Management of Retinal

Vascular Occlusions

University of Florida - Jacksonville

 CRAO
 Central Retinal Artery Occlusion
– Painless vision loss ocurring over several
seconds
– May have preceding h/o amaurosis episodes
– Visual acuity CF’s to LP unless cilioretinal
sparing
– NLP suggests choroidal or optic nerve
involvement
 Emboli visible in 20-40%
 Most common variant is glistening, yellow
cholesterol embolus (Hollenhorst plaque).
– Most commonly arise from atherosclerotic deposits in
the carotid arteries
 Calcific emboli less common
– Tend to be larger and cause more severe obstructions.
– Usually originate from the cardiac valves
 Low interobserver agreement on type of
plaque, therefore fundus appearance should
not be only guidance for workup
 Visible retinal arterial embolus is associated
with increased mortality
– Mortality rate(cardiac disease) of 56% over
nine years as compared to a rate of 27% during
the same time in an age-matched control group
without arterial emboli
 20% of eyes develop rubeosis
– Develop at a mean of 4-5 weeks after
obstruction
– 65% regress with PRP
 Ischemic necrosis of inner layers of retina
causes whitening of posterior pole except in
fovea, cherry red spot due to ability to see
through to RPE and choroid
 Opacification requires hours to become
apparent
 Opacification diminishes outside posterior
pole
 Histopathologic findings in chronic branch retinal artery obstruction elucidate the
damage to the inner retina with arterial obstructive disease. The retina on the right is
unaffected, whereas on the left the inner layers have atrophied to the inner nuclear
layer. (Courtesy of Dr Jerry A. Shields, Philadelphia and the Armed Forces Institute
of Pathology, Washington D.C.)
 Retinal opacification resolves over 4-6
weeks leaving optic nerve pallor, NFL
dropout, and arteriolar attenuation
 With severe obstruction may see boxcarring
of arteries and veins
 CRAO
 IVFA
– May have delayed retinal arterial filling
– Most sensitive sign is delayed arterio-venous
transit time(Normal <= 11 seconds)
 ERG
– Decreased B-Wave amplitude(Muller/bipolar
cells)
 BRAO
 Retinal whitening only in area perfused by
affected branch
 Same systemic associations as CRAO
 Combined retinal artery and vein occlusion
– H/o sudden vision loss
– Retinal opacification with cherry-red spot
combined with hemorrhagic component, dilated
and tortuous retinal veins, swollen optic disc,
and marked retinal edema in posterior pole
– Workup similar to CRAO, aminoglycoside
toxicity within differential
 CRAO
 Systemic Associations
– Most common include emboli, intraluminal
thrombosis, hemorrhage under an
atherosclerotic plaque, vasculitis, spasm,
circulatory collapse, dissecting aneurysm, and
hypertensive arterial necrosis
– HTN in 2/3 of patients, DM in ¼ of patients
 Systemic Associations
– Structural cardiac pathology was seen in nearly
50% of patients with acute retinal arterial
occlusion though only 10% of these patients
had pathology severe enough to warrant
anticoagulation or cardiac surgery
 CRAO
 Systemic Associations
– Study by Inatomi – TTE found cardiac lesions
in 27% of patients, TEE found lesions in 59%
– 18% of patients with carotid artery stenosis
60% or greater
 Etiology Retinal Arterial
Occlusion
 Systemic arterial hypertension (via
atherosclerotic plaque formation)
 Cardiac valvular disease
 Left ventricular hypertrophy
 Thrombus after myocardial infarction
 Cardiac myxoma
 Tumors
 Intravenous drug abuse
 Lipid emboli (pancreatitis)
 Purtscher's retinopathy (trauma)
 Loiasis
 Radiologic studies (carotid angiography,
lymphangiography, head and neck corticosteroid
injection, retrobulbar injection)
 Deep vein thrombosis (via paradoxical embolus
through cardiac wall defect)
 Traumatic causes
– Retrobulbar injection
– Orbital fracture repair
– Anesthesia
– Penetrating injury
– Nasal surgery
– Eyelid capillary hemangioma injection
 Coagulation abnormalities
– Sickle cell disease
– Homocystinuria
– Oral contraceptives
– Platelet abnormalities
– Pregnancy
– Lupus anticoagulants
 Coagulation abnormalities
– Protein S deficiency
– Protein C deficiency
– Antithrombin III deficiency
– Activated protein C resistance
– Factor V Leiden abnormalities
 Ocular Conditions
– Prepapillary arterial loops
– Optic disc drusen
– Increased intraocular pressure (with sickling
hemoglobinopathy)
– Toxoplasmosis
– Optic neuritis
 Collagen Vascular Disease
– Systemic lupus erythematosus
– Polyarteritis nodosa
– Giant cell arteritis
– Wegener's granulomatosis
 Other vasculitides
– Orbital mucormycosis
– Radiation retinopathy
– Behçet's disease
 Miscellaneous
– Ventriculography
– Fabry's disease
– Sydenham's chorea
– Migraine
– Hypotension
– Fibromuscular hyperplasia
– Nasal oxymethazolone use
– Lyme disease
 Workup/Treatment
 Cardiac history, h/o IV drug abuse
 TTE if cardiac history/risk or young patient
 Carotid Dopplers in patients over 30 years
 If age > 55 years without emboli on exam obtain
ESR (GCA accounted for 1-2% in series at Wills
Eye)
 Homocysteine in young patients/no other etiology
identified
 Antigoagulation studies (Protein C and S, Anti
thrombin III)
 Treatment
 Studies in rhesus monkeys show
irreversible damage at 90-100 minutes
 In clinical situations rarely a complete
obstruction therefore timescale may differ
 Recommended to treat if seen within 24
hours
 Treatment
 Ocular Massage
– Study by Russell showed 16% increase in
retinal arterial diameter when IOP increased by
60mmHg
– Study by Ffytche showed 86% increase in flow
when increase in IOP followed by sudden
decrease
 Treatment
 95% oxygen/5% carbon dioxide mixture
– May produce normal pO2 at retinal surface via
diffusion from choroid
 AC paracentesis
– Attempt to increase arterial perfusion pressure
– Study by Atebara in 40 patients showed no
significant benefit over 47 patients without this
therapy
 Treatment
 Antifibrinolytic agents
– No randomized study, not currently
recommended
– With supraorbital artery injection 100 times
dose is delivered compared with IV, study by
Watson noted 50% improvement
 Laser therapy to emboli vs. PPV with
manipulation of emboli
 CRVO
 Sudden painless loss of vision vs. gradual
vision loss with less severe occlusions
 DBH/flame-shaped in all quadrants
 Dilated/tortuous venules
 Disc edema, macular edema, and CWS
present to varying degrees
 CRVO
 Retinal heme with gradually resolve, may
have subsequent RPE changes
 Macular edema may persiste after
resolution of heme
 Epiretinal membranes may form
 Shunt vessels may form on disc
 Neovascular proliferation
– Includes NVD, NVE, NVI/NVG
– NVA may occur without NVI in 6-12%
– NVI/NVA present in 16% of eyes with 10-29
disc areas of nonperfusion and 52% of eyes
with 75 or more disc areas of nonperfusion in
CVOS
 NVI/NVA
– In CVOS occurred in 5% of eyes 20/40 or
better, 14.8% in eyes with 20/50 to 20/200, and
30.8% in eyes with worse than 20/200 acuity
 CVOS criteria
– Perfused CVO (also termed nonischemic,
incomplete or partial) - less than 10 disc areas
of capillary nonperfusion
– Generally less hemorrhages
– Generally better visual acuity
 CVOS criteria
– Nonperfused CRVO – 10 or more disc areas of
capillary nonperfusion
– Generally more hemorrhages, disc edema, and
macular edema
– Indeterminate when extent of hemorrhages
prevents full evaluation of extent of capillary
nonperfusion
 CVOS
– 10% of perfused vs. 35% nonperfused
developed NVI/NVA
– 34% of initially perfused eyes converted to
nonperfused status after 3 years
– 38 eyes (83%) with an indeterminate CVO at
baseline were ultimately determined to be
nonperfused
 ERG
– Reduction to 60% or less of normal mean b-
wave amplitude suggests ischemic CRVO
 Pathogenesis
 Histopathologic studies of eyes enucleated with
h/o CVO demonstrated a thrombus occluding the
lumen of the central retinal vein at or just
proximal to the lamina cribrosa
 In retrolaminar portion of the optic nerve central
retinal artery and vein are aligned parallel to each
other with common tissue sheath
 Central retinal artery and vein are naturally
compressed as they cross through the rigid sieve-
like openings of lamina cribosa
 Central retinal artery and vein are naturally
compressed as they cross through the rigid
sieve-like openings of lamina cribosa
 Pathogenesis
 May be subject to compression from
mechanical stretching of the lamina from
increases in intraocular pressure, causing a
posterior shift or bowing of the lamina with
subsequent impingement on the central
retinal vein
 Pathogenesis
 Hemodynamic alterations may produce
stagnant flow and subsequent thrombus
formation in the central retinal vein,
including diminished blood flow, increased
blood viscosity, and an altered lumen wall
(Virchow's triad)
 Pathogenesis
 Experimentally, occlusion of both the
retrolaminar CRA and CRV, posterior to
the lamina cribrosa and before collateral
channels branch from the main trunk, was
required to produce the clinical appearance
of ischemic CVO. This implies that
concurrent retinal artery insufficiency or
occlusion may play a role in an ischemic
CVO
 Systemic Associations
 Systemic vascular diseases: Diabetes
mellitus, hypertension, carotid insufficiency
 Ocular diseases: Open angle glaucoma,
ischemic optic neuropathy, pseudotumor
cerebri, tilted optic nerve heads, optic nerve
head drusen
 Hematologic alterations: Hyperviscosity
syndromes: dysproteinemias (multiple myeloma),
blood dyscrasias (polycythemia very, lymphoma,
leukemia, sickle cell disease or trait). Anemia,
elevated plasma homocysteine, factor XII
deficiency, anti-phospholipid antibody syndrome,
activated protein C resistance, protein C
deficiency, protein S deficiency
 Inflammatory/autoimmune vasculitis: Systemic
lupus erythematosus
 Medications: Oral contraceptives,
diuretics, hepatitis B vaccine
 Infectious vasculitis: HIV, syphilis, herpes
zoster, sarcoidosis
 Other: After retrobulbar block,
dehydration, pregnancy
 Workup
 Generally no workup indicated if > 60 y/o and
known systemic vascular risk factors
 Limited systemic work up for those with a prior
occlusion in the fellow eye, prior systemic
thrombotic disease, family history of thrombosis,
or other symptoms suggestive of a hematologic or
rheumatologic condition
 Initial laboratory investigation may include ESR,
ANA, antiphospholipid antibody, and fasting
plasma homocysteine levels
 Treatment
 Identify systemic vascular risk factors
 Pentoxyfilline improved retinal vascular
flow velocity, found in small retrospective
series to improve ME, however no VA
improvement
 Treatment
 CVOS
– Grid laser for ME showed no improvement in
VA, 31% showed resolution of ME
– PRP recommended for patients with NVI/NVA,
no benefit from prophylactic therapy(NVI in
20% early treatment(n=90) vs. 34% no early
treatment(n=91))
– Prophylactic PRP may be considered for high
risk cases with poor anticipated follow up
 Treatment
 Chorioretinal venous anastomosis(CRA) have
been created surgically through a trans-retinal
venipuncture technique or laser energy delivered
through argon or Nd-YAG systems directed at a
branch retinal vein to rupture the posterior vein
wall and Bruch's membrane
 Successful CRA creation is reported in 10-54% of
perfused CVO with subsequent conversion to
ischemic CVO in 0-8% of eyes
 Treatment
 Radial Optic Neurotomy
– Opremcak and colleagues have proposed combining pars
plana vitrectomy with transvitreal incision of the nasal
scleral ring to release pressure on the central retinal vein at
the level of the scleral outlet
– Retrospective report of 11 eyes by Opremcak and colleagues,
successful RON was performed with no complications.
There was clinical improvement in retinal hemorrhages and
venous congestion. With a mean follow up of 9 months, 73%
of patients had improved Snellen acuity; Two eyes with
preoperative INV had worsening of acuity associated with
the development of neovascular glaucoma
 Treatment
 RON
– Recent study total of 117 male and female
patients, age >40 years (range 44-93 years)
with CRVO and severe loss of vision (visual
acuity of ≤20/200), underwent pars plana
vitrectomy with radial optic neurotomy
 Treatment
 RON
– Anatomic improvement of CRVO was found in 95% (106
of 111) of patients. Disc edema improved in by 1 week
– Visual acuity improved in 71% (79 of 111) of patients, with
an average of 2.5 lines of vision gained (range 1-12 lines).
Two or more lines of improvement were found in 53% (59
of 111) of patients, three or more in 41% (45 of 111), four
or more in 25% (27 of 111), and six or more in 14% (14 of
111)
– Twenty-three percent (25 of 111) of patients had unchanged
visual acuity, and 6% (7 of 111) had worse visual acuity
 Treatment
 Intravitreal triamcinolone
– Study by Ramezani
– CMT before, 2 and 4 months after injection was 565
(50), 259 (15), and 290 (53) microns in the treatment
group and 629 (43), 470 (62) and 413 (59) microns in
the sham group, respectively. The 2- month difference
was significant (P=0.003). The difference between VA
changes (0.39 logMAR) was significant only at 1
month (P=0.013)
 Treatment
 Intravitreal triamcinolone
– Study by Goff et al, retrospective
– Twenty-nine eyes were treated with intravitreal
injection. The median initial Early Treatment Diabetic
Retinopathy Study visual acuity was 20/250 (median
logMAR, 1.1). The median visual acuity 3 months after
injection was 20/125 (median logMAR, 0.8). This
difference was statistically significant. The median
final visual acuity was 20/250 (median logMAR, 1.1).
This difference in visual acuity was not statistically
significant
 Treatment
 Intravitreal Avastin
– Study Iturralde et al, retrospective, no adverse events
– There were 16 eyes of 15 consecutive patients
Intravitreal triamcinolone had been previously
administered to 9 patients. The patients received a
mean of 2.8 injections of bevacizumab per eye. The
mean central macular thickness at baseline was 887
microm and decreased to a mean of 372 microm at
month 1 (P < 0.001). The mean baseline acuity was
20/600 (logMAR = 1.48) and the mean acuity at month
1 was 20/200 (logMAR = 1.05)
 Treatment
 Intravitreal Avastin
– At last follow-up, a mean of 3 months after the
first injection, the mean visual acuity was
20/138 (logMAR = 0.84), which was
significantly better than baseline (P < 0.001).
Visual acuity improvement, defined as a
halving of the visual angle, was seen in 14 of
the 16 eyes