Crvo treatment

Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 CENTRAL RETINAL VEIN OCCLUSION

Treatment of Macular Oedema Causing Loss of
Vision in Central Retinal Vein Occlusion (CRVO)
Ozurdex versus Lucentis Pictogram

CRVO treated with
CRVO treated with Ozurdex
Lucentis at 6 months
at 6 months

Percentage of patients who had gained 3 lines of vision
Percentage of patients who had no change in their vision
Percentage of patients who lost three lines of vision

What is CRVO?
Central Retinal Vein Occlusion is a blockage of the main vein in the retina at
the back of the eye. It can cause macular oedema, which is swelling of the
central part of the retina. Macular oedema is typically associated with loss of
vision, particularly loss of sharpness of vision, such as the ability of reading
or recognising faces and objects.
Can CRVO cause additional problems during the course of the
In addition to loss of sharp vision Central Retinal Vein Occlusion can also
cause loss of blood supply to the retina and reactive growth of new
abnormal blood vessels at the back of the eye (Proliferative Retinopathy)
or at the front of the eye (Rubeotic Glaucoma). These are complications of
CRVO that are explained in more detail further on.
Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012
What causes CRVO?
The cause of CRVO is not well known. However, that are known risk factors
such as age, smoking, raised cholesterol and lipids (fat) in the blood, raised
blood pressure and in younger patients, inflammation or clotting disorders.
The risk factors contribute to hardening of the retinal arteries. Retinal
arteries and veins are lodged in a tight space at the origin of the optic nerve
from the eye. Individual variation in the anatomy (shape and size) of the
optic nerve at its origin add to the risk factors in causing progressive sludge
of blood flow and eventually clotting of the main retinal vein in the optic

What happens without treatment?
It’s important to remember that each case of retinal vein occlusion is unique
and that macular oedema is the main cause of loss of vision in CRVO.
Occasionally patients may get better without treatment. For this reason a
few weeks of observation period may be appropriate to identify patients that
recover spontaneously and may not need any treatment. However, this
happens only in 1 in 10 or less of affected eyes and even when this happens
usually patients are left with some degree of permanent visual abnormalities,
such as slightly blurred visions.
The majority of patients with CRVO do not recover vision and often get
worse if left untreated for several months. There is some evidence that
delaying treatment for months may reduce the chances of visual recovery
once treatment is started.

How is CRVO treated?
The current main options are about a choice between Lucentis and
There is an impression that Lucentis may be superior to Ozurdex when
comparing results from the pivotal clinical trials for each drug. However,
these studies had different design and did not truly compare the two
treatments head-to-head. Therefore it is not possible to conclusively know if
Lucentis is superior to Ozurdex or viceversa.
Head-to-head comparative studies of Lucentis versus Ozurdex are under
way. One of them is being conducted at the Macular Unit at the Hospital of
St Cross, Rugby, with Mr Pagliarini being the Principal Investigator.

Is there a restriction in using Lucentis in the NHS?

Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 Lucentis is licensed for treating macular oedema in retinal vein occlusions.
However, it has yet to be approved by NICE for its use in the NHS, although
it is currently being evaluated. Lucentis can be used in private practice or as
part of an ethically approved clinical research study.
What is Ozurdex?
is a biodegradable implant containing the steroid Dexamethasone.
Ozurdex is licensed for treating macular oedema in retinal vein occlusions
and is approved by NICE for use in the NHS.
The Ozurdex implant is injected into the eye with a variant of a procedure
called intravitreal injection.

How is Ozurdex injected into the eye?
The implant is a small rod injected into the eye with a special technique that
creates a self sealing wound “shelved” through the eye wall, on the white of
the eye approximately 3.5-4.0 mm behind the iris. The implant is injected
using a special applicator device shaped like a pen. The tiny rod-shaped
implant rests into the vitreous, the gel-like material that fills the eye. The
implant slowly dissolves gradually releasing dexamethasone. The steroid
dexamethasone blocks chemical pathways that lead to inflammation and
leakage from retinal blood vessels.
How many injections of Ozurdex would I need?
It’s important to remember that each case of retinal vein occlusion is unique.
We do not have long term data on the benefit of Ozurdex. The manufacturer
indicated that Ozurdex last for 6 months. However, clinical experience
suggests that the benefit of Ozurdex lasts for only 2-3 months.
It seems that 80% of patients need more than 1 Ozurdex implant. How many
it is unclear.
It is recommended that patients being treated in centres that take part in
research using prospective anonymised data collection to understand the
benefit and safety of Ozurdex take part into research, if offered, to help their
ophthalmologists understand better how to use Ozurdex in CRVO.
What are the side effects of Ozurdex?
Approximately 1:6 to 1:8 treated eyes experience raised eye pressure or
glaucoma and need treatment with eye drops. Usually this resolves as the
effect of Ozurdex wanes off. Approximately 1:1000 patients may require
glaucoma surgery.
Risks associated with the intravitreal injection procedure
Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 Common side effects of the intravitreal procedure and advice include: • You may experience temporary visual blurring after receiving an injection and should not drive or use machines until this has resolved. • You are likely to have some discomfort for the first 24 hours. If the discomfort does not ease off and turns into pain contact the ophthalmologist or the nearest eye casualty Uncommon complications related to the injection procedure, i.e. not related to the injected drug, include: • Endophthalmitis, a severe infection inside the eye • Large bleeding inside the eye or within the eye wall. • Bleeding on the surface of the eye at the site of injection is common but it is not a reason of concern as it disappears within 2 to 10 days without causing any problem. • Corneal abrasion, a painful “scratch to the eye” due to excessive penetration in the cornea of the disinfectant used to reduce the risk of endophthalmitis, occurring in 1:100 injections
Some of the complications may be severe and require hospital admission,
such as endophthalmitis and retinal detachment.
Fortunately, complications related to the injection are rare. This means they
occur in 1:2000 injections or less. To put things into perspective cataract
surgery, a procedure deemed to be safe, has more than double the risk of
severe complications than intravitreal injections.
What should I do if I develop pain after an intravitreal injection?
The general advice is to contact the ophthalmologist or the nearest eye
casualty if there is pain after the intravitreal injection procedure.
Endophthalmitis is the most dreaded complication because it can cause
severe and permanent loss of vision and requires emergency hospital
Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 admission. The main two reasons for having pain after an intravitreal injection procedure are:
Corneal abrasions cause sharp pain within the first 24 hours of the
procedure. The pain is worse with blinking and is associated to intense
tearing and intolerance to light. The pain may give the patient a bad night
sleep but starts easing off with time.
Corneal abrasions are self-healing over a few days. However, they heal
faster with an ointment and an eye pad. Therefore, if the post-injection
discomfort turns into pain it is recommended to contact the ophthalmologist
or the nearest eye casualty.
The main feature of endophthalmitis is pain that gets worse rather than
better. If the pain starts between day 1 and 7 after the injection it must be
considered to be endophthalmitis until proven otherwise and must be
reported immediately by the patient to the ophthalmologist or the nearest
eye casualty.
What is Lucentis?
is part of a class of drugs grouped under the general term of anti-
. Other anti-VEGF drugs used in eye disease are Avastin and
Anti-VEGF drugs
work by blocking chemical pathways based on VEGF
(Vascular Endothelial Growth Factors). These are small proteins that when
produced in excess into the eye cause leakage of fluid and blood from the
retinal vessels. VEGF also cause growth of abnormal blood vessels at the
back of the eye or at the front of the eye resulting in two dreaded
complications of CRVO known respectively as Proliferative Retinopathy and
Rubeotic Glaucoma.
How Lucentis or other anti-VEGF drugs are injected into the eye?
Anti-VEGF drugs are injected into the vitreous, the jel-like substance that fills
the eye. The injection is placed through the eye wall, on the white of the eye
approximately 3.5-4.0 mm behind the iris. Anti-VEGF are fluid drugs. The
needle used to inject fluid drugs is tiny and much smaller than the needle of
the Ozurdex device. The needle is not seen by the patient during the
Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 injection. However, whilst the drug is injected fluid may be seen swirling
around into the eye.

Aflibercept (VEGF Trap-eye or VTE)
is a newer drug which has been
shown to have a similar effect to Lucentis in retinal vein occlusions. It seems
it lasts longer in the eye than Lucentis, potentially requiring less frequent eye
injections. It is currently undergoing the regulatory process of licensing in
Europe and will be soon available in the UK, although not in the NHS until
NICE approval.
Avastin is an anti-VEGF drug licensed to treat cancer but not eye disease.
However, given the much lower cost than Lucentis or Aflibercept it has been
used worldwide as a “low cost” alternative to treat a variety of eye diseases.
NICE does not review unlicensed drugs. Therefore Avastin is not approved
by NICE for treatment of CRVO.
Is there any other potential benefit of using Lucentis or other anti-
VEGF drugs for treating CRVO?
and Avastin have been used to treat complications of central
retinal vein occlusions such as rubeotic glaucoma with excellent results.
There are anecdotal reports that Lucentis reduces the risk of CRVO
complications such as proliferative retinopathy and rubeotic glaucoma in
patients with treated with Lucentis for their for macular oedema.
What are the complications of Lucentis and other anti-VEGF drugs?

Laser treatment has no role in treating macular oedema in CRVO and in
restoring vision.
However, laser treatment can be very effective in treating complications of
that, if untreated, may cause further vision loss or a painful eye:
Rubeotic Glaucoma
Proliferative Retinopathy.
These are complications that may occur in the first few months after the onset of CRVO and only rarely a few years later. Patient Information, Author Mr Sergio Pagliarini, Ver Nov 2012 In Proliferative Retinopathy abnormal blood vessels grow onto the retina.
These vessels are frail and at risk of bleeding inside the eye.
If proliferative retinopathy is detected during follow-up, scattered retinal laser
photocoagulation is applied to the affected areas to reduce the risk of
bleeding. This type of laser treatment is referred to as Panretinal
Photocoagulation (sector PRP)
or Scattered Retinal Photocoagulation.
In Rubeotic Glaucoma abnormal blood vessels grow at the front of the eye
where water is drained out of the eye. They cause raised eye pressure that
is difficult to control.
Raised eye pressure may cause chronic pain. Rubeotic glaucoma can
cause a blind and painful eye.

Laser treatment with panretinal photocoagulation (PRP) reduces the
chances of the eye becoming painful, but it cannot restore vision for patients
with rubeotic glaucoma.
Panretinal photocoagulation (PRP) laser treatment is offered to those
patients who develop high risk features for progression to rubeotic glaucoma
during follow up.
The laser procedure used to treat raised eye pressure in rubeotic glaucoma
is referred to as cyclodiode laser.
This document is used by Mr Pagliarini to advise his patients in his private
rooms. It is available to the public through Mr Pagliarini’s personal web site.
Mr Pagliarini takes no responsibility for the use of this document outside the
scope of advising patients in his own private rooms.

November 2012


No job name

J. Nat. Prod. 2005, 68, 1071-1075 Phenanthroindolizidine Alkaloids from the Stems of Ficus septica Amooru G. Damu,† Ping-Chung Kuo,†,| Li-Shian Shi,†,| Chia-Ying Li,† Chang-Sheng Kuoh,‡ Pei-Lin Wu,† andTian-Shung Wu*,†,§ Department of Chemistry, National Cheng Kung University, Tainan, Taiwan, Republic of China, Department of Life Science,National Cheng Kung University


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