VENO OCCLUSIVE

DISEASE OF RETINA

Anjana Sapkota
1st Year Resident
CONTENTS
• RETINAL VEIN OCCLUSION:
• Introduction
• Epidemiology
• Classification

• CENTRAL RETINAL VEIN BRANCHED RETINAL VEIN

OCCLUSION: OCCLUSION:
• Pathogenesis • Pathogenesis
• Etiology • Etiology
• Management • Management
• History • History
• Clinical examination • Clinical examination
• Investigations • Investigations
• Treatment • Treatment
 INTRODUCTION

• Obstruction of the retinal

venous system, and may involve
the central retinal vein or a
branch retinal vein.

• Second common cause of

blindness after diabetic
retinopathy.
• Cause: obstruction to venous flow due to external compression or disease of the
vein wall.

• Associated risk factors: Multifactorial

• Classification:
• Site of involvement
• Extent of retinal perfusion
EPIDEMIOLOGY

• Globally, an estimated 16.4 million adults are affected by RVO (2.5 million by
CRVO and 13.9 million by BRVO).

• BRVO was more common than CRVO, ranging from 3 to 10 times more prevalent.

• Bilateral RVO is rare, affecting fewer than 10% of individuals with RVO.
• CRVO:
o Prevalence = 0.1% 0.5%
o Nonischemic CRVO more common than Ischemic CRVO
o No racial predilection
o Men > women
o >90% CRVO occurs in > 50 years age

• BRVO:
o Prevalence = 0.5–2.0%
o STBRVO is the most common.

Ophthalmology. 2010 Feb;117(2):3139.e1. doi: 10.1016/j.ophtha.2009.07.017. The prevalence of retinal vein occlusion:
pooled data from population studies from the United States, Europe, Asia, and Australia. Rogers S1, McIntosh RL,
Cheung N, Lim L, Wang JJ, Mitchell P, Kowalski JW, Nguyen H, Wong TY; International Eye Disease Consortium
CLASSIFICATION

• Central retinal vein occlusion (CRVO)

• Nonischemic CRVO
• Ischemic CRVO

• Branch retinal vein occlusion (BRVO)

• Major BRVO
• Macular BRVO

• Hemicentral retinal vein occlusion (HCRVO)

• Nonischemic HCRVO
• Ischemic HCRVO
CRVO: PATHOGENESIS

Compression of vein by sclerotic

central retinal artery behind
lamina cribosa.

Turbulent blood flow

Thrombus formation
 Venous blockage

back pressure on
capillaries

Endothelial junction
dysfunction

leakage of fluid & blood

(edema / hemorrhages)

• Severe nonperfusion
leads to ischemia
CRVO  resistance to venous flow blood stagnation & ischemia stimulates
production of VEGF (vascular endothelial growth factor)

Neovascularization capillary leakage (edema)

Natural history of CRVO

• NONISCHAEMIC CRVO:

• Completely resolution10%

• Macular edema resolve30% in 615 months

• About 50%VA is 6/60 or worse

• 1/3rd progress to ICRVO in 612 months

• Neovessels develop33% in 1215 months

Central Vein Occlusion Study Group. Baseline and early natural history report. Arch Ophthalmol. Aug 1993;111(8):108795
ISCHAEMIC CRVO

• 90% cases VA is 6/60 or worse

• Macular edema resolves73% in 15 months

• Neovascular glaucoma>60% in 12 yrs

• About 10% develop RVO in same or fellow eye in 2 yrs

• Vitreous hemorrhage10 % of CRVO by 9 months

ETIOLOGY

• Alterations in blood flow, hyper viscosity, and vessel wall

abnormalities (Virchow’s triad) enable thrombus formation in central
retinal vein.
EXTERNAL COMPRESSION

Arteriosclerosis of CRA (HTN, DM, Hyperlipidemia)

 Glaucoma (5 times more likely to have CRVO)

 Papilledema

 Thyroid eye disease

 Orbital space occupying lesions

 Cavernous sinus thrombosis

 Closed Head trauma

 Retrobulbar injections
DISEASE OF VESSEL WALL

 Systemic Vasculitis

• TB

• AIDS

• Syphilis

• SLE

 Localized inflammation

• Sarcoidosis

• Serpiginous choroiditis
HEMATOLOGICAL DISEASE (RISK
FACTORS)
• Clotting disorders
– Lupus anticoagulant deficiency
– Anticardiolipin antibodies
• Drugs
– Protein C & Protein S deficiency
– Oral contraceptive
– Antithrombin III deficiency
– Diuretics
– Antiphospholipid antibodies

• Blood dyscrasia
• Nephrotic syndrome
– Lymphoma
– Leukemia
• Paraproteinemia – Polycythemia vera
– Multiple myeloma – Sickle cell disease
– Cryoglobulinemia
MANAGEMENT
HISTORY

• Complains of:
• Painless loss of vision (mild to severe)
• Usually unilateral

• Past & Personal History:

• HTN, DM, smoking
• Hyperlipidemia
• Bleeding or clotting disorders
• Glaucoma
• Oral contraceptive use
• Head trauma / retrobulbar inj
Examination

• Best Corrected Visual Acuity

• Pupillary reactions:
Assess RAPD
• Iris:
Rubeosis iridis
• Gonioscopy:
Rule out neovascularization in Angle
• IOP
Fundus findings

• Retinal hemorrhages in 4 quadrants

• Extensive hemorrhages  blood & thunder

appearance

• Dilated tortuous veins

• Cotton wool spots

• Macular edema
Optic disc
• Disc edema

• Optociliary shunts (collateral channels

between the retinal and ciliary
circulations)/ atrophy. D/D of optociliary
shunts?
• Neovascularization

Vitreous hemorrhage
Non ischemic Vs ischemic CRVO

CHARACTERISTICS NONISCHEMIC ISCHEMIC

Occurrence 2/3rd 1/3rd

Visual acuity >20/100 (>6/36) <20/100 (<6/60)

Afferent pupillary defect Rare Yes

Cotton wool spots Few Multiple
Hemorrhage pattern Scattered Extensive

FFA Good perfusion Nonperfusion >10DD

ERG Normal Reduced b/a wave ratio

Anterior segment Unusual 60%

neovascularization
Risk of neovascularization Low High
VF defect Rare Common

Prognosis 50%6/60 or better 60%Rubeosis & NVG

Fig: Non ischemic CRVO Fig: Ischemic CRVO
Complications

• Macular edema

• Neovascularization (NVI>NVD>NVE)

• Neovascular glaucoma (100 days Glaucoma)

• Vitreous hemorrhage

• Optic atrophy
Differential diagnosis

• Ocular ischemic syndrome

• Diabetic retinopathy

• Papilledema

• Hypertensive retinopathy

• Radiation retinopathy

• Retinopathy due to anemia

Ocular Investigations

1. FLUORESCEIN ANGIOGRAPHY

Useful for detecting…

• Capillary non perfusion

• Neovascularization

• Macular edema

• Differentiate between ICRVO & NICRVO

• >10 DD retinal non perfusion is termed as Ischemic CRVO

• FFA findings

• Delayed arteriovenous transit

• Nonperfusion areas hypofluorescence

• Leakage from NVD, NVE

• Arteriovenous collaterals

• Staining along the retinal veins

• Macular edema: parafoveal and
paramacular capillary leakage ( appears as
hyperfluorescence increases in size and
intensity with time, often in a petalloid type
pattern)

• Limitations
Little information in early
stages (extensive hemorrhages- blocked
fluorescence)
2. OCT
• To assess presence of macular
edema, epiretinal membrane
formation, subretinal fluid
accumulation following CRVO

3. ERG
• Reduced b wave amplitude
• Reduced b:a ratio
• b:a ratio < 1 suggests an
Ischemic CRVO
Medical Investigations

• ALL PATIENTS • Plasma protein

• CBC & ESR • Electrophoresis
• Renal function tests • Thyroid function
• Random blood glucose • ECG
• Lipid profile
• ACCORDING TO CLINICAL INDICATION
• Thrombophilia screen

• Anticardiolipin antibody

• CRP

• Serum ACE

• Autoantibodies

• CXR

• Fasting homocystine levels

 Treatment

• Different approaches:
1. Observation

2. Laser Photocoagulation

3. Intravitreal Steroids

4.Intravitreal Anti VEGF

5. Surgery
CVO study

Purpose:
1. Prophylactic panretinal photocoagulation (PRP) in ischemic central vein
occlusion (CVO) prevents development of iris neovascularization or any angle
neovascularization.

2. To assess whether grid pattern photocoagulation therapy will reduce loss of

central visual acuity due to macular edema secondary to CVO.
Groups

A. Eyes with extensive retinal ischemia(at least 10 disc areas of non perfusion)
were randomly assigned to receive panretinal photocoagulation Vs no
treatment unless iris neovascularization developed.

B. Eyes with visual loss ascribable to macular edema were randomly assigned to
receive grid pattern photocoagulation Vs no treatment.
Results

1) Prophylactic PRP did not prevent the development of NVI in eyes

with >10 disc areas of retinal capillary nonperfusion confirmed by
FFA.

2) Macular grid photocoagulation was effective in reducing

angiographic evidence of macular edema but did not improve visual
acuity in eyes with reduced vision due to macular edema from CVO.

The Central Vein Occlusion Study Group A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion:
The Central Retinal Vein Occlusion Study Group N Report. Ophthalmology 1995;102: 143444.
Score CRVO

• Standard care vs. Corticosteroids for Retinal vein occlusion study

• Standard care: observation

• Duration of study: November 2004 and February 2008

• Funded by national eye institute in May 2003

• Multicenter RCT

• 271 participants

The SCORE study research group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to
treat vision loss associated with macular edema secondary to central retinal vein occlusion. The Standard Care vs Corticosteroid for Retinal
Vein Occlusion (SCORE) Study Report 5. Arch. Ophthalmol. 127
Rationale for use of steroid

• Reduce edema resulting from breaks in the blood retina barrier by reducing both
intraocular inflammation and capillary permeability.

• Increase expression of tight junction proteins.

• Decreases the induction of VEGF.

• Purpose: To compare visual acuity outcome in participants with vision loss
associated with macular edema secondary to CRVO.

• Groups:
I. Intravitreal injections of triamcinolone 1mg Vs standard care
II. Intravitreal injections of triamcinolone 4mg Vs standard care
III. Intravitreal injections of triamcinolone 1mg Vs 4mg

Follow up visits and retreatment as often as every 4 months.

 Conclusion:

1. Both triamcinolone groups were superior to the observation group with

respect to visual acuity at the primary outcome visit (12months)

2. On OCT, all 3 groups had a reduction on retinal thickness from baseline to 24

months. The 1 mg dose has a safety profile superior to that of 4 mg dose.

3. The 1 mg dose has a safety profile superior to that of 4 mg dose.

Complication

• Intravitreal steroid related adverse events:

1. cataract
2. increased intraocular pressure

• Injection related adverse events:

1. noninfectious and infectious endophthalmitis
2. retinal detachment
3. vitreous hemorrhage
4. lens injury
CRUISE (Ranibizumab for the Treatment
of Macular Edema after CRVO Study.
• Purpose: To study the Efficacy and Safety of Ranibizumab Injection in Patients
With Macular Edema Secondary to Central Retinal Vein Occlusion

• Duration of study: Between July 2007 and December 2008,

• Groups: 392 patients diagnosed with CRVO were randomized

• Group 1: monthly intraocular injections of 0.3 mg ranibizumab,
• Group 2: monthly intraocular injections of 0.5 mg ranibizumab ,
• Group 3: sham injections,

Done for 6 months, with a further 6 months followup.

Campochiaro PA, Hafiz G, Shah SM et al Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical
stimulator. Mol. Ther. 16
• Results:

• At month 6, patients in the 0.3 and 0.5mg ranibizumab treatment

groups had gained a mean of 12.7 and 14.9 letters, respectively,
compared with 0.8 letters in the sham group.
• The improvement in BCVA letter score after injection of ranibizumab was
rapid (7 days after the first injection, patients gained an average of 9 letters).

46.2 and 47.7% of patients in the 0.3 and 0.5mg ranibizumab groups,
respectively, had gained ≥15 letters from baseline BCVA, compared with 16.9%
of patients in the sham group.
• Rapid reduction in central foveal thickness after treatment with ranibizumab:
at day 7, the mean reduction from baseline Central Retinal Thickness was
>250 μm in both ranibizumab groups, compared with no reduction in the
sham group.

• No events of endophthalmitis, retinal tear or retinal detachment during the

6month treatment period.
SURGICAL TREATMENT

• Surgical decompression of CRVO (radial optic neurotomy)

• Involves sectioning the posterior scleral ring, and retinal vein cannulation
with an infusion of tissue plasminogen activator (tPA) .
Treatment Guidelines for Patients Who
Have Central Retinal Vein Obstruction

• Panretinal photocoagulation if intraocular neovascularization present

• Lower intraocular pressure if elevated
• Treat underlying medical conditions
• Macular edema generally does not respond to grid laser .
MANAGEMENT OF COMPLICATIONS:
NEOVASCULAR GLAUCOMA
1. Medical treatment:
• IOP lowering agents : to reduce IOP and ocular pain.
• Topical corticosteroids to reduce any inflammatory component that may be
present.

2. Panretinal photocoagulation:
• To reduce posterior segment ischemia and recover the homeostatic balance
between proangiogenic factors and antiangiogenic factor.
3. Surgery:
• Transcleral cyclophotocoagulation with and without the use anti VEGF has
been shown to be effective in lowering IOP and relieving pain in advanced
cases of NVG.
Vitreous Hemorrhage

• 1. Pars plana vitrectomy

Followup

• PRESENTING VISUAL ACUITY OF 20/40 (6/12) OR BETTER

Examinations every 1–2 months for 6 months after diagnosis
Annual examinations as the patient's condition stabilizes

• PRESENTING VISUAL ACUITY BETWEEN 20/50 (6/15) AND 20/200 (6/60)

Examinations monthly to bimonthly (at the physician's discretion, based on which end
of the spectrum the visual acuity lies) for the first 6 months after diagnosis
Examinations every 6 months to yearly afterward
• PRESENTING VISUAL ACUITY OF 20/200 (6/60)
Examinations every month for the initial 6 months

Then every 2 months until 8 months after presentation

Then every 4 months until 2 years after presentation

HEMICENTRAL RETINAL VEIN
OBSTRUCTION
• In about 20% of eyes, the central retinal
vein enters the optic nerve as two
separate branches, the superior and
inferior, prior to merging as a single
trunk posterior to the lamina cribrosa.

• Obstruction of one of the dual trunks

within the substance of the optic nerve
results in a hemicentral retinal vein
obstruction.
• Visual prognosis - better than in
CRVO.
• Macular edema- common
• Prognosis appears to correlate
with the extent of retinal perfusion
BRVO

• Venous occlusion at any branch of the central retinal vein

• Classified as major or macular
• Major BRVO - occlusion of a retinal vein that drains one of the
quadrants
• Macular BRVO - Occlusion of a venule within the macula
INCIDENCE

• Superotemporal quadrant (most common)- 58.166%

• Inferotemporal quadrant (29%)
• Nasal quadrants (12.9%)
CLASSIFICATION

• Perfused (Nonischemic)

• Nonperfused (Ischemic)
Defined as > 5 disc diameters of nonperfusion on fluorescein
angiography (FA)
PATHOGENESIS

• MULTIFACTORIAL

• THREE MECHANISMS MAY BE

INVOLVED

• Common adventitial sheath of

retinal artery and vein provides DEGENERATIVE
ABNORMAL
COMPRESSION OF
settings for occlusion. CHANGES
VEIN AT OF
HEMATOLOGICAL
ARTERIOVENOUS
VESSEL WALL
(A/V)FACTORS
CROSSING
MANAGEMENT

History
 Asymptomatic

 Sudden painless vision loss

 Visual field defect

 Usually unilateral
Cause of visual decline in BRVO

Macular edema

Macular ischemia

Hemorrhage over the fovea

Vitreous hemorrhage from

neovascularizations of the retina or
the optic disc

Epiretinal membrane/vitreomacular
traction

Retinal Detachment: Most commonly

Fig: localized retinal detachment
tractional with retinal tear in a case of Old
BRVO
EXAMINATION/SIGNS

Visual acuity :
Range from 20/20 (6/6) to counting fingers

Anterior Segment:
Usually normal unless neovascularization develops
 FUNDUS FINDINGS

 Retinal hemorrhages confined to the distribution

of a retinal vein (characteristic)

 Flame shaped hemorrhages predominate.

• Dilated and tortuous vein
• Closer the occlusion to the optic nerve, the
more extensive the retinal damage and visual
impact

 Mild obstructions small amount of hemorrhage.

 Complete obstructions result in

Extensive intraretinal hemorrhages
Cotton wool spot formation
 If macula involved Macular edema or
hemorrhage decreased visual acuity.

If the macula spared a branch retinal vein

obstruction may be asymptomatic, found only on
routine fundoscopy.

Old BRVO –
• Segmental microvascular abnormalities,
intraretinal collateral vessels draining across
the median raphe.
• In nonperfused cases, sclerosis and
sheathing of the retinal veins and arteries in
the distribution of the occlusion may be
observed Fig: Old Superotemporal BRVO
 Ocular Investigation

 Fluorescein angiography
–Delayed venous filling in the affected
vessel.

– Staining & leakage of dye from vessel

– Macular edema

– Capillarynonperfusion…
hypofluorescence

– Collaterals & new vessels can be

differentiated
 Optical coherence tomography (OCT )
– Measure retinal thickness quantitatively
– Useful in the follow up of patients with macular edema secondary to BRVO
Differential Diagnosis

 Hypertensive retinopathy

 Diabetic retinopathy

 Ocular ischemic syndrome

 Juxtafoveal retinal telangiectasia

 Radiation retinopathy
TREATMENT
BVOS Group – 1984 and 1986

Goal:
• To assess if photocoagulation can:

(1) Prevent neovascularization,

(2) Prevent vitreous hemorrhage, and

(3) Improve vision in eyes with macular edema with ≤ 20/40 from BRVO.

• Total patients: 319+ 82+139

• Duration: mean of 3.1 years

1. Eyes with ≥ 5 disc diameters of nonperfusion without NV treated with
either scatter laser or no laser.

2. Eyes with NV treated with either scatter laser or no laser.

3. Eyes with BRVO and macular edema and visual acuity of ≤ 20/40 (6/12)
randomized to grid laser or no laser.
• Results
• 319 eyes recruited. 12% in treated eyes developed NV and 22% in non treated eyes developed NV.
However, no change in visual acuity from baseline.

• 82 eyes recruited. 29% of treated eyes developed VH and 61% of non treated eyes developed VH.
12% of eyes that developed VH had vision loss.

• 139 eyes recruited. 65% of treated eyes gained two or more lines from baseline, compared with
17% of non treated eyes. Overall, treated eyes gained 1.33 lines compared to non treated eyes
gained 0.23 lines of vision.

• Conclusion
• Eyes randomized to grid laser had visual acuity gain.

 Anonymous. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A
randomized clinical trial. Branch Vein Occlusion Study Group. Arch Ophthalmol 1986; 104(1): 3441. PMID: 2417579
SCOREBRVO – 2009

• Total patients: 411 patient with macular edema due to BRVO.

• Duration: 12 months.

• Objective: Compare efficacy and safety of 1mg and 4mg doses of preservative
free intravitreal triamcinolone with standard care (grid laser).

• Randomized to 1mg, or 4mg preservative free intravitreal triamcinolone or

macular grid laser.
Results:

• All three groups had equivalent percentage of patients with gain of ≥ 15 letters
from baseline at 12 months.

• The rate of elevated intraocular pressure and cataracts were similar between the
grid laser and 1mg groups; however, both adverse effects were significantly
higher in the 4mg group.
• Summary:
• There was no difference identified in visual acuity at 12 months for the standard
care group compared with the triamcinolone groups; however, rates of adverse
events (particularly elevated intraocular pressure and cataract) were highest in
the 4mg group.

• Scott IU, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss
associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion
(SCORE) study report 6. Arch Ophthalmol 2009; 127(9): 111528.
BRAVO – 2011

BRAVO (The Ranibizumab for the Treatment of Macular Edema following Branch
Retinal Vein Occlusion: Evaluation of Efficacy and Safety).

Total patients recruited: 397 with BRVO and macular edema

Duration: 12 months

Randomized to Ranibizumab 0.3mg, Ranibizumab 0.5mg, and sham/Ranibizumab

0.5mg (with Ranibizumab administered during observation period based on
specific criteria). 
Results:
• At 6 months, the mean letter gain was 16.6 and 18.3 in the 0.3mg and 0.5mg ranibizumab
groups and 7.3 in the sham group.

• 54.5% of sham group received rescue laser compared with 18.7% and 19.8% in the 0.3mg
and 0.5mg ranibizumab groups.

• At 12 months, the mean letter gain was 16.4 and 18.3 in the 0.3mg and 0.5mg groups, and
12.1 in the sham/0.5mg group.
Summary:
• Ranibizumab had better vision improvement than grid laser at 6 months.

• As needed ranibizumab is able to maintain the benefits achieved after monthly

scheduled injections of ranibizumab with macular edema from BRVO.

• Campochiaro PA, et al. Ranibizumab for macular edema following branch retinal vein occlusion: sixmonth primary end point
results of a phase III study. Ophthalmology 2010;117:110212. PMID: 20398941
SURGICAL TREATMENT

• Sheathotomy:

There is no overall improvement in BCVA; however, there was improvement in vascular

perfusion.

• Vitrectomy:
In those cases where neovascular complications such as non clearing vitreous
hemorrhage, pars plana vitrectomy may be considered
Treatment Guidelines for BRVO and
Macular Edema
• FOR MACULAR EDEMA, VISUAL ACUITY OF 20/40 (6/12) OR WORSE
Wait for clearance of retinal hemorrhage to allow adequate fluorescein angiography

Determine if decreased visual acuity is caused by macular edema (versus macular non
perfusion)

If macular edema explains visual loss, and no spontaneous improvement has occurred by 3
months, grid macular photocoagulation is recommended

If capillary non perfusion explains decreased visual acuity, laser treatment is not advised.
Treatment Guidelines for BRVO and
Neovascularization
Good quality fluorescein angiography is obtained after retinal hemorrhages have cleared
sufficiently.

If more than five disc diameters of nonperfusion are present, the patient should be
followed at 4month intervals to seek the development of neovascularization.

If neovascularization develops, panretinal photocoagulation to the involved retinal sector

should be applied using argon laser to achieve “medium” white burns, 200–500?mm in
diameter—one burn width apart to cover the entire involved segment.
COURSE AND PROGNOSIS

Without treatment:
• 1/3rd patients: visual acuity better than 20/40 (6/12).
• 2/3rd patients: decreased visual acuity secondary to macular edema, macular
ischemia, macular hemorrhage, or vitreous hemorrhage.

 Laser treatment for macular edema:

• Significantly enhances the chance that the patient's baseline visual acuity will
improve by two lines (65% versus 37%).
 Patients should be followed up every 3–4 months.

 Approximately 20% of patients with branch retinal vein occlusion will develop
neovascularization.

• Of these patients, about 60% will have episodic vitreous hemorrhages.

• Fortunately, laser treatment (sector PRP) can reduce this by one half to 30%.
REFERENCES
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