-accepted treat-

The retinal ganglion cells infarcted in a central retinal ar-
tery occlusion (CRAO) are the somata of the optic nerve
axons, part of the central nervous system.26,65 Conse-
quently, CRAO with inner retinal infarction is a small vessel
stroke which usually has a devastating consequence, severe
loss of vision in the affected eye. 11,15,26,37,56,76,84,98 At pre-
sent, there is no generally accepted, evidence-based ther-
apy for nonarteritic CRAO15,26,27,35,61,70,76,84 in contrast to
ment protocols.20,22,31,40,58,75,82 Widely divergent and
controversial therapeutic options for CRAO reflect the
desperation of treating physicians and disparate conflicting
studies.11,32,35,63,70,84,94,98
We examine reasons why treatment of nonarteritic CRAO
remains problematic and then suggest a provisional new
approach to treatment based on updated understanding of
CRAO pathophysiology and analysis of current therapeutic
options and their rationales.

Declarations of interest: none.

* Corresponding author: Argyrios Chronopoulos, MD, Department of Ophthalmology, Hospital of Ludwigshafen, Johannes Gutenberg-
Mainz University teaching hospital, Bremserstraße 79, 67063 Ludwigshafen am Rhein, Germany. Tel.: þ49 (0) 621 503-3058; Fax: þ49 (0)
621 503-770030.
E-mail address: aris_c@web.de (A. Chronopoulos).
0039-6257/$ e see front matter ª 2019 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.survophthal.2019.01.011
444 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
2. Reasons for lack of strong evidence-based
CRAO treatment
Treatment of CRAO is controversial and generally felt to be
unsuccessful, without strong evidence-based medical ratio-
nale for several reasons (outlined in Table 1).
2.1. Insignificant collateral circulation
There is insignificant central retinal artery (CRA) collateral
circulation at and distal to the usual site of CRAO, which
predisposes to early infarction after CRAO. Most CRAOs are
nonarteritic, with occlusion generally occurring at the lamina
cribrosa of the optic nerve head or at the prelaminar surface of
the optic disc11,26,64,90 where the CRA is essentially an end
artery with only microscopic collateral circulation in and
around the optic nerve head.64,94 Consequently, complete CRA
blockage at this site results in profound ischemia of the retinal
ganglion cells, followed rapidly by their infarction. Although it
has been suggested that CRAO most often occurs where the
CRA enters the dural sheath of the optic nerve,42,43,87,88 this
concept is not supported by careful review of the underlying
references.
In contrast to the retinal ganglion cell layer, many areas of
the brain have effective collateral circulation that facilitates
survival of ischemic tissue and contributes to an “ischemic
penumbra” around a core zone of infarction.5,69 The concept
of ischemic penumbra has been applied to CRAO56,62; how-
ever, it is most probably not appropriate because the CRA
alone supplies the entire ganglion cell layer of the retina
without collateral circulation except for a tiny zone of collat-
eral capillaries around the optic disc. Cilioretinal arteries,
present in over 20% of eyes, spare the areas of inner retina that
they supply but are not collaterals to the CRA.61,64,85 Further-
more, diffusion of oxygen from the choroidal circulation
which supplies the outer retinal layers is not normally suffi-
cient to prolong survival of the inner retina.99,100
2.2. Tiny CRA lumen
The CRA is small with a correspondingly tiny lumen that
makes it particularly vulnerable to occlusion, which leads to
ischemia and inner retinal infarction. Flow through a circular
Table 1 e Reasons why there is no strong evidence-based
treatment for CRAO
1. Insignificant collateral circulation distal to CRAO predisposes to
infarction after occlusion
2. CRA lumen is tiny and easily occluded
3. Retinal ganglion cells are the somata of the optic nerve axons,
part of central nervous system, highly vulnerable to ischemia
4. Embolic CRAO is common and resistant to thrombolysis
5. CRAO studies are problematic:
a. rare disease
b. pressure to treat, “do something helpful”
c. poorly controlled studies with differing inclusion criteria
d. studies combine complete and incomplete CRAOs
CRA, central retinal artery; CRAO, central retinal artery occlusion.
Table 2 e Outline of provisional CRAO treatment
1. Painless, acute, severe, visual loss requires emergency
ophthalmic examination.
2. Diagnose CRAO signs without delay.
3. Diagnose and obtain consultation for severe systemic
hypertension.
4. Rule out CRAO caused by giant cell arteritis.
5. Diagnose and treat only incomplete CRAO.
6. Perform emergency anterior chamber paracentesis at the slit
lamp for incomplete CRAO.
7. Lower IOP for a few days with oral acetazolamide and topical
medications.
8. Other therapies for incomplete CRAO may be attempted ac-
cording to local protocols.
9. Refer immediately all CRAO patients (complete and incomplete)
to a stroke unit or emergency service after ophthalmic diagnosis
and treatment.
CRA, central retinal artery; CRAO, central retinal artery occlusion;
IOP, intraocular pressure.
vessel is proportional to the square of its diameter. The
luminal diameter of the retrolaminar CRA is between 0.12 and
0.17 mm.30,74,97 Assuming an approximately circular lumen,
the cross-sectional area of the CRA lumen at the optic nerve
head is more than 40 times smaller than a 1-mm diameter
circular lumen. Also, the small size of the CRA qualifies
inner retinal infarction from CRAO as a small vessel stroke,
defined by a vessel diameter less than 200 mm.54 Small vessel
cerebral strokes do not have well-accepted, evidence-based
treatment.51,86
2.3. Rapid infarction of central nervous system tissue
Retinal ganglion cells are part of the central nervous system
that suffers infarction rapidly, within 15 minutes, after com-
plete vascular occlusion.5,55,57,77,81 Similarly after complete
CRAO, ganglion cell infarction occurs after only about 15 mi-
nutes or less of absent blood flow90 as in other parts of the
central nervous system, rather than 90e240 minutes which
has been generally accepted in the ophthalmic liter-
ature.11,35,44e46,48,56,61,66,84,85,94 This is very important because
it means that the window of opportunity for treatment of a
complete CRAO is impossibly small. Nevertheless, it is pre-
mature to conclude that treatment of CRAO is always futile as
has been asserted35 because many CRAOs are incomplete with
reduced, but persistent, residual retinal arterial flow which
may allow inner retinal survival for much longer than
15 minutes.2,56,84,91
2.4. CRAO often embolic
Embolic CRAO is felt to be most common, and a large fraction
of emboli are cholesterol or calcific27,60,94,79,84 and resistant to
thrombolysis, the subject of many experimental studies on
CRAO treatment.2,8,14,30,35,56,84
2.5. Study of CRAO difficult
Studying CRAO treatment is relatively difficult for several
reasons.
 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
2.5.1. Uncommon disease
CRAO is relatively infrequent, which makes collection of a
large series of cases problematic.14,35,37,94
2.5.2. Pressure to treat
The catastrophic visual consequences of CRAO weigh heavily
on treating doctors who often feel they must administer
aggressive therapy to try to help. Consequently, they try
combinations of various treatments with only anecdotal,
theoretical, or unvalidated efficacy.
2.5.3. Poor study design or execution
Although most studies of various CRAO treatments have
failed to show a significant beneficial effect, those that have
claimed a benefit from treatment often have differing inclu-
sion criteria, are poorly controlled, or have reported conflict-
ing results compared with other studies.35,56,67
2.5.4. Inclusion of complete and incomplete CRAOs
Almost all studies on CRAO treatment have included both
complete and incomplete CRAOs when analyzing treatment
efficacy, confounding discovery of possible treatment benefit
in the incomplete CRAO cohort.
3. Overview of common CRAO treatment
options
With the goal of developing an updated approach to CRAO
treatment, we first outline the rationales for common CRAO
therapeutic modalities, none of which is widely recognized as
effective, as well as some of their more important or common
potential adverse effects and drawbacks.
3.1. Lowering intraocular pressure
Lowering intraocular pressure (IOP) to increase CRA perfusion
to the inner retina has a strong therapeutic rationale and is
commonly performed.11,26,67,70,84,94,98 Lowering IOP decreases
extramural retinal arterial tissue pressure and increases
relative perfusion pressure; this should increase flow in a
partial occlusion and also help dislodge and push distally CRA
embolus or thrombus. Lowering IOP is performed in several
different ways.
3.1.1. Anterior chamber paracentesis
Anterior chamber paracentesis is often performed for CRAO,
is effective instantaneously, and results in an immediate,
profound IOP drop to single digits or zero.1,6,26,37,49,56,67,98
Although anterior chamber paracentesis is simple to
perform by an ophthalmologist at the slit lamp microscope, it
has only anecdotal efficacy and entails risks of complications
including traumatic cataract and other intraocular trauma,
hyphema, and endophthalmitis, which have caused it to be
criticized as a dangerous therapy for CRAO.6,33,92 It is impor-
tant to consider risks of AC paracentesis in comparison to the
natural history of CRAO, with less than 10% of nonarteritic
CRAO patients having meaningful recovery of vision.15,47 AC
paracentesis appears to be becoming a more common
outpatient procedure with a low rate of complications for the
445
diagnosis of uveitis using needle and syringe or micropipette,
for treatment of acute glaucoma, to normalize IOP after
intravitreal injections, and for CRAO.7,23e25,37,53,92,93,98 In
reviewing the recent reports of AC paracentesis, there
were 1610 cases performed by needle and syringe or micro-
pipette and 24 by blade with one complication of cataract
requiring surgery and one small focal cataract in another
case for a rate of 0.12% (2/1634) and no case of
endophthalmitis.7,23e25,33,53,92,93 Serious complications might
be further minimized with careful patient selection and
simplified technique without aspiration of aqueous humor as
outlined later in this article.
3.1.2. Pharmacological IOP reduction
Pharmacological lowering of IOP by intravenous, oral, and
topical ocular hypotensive agents has a much slower and less
profound effect than anterior chamber paracentesis but
could be helpful by maintaining lowered IOP for some
days.26,56,67,70,80,85,94 Intravenous mannitol and acetazolamide
are commonly administered as emergency therapy for CRAO,
but act gradually over about an hour. Intravenous mannitol
complications are rare, but acute urinary retention may occur
in males with prostatic hypertrophy, particularly in the
emergency setting where patients have high circulating
catecholamine levels secondary to stress and fear. The rapid
circulatory volume increase after intravenous mannitol rarely
may trigger angina pectoris. Also, it is important to rule out
chronic congestive heart failure by appropriate history and
physical examination before administering intravenous
mannitol because acute congestive heart failure may be
precipitated by the sudden increase in intravascular volume
before diuresis occurs.68 Electrolyte disturbances are rare if
intravenous mannitol is administered only once and avoided
in kidney failure. Allergic reactions to acetazolamide are rare,
but renal calculus formation may be precipitated in predis-
posed individuals. Topical pharmacological lowering of IOP
may be performed with beta blocker, carbonic anhydrase in-
hibitor, apraclonidine, and prostaglandin analogs. These
agents have little short-term risk, except for topical beta
blockers that can precipitate cardiac arrhythmia and bron-
chospasm in susceptible patients.
3.1.3. Ocular massage
Ocular massage or intermittent ocular compression often is
performed to lower IOP, but without confirmed
benefit.11,15,26,35,56,67,84,98 Continuous compression from the
use of a mercury bag or Honan balloon elevates IOP and de-
creases retinal arterial perfusion pressure until ultimately
reducing IOP after compression is relieved; consequently,
during the time of continuous compression, CRAO may be
exacerbated.59
3.2. Dilate the CRA
Dilating the CRA may increase perfusion pressure and help
thrombus or embolus to move distally and has been attemp-
ted by retrobulbar injection of pharmacologic vasodilators
such as tolazoline or local anesthetic, sublingual isosorbide
dinitrate or nitroglycerine, oral pentoxifylline, and breathing
elevated levels of carbon dioxide6,10,26,27,34,35,63,70,84,85,98;
446 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
however, none of these methods has been demonstrated to be
effective.26,67,70,94 Pharmacological agents which act systemi-
cally may actually decrease perfusion pressure in the CRA by
shunting blood to other parts of the body. Similarly, vasodi-
lator administered by retrobulbar injection may dilate retro-
bulbar vessels and might tend to shunt blood away from the
CRAO at the optic nerve head. Breathing elevated carbon di-
oxide will tend to dilate the cerebral vessels and also may tend
to shunt blood away from the CRA.29 Furthermore, with CRAO,
there is already a strong local stimulus for CRA vasodilation
because of hypoxia and hypercarbia at the site of and distal to
the occlusion so further therapeutic maneuvers of this nature
are not likely to be helpful. Retrobulbar injection carries risks
including retrobulbar hemorrhage and globe perforation and
systemic reaction from accidental intravascular injection.
3.3. Increase oxygenation
The oxygen content of blood of patients with CRAO may be
increased by using a hyperbaric chamber.37,66,84 This contro-
versial therapy might be useful for incomplete CRAO as a
temporizing measure to facilitate survival of ischemic inner
retina; however, it is frequently not readily available and,
when available, is usually started hours after onset of CRAO
and isolates the patient from other therapeutic maneuvers
during hyperbaric therapy.11,37,98 The duration of hyperbaric
therapy is problematic. Note that hyperbaric oxygen is not a
generally accepted treatment for cerebral stroke or for
myocardial infarction.
3.4. Isovolemic hemodilution
Hemodilution therapy has been attempted to decrease blood
viscosity33,67,98 but is counterproductive because the induced
acute anemia decreases arterial oxygen-carrying capacity.
This therapy is not considered for ischemic stroke or
myocardial infarction. It may be useful in rare cases of poly-
cythemia associated with CRAO.
3.5. Anticoagulation
Anticoagulation with various agents has not been shown to be
an effective treatment of CRAO.11,26,33,94 In particular, CRAO
from calcific and cholesterol emboli are likely to be resistant to
anticoagulation therapy. The risks and contraindications
associated with anticoagulation are well known.
3.6. Dislodge or fragment thrombus or embolus
It has been postulated that oscillating IOP produced by ocular
massage might dislodge or facilitate fragmentation of CRA
thrombus or embolus, but evidence for this is only anecto-
dal.2,11,56,85 Experimental direct laser treatment to break up
CRA embolus has been reported but also has a risk of intra-
ocular hemorrhage.39,60,78
3.7. Thrombolysis
Despite some early positive experience and continuing con-
troversy, intravenous thrombolysis has largely been
abandoned for CRAO because of inefficacy and serious com-
plications.2,8,14,21,35,41,56,63,76,84,98 Although early studies of
intravenous thrombolysis for ischemic cerebral stroke
showed no benefit and grave risk, more recent studies have
caused intravenous recombinant tPA (alteplase) to be adopted
enthusiastically for treatment of cerebral ischemic strokes,
subject to extensive exclusion criteria and an associated small
risk of hemorrhage, particularly hemorrhagic stroke.13,31,75,82
Unfortunately, less than 10% of ischemic stroke patients
meet eligibility criteria for intravenous tPA within 4.5 hours,
and some controversy persists regarding the benefits versus
the risks of intravenous tPA.4,17,18,28,38,95
Selective intraarterial thrombolysis (IAT) is now widely
accepted as treatment for many acute cerebral ischemic
strokes from occlusion of much larger vessels than the CRA,
ideally within the first 90 minutes of diagnosis and also sub-
ject to extensive exclusion criteria.20,58 Unfortunately, despite
the enthusiastic adoption of selective IAT for stroke by neu-
rologists and interventional neuroradiologists, only a small
fraction of ischemic stroke patients have benefit, and also
there is associated risk of serious hemorrhagic complications,
particularly intracerebral hemorrhage.20 Evolving techniques
of surgical thrombectomy also are offered in selected cases at
some centers for large vessel cerebral ischemic stroke.22,40
There has been and continues to be enthusiasm for adopting
selective IAT for treatment of CRAO2,29; however, IAT for
CRAO remains of unproven value, and hemorrhagic compli-
cations have occurred.1,3,12,26,35,71,79,96 The one randomized
controlled trial of IAT for CRAO did not show significant
benefit and had a high rate of serious complications.83 It is
likely that the significant proportion of CRAOs from calcific or
cholesterol emboli cannot respond well to thrombolysis.35 A
recent systematic review and meta-analysis concluded that
further randomized trials are needed to demonstrate benefit
and safety of IAT for acute CRAO.72 The time necessary to
evaluate, refer, and perform intraarterial selective thrombol-
ysis by a neuroradiology unit for CRAO is somewhat
problematic.
Recently intraretinal IAT consisting of posterior vitrectomy
and retinal arterial injection of recombinant tPA with a 47
gauge microcannula has been performed in a small uncon-
trolled series of patients.52 It remains to be investigated if this
therapy is effective in controlled trials.
4. Treatment guidelines
Based on current understanding of CRAO pathophysiology
and the rationales for various forms of treatment, we suggest
a provisional CRAO treatment regimen as outlined in Table 2.
Although we do not have experience or data to support our
proposed treatment approach, we hope that evidence-based,
effective therapy may be discovered in future well-designed,
carefully executed clinical trials. We suggest that in cases of
incomplete acute CRAO accompanied by profound visual loss,
treatment normally be offered because persistent perfusion
may allow some inner retinal survival even after hours or
days.77 Cases presenting with old incomplete CRAO accom-
panied by inner retinal atrophy and optic atrophy are not
 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
likely to benefit from treatment but still need workup to try to
discover an underlying etiology of CRAO.
4.1. Emergency examination
Painless acute severe visual loss requires emergency
ophthalmic examination.
4.2. Diagnose CRAO
In patients with painless, sudden, severe visual loss, diagnose
CRAO without delay based on typical signs15,26,35,70,84,94:
- a relative afferent pupillary defect;
- a cherry red spot, although this can be hard to recognize in a
recent CRAO;
- segmentation of retinal blood columns (box-carring) and
slow or stagnant flow of the box-cars in retinal arteries, very
important signs but only occasionally present;
- diffusely narrowed retinal arteries, also seen in ocular
ischemic syndrome;
- spontaneous pulsation of the CRA, an indication of poor
perfusion with CRA filling during systole and collapse during
diastole; however, this is rarely seen and may occur in
ocular ischemic syndrome;
- embolus in the CRA or emboli in retinal arterial branches,
taken to be diagnostic of embolic CRAO when associated
with other signs of CRAO.56,84
4.3. Diagnose severe systemic hypertension
Vasospasm in hypertension is an uncommon cause of CRAO,
and uncontrolled severe systemic hypertension is a risk factor
for cerebral stroke and should be immediately managed by
internal medical or neurological consultation concurrent with
the evaluation and treatment of CRAO84; however, treatment
of hypertension might risk decreasing ocular perfusion and
potentially worsen outcomes.9,16 Some systemic hypertension
in CRAO patients may be secondary to fear and anxiety
associated with acute visual loss and the “white coat
syndrome”.
4.4. Rule out giant cell arteritis
About 1-2% of CRAO cases are caused by giant cell arteritis
that requires immediate treatment of the underlying dis-
ease.15,61 Symptoms and signs of giant cell arteritis should be
specifically sought, and sedimentation rate and C reactive
protein blood test should be obtained in patients older than
50 years without an obvious predisposing cause of CRAO, such
as cholesterol or calcific retinal embolus.15
4.5. Treat incomplete CRAO
Determine which cases of CRAO are incomplete and offer
treatment to try to improve CRA perfusion only for incomplete
CRAO. We believe it is important to quickly distinguish com-
plete from incomplete CRAO,15,80,84 to select incomplete oc-
clusion CRAO patients who might benefit from treatment, and
447
to exempt those patients from treatment who have already
had irreversible inner retinal infarction from complete oc-
clusion. Visual acuity is not a useful guide because central
vision may be severely impaired with severe retinal
ischemiaeabsent infarction; conversely, perfect central vision
may be present with complete CRAO and inner retinal
infarction when a cilioretinal artery perfuses and spares the
central macula.70,98 A cherry red spot of the macula is an
important sign, but occasionally may occur from inner retinal
ischemia without ganglion cell infarction, so it is not a
completely reliable indicator of inner retinal infarction37,89; it
also may be absent or subtle after very recent complete CRAO
with inner retinal infarction. Discriminating complete from
incomplete CRAO can be based on the findings explained in
the following paragraphs.
4.5.1. Box-carring
Segmentation of the retinal arterial blood columns (box-car-
ring) and stagnant, slow, or absent flow of the segmented
blood columns on ophthalmoscopy are pathognomonic signs
of complete CRAO. If segmentation and sluggish flow of the
segmented blood columns are observed repeatedly for
10e12 minutes, it is likely that retinal infarction has occurred,
and treatment therefore will be futile. A single initial obser-
vation of these signs is an important, but not infallible, indi-
cation of irreversible inner retinal infarction because some
degree of reperfusion may occur spontaneously at any time
and intermittently. The absence of segmentation of the blood
columns in a CRAO does not rule out inner retinal infarction.
4.5.2. Spontaneous pulsatile CRA emptying
Spontaneous filling of the CRA on systole and collapse with
retrograde flow on diastole indicates no CRA flow but is rarely
present.
4.5.3. Digital retinal artery compression
Easy blanching of the retinal arteries observed with ophthal-
moscopy while performing gentle digital compression of the
eye through the eyelid (a qualitative form of oph-
thalmodynamometry) is a sign of persistent retinal arterial
perfusion.
4.5.4. Delayed CRA filling
Severely delayed retinal arterial filling time on fluorescein
angiography or angioscopy can confirm severe or complete
CRAO in cases where ophthalmoscopic signs are insufficient
to make a determination.36,69 Fluorescein angiography can be
done in a time-efficient manner in most practices, and clini-
cians are more familiar and comfortable with interpretation of
angiography than angioscopy; however, in situations where a
fundus camera is not readily available for angiography, fluo-
rescein angioscopy can be performed.50 Fluorescein angio-
scopy, rather than angiography, is easy and fast to perform
and does not require a fundus camera.50 After intravenous
injection of 5 mL of 10% sodium fluorescein, the retina is
viewed with an indirect ophthalmoscope fitted with an
appropriate blue filter for illumination of the fundus to stim-
ulate the fluorescein in the retinal vessels and yellow filters in
front of the eyepieces for viewing the fluorescence appearing
in the retinal circulation. Normally, the retinal arterial tree
448 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
fills after one circulation time, around 12e14 seconds, if in-
jection is performed appropriately over 3e5 seconds with a 21
gauge or larger butterfly needle. Smaller needles require too
much syringe pressure, which is dangerous and tends to make
the injection procedure too long, frustrating accurate assess-
ment of retinal arterial filling time. If retinal arterial filling is
severely delayed, it means severe CRAO is present. A signifi-
cant delay in arterial filling also occurs in ocular ischemic
syndrome.
4.6. Paracentesis
Perform emergency anterior chamber paracentesis at the slit
lamp for incomplete CRAO to suddenly and dramatically
lower IOP and increase CRA perfusion pressure. Paracentesis
of aqueous humor is unequaled for producing an immediate,
profound drop in IOP, especially when compared to pharma-
cological lowering of IOP, which is still widely advocated for
CRAO. Although this procedure is controversial and of un-
proven efficacy, it has never been applied selectively to
incomplete CRAOs, and we feel that complications can be
minimized by careful patient selection and attention to
technique as discussed in the following paragraphs.
4.6.1. Patient selection
Patient selection criteria include a collaborative patient, a
normal depth or deep anterior chamber, and informed
consent.
4.6.2. Microscope magnification
Evacuation of aqueous humor by anterior chamber para-
centesis is normally performed by an ophthalmologist using a
slit lamp microscope or an operating microscope.
4.6.3. Hand braced
The surgeon’s hand must be braced on the patient’s face and
not on the frame of the slit lamp or wrist rest so that if the
patient moves, the surgeon’s hands will move in tandem.
4.6.4. Antiseptic preparation
After several drops of topical local anesthetic, antiseptic
preparation of the ocular surface with ophthalmic povidone
iodine or an equivalent solution is performed.
4.6.5. Lids controlled
A sterile speculum or an assistant is used to hold the lids open.
4.6.6. Incision with drainage
A superblade or preferably a straight, spear-shaped, double-
edged, 20 gauge vitrectomy knife is used to make an iris-
parallel incision in temporal peripheral cornea, just like a
side port incision for phacoemulsification. As the blade is
withdrawn, the posterior lip of the incision is depressed by the
knife tip until a couple of drops of aqueous egress, producing
visible shallowing of anterior chamber. In this fashion, a self-
sealing incision is created. It has been suggested to use a 27
gauge needle on syringe to aspirate 0.1e0.2 ml of aqueous11,12;
however, we feel that this technique is both more difficult and
more likely to result in complications from intraocular trauma
by the needle because it is difficult to hold the syringe securely
without movement and simultaneously withdraw the syringe
plunger, whether performed by one or two people.
4.6.7. Topical antibiotic
Antibiotic eye drops may be instilled, although their efficacy is
unproven for this procedure. IOP may be measured to docu-
ment the pressure drop and visual acuity rechecked.
4.6.8. Shield
An eye shield may be applied to prevent eye rubbing that
might open the incision, especially during sleep, for about
10 days.
4.6.9. Postoperative pain or redness
The patient is instructed to immediately report eye redness or
pain that could be a sign of endophthalmitis.
4.7. Pharmacological IOP lowering
Lowering of IOP by pharmacological treatment for a few days
with oral acetazolamide and topical ocular hypotensive
medications subsequent to anterior chamber paracentesis
might be prudent to continue to facilitate higher CRA perfu-
sion pressure.
4.8. Other therapy
Additional therapy in cases of incomplete occlusion may be
attempted, according to availability and local protocols,
particularly if part of a controlled study, such as hyperbaric
oxygen that might help rescue ischemic retina until improved
perfusion occurs.37,84 We are not enthusiastic about intrave-
nous fibrinolysis and skeptical of selective arterial fibrinolysis
outside of controlled trials for CRAO because of inconsistent
results in studies so far, extensive inclusion and exclusion
criteria, and associated complications; furthermore, throm-
bolysis in any form has not been shown to be useful for small
vessel cerebral stroke.
4.9. Urgent referral for systemic workup
After emergency ophthalmic diagnosis and treatment, im-
mediate referral of all CRAO patients, both complete and
incomplete, to a stroke unit or emergency service is important
to diagnose an underlying cause of CRAO, such as giant cell
arteritis, ulcerating carotid atheroma, embologenic cardiac
abnormalities, and hematologic conditions associated with
hypercoagulability and hyperviscosity. These predispose to
comorbidities such as cerebral stroke and myocardial infarc-
tion within a short period of time.15,19,27,73,84 Emergency ser-
vices to which CRAO patients are referred for evaluation may
not recognize that CRAO is a stroke requiring urgent evalua-
tion. It is therefore important to communicate specifically
using the word “stroke” to characterize CRAO and emphasize
that CRAO is associated risks within a short time window.
CRAO patients under the age of 50 years and without an
evident etiology require a more extensive workup to try to
discover an underlying cause.
 s u r v e y o f o p h t h a l m o l o g y 6 4 ( 2 0 1 9 ) 4 4 3 e4 5 1
5. Conclusion
The CRA is a tiny end artery that supplies to the central ner-
vous system tissue, the ganglion cell layer of the retina, and
the axons that form the optic nerve. Retinal ganglion cell
infarction from complete CRAO is a small vessel stroke that
evolves in 15 minutes or less; however, CRAO is often
incomplete and variable, which may allow the inner retina to
survive much longer. Although there is no generally accepted,
evidence-based therapy for CRAO, we suggest a provisional
treatment protocol pending future advances that includes:
- prompt diagnosis
- ruling out acute severe systemic hypertension and giant cell
arteritis
- treatment only for incomplete CRAO by immediate anterior
chamber paracentesis to achieve an acute profound drop in
IOP, followed by a few days of pharmacological IOP lowering
- other therapy according to local protocol, ideally part of a
controlled study
- urgent medical evaluation for all patients with both com-
plete and incomplete CRAO after initial ophthalmic man-
agement to discover and treat an underlying cause CRAO
predisposing to comorbidities. We hope that future
controlled studies on incomplete CRAO will yield positive
therapeutic results.
6. Method of literature search
The literature was searched on the MEDLINE database using
PubMed for articles in English, French, and German published
since 1960 using the keywords: “central retinal artery occlu-
sion", "retinal infarction", "retinal ischemia" "retinal stroke".
For other foreign language publications, no translation was
obtained; however, abstracts found to be relevant were
reviewed. All returned articles and their references were
screened for relevant data to pathophysiology and treatment
of CRAO. We included articles related to treatments in wide-
spread clinical use and excluded most of those related to
unusual experimental procedures. We excluded articles about
CRAO secondary to a surgical procedure.
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