DR WANI'S TALK ON CRVO FOR RESIDENTS KLE 14 JAN 2023.pptx

CENTRAL RETINA VEIN
OCCLUSION
Dr. Vivek Wani MS FRCSEd
14th January
2023
CRVO for KLE RESIDENTS 1

14th January 2023
CRVO for KLE RESIDENTS
2
Happy Sankranti

DESCRIBE THE FUNDUS
PICTURE
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OBJECTIVES OF THE TALK
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At the end of the talk the students should know
the outlines of CRVO management under the
following headings
 How CRVO occurs
 Risk factors for CRVO
 Diagnosis
 Investigations
 Treatment

CRVO
I) Introduction
II) Incidence and prevalence
III) Risk factors
IV) Pathogenesis
V) Pathology
VI) Clinical features
VII) Investigations
VIII) Treatment
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I. Introduction
 Retinal vein occlusions RVOs
(BRVO+CRVO+HEMI-CRVO) are 2ND
most common retinal vascular diseases-
which is the most common?
 (1ST is Diabetic Retinopathy)
 Branch Retinal vein occlusions(BRVO)>
CRVOs
 BRVO -80%;CRVO-20%
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II. CRVO prevalence AND
incidence
 Prevalence- CRVO was 0.8/1000 and BRVO was 4.4
per 1000 population aged 30 years and above
(RVOs- 5.2/1000)
ROGERS ET AL –Ophthalmology 2010
 The incidence of RVO 16 persons per 10,000/ year in
persons aged 50 years and above -CRVO is
3/10000 , BRVO is 13/ 10000 per year
Arch Ophthalmol. 2006;124:726-732
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III.CRVO-risk factors
CRVO is multifactorial
in origin, in which
Virchow’s triad of
abnormalities of
blood flow
vessel walls
blood coagulability
all play a role
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CRVO RISK FACTORS
A.Systemic
B. Ocular
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III A) Systemic Risk factors
a) Age –Higher age. 90% of CRVOs are >50 years old
(Arch Ophthalmol. 2008;126:513-518)
b) Hypertension –present in 64% of patients with
RVO
c) Diabetes mellitus-present in 10%-25% of RVO cases
d) Obesity
e) Cardiovascular diseases
f) Hyperlipidemia -35% cases - cholesterol>6.5 mmol/l
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III A. CRVO-Risk factors
g) Inflammatory diseases –
they cause retinal vasculitis
(pts aged<45 yrs)
ENDOTHELIAL DAMAGE
 Sarcoidosis
 Behçet's disease
 Wegener’s granulomatosis
 Goodpastures syndrome
 Other diseases with retinal
vasculitis
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IIIA) Risk factors
h) Myeloproliferative disorders (to be considered pts <45
years)-STASIS OF BLOOD FLOW
 Polycythemia
 Abnormal plasma proteins(myeloma, Waldenstrom
macroglobulinaemia)
 Leukemias
i) Thrombophilic disorders (to be considered in patients <45
years old)-BLOOD-- hypercoagulability
 Hyperhomocysteinaemia-strong evidence present
 Anti phospholipid antibodies (lupus anticoagulant and anti
cardiolipin) –strong evidence present
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IIIA) CRVO –Risk factors
j) Inherited disorders of hypercoagulability -BLOOD
 Factor V Leiden deficiency
 Protein C deficiency
 Protein S deficiency
k) More unusual associations
 Oral contraceptives
 Chronic renal failure
 Other secondary causes of hypertension and diabetes (e.g.
Cushing's syndrome)
 Secondary causes of hyperlipidaemia (e.g. hypothyroidism)
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CRVO Risk factors-B) Ocular
1. GLAUCOMA-CRVO>BRVO (5 times more
likely to have CRVO if glaucoma is present)
2. Retinal vasculitis –Eales disease
3. Carotid cavernous fistula
4. Orbital tumors
5. Orbital hemorrhage or proptosis due to orbital
cellulitis
 Disc drusens
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Ocular risk factors Eale’s disease
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Carotid cavernous fistula
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Risk factors for RVO
1. Lattanzio R, et al. Ophthalmologica 2011;225:135-43
2. Cheung N, et al. Invest Ophthalmol Vis Sci 2008;49:4297-302
3. Eye Disease Case-Control Study Group. Arch Ophthalmol 1996;114:545-54
Increased
risk of
RVO
↑Age1,2,
smoking
Diabetes1,3
Renal
dysfunction2
Hyperlipidemia1,2,3
Hyperhomo-
cysteinemia1
↑Intraocular
pressure1
Hypertension1,2,3
Cardiovascular
disease3
Glaucoma1,3
Decreased
risk of
RVO
↑Exercise3
Mild-to-moderate
alcohol
consumption3
↑Postmenopausal
estrogen use in
women3
↑Education2,3
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IV. PATHOGENESIS-CRVO
 The occlusion of the
CRV occurs at the
level of lamina
cribrosa or just behind
 The occlusion occurs
due to formation of a
thrombus in the vein
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Lamina cribrosa
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Why at lamina cribrosa?-conditions that favor
occlusion at this place
 Narrow lumen of CRV and
CRA in lamina cribrosa –
tunnel in LC is narrow
 Common adventitial sheath
envelopes CRA and CRV in
lamina cribrosa
 So an atherosclerotic CRA
can compress CRV & cause
turbulence of flow
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IV. CRVO-pathogenesis Green et al
 Blood flow is turbulent in CRV in LC
 If Atherosclerosis +---CRA hardens and
presses on CRV-lumen of CRV further narrows
–turbulence
 Turbulence and pressure by CRA causes
endothelial damage of CRV
 Exposure of the collagen of vessel wall -
platelets aggregate and thrombus formation
take place
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Pathogenesis -Further changes in
retina
CRV
O/BR
VO
Increased venous
and capillary
pressure
Hypoxia of
drained
retina
Endothelial
damage
/death of
capillaries
Capillary
leakage in to
extracellular
sp
Pressure in
Ex.cellular
space
VEGF
NVI
NVA
NVD
Reduced
blood flow
MACULAR EDEMA
IL6
IL 8
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IV. Pathogenesis
 Damage to retina and vision depend upon
1. Rapidity of development of CRVO
2. Degree of occlusion –Mild, moderate or severe
3. Availability of collateral pathways
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V. Pathology
 Ischemic CRVO -haemorrhagic infarction of
the retina -the inner retinal layers
 Neovascularization of the iris and angle
 Less frequently –NVD may occur
 However NVE rare
 Later changes include thickening of the retina
and reactive gliosis
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Histopathology
Histopathology of central retinal vein occlusion (CRVO). Note the intraretinal hemorrhages in various
layers of the retina (arrows) and the eosinophilic proteinaceous exudates in the outer plexiform layer
(asterisk) and subretinal space (S)
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VI. Clinical Features-Presentation
 Sudden UNILATERAL painless DECREASE of vision
 Fairly sudden decrease but not as much as CRAO
 Decrease of vision varies from just blurring of vision to
severe loss of vision
 No redness, pain or watering in fresh cases in most cases
 Very few patients may have mild redness and photophobia in
the initial few days or few weeks
 If a patient presents with pain and severe redness it is due to
NVG a complication of CRVO-LATE
 Asymptomatic -Routine examination may reveal old CRVO
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VI. Clinical features-signs
The signs of CRVO are mainly
 VA
 RAPD
 Fundus findings
 Degree/severity of the clinical features
depend upon the type of CRVO
 Two types are recognized –ischemic and
non ischemic
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Classification of CRVO
 Ischemic and Non ischemic (20% and 80%)
 Ischemic is also called non-perfused or
hemorrhagic
 Non ischemic is known as perfused
 Some cases are classified in to Indeterminate
group where the definite classification in to
ischemic or non ischemic is not possible
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Why classification is important?
 Prediction of the risk of neovascularization
and risk of NVG
 To give visual prognosis
 Decision as to appropriate follow-up
intervals
 Treatment to initiate in cases of CRVO with
macular edema
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VIb. Clinical exam
 VA -HM to 20/30 depending upon ischemic or non
ischemic
 Extremely important to record the
presenting BCVA
 RAPD+ strongly positive in ischemic cases
 SLE Biomicroscopy- rarely CCC, AC clear or few
cells, iris- look for NVI in undilated eye
 Gonioscopy to rule out NVA
 IOP-usually low in initial phase in non-gl pts,
important to rule out glaucoma in both eyes
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VIb. CRVO-FUNDUS
 Findings vary according to it is ischemic or
nonischemic
 Media-usually clear -rarely there may be -vitr hg in
fresh cases of CRVO
 Disc –may be normal or hyperemic, swollen, covered
and surrounded by hgs and CWS
 Disc cup may or may not be obliterated
 Venous pulsations are absent
 Fundus findings like hgs, CWS are less marked in non
ischemic
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Obliterated cup, borders blurred,
hyperemic, hgs and CWS on the disc &
surrounding areas
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Ischemic CRVO-cup is present
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Retinal findings in CRVO
 Veins-markedly dilated, tortuous and dark colored –
blood flow is slow
 Retinal Hgs most important and obvious sign
 All shapes of hgs seen
 Superficial hgs+++, confluent, some large hgs covering the
underlying retina, dot and blot hgs
 Hgs more in the posterior pole covering macula
 Sometimes hgs break in to subhyaloid space and vitreous
 BLOOD AND THUNDER APPEARANCE OR Tomato
ketchup appearance
 Cotton wool spots are common and are scattered
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Veins-dilated, tortuous, dark, cotton
wool spots
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CONFLUENT HGS
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RETINAL EDEMA
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Ischemic CRVO
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All shapes of hgs seen
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Fundus
 Microaneurysms are not seen in acute stage
Macula
 May appear normal in nonischemic or few hgs
 Hemorrhages+++ in ischemic
 Edema -diffuse or cystoid
 Subretinal fluid may be +
 Visual loss occurs because of macular edema, ischemia
capillary non-perfusion, overlying hemorrhages (either
retinal or vitreal), or a combination of all these
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RE CRVO macular edema with
hgs
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LE macular edema
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Course of CRVO
 Hemorrhages, CWS, venous dilatation and
tortuosity gradually disappear over many
months
 Few flame-shaped hemorrhages and dot
hemorrhages, CWS –may remain for years
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Course of CRVO
 Optico ciliary shunt vessels may develop in
about 50% of patients on the disc surface -3
to 14 months
 These are collateral vessels between the
obstructed disc capillaries and the
unobstructed choroidal or pial capillaries
 Blood flows from high pressure retinal
circulation to low pressure choroidal circulation
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OPTICO CILIARY SHUNT
VESSELS
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Opticociliary shunt vessels
 They are differentiated from NVD by
 ?
 ?
 These retinochoroidal collateral veins, may
protect against anterior segment
neovascularization but may not be associated
with a better visual prognosis
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VI. C CRVO -late changes
 Sheathing of veins around the disc
 The disc - nearly normal/some blurring
of the margins/ sometimes optic
atrophy is present
 Rarely NVD
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Chronic changes-MACULA
 Macular cysts n macular edema
 Macular hole-PTMH or full thickness
 Pigment clumping or stippling or atrophy in macula
 Persistent macular haemorrhage, even years after the
occlusion may +
 Hard exudates with irregular circinate configuration
around the macula and become more prominent months
later
 Occasionally an epiretinal membrane
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MACULAR CHANGES
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VII. Investigations
 Systemic –BP and systemic evaluation
 LAB----CBC, ESR, peripheral smear, BS,
LIPID profile
 OCT
 FFA
 ERG
 Visual field-perimetry
 In most patients who are older with known risk
factors OCT, FFA, BP, CBC, ESR, BS are
enough 14th January 2023
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VII. Investigations
However in younger patients (<50 years) with no
systemic known risk factors more extensive
investigations are needed to assess the possible
etiology
 Rule out Sarcoidosis, Behcet’s disease and other
collagen vascular disorders ( X ray chest, ACE, HLA
typing, systemic work up)
 Plasma Homocystein levels
 Anti phospholipid antibody
 Protein C ,Protein S levels, Factor V Leiden factor
levels
 Rule out hyper viscosity syndromes-leukemias,
macroglobulinemia etc
 Rule out oral contraceptives in females
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FFA in CRVO ischemic
 Dye fills up delayed in venous tree AND capillary
networks
 Blockage of flourescence due to retinal hgs
 Extensive leaking of fluorescein into the retina, -in
macular area
 FAZ may be enlarged
 Capillary non-perfusion in midperiphery- >10DD ---
may be masked by hgs
 Late-phase photographs show patchy extravascular
areas of fluorescence and staining of the retinal veins
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FFA
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FFA late
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FFA in ischemic VS non ischemic
CRVO
 The amount of non-perfusion or ischemia is
determined by inspecting the fluorescein
angiogram-MIDPERIPHERY
 In ischemic cases drop out areas measure=10 DD
or more and in nonischemic they measure<10 DD
However this is questionable
 Also it is difficult to interpret FFA in fresh cases
because of blocking of fl by hgs
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Non ischemic CRVO-FFA
 A prolonged venous transit time
 Mild staining of the walls of veins, and varying
degrees macular leakage may be present
(including cystoid macular edema)
 Capillary nonperfusion is not a prominent
feature
 If present <10DD areas in midperiphery
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Further course
 Some eyes with nonischemic CRVO convert to
ischemic type up to 34%----- half of them within 4
months rest up to 3 years - Arch Ophthalmol 1997
;115:486-91
 ?progression of the vein occlusion or ? progressive
retinal capillary nonperfusion is unknown
 Conversion is higher for older patients
 Macular edema is most important cause of DV in those
who are not converting in to ischemic type
 Pigmentary changes in macula can be late changes
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OCT
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 Extremely useful noninvasive technique to
examine the macula
 Useful in initial assessment and for follow up
during treatment
 May be normal in nonischemic
 Macular edema –spongy, cystoid, SRF
 Late cases may show- atrophy of retina, RPE,
PTMH FTMH or ERM

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Other investigations
 ERG –reduced b wave amplitudes in ischemic
cases
 ERG- B/A RATIO 60% of the normal both
scotopic and photopic
 Perimetry –in ischemic cases contracted
visual fields and central field defects
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VIII. Complications of CRVO
 The most serious complication of central retinal
vein occlusion is ------NVG
 Macular edema is another complication of CRVO
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Risk factors for Ischemic type of
CRVO
The following conditions showed a significant
association with ischemic CRVO:
 Cardiovascular disease
 DM
 ECG abnormalities
 Low albumin-globulin ratio
 High α1-globulin
(Data from The Eye Disease Case-Control Study Group:
Risk factors for central retinal vein occlusion. Arch Ophthalmol 1996)
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OCULAR RISK FACTORS FOR
NVI/NVA
 Poor initial visual acuity (P < .001)
 amount of nonperfusion seen by fluorescein
angiogram (P < .001)
 venous tortuosity (P = .02)
 extensive retinal hemorrhages(P = .07)
 duration less than 1 month (P = .08)
CVOS STUDY -726 EYES Arch Ophthalmol 1997 ;115:486-91
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Neovascularization in CRVO
 Iris (NVI) and angle—NVA
 NVD rare , NVE is extremely uncommon
 NVA Can develop from 2 weeks to years after
CRVO- so follow up every two weeks initially
 Most occur within 3-6 months
 NVI/NVA seen in 35% (61/176) of ischemic
/indeterminate CRVO and 10% (56/538) in non
ischemic CRVO
 Not all cases of NVI/NVA are NVG
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Incidence of NVG
 Incidence varies
 2% in CRVO study and 23% in some other studies
 DO GONIOSCOPY EVERY TWO WEEKS in
ischemic cases
McIntosh et al Ophthalmology 2010;117:1113–1123 systematic review (3271eyes!)
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Ischemic VS Non ischemic CRVO
Factor Ischemic Non ischemic
Age Older age av-68 Younger by 5 yrs av 63
VA Poor initial vision
90% have VA<3/60
Better initial vision >
60% have VA>6/60
RAPD Strong RAPD Absent or mild
Disc Swollen Not swollen or mild
Retinal
Hgs, CWS
++++ ++
Macula Hgs, edema ++ Less marked or
normal
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Ischemic VS Non ischemic CRVO
Factor
Ischemic Non ishemic
Visual field
Reduced VF with central
scotoma
Normal or less reduced
ERG Reduced B Wave Normal or borderline
FFA Drop out areas >10 dd, leakage
in macular areas ,staining of
veins
Less drop out areas <10
dd , less marked leakage
NVI/NVA More common less common
NVG Common-up to 25 % Less common -<10%
Prognosis
for VA
Not good Good
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Which signs and tests best
detect/predict ischemic CRVO?
 RAPD
 ERG
 RAPD+ERG –predicted ischemic in 97% of
cases
 Perimetry –next most reliable
 Visual acuity
 FFA
 Fundus appearance –least reliable
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Few odd facts
 Fellow eye in a patient with CRVO has 5% risk of
developing CRVO in 3 years
 Bilateral simultaneous CRVO is known to occur
mainly in patients with systemic illnesses with
predisposition to CRVO
 CRVO can occur with cilioretinal artery occlusion
or with CRAO
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CRAO with Cilioretinal artery
occlusion
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IX. Treatment of CRVO
 AIMS OF TREATMENT
 Of course treat or optimize the inciting cause like
HT, hyperlipedemia and others
 CAN WE Reverse the obstruction in the CRVO
THAT IS DISLODGE the thrombus?
 Prevent the complications-NVG
 Treat the complications –macular edema and NVG
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A) Reverse or remove the
obstruction
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
Systemic anticoagulation
Anticoagulants can be harmful for CRVO
Ophthalmology 2011 ;118:1603-11
Don’t stop anti coagulants if they are already on them

Local anticoagulation -PPV with R-TPA(recombinant tissue
plasma activator) injection in to vitreous or in to the vein
directly

Hemodilution (heparin, erythrocytopherisis)

Systemic immunosuppression
 PPV with radial optic neurotomy/laminar puncture-by cutting
the lamina cribrosa with a radial cut it is presumed the
pressure reduces there and the vein dilates and thrombus
dislodges

Radial optic neurotomy
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 Though small studies have shown effect, none
of the studies were large and/or randomized
and hence these modalities of treatment are
not followed by all

B) Prevent complications
 The most important complication is NVG
 NVG develops due to hypoxic retina producing
cytokine -VEGF
 So can we do the PRPC to decrease the VEGF
production? And prevent the NVG before it
develops?
 When do we do the PRPC to prevent NVG?
 CVO RCT study showed that to prevent NVG –
apply PRPC-only if any NVA or two clock hours of
NVI develop and not before
Ophthalmology 1995;102(10):1434-44.
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C) Treat Complications
 Macular edema
 NVI/NVA and NVG
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i) Macular edema due to CRVO
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 It is an important cause of reduction in VA in CRVO
and BRVO
Macular edema in ischemic cases is not amenable
to treatment
But there are many options to treat in non-ischemic
cases (we will discuss these)

Treatment of macular edema
 Role of LASER- macular grid
photocoagulation in CVO related macular
edema
 Not effective -----proved by a
randomized study of 155 cases
of CVO
CVO STUDY-- Ophthalmology 1995; 102:1425-33
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Establish collaterals to relieve the
obstruction to treat macular edema
 By laser-
 -Use laser to cause a break in the Bruch’s membrane
 Then by laser make a small hole in the vein near the area of
Bruch’s membrane break
 Anastomoses develop -thus retinal circulation by passes the CRV
 However it is recommended for non ischemic type only
Arch Ophthalmol 1995 ;113:456-62
Ophthalmology 2010 ;117:954-65
Again no large study has been conducted to prove the efficacy of the
methods
Complications are common
Not popular technique
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The present treatment modalities
for macular edema
1. Intravitreal anti VEGF injection
 Avastin (Bevacizumab)
 Ranimizumab(Lucentis)
 Pegaptanib (Macugen) –not used any more
 VEGF trap –Aflibercept(EYLEA)
2. Intravitreal steroid injection
 Triamcinolone
 Dexamethasone depot-Ozurdex implant
 Fluocinolone implant –ILUVIEN implant
3. Surgical- PPV with ILM peeling for resistant
edema
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1) Anti VEGF injections
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Ranibizumab -0.5 mg
Bevacizumab-1.25mg
Aflibercept-2mg

a) Bevacizumab(avastin)
 Monthly injections x6 mo increased VA by 16
letters-3 lines
 Delayed treatment especially in older
individuals yielded poorer results
Epstein et al Ophthalmology 2012
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b) Ranibizumab - CRUISE
TRIAL
 Ranibizumab 0.3 mg and 0.6mg or sham injection were
used in three groups of patients(130 patients in each
group)
 All CRVO were perfused
 Gain of ≥15 letters 47-50% in Ranibizumab group vs
33% in sham group at the end of 12 months
 Mean change in VA was 13-14 letters in Lucentis group
vs 7 letters in sham group
Ophthalmology 2011
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0
5
10
15
20
0 D7 1 2 3 4 5 6 7 8 9 10 11 12
Sham (n=130) Ranibizumab 0.5 mg (n=130) Sham/ranibizumab 0.5 mg (n=110)
43% had BCVA OF ≥ 20/40 in
Ranibizumab groups vs only
30% in sham group
Mean
change
(±SE)
in
BCVA
from
baseline
(ETDRS
letters)
*P<0.0001 versus sham (ANCOVA t-test),
**P<0.001 versus sham/0.5 mg group (post hoc analysis, pair-wise ANOVA)
Randomized patients/LOCF
Sham patients received ranibizumab 0.5 mg PRN treatment from Month 6 to 11;
vertical bars are ±1 SE of the mean PRN-VA≤20/40 OR CFT≥250MU
1. Brown DM et al. Ophthalmology 2010;117:1124–
33
2. Campochiaro et al. Ophthalmology
2011;118:2041-49
14.9*
0.8
Time (month)
Primary endpoint
13.9**
7.3
CRUISE: Ranibizumab treatment led to rapid
and significant VA gain in CRVO patients1,2
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*p<0.0001 versus sham (pairwise ANOVA),
**p<0.001 versus sham/ranibizumab 0.5 mg (post hoc analysis, pairwise ANOVA);
Randomized set, LOCF (last observation carried forward);
Sham patients received ranibizumab 0.5 mg PRN treatment from Month 6 to 11
Vertical bars are ±1 SE of the mean
1. Brown DM et al. Ophthalmology 2010;117:1124–
33
-345.2*
-347.4**
-157.7
-273.7
-400
-350
-300
-250
-200
-150
-100
-50
0
50
0 1 2 3 4 5 6 7 8 9 10 11 12
Mean
change
(±SE)
in
CFT
from
baseline
(µm)
Sham (n=132) Ranibizumab 0.5 mg (n=131) Sham/ranibizumab 0.5 mg (n=115)
Time (month)
CRUISE: rapid, sustained and significant CFT
decrease with ranibizumab
Significant reduction in CFT with ranibizumab monthly versus sham (P<0.0001) at
Month 6, sustained with PRN treatment over 12 months1,2
SUPPL
MAIN
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Ranibizumab (accentrix, lucentis,
ranieyes)
14th January 2023
105
 FDA has approved ranibizumab for treatment
of decreased vision due to macular edema in
cases of nonischemic CRVO after CRUISE
TRIAL

c) VEGF TRAP-AFLIBERCEPT OR
EYLEA
 A new drug that traps VEGF
 VEGF receptor fusion protein –DECOY-that binds
all forms of VEGF-A,VEGF B and placental
growth factor (PlGF), another member of the
VEGF family also believed to have similar
properties to VEGF
 It is supposed to have more affinity-200 times-
for VEGF than the natural receptors of VEGF
14th January 2023
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COPERNICUS RCT: mean change in
BCVA
*p < 0.001 versus sham; ** p < 0.0001 versus sham
Study sponsored by BAYER
Missing data were imputed using the last-observation-carrier-forward
method.
4
0 8 12 16 20 24 28 32 36 40 44 48 52
Time (weeks)
-4.0 All patients
PRN
-6
-4
-2
0
2
4
6
8
10
12
14
16
18
20
Mean
change
in
BCVA
(ETDRS
letters)
+17.3*
+16.2*
+3.8
12.4 letter
differenc
e
IAI 2Q4+PRN Sham+ IAI PRN
100
64 76 88
+13.0**
+1.5
1. Brown DM, et al. Am J Ophthalmol 2013;155:429-37
2. Heier JS, et al.Ophthalmology 2014;121:1414-1420
MAIN
# injections (IAI 2 mg group)
Year 1: 8.7
Year 2: 3.3
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GALILEO: mean change in BCVA
*p < 0.0001 versus sham; ** p < 0.01 versus sham
Study sponsored by BAYER
Missing data were imputed using the last-observation-carrier-forward method.
Sham IAI
0 4 8 12 16 20 24 28 32 36 40 44 48
52
0
2
4
6
8
10
12
14
16
18
20
Mean
change
in
BCVA
(ETDRS
letters)
+3.3
+18.0*
+16.9*
+3.8
76
+13.7**
+6.2
1. Holz FG, et al. Br J Ophthalmol 2013;97:278-84
2. Ogura Y et al. Am J Ophthalmol 2014;158:1032–1038
Time (weeks)
MAIN
# injections (IAI 2 mg group)
Year 1: 8.5
Year 2 (52w  76w): 1.3
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14th January 2023
109
 FDA has approved aflibercept for
treatment of macular edema due
to CRVO nonischemic type

Which anti VEGF is better?
14th January 2023
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 LEAVO study compared ranibizumab, aflibercept and
bevacizumab in the treatment of ME with CRVO
 The mean (SD) gain in BCVA letter score was 12.5
(21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and
9.8 (21.4) for bevacizumab at 100 weeks
 Aflibercept was non inferior to ranibizumab
 Non inferiority of bevacizumab versus ranibizumab was
not conclusive
JAMA Ophthalmol. 2019 Nov; 137(11): 1256–1264.

14th January 2023
111

Can we use anti VEGF for ME in ischemic CRVO?
RAVE: ranibizumab therapy improves vision in patients
with severe CRVO
Brown DM, et al. Retina 2014; 34:1728–1735,
Mean (±SE) change in BCVA from baseline (No. of Letters)
Month 9 Month 12 Month 24 Month 36
+21.1±4.4 +14.1±4.5 +13.4±5.8 +21.4±8.3
n = 16 n = 17 n = 10 n = 9
Monthly Observation Months PRN
0 6 12 18 24 30 36
35
30
25
20
15
10
5
0
Mean
change
in
ETDRS
BCVA
score
(No.
of
letters)
MAIN
14th January 2023
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RAVE STUDY
 However the neovascular complications
developed in nearly 50% but developed
at average of 24 months
 This is later than in the CRVO study in
which majority develop neovascularization
within3 months
 Only 40% ended up with VA<20/400
against 93% in natural history studies
Brown DM, et al. Retina 2014; 34:1728–1735
Hayreh SS et al. Ophthalmology 1983;90:488–506
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115

57 YEARS OLD ONE EYED MALE WITH CRVO IN JUNE
22 VA CF 2 MTRS
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FOUR INJECTIONS LATER VA
6/24
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A meta analysis of treatment for
ischemic CRVOs –conclusions
14th January 2023
118
 No intervention is effective in a population of
exclusively iCRVO cases
 Anti-VEGF treatment, which is highly effective
in CRVO without ischemia, does not prevent
neovascularization in iCRVO
 Existing treatments reduce only the
complications of iCRVO
 They do not improve visual acuity
Bradshaw et al BMC Ophthalmol 2016; 16: 104.

How long to treat ME due to
CRVO
14th January 2023
119
 RETAIN STUDY
 4 years of follow up
 56% of CRVO patients still required anti-VEGF
injections to treat recurrent edema (every
2 months)
 And in those patients the mean number of
injections was 28.4
 Though ME resolved with treatment, macular
damage due to recurrent edema and these
patients had a guarded visual prognosis

Anti VEGF advantages and
disadvantages
Disadvantages
 Effective only in non ischemic
 They need to be given every
month for three months--then
SOS
 First year as many as 6
injections
 Recurrence of edema is
common
 Regular follow ups are
needed
 Systemic side effects are a
concern
 Cost of ranibizumab and
aflibercept are prohibitive
 Endophthalmitis and RD are
rare but do occur
Advantages
 Very effective in improving VA
and decreasing edema
 Reduce chances of NVA and
NVI
 Very easy treatment
 Whether it prevents
conversion to ischemic type is
not known
14th January 2023
120

2. Intravitreal steroids for ME due
to CRVO
14th January 2023
121
 Triamcinolone acetonide
 Dexamethasone depot injection(OZURDEX)
 Fluocinolone depot injection(ILUVEAN)

2 a -Intravitreal TA steroid
injection
 Cheap, lasts for three months
 The SCORE (Standard care vs. COrticosteroid
forREtinal vein occlusion) study showed that
 Intravitreal injection of 1 mg or 4 mg
 Gain of 15 letters or more of vision occurred in 27% in
injection group against 7% only in observation
 It is better to use 1mg dose than 4 mg for its safety
profile
Arch Ophthalmol. 2009 ;127(12):1648
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122

Intravitreal TA injection
 Advantage is cheap and easy treatment
 Disadvantages are side effects
 Effect lasts for three months so repeat injections are
needed less often
 Raised IOP in 35% needing medications
 Some of them need surgery for high IOP
 Cataract is the second common complication-90%
 Endophthalmitis
Are sparingly used now after the availability of anti
VEGF drugs and STEROID depot inj
14th January 2023
123

2 b. Intravitreal steroids –depot
injections
 The intravitreal slow release biodegradable
device with dexamethasone –Ozurdex -0.7mg
 Advantage –effect lasts for 3-6 months
 IOP, cataract concerns remain however but
are less marked than Triamcinolone inj
Ophthalmology. July 2011
14th January 2023
124

GENEVA STUDY MEAN CHANGE
IN BCVA
Haller J, et al, Ophthalmology 2010;117:1134–46
14th January 2023
125

14th January 2023
126
 FDA has approved the use of OZURDEX FOR
ME associated with non ischemic CRVO
 OZURDEX is usually used when anti VEGF
treatment stops producing desired results
 It may be used as first line of treatment in
cases
 Who are reluctant for monthly injections
 Recent cardiac event or stroke

2c. Fluocinolone acetonide
implant(ILUVIEN) study
 A study of 24 eyes one implant at baseline
 At 1, 2, and 3 years after implantation, mean visual acuity
showed gains of 4.5 (P 0.52), 8.2 (P 0.07), and 3.4 (P 0.64)
letters, respectively,
 Mean CFT improved by 247 (44%; P 0.002), 212 (38%; P
0.001), and 250 m (45%; P0.001), respectively
 The advantage is effect of one injection lasts up to 3 years
 During the study period, all phakic eyes ultimately underwent
cataract extraction, and 5 -25% eyes underwent glaucoma
surgery.
Jain et al. Ophthalmology 2012;119:132–137
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127

Anti VEGF versus intravitreal
steroid implant
14th January 2023
128
 Both are effective for macular edema associated
with CRVO
 Steroid implant –effect lasts 3 months so cost
effective and systemic side effects are not known
but IOP and cataract are concerns
 Anti VEGF- no cataract or IOP spikes and very
effective in improvement of VA but more repeated
injections and cost are concerns
 A meta analysis favored anti VEGFs over steroid
implants
Gao et al. BMC Ophthalmology (2019) 19:8

3.Surgical- PPV with ILM peeling
for resistant edema
14th January 2023
129
 Evidence to support is not strong and usually
not recommended

Treatment of complications –NVI,
NVA AND NVG
NVG –
 PRPC
 Antigl med
 Atropine, steroid drops
 ANTI VEGF INJ
 Shunt surgery
 Cyclo-destructive procedures
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THANKS A LOT FOR YOUR
ATTENTION!
14th January 2023
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137

DR WANI'S TALK ON CRVO FOR RESIDENTS KLE 14 JAN 2023.pptx

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