Understanding

Retinal Vein
Occlusion (RVO)

What is the retina?1

Light-sensitive tissue lining the inner surface of the eye

Converts visual images into electric signals and sends them via
the optic nerve to the brain

What are retinal veins?2

Small blood vessels that carry blood away from the retina towards
the heart

The central retinal vein runs through the optic nerve. Smaller retinal
veins running along the inner retina drain blood into the central
retinal vein

Branch
retinal vein

Retina
Iris

Macula

Lens

Pupil
Cornea

Central
retinal vein

Optic
nerve

What is retinal vein occlusion (RVO)?2,3

RVO is a blockage of a vein or veins that carry blood away from

the retina, preventing adequate blood flow in the affected area

The walls of the vein may leak blood and excess fluid into the

retina, causing swelling of the macula, which is a part of the retina

in the back of the eye that provides sharp, detailed central vision

It typically occurs in middle-aged and elderly patients over 50

years old with equal sex distribution4

How does RVO affect your vision?5,6

Swelling of the macula (macular edema) is the most common

cause of reduced vision in patients with RVO

Other causes of reduced vision include retinal haemorrhages

(blood clots) and macular ischaemia (reduced blood flow)

Vision may become blurred and distorted

Few people will get RVO in both eyes
Blurred
vision

Distorted
vision

What are the consequences of RVO?3,7

RVO may lead to new, abnormal blood vessels growing in the

front part of the eye, causing neovascular glaucoma (increased

pressure in the eyeball)
This may lead to partial or complete loss of vision in the
affected eye

RVO is the second most common cause of blindness due to retinal

vascular diseases

What are the different types of RVO?2,6

RVO is classified according to where the obstruction is located. There
are two main forms of RVO, namely:
CRVO

1. Central RVO (CRVO)

Haemorrhages
in retina

A type of RVO in which the

Site of vein
obstruction

blockage occurs in the main

retinal vein at the back of the eye

2. Branch RVO (BRVO)

A type of RVO in which the vein

blockage occurs in the small
retinal veins in the inner portion
of the eye

More common than CRVO

BRVO

Haemorrhages
in retina
Obstructed vein
Normal vein

What are the risk factors for developing

RVO? 4,6,7
RVO tends to occur more frequently in those over 50 years of age.
Other risk factors include:

High blood pressure

Diabetes mellitus
High cholesterol levels
Hardening of the arteries (atherosclerosis)
Glaucoma
Smoking
Obesity
3

How is RVO detected? 2,3,6

Detecting or making the diagnosis of RVO requires a careful and
comprehensive eye examination, which includes:

Visual acuity test

This test measures how well you see at various distances

Tonometry

An instrument is used to measure the fluid pressure inside

your eye

Dilated fundus exam

Drops are placed in the eyes to dilate the pupils

Using a special magnifying lens, your eye-care professional

examines your retina and optic nerve for signs of nerve damage
and other eye problems

Optical coherence tomography (OCT) 9

This technique uses long wavelength light to measure retinal

thickness
OCT produces high-resolution cross-sectional images of the retina
Used to detect and measure fluid build-up and monitor the
disease

Fluorescein angiography

A special dye is injected into your arm and pictures are taken as

the dye passes through the blood vessels in the retina

This test allows your eye-care professional to identify any leaking
blood vessels and recommend appropriate treatment.
Your eye-care professional may also perform visual field tests that
check your side vision and tests, using an opthalmoscope, to evaluate
the severity of the blockage.

What is the treatment for RVO? 7,10

Even though people with RVO may regain vision without treatment, vision
rarely returns to normal. Studies have shown that RVO treatment resulted
in significant vision gains compared with no treatment.11
Treatment options for RVO (if macular edema is present) include:

Focal laser treatment

A high-precision laser is used to make tiny burns at areas of retinal

leakage around the macula

These burns slow leakage and reduce the amount of fluid in the retina
This procedure also stabilizes vision and reduces the risk of vision loss
Intravitreal injection therapy

Direct injection of a drug into the eyes

Inhibits leakage and abnormal blood vessel growth to prevent vision loss
An intravitreal steroid implant is also indicated for treatment of
macular edema following BRVO or CRVO3

How does intravitreal injection

therapy work? 6,12
Mechanism

Procedure

A drug blocks the action of a

Sterilization and anaesthesia

growth factor called vascular

endothelial growth factor
(VEGF) that stimulates the
growth of abnormal blood
vessels, thereby inhibiting
their growth

of the eyes

Direct injection of an anti-

VEGF drug into the vitreous

fluid

Injection is repeated monthly

until vision becomes stable

What is Lucentis (Ranibizumab)?6

Lucentis belongs to a group of anti-VEGF treatments

It prevents VEGF-A, a substance that can affect vision, from

causing further damage to the eye and can even repair some of
the damage that has occurred
Lucentis is approved by the United States Food and Drug
Administration and the European Commission to treat vision loss
due to macular edema following RVO13,14

Efficacy of Lucentis11

The efficacy and safety of Lucentis

in treating macular edema

following RVO was studied extensively in two clinical trials
Branch Retinal Vein Occlusion: Evaluation and of Efficacy and
Safety (BRAVO) and Central Retinal Vein Occlusion Study:
Evaluation of Efficacy and Safety (CRUISE)
The HORIZON trial went on to provide longer-term data upon
completion of the BRAVO and CRUISE trials
Mean change from baseline
(Letters)

Improvements in visual acuity

Treatment with monthly Lucentis

25

BRAVO

HORIZON

(n=397)

(n=304)

resulted in improvements in
15
visual acuity (VA) in BRVO and CRVO,
which was maintained for as
10
long as 12 months

20

Mean change
in VA

+19.2
+16.8
+13.2

Mean change
in VA

+17.5

104
103
97

73

aseline
M12

Mean change from initial

baseline (m)

Mean change from baseline

(Letters)

104
103
96

in VA

150

Mean change

in VA
-360.7Mean change
104
+19.2
in VA
+16.8
-307.4 200
103
-330.6
+13.2
-298.5 250
96
0
-291.4
Baseline
-300
-304.2

Mean change
in VA

104n
103
9772

65
M12
63

+17.5
+14.9
+15.6

in VA

-307.4

-330.6
73 -298.5
66
-291.4
66
-304.2

6
9
Month

12

103
72
96 0
65
63
5

Mean change
in VA

+16.2
+14.9
+9.4

98
106
96

-291.4
-304.2

65
+12.0
63

Mean change
in VA

+8.2
+7.6

51
70
60

Baseline
M12
3
6
9
12
Month
350

*At 6 months, all patients were evaluated and were eligible to receive Lucentis 0.5 mg if the study eye had a best corrected VA of 20/40 or worse.BRAVO,
400 Evaluation of Efficacy and Safety; CRUISE, Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety; VA,
Branch
Occlusion:
25 Retinal Vein
HORIZON
CRUISE
visual acuity.
450
(n=392)
(n=304)

hange from baseline

(Letters)

Mean change from baseline

(Letters)

+14.9
66
11,15,16
Ranibizumab
0.5
Figure 1. Lucentis resulted in improvements in VA from baseline over
12 months
+15.6 mg
66
0
Ranibizumab 0.5
mg
Ranibizumab
0.3/0.5
mg
Baseline
M12
3
6
9
12
Ranibizumab 0.5 mg
Ranibizumab 0.3/0.5 mg
Sham/0.5Month
mg*
Ranibizumab 0.3/0.5 mg
Sham/0.5 mg
25
25
BRAVO
HORIZON
HORIZON
CRUISE
Sham/0.5 mg
(n=397)50
(n=304)
(n=392)
(n=304)
20
BRAVO
HORIZON
20
0
(n=397)
(n=304)
15
BRAVO
HORIZON
15
50
Mean change
Mean change
(n=397)
(n=304)
n
n10
HORIZON
in VA
in VA
100
10
Mean change 104 n
Mean change
(n=304)
-330.6
72
-360.7
n

20
15

10
5

6
Month

Baseline
M12
3
9
12

100

Mean change

6
Month
CRUISE
Mean change

M12
12

6
Month

HORIZON

12

Reductions in central foveal thickness

The fovea is a small indentation near the centre of the macula that
is packed with light-sensing cells17

When macular edema is present, the thickness of the fovea

may exceed the surrounding retina, causing the indentation to

disappear

Treatment with monthly Lucentis

resulted in significant reductions

in central foveal thickness (CFT) over 12 months

Ranibizumab 0.5 mg

11,15,16
Figure 2. Lucentis resulted in reductions in CFT from baseline
over
12 months
Ranibizumab
0.3/0.5
Ranibizumab
0.5mg
mg

Mean change from initial

baseline (m)
Mean change from initial
baseline (m)

Ranibizumab 0.5 mg
Ranibizumab 0.5 mg
Ranibizumab 0.3/0.5 mg
Ranibizumab 0.3/0.5 mg
Sham/0.5 mg
50
BRAVO
Sham/0.5 mg
0 50
(n=397)
BRAVO
50

Mean change
(n=397)
n
HORIZON
in VA
Mean change
(n=304)
-360.7
104

0
BRAVO
100 50
(n=397)
HORIZON
150
Mean change100n
(n=304)

in
VA
200
150
-360.7Mean change
104
250 200
in VA

-307.4
103
-300 -330.6
-298.5
25096
-291.4
350 -304.2
-300

104
103
96

400 350
450 400

72
65
63

Baseline
450

6 100
Month 0

Mean change from initial

baseline (m)
Mean change from initial
baseline (m)

aseline
M12

in VA

200
Mean
change
-484.6
98
300
in VA
-459.5
106
-412.2
300
400
-481.4
97
-370.9
400
500 -418.7

-307.4
-330.6
-298.5
-291.4
-304.2

Baseline
M12
3
6
9
9
12 CRUISEMonth
(n=392)
CRUISE
100
(n=392)
Mean change
HORIZON
n
0
in VA
(n=304)
Mean change
98
-484.6

CRUISE
100
(n=392)
HORIZON
100
(n=304)
Mean200
change
n
98
106
97

in VA
-307.4 Mean
103
change
-360.7
-298.5
96
in VA

51
69
57

104 n
103
72
96
65
63

M12
12

HORIZON
(n=304)
HORIZON

Mean change
(n=304)
in VA

6
9
3 Month 6
Month
HORIZON
(n=304)
HORIZON

(n=304)
Mean change
in VA

-459.5 in VA 106
Mean
change 98 n
-484.6
97
-481.4
in VA
-459.5
106
-412.2
51
-481.4
97
-370.9
69
-418.7
57

600 500

Baseline
600

Mean change
-330.6
72
-291.4 in VA 65
-330.6
-304.2
63
-291.4
-304.2

M12

Sham/0.5
mg
Ranibizumab
0.3/0.5 mg
Sham/0.5 mg*

72
65
63

12

12

Mean change
51
-412.2
-370.9 in VA 69
-412.2
-418.7
57
-370.9
-418.7

51
69
57

M12
3
6
9
12
Baseline
M12
3 Month 6
9
12
*At 6 months, all patients were evaluated and were eligible to receive Lucentis 0.5 mg if the study eye had a mean
CFT of >250 m.
Month
M12
3
6
9
12
BRAVO, Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety; CFT, central foveal thickness; CRUISE, Central Retinal Vein Occlusion
Month
3 Evaluation
6 of Efficacy 9and Safety. 12
Study:
Month

aseline
M12

Safety of Lucentis 15,16

The safety profile of Lucentis in macular edema following RVO has
been well documented. In the BRAVO and CRUISE studies, the most
common side effects to the eye were:

Increased redness in the whites of the eye

Eye pain
Small specks in field of vision
Foreign body sensation in the eye
Serious side effects related to the injection procedure were rare with
Lucentis, which included:

Serious eye infection

Detached retina
Cataracts
The most common non-eye related side effects were:

Nose and throat infections

Headache
Influenza
Sinusitis
Uncommonly, some patients
on Lucentis have had
strokes or heart attacks.
Please consult your eye-care
professional or doctor for
further detailed advice.
*Please refer to the product information for
additional details on drug safety

How can RVO be prevented? 6,7

RVO is a sign of general vascular disease. The same measures that
are used to prevent these vascular diseases (such as coronary artery
disease) may also play a role in decreasing the risk of RVO.

Consume a low-fat diet

Dietary fat and cholesterol can harden into plaques that may

obstruct blood flow and increase the risk of RVO. A low-fat diet
may help maintain your vision

Exercise regularly

Regular physical activity can help lower the risk of cardiovascular

disease and RVO, as well as help you maintain an ideal weight

Quit smoking

Quit smoking to reduce your risk of developing RVO

Have your eyes checked regularly

Some people with RVO may not notice any symptoms

It is therefore important to have your eyes checked regularly as
some RVO cases are only detected through routine eye exam

Manage your other diseases

Follow your doctors instructions for controlling other conditions

that you may have (eg, high blood pressure, high cholesterol levels)
to reduce the risk of RVO

Aspirin or other blood thinners may help prevent blockages in the

other eye

LUCENTIS
Note: Before prescribing, consult full prescribing information.
Presentation: Ranibizumab. Each vial contains 2.3 mg of ranibizumab in 0.23 mL solution.
Indications: Treatment of neovascular (wet) age-related macular degeneration (AMD). Treatment of visual impairment due to
diabetic macular edema (DME). Treatment of visual impairment due to macular edema secondary to retinal vein occlusion (branch
RVO or central RVO).
Dosage: The recommended dose is 0.5 mg (0.05 mL) given as a single intravitreal injection. Treatment is given monthly and
continued until maximum visual acuity is achieved, confirmed by stable visual acuity for three consecutive monthly assessments
performed while on Lucentis treatment. Patients should be monitored monthly for visual acuity. Treatment is resumed with monthly
injections when monitoring indicates a loss of visual acuity due to wet AMD, DME or macular edema secondary to RVO and continued
until stable visual acuity is reached again for three consecutive monthly assessments. The interval between two doses should not be
shorter than 1 month. Lucentis and laser photocoagulation in DME or in branch RVO: Lucentis has been used concomitantly with
laser photocoagulation in clinical studies. When given on the same day, Lucentis should be administered at least 30 minutes after laser
photocoagulation. Lucentis can be administered in patients who have received previous laser photocoagulation. Lucentis must be
administered by a qualified ophthalmologist using aseptic techniques. Broad-spectrum topical microbicide and anaesthetic should be
administered prior to the injection. The patient should be instructed to self-administer antimicrobial drops four times daily for 3 days
before and after each injection. Not recommended in children and adolescents.
Contraindications: Hypersensitivity to ranibizumab or to any of the excipients, patients with active or suspected ocular or periocular
infections, patients with active intraocular inflammation.
Precautions/Warnings: Intravitreous injections have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Therefore proper aseptic injection techniques must be
used. Patients should be monitored during the week following the injection to permit early treatment if an infection occurs. Transient
increases in intraocular pressure (IOP) have been seen within 60 minutes of injection of Lucentis. Sustained IOP increases have also
been reported. Intraocular pressure and the perfusion of the optic nerve head must be monitored and managed appropriately. There
is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. A numerically higher stroke rate was
observed in patients treated with ranibizumab 0.5 mg compared to ranibizumab 0.3 mg or control, however, the differences were not
statistically significant. Patients with known risk factors for stroke, including history of prior stroke or transient ischemic attack should
be carefully evaluated by their physicians as to whether Lucentis treatment is appropriate and the benefit outweighs the potential risk.
As with all therapeutic proteins, there is a potential for immunogenicity with Lucentis. Lucentis has not been studied in patients with
active systemic infections or in patients with concurrent eye conditions such as retinal detachment or macular hole. There is limited
experience with treatment of patients with prior episodes of RVO and of patients with ischemic branch RVO (BRVO) and central RVO
(CRVO). In patients with RVO presenting with clinical signs of irreversible ischemic visual function loss, treatment is not recommended.
Should not be used during pregnancy unless the expected benefit outweighs the potential risk to the fetus. For women who wish to
become pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving a child; use of effective contraception recommended for women of child-bearing potential; breast-feeding
not recommended. Following treatment patients may develop transient visual disturbances that may interfere with their ability to drive
or use machines. Patients should not drive or use machines as long as these symptoms persist.
Interactions: No formal interaction studies have been performed.
Adverse reactions: Very common adverse reactions are: intraocular inflammation, vitritis, vitreous detachment, retinal hemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival hemorrhage, eye irritation, foreign body sensation in eyes, lacrimation increased, blepharitis, dry eye, ocular hyperemia, eye pruritus, intraocular pressure increased, nasopharyngitis, headache,
arthralgia. Common adverse reactions are: retinal degeneration, retinal disorder, retinal detachment, retinal tear, detachment of
the retinal pigment epithelium, retinal pigment epithelium tear, visual acuity reduced, vitreous hemorrhage, vitreous disorder, uveitis,
iritis, iridocyclitis, cataract, cataract subcapsular, posterior capsule opacification, punctuate keratitis, corneal abrasion, anterior chamber flare, vision blurred, injection site hemorrhage, eye hemorrhage, conjunctivitis, conjunctivitis allergic, eye discharge, photopsia,
photophobia, ocular discomfort, eyelid edema, eyelid pain, conjunctival hyperemia, stroke, influenza, urinary tract infection*, anemia,
anxiety, cough, nausea, allergic reactions (rash, pruritus, urticaria, erythema). Uncommon adverse reactions are: blindness,
endophthalmitis, hypopyon, hyphema, keratopathy, iris adhesions, corneal deposits, corneal edema, corneal striae, injection site pain,
injection site irritation, abnormal sensation in eye, eyelid irritation. Serious adverse events related to intravitreal injections included
endophthalmitis, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract.
* observed only in the DME population
Packs and prices: Country specific.
Legal classification: Country specific.
References: IPL Jun 2011 + EMA Jan 2012

10

References:
1. MedlinePlus. Retina. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/002291.
htm. Accessed 9 January 2013.
2. PubMed Health. Retinal vein occlusion. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004583/. Accessed 9 January 2013.
3. Fonrose M, et al. Retinal Vein Occlusion. Available at: http://emedicine.medscape.com/article/798583. Accessed 9 January 2013.
4. The Royal College of Ophthalmologists. Interim Guidelines for Management of Retinal Vein
Occlusion 2010.
5. National Eye Institute, National Institutes of Health. SCORE Study Results.
Available at: http://www.nei.nih.gov/score/score_background.asp. Accessed 21
January 2013.
6. Lucentis for Retinal Vein Occlusion website. Available at: http://www.lucentis.com/lucentis/
rvo/about_rvo.html. Accessed 15 January 2013.
7. MedlinePlus. Retinal vein occlusion. Available at: http://www.nlm.nih.gov/medlineplus/ency/
article/007330.htm. Accessed 21 January 2013.
8. Rogers S, McIntosh R, Cheung N, et al. The prevalence of retinal vein occlusion: Pooled
data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology 2010;117(2):313-319.
9. Hee MR, Puliafito CA, Duker JS, et al. Topography of diabetic diabetic macularedema with
optical coherence tomography. Ophthalmology 1998;105(2):360-370.
10. National Eye Institute, National Institutes of Health. Facts about diabetic retinopathy.
Available
at:
http://www.nei.nih.gov/health/diabetic/retinopathy.asp.
Accessed 21 January 2013.
11. Heier JS, et al. Ranibizumab For Macular Edema Due To Retinal Vein Occlusions: Long-Term
Follow-Up In The HORIZON Trial. Opthalmology 2012;119(4):802-809.
12. National Eye Institute, National Institutes of Health. Facts about age-related macular degeneration. Available at: www.nei.nih.gov/health/maculardegen/armd_facts. Accessed 21
January 2013.
13. Genentech Press Releases. FDA Approves Lucentis (Ranibizumab Injection) for the Treatment of Macular Edema Following Retinal Vein Occlusion. Available at: http://www.gene.
com/media/press-releases/12827/2010-06-22/fda-approves-lucentis-ranibizumab-inject/.
Accessed 21 January 2013.
14. Novartis Media Releases. Novartis gains European Commission approval for Lucentis to
treat vision loss due to macular edema secondary to RVO. Available at: http://www.novartis.
com/newsroom/media-releases/en/2011/1521251.shtml. Accessed 21 January 2013.
15. Campochiaro PA, Heier JS, Feiner L, et al; BRAVO Investigators. Ranibizumab for macular
edema after branch retinal vein occlusion: six-month primary end point results of a phase III
study. Ophthalmology 2010;117:1102-1112.
16. Brown DM, Campochiaro PA, Singh RP, et al; CRUISE Investigators. Ranibizumab for macular edema after central retinal vein occlusion: six-month primary end point results of a phase
III study. Ophthalmology 2010;117:1124-1133.
17. National Eye Institute, National Institutes of Health. Facts about histoplasmosis. Available at: http://www.nei.nih.gov/health/histoplasmosis/histoplasmosis.asp. Accessed 21
January 2013.

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