Download Retinal conditions — Part 1

AD_ 0 2 7 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
2 7
1 4 / 4 / 1 1 ,
1 0 : 3 6
AM
HowtoTreat
PULL-OUT SECTION
www.australiandoctor.com.au
inside
COMPLETE HOW TO TREAT QUIZZES ONLINE (www.australiandoctor.com.au/cpd) to earn CPD or PDP points.
Eye anatomy
Clinical
assessment of
retinal pathology
Investigations
Diabetic
retinopathy
The authors
ASSOCIATE PROFESSOR
SAMANTHA FRASER-BELL,
clinical academic, Sydney Eye
Hospital and Save Sight Institute,
University of Sydney; and visiting
medical officer, Royal North Shore
Hospital, St Leonards, NSW.
PROFESSOR MARK GILLIES,
clinical academic, Sydney Eye
Hospital and Save Sight Institute,
University of Sydney, NSW.
Retinal conditions
— Part 1
This is the first part in a two-part series comprising an overview of retinal anatomy, common symptoms of retinal
conditions, retinal investigations, and common and important conditions affecting the retina. This week focuses on
assessment, investigations and diabetic retinopathy. Next week concludes with a look at retinal dystrophies,
inflammatory and infectious retinal conditions, retinal vessel occlusion and emboli, central serous retinopathy,
hypertensive retinopathy, retinal arterial macroaneurysm and vitreoretinal surgery.
Background
RETINAL conditions are a significant cause of visual impairment and
blindness in Australia. In particular, age-related macular degeneration is the most common cause of
blindness in people aged 50 and
over, while diabetic retinopathy is
the most common cause in working-aged people.
Since many retinal conditions
reflect underlying systemic disease,
their management involves the
patient’s GP. It is desirable that GPs
have an understanding of retinal
conditions to facilitate timely referral. These conditions can be
broadly subdivided into those that
need vitreoretinal surgery and those
that can be treated medically
(which includes the use of laser
and intravitreal injections).
Examples of surgical conditions
include:
• Epiretinal membrane.
• Macular hole.
• Retinal detachment.
• Vitreous haemorrhage.
Medical retinal conditions
include:
• Diabetic retinopathy.
www.australiandoctor.com.au
• AMD.
• Central serous retinopathy.
• Retinal vein occlusions.
• Retinal arteriolar occlusion.
• Retinal dystrophies.
AMD was covered last year in a
How to Treat article (29 October
2010) and is therefore not
addressed in this article.
cont’d next page
22 April 2011 | Australian Doctor |
27
AD_ 0 2 8 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
2 8
1 4 / 4 / 1 1 ,
1 0 : 3 8
AM
HOW TO TREAT Retinal conditions — Part 1
Anatomy
THE retina is the internal
photosensitive layer of the
eye. Extending from the scalloped margin of the ora serrata anteriorly to the optic
nerve head, it has a surface
area of about 266mm. 2 It
contains neuronal connections to the optic nerve,
thence to the brain.
Although there are 10 histological layers of the retina
(see figure 1), it is commonly
divided into two main
layers: the neural (sensory)
layer and the retinal pigment
epithelium.
The retina contains photoreceptors — rods and
cones. There are about five
million cones, most densely
packed within the fovea centralis and 100 million rods
spread
predominantly
throughout the peripheral
retina.
The macula (or macula
lutea –‘yellow spot’) is an
oval zone of yellow colouration with a diameter of
about 5.5mm, situated
between the temporal
arcades (the superotemporal
and inferotemporal arteries/
veins), and with the foveola
at its centre (figure 2). The
fovea is a 1.5mm depression
in the centre of the macula.
The average thickness of the
fovea is about 0.25mm,
roughly half that the adjacent parafoveal area. The
central 0.35mm of the fovea
is the foveola, which is
located in a retinal capillaryfree zone that measures
about 0.5mm in diameter.
The macula is responsible
for fine vision, such as reading and recognising colours
and faces.
The uveal layer is the term
describing the pigmented vascular middle layer of the eye
between the retina and the
sclera. It is traditionally
divided into three areas, from
front to back — the iris,
ciliary body and choroid.
The retina receives its
nutrition from two circula-
Figure 2: Photograph of left fundus showing the optic disc (left)
and macula (centre).
Figure 1: Histological layers of the retina.
Choroid (in the uveal layer
adjacent to the retina)
Pigment epithelium
Photoreceptor layer
Outer limiting membrane
Outer nuclear layer (nuclei
of photoreceptors)
Figure 3: Fundus fluorescein angiography — normal study in
arteriolar-venous phase.
Outer plexiform layer
(synapses)
Inner nuclear layer
Inner plexiform layer
(synapses)
Ganglion cell layer
Nerve fibre layer
Inner limiting membrane
tory systems — the retinal
blood vessels and the
choroidal blood vessels. The
outer one-third is supplied
by the choroid/choriocapillaris, and the inner twothirds from the central retinal artery, a branch of the
ophthalmic artery. The central retinal artery is a small
muscular artery. It divides
into a superior and inferior
branch at the optic nerve
head. The vessels further
divide into superotemporal,
inferotemporal, superonasal
and inferonasal arterioles to
supply each quadrant of the
eye. Ophthalmoscopically,
retinal veins are darker in
colour and thicker than retinal arterioles. Retinal blood
vessels
maintain
the
blood–retinal barrier (similar to the blood–brain barrier).
The best way to study the
retinal circulation is with
fundus fluorescein angiography. The non-fenestrated
endothelium of retinal arterioles does not normally permit
leakage of fluorescein. In the
fundus fluorescein angiography in figure 3, the perifoveal
capillary-free zone is seen. The
fundus fluorescein angiography is in the early arteriolarvenous phase of the study, as
evidenced by lamellar flow in
the veins.
The vitreous is the transparent colourless gel that
fills the space between the
posterior surface of the lens
and the retina. Although in
contact with the retina, it is
not generally adherent
except at the anterior border
of the retina, at the macula
and around the optic nerve.
With age it can pull away
from the retina as it degenerates and liquefies, leading to
floaters as seen in a posterior vitreous detachment.
Sometimes when it pulls
away it causes a tear in the
retina, which can lead to
retinal detachment.
Clinical assessment of retinal pathology
Symptoms
Scotoma
A SCOTOMA is a black or blurred
area usually central or just offcentre. Scotomas are commonly
associated with macular pathology,
such as AMD, diabetic maculopathy and macular holes.
Urgency of review of possible
retinal problems
Same-day review
• Sudden loss of vision
• Sudden onset of flashes and
floaters
• Sudden visual field loss
• Sudden scotoma
Distortion
Straight lines appear wavy. This
‘metamorphopsia’ of central vision
is usually due to macular retinal
thickening or subretinal fluid,
which may occur in conditions
such as ‘wet’ AMD, central serous
retinopathy, or surface retinal wrinkling, as is seen with epiretinal
membranes.
Floaters
These can also be described as cobwebs or black specks or dots.
28
| Australian Doctor | 22 April 2011
Review within days
• Distortion
• New/sudden blurred vision
• Photosensitivity
• New floaters
These are generally due to vitreous
opacities casting shadows on the
retina. They commonly occur with
posterior vitreous detachment but
can also be a feature of vitritis, vitreous haemorrhage, retinal tear and
retinal detachment.
Flashes
These usually imply mechanical
traction on the retina such as
occurs in posterior vitreous detachment and retinal detachment, as
the vitreous can ‘tug’ on the retina
before detaching from it peripherally. Migraines affecting the visual
cortex can also cause flashes, but
these tend to be in a zigzag pattern
and are bilateral. Other causes are
impending retinal artery occlusion,
which may be vascular in origin or
due to anterior ischaemic optic
neuropathy such as can occur with
giant cell arteritis. A rare cause is
autoimmune retinopathy.
Loss of visual field
Sudden symptomatic loss of visual
field in one eye can be caused by
retinal detachment or retinal vascular disease such as with retinal vein
www.australiandoctor.com.au
or artery occlusion. It can also be
caused by optic neuritis and anterior ischaemic optic neuropathy
which may be non-arteritic or
arteritic (associated with giant cell
arteritis). Of course, visual field
defects can also be due to neurological causes, such as an occipital stroke
causing homonymous hemianopia.
Sudden total vision loss
Sudden total vision loss in one eye
can be due to conditions such as
total retinal detachment, central retinal artery occlusion, optic neuritis
and anterior ischaemic optic neuropathy.
Transient loss of vision is
referred to as amaurosis fugax,
which is usually unilateral. Retinal
emboli may be seen ophthalmoscopically in these cases. Visual
obscurations, lasting seconds, occur
with raised intracranial pressure.
Increased photosensitivity
Increased photosensitivity, especially in the presence of a unilateral red eye, can indicate intraocular inflammation (uveitis).
Any elderly patient who complains
of visual symptoms or visual field
defects with headache should be
asked about jaw claudication (pain
with chewing) and generalised aches
and pains, examined for tenderness
over the temporal artery, and have
an ESR, CRP and platelet count
ordered. There should be a low
threshold for referral to a rheumatologist or an ophthalmologist to
exclude giant cell arteritis, because
untreated this can progress to irreversible bilateral blindness.
cont’d page 30
AD_ 3 0 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
3 0
1 4 / 4 / 1 1 ,
1 0 : 4 0
AM
HOW TO TREAT Retinal conditions — Part 1
from page 28
Figure 4: An Amsler grid can be used to test for symptoms of distortion and
scotoma, which are common in patients with macular problems.
History
Taking a medical, ocular and family
history is often helpful in patients
with retinal problems. Retinal vein
occlusion, retinal artery occlusion
and diabetic retinopathy, for example, are more common in patients
with cardiovascular risk factors (systemic hypertension, smoking, elevated blood glucose, hypercholesterolaemia) or with a previous history of
cardiovascular disease or stroke.
People with retinal tears or detachment may have a previous history or
family history of retinal detachment,
previous ocular surgery, trauma or
myopia (short-sightedness).
There may be a family history of
AMD (or undiagnosed poor vision)
in patients with this condition, and
those who smoke tend to develop the
disease at an earlier age (10 years
earlier on average than non-smokers).
Patients with retinal dystrophies
may or may not have a family history, as the inheritance of these conditions is commonly autosomal recessive.
quently. If the vision is less than 6/6
(normal), a pinhole can refine refraction either used over spectacles or
used in place of spectacles. Generally if the reduced vision is due to a
retinal cause, a pinhole will not
improve vision.
Amsler grid
An Amsler grid is a useful screening
tool for macular pathology (figure
4). It helps identify distortion and
scotomata in the central visual field.
The following instructions are given
to the patient:
1. Wear the glasses that you normally
wear for reading.
2. Hold the grid about 30cm from
your face in a well-lit room.
3. Cover one eye.
4. Focus on the centre dot with your
uncovered eye:
— can all of the grid be seen?
— are there blank or dark areas, and
if so, where? They can be marked
on the chart.
— are any lines wavy or distorted?
Again they can be marked on the
chart.
5. Repeat with the other eye.
patient’s distance glasses, is the most
important examination for evaluating patients with visual symptoms.
A Snellen chart is used most fre-
Examination
Visual acuity
Visual acuity, measured using the
Relative afferent pupillary defect
A relative afferent pupillary defect
(RAPD, or ‘Marcus Gunn’ pupil) is
an important sign that indicates an
optic nerve problem (such as optic
neuritis) or severe retinal disease in a
patient with visual loss. The swinging
light test is a test of the afferent pathway (ie, detection of light), rather
than the ability of the iris to constrict
(efferent pathway). It is performed
in a dim room (not dark, as you need
to be able to see the pupillary reactions).
The patient fixes on a target in
the distance. A bright focused light
(such as from a direct ophthalmoscope) is shone into one eye and
then the other. First note a direct
pupillary response (the pupil constricts when light is shone into it),
then a consensual response (the
other eye’s pupil also constricts).
To look for a relative afferent
pupillary defect, light is shone into
one eye for about three seconds
then quickly swung across to the
fellow eye. The reaction of the
fellow eye is observed. If there is
this defect, the pupil will dilate
when the light is swung across, as
light shone into the affected eye
causes less constriction of both
pupils than the unaffected eye (or
less affected eye, since it measures a
relative defect, rather than an
absolute).
Investigations
Fundus fluorescein
angiography
THIS is an important diagnostic test used by ophthalmologists to assess retinal and
choroidal vascular disease. The
most common conditions for
which fundus fluorescein
angiography is performed are:
• Diabetic retinopathy.
• AMD.
• Retinal vein and artery
occlusions.
• Central serous retinopathy.
• Inflammatory eye conditions
affecting the retina and
choroid (uveitis).
Figure 3 (page 28) shows a
normal fundus fluorescein
angiography study.
The fluorescein dye, given
intravenously, is usually well
tolerated, but the following
complications can occur:
• Nausea in 2-3%.
• Vomiting in 1-2%.
• Urticaria or pruritus in 0.30.5%.
• Vasovagal reactions.
• Injection-site complications.
In addition, there are the
uncommon but serious complications:
• Anaphylaxis.
• Severe asthma or bronchospasm.
• Cardiac arrhythmia.
• Myocardial infarction.
• Cardiac arrest.
• Seizure in one in 190018,000.
• Death in one in 50,000222,000.
Optical coherence
tomography
Optical coherence tomography
has revolutionised the investigation of macular disease
(figure 5). It is non-invasive
and non-contact, allowing
transpupillary imaging of retinal structures with a resolu-
30
| Australian Doctor | 22 April 2011
Figure 5: Optical coherence tomography — normal study.
Macular thickness: macular cube 512 × 128
OD
OS
Figure 6: A: Normal B-scan ultrasound. B: B-scan ultrasound
showing fluid (red arrow) in Tenon’s layer (black layer outside
the scleral coat) with a thickened sclera (white layer),
consistent with posterior scleritis.
A
500μm
400μm
300μm
200μm
ILM-RPE thickness (μm)
100μm
Overlay: !LM-RPE Transparency 50%
ILM-RPE
ILM
B
RPE
Central
subfield
thickness
μm
ILM-RPE 188
tion of about 5μm. Cross-sectional images are produced
using laser interferometry.
Optical coherence tomography allows qualitative and
quantitative measures of retinal thickness, oedema and
subretinal fluid and is used for
diagnosis and follow-up of
conditions such as:
• Macular oedema from all
causes, including diabetes.
Volume
mm3
Average
thickness
μm
9.9
274
• Retinal vein occlusion and
inflammation.
• Subretinal fluid in AMD.
• Central serous retinopathy.
• Vitreoretinal pathology such
as epiretinal membrane,
macular hole and vitreomacular traction.
B-scan ultrasonography
Ultrasound examination of the
posterior segment of the eye is
www.australiandoctor.com.au
used when there are media
opacities preventing direct
visualisation, such as very
dense cataract and/or vitreous
haemorrhage. In such cases
ultrasound can be used to
assess for retinal detachment,
for example. It is also useful
to demonstrate thickening of
the scleral coat of the eye seen
in posterior scleritis and for
evaluation of choroidal lesions,
such as choroidal melanoma
(figure 6).
AD_ 0 3 1 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
3 1
1 4 / 4 / 1 1 ,
1 0 : 4 2
AM
Diabetic retinopathy
Epidemiology
DIABETIC retinopathy is the
leading cause of legal blindness and visual impairment
among working-age adults in
Australia and other industrialised countries. It is estimated
that the number of people
with diabetes worldwide will
double by the year 2025,
resulting in about 380 million
by 2025, of whom 40% are
expected to have some form
of diabetic retinopathy.
Apart from visual morbidity, there is good evidence to
suggest that the presence of
diabetic retinopathy also signifies an increased risk of systemic vascular complications,
including stroke, ischaemic
heart disease, heart failure
and nephropathy. There is
clearly a need to develop
strategies to identify persons
at risk of diabetic retinopathy, allowing prevention of
visual loss and early intervention.
In Australians with diabetes:
• Half have diabetic retinopathy.
• One-eighth have visionthreatening retinopathy.
• One-tenth of those without
diabetic retinopathy will
develop it each year.
• With pregnancy:
— one-quarter with no diabetic retinopathy will
develop it.
— one-quarter with nonproliferative diabetic
retinopathy will develop
proliferative diabetic
retinopathy.
Duration of diabetes, poor
glycaemic control, and concomitant systemic hypertension are the major risk factors for the development and
progression of diabetic
retinopathy.
The Wisconsin Epidemiologic Study of Diabetic
Retinopathy, a populationbased cohort study of diabetes conducted in the 1980s,
showed that the prevalence of
diabetic retinopathy ranged
from 17% in those with type
1 diabetes for less than five
years, to almost 100% in
those with type 1 diabetes for
more than 15 years. 1 For
people with type 2 diabetes,
prevalence of retinopathy
ranged from 29% to 78% in
those with disease for less
than five years, to 78% in
those with diabetes for more
than 15 years.2
The importance of good
glycaemic control for delaying the development and progression of diabetic retinopathy was confirmed in two
landmark clinical trials — the
Diabetes Control and Complications Trial and the UK
Prospective Diabetes Study.3,4
The more recent Diabetic
Retinopathy Candesartan
Trials (DIRECT) indicated
that blocking the renin–
angiotensin system with candesartan had beneficial effects
on diabetic retinopathy. 5,6
Figure 7: Mild non-proliferative diabetic retinopathy —
microaneurysms only.
Figure 8: Diabetic macular oedema. Clinically significant
oedema with hard exudates and retinal thickening.
Figure 9: Diabetic macular oedema. Optical coherence
tomography showing cysts within the retina due to diabetic
macular oedema.
Figure 10: Severe non-proliferative diabetic retinopathy —
haemorrhages in four quadrants.
Proliferative retinopathy
This develops after severe nonproliferative retinopathy. Further increases in retinal
ischaemia trigger production
of vasoproliferative factors,
such as vascular endothelial
growth factor (VEGF), that
stimulate new vessel formation
(retinal neovascularisation)
which occurs on the inner (vitreous) surface of the retina and
may extend into the vitreous
cavity.
These new blood vessels
(seen on the optic disc and
elsewhere) are prone to bleeding, causing vitreous haemorrhage (figure 11). The neovascularisation
can
be
accompanied by preretinal
fibrous tissue, which can contract, resulting in tractional
retinal detachment.
The new blood vessels can
also grow on the iris and into
the angle of the anterior chamber of the eye, causing
neovascular glaucoma due to
blockage of flow of aqueous
out of the eye, resulting in
extremely high intraocular
pressures. This can lead to the
development of a blind,
painful eye.
Screening and prevention
of diabetic retinopathy
Figure 11: Proliferative diabetic retinopathy — new vessels on
the optic disc and elsewhere, including overlying the
superotemporal arcade and temporal to the macula. Note the
venous loops off the inferotemporal arcade, and haemorrhages.
The GP has a pivotal role in
optimising blood glucose and
blood pressure control and
treating hypercholesterolaemia, therefore preventing or
minimising progression of diabetic retinopathy. All patients
with diabetes should be
screened for diabetic retinopathy, as timely ophthalmic care
such as laser can prevent much
of the blindness from diabetic
retinopathy.
See the box on page 32
for the current guidelines
for screening for diabetic
retinopathy.
Classification of diabetic retinopathy
• Mild non-proliferative diabetic retinopathy (NPDR):
microaneurysms only (figure 7)
• Moderate NPDR: more than mild, but less than severe NPDR
(figure 8)
• Severe NPDR: four quadrants with significant haemorrhage,
two quadrants with venous beading and/or one quadrant with
intraretinal microvascular abnormalities (figure 10)
• Proliferative diabetic retinopathy: neovascularisation of the
disc or elsewhere in the retina (figures 11 and 12-14, page 32)
However, in both DIRECT
studies the effects were
achieved in participants with
early retinopathy only and
may have been related to the
blood-pressure-lowering
effects.
Another recent major trial,
the Fenofibrate Intervention
and Event Lowering in Diabetes (FIELD) study, has provided encouraging new findings. The FIELD study
showed that fenofibrate, a
lipid-lowering fibrate, reduced
the need for laser treatment
of sight-threatening diabetic
retinopathy (either for macular oedema or proliferative
retinopathy) by 31% over five
years. 7 This result was
achieved in patients with type
2 diabetes who already had
good control of blood sugar
and blood pressure.
Fenofibrate also reduced
the risk of total cardiovascular events and progression to
nephropathy. Although
fenofibrate has clear lipidlowering effects, lipid concentrations were similar in the
intervention and control
groups, so fenofibrate may
have other as-yet unknown
modes of action through
lipid-independent pathways,
such as inhibiting the secretion of vascular endothelial
growth factor, apoptosis or
local inflammation.
Pathology
The classification of diabetic
retinopathy is described in the
box above and illustrated in
figures 7-14.
Non-proliferative retinopathy
Diabetic retinopathy is a
microangiopathy. Hyperglycaemia induces loss of function and death of intramural
pericytes, causing weakness
www.australiandoctor.com.au
and saccular outpouching
(microaneurysms) (figure 7),
making the retinal blood vessels leaky, and thickening of
the basement membrane,
which may contribute to capillary occlusion.
Increased permeability of
the retinal vessels results in
leakage of fluid and proteinaceous material, which clinically
appears as retinal thickening
(oedema) and hard exudates
(lipid deposits), which preferentially affect the macula (ie,
diabetic macular oedema)
(figure 8).
Capillary occlusion leads to
retinal ischaemia such as is
seen with ‘cotton wool spots’
(infarcts of the retinal nervefibre layer), and deep retinal
haemorrhages (figure 10).
More extensive retinal
hypoxia triggers compensatory
mechanisms within the eye to
provide enough oxygen to tissues, including venous calibre
abnormalities, such as venous
beading, loops, and dilation,
and intraretinal microvascular
abnormalities.
Treatment of diabetic
retinopathy
Role of the GP
Tight control of blood glucose,
cholesterol level and systemic
blood pressure is vital. If there
is worsening of diabetic
retinopathy beyond that
explained by diabetic control,
it is worth ordering an FBC
and EUC since anaemia and
renal disease can be the cause.
If HbA 1c levels are very
high, they should be reduced
gradually, as sudden improvement of glycaemic control can
be associated with quite
marked exacerbation of existing retinopathy, a phenomenon known as ‘early worsening’.
If the diabetic retinopathy is
asymmetrical (for example,
severe non-proliferative diabetic retinopathy in one eye
and mild non-proliferative diabetic retinopathy in the other)
carotid ultrasonography is
warranted. Interestingly, significant stenosis may protect
against the development of
diabetic retinopathy on that
cont’d next page
22 April 2011 | Australian Doctor |
31
AD_ 0 3 2 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
3 2
1 4 / 4 / 1 1 ,
1 0 : 4 3
AM
HOW TO TREAT Retinal conditions — Part 1
from previous page
Figure 12: Proliferative diabetic retinopathy — fundus
fluorescein angiography shows areas of peripheral
hypofluorescence, consistent with ischaemia, and areas of
hyperfluorescence in the areas of neovascularisation of the disc
and elsewhere.
side. The diagnosis of carotid
stenosis is to prevent CVA or
death rather than to treat the
diabetic retinopathy.
Aspirin has not been shown
to improve or worsen diabetic
retinopathy, although since
atherosclerosis is more
common in those with diabetes, it is often prescribed.
Figure 14: Proliferative diabetic retinopathy — fluorescein
angiography shows widespread capillary drop-out
(hypofluorescent areas), including macular ischaemia. There is
neovascularisation of the optic disc (shown by
hyperfluorescence indicating leakage of dye from the new
vessels).
A
Role of the ophthalmologist
Laser photocoagulation of the
retina remains the mainstay of
treatment of diabetic retinopathy. Laser is effective in reducing the risk of severe visual loss
in people with proliferative
diabetic retinopathy and
reducing the risk of moderate
visual loss in eyes with clinically significant diabetic macular oedema. Less commonly it
improves vision.
Other specialist treatments
include vitreoretinal surgery
and intravitreal injections.
Figure 13: Proliferative diabetic retinopathy with tractional
epiretinal membrane extending from the optic nerve temporally
through the macula.
B
Clinically significant
macular oedema — sightthreatening
maculopathy
Retinal thickening that
involves, or is close to, the
centre of the macula (fovea) is
termed clinically significant
macular oedema (figure 8,
page 31). Over three years this
is associated with a 31% risk
of further moderate visual loss
(about three lines on the
Snellen visual acuity chart).
Macular grid laser reduces this
risk to about 12%.
Fundus fluorescein angiography is often performed to
identify the areas of leakage
and areas of capillary closure
to help estimate visual prognosis and to guide macular
laser treatment. Optical coherence tomography is another
useful investigation that can be
performed more often because
it is non-invasive (figure 9,
page 31). It shows areas of
retinal thickening but does not
show the areas responsible for
the leak or areas of non-perfusion.
Laser for diabetic macular
oedema consists of a light
application over the areas of
thickening and leak. It cannot
be applied to the centre of the
macula because it would
cause irreversible damage and
loss of vision. Although laser
treatment is effective in reducing the risk of visual loss from
diabetic macular oedema, it
only improves visual acuity
significantly in about 15% of
eyes and does not halt progressive loss of vision in all
eyes. Thus, there is a pressing
need to improve the treatment
of diabetic macular oedema.
Newer treatments for diabetic macular oedema that
involve the fovea include
intravitreal injection of steroid
(such as triamcinolone acetonide) and anti-VEGF agents
(such as bevacizumab and
ranibizumab). In a randomised controlled study of
eyes with diffuse diabetic
macular oedema refractory to
laser treatment, there was an
average improvement in
32
Laser
photocoagulation
of the retina
remains the
mainstay of
treatment of
diabetic
retinopathy.
| Australian Doctor | 22 April 2011
Current guidelines for screening for diabetic
retinopathy
When
• At the time of diagnosis (except in children, when screening
should begin at puberty)
• If no diabetic retinopathy is found, screening should be repeated
every 1-2 years
By whom
• A qualified and trained person, who may be an optometrist, an
ophthalmologist, an endocrinologist or a GP
What it entails
• Visual acuity testing
• Dilated retinal examination
Referral to ophthalmologist
• Any pregnant woman with diabetes
• Macular lesions such as microaneurysms or macular
oedema/hard exudates
• Poor glycaemic control, or sudden marked improvement
(eg, a person with type 2 diabetes with very high HbA1c
levels starting insulin)
• Follow-up depends on the extent of retinopathy present
visual acuity of five letters
(one line) at two years in
patients who received intravitreal steroid (triamcinolone
acetonide).8
Results from the READ II
study have shown intravitreal
ranibizumab 0.5mg to also be
more effective than laser in
reducing diabetic macular
oedema and improving
vision, with visual acuity
improving by an average of
eight letters, compared with
a one-letter loss in the laser
group.9 About 25% of treated
patients had at least a threeline gain in visual acuity.
Results from the BOLT
study have shown similar
results with bevacizumab.10
Although these results look
promising, intravitreal injections for diabetic macular
oedema are still considered
off-label treatments in Australia.
Proliferative diabetic
retinopathy
Retinal neovascularisation on
the disc or elsewhere is associated with a risk of:
• Vitreous haemorrhage.
• Tractional retinal detachment.
• Iris neovascularisation.
• Neovascular glaucoma.
Proliferative diabetic
retinopathy is associated
with a 26% risk of severe
visual loss (defined as visual
acuity worse than 6/120)
over two years. This is
halved with argon laser panretinal photocoagulation, in
which multiple heavy laser
burns are applied to the
peripheral retina to ablate
the ischaemic retina, thereby
www.australiandoctor.com.au
reducing the VEGF drive for
new vessel formation. Multiple sessions are typically
required. Peripheral laser is
much more uncomfortable
than macular laser. It can
cause restriction of peripheral visual field, which may
affect night vision and, less
often, driving vision.
Off-label use of anti-VEGF
agents such as bevacizumab,
which cause rapid regression
of the new vessels after
intravitreal injection, are
useful to gain time to apply
the peripheral laser, but they
only have a temporary effect
(usually 4-6 weeks).
Surgery for diabetic
retinopathy
If vitreous haemorrhage prevents the application of
peripheral retinal laser, or if
the haemorrhage fails to
clear, or if the patient has
poor vision in the other eye,
vitrectomy may be indicated
to remove the blood.
Other reasons for surgery
include tractional retinal
detachment, vitreomacular
traction and epiretinal membrane, which can all occur
secondary to proliferative
diabetic retinopathy.
Cataract in patients with
diabetic retinopathy
It is imperative that diabetic
retinopathy that has reached
the threshold for laser treatment is treated as much as
possible before cataract surgery, as both macular
oedema and proliferative
retinopathy can worsen after
cataract surgery.
References
1. Klein R, et al. The
Wisconsin epidemiologic
study of diabetic
retinopathy. II.
Prevalence and risk of
diabetic retinopathy
when age at diagnosis is
less than 30 years.
Archives of
Ophthalmology 1984;
102:520-26.
2. Klein R, et al. The
Wisconsin epidemiologic
study of diabetic
retinopathy. III.
Prevalence and risk of
diabetic retinopathy
when age at diagnosis is
30 or more years.
Archives of
Ophthalmology 1984;
102:527-32.
3. UK Prospective Diabetes
Study (UKPDS) Group.
Intensive blood-glucose
control with
sulphonylureas or insulin
compared with
conventional treatment
and risk of complications
in patients with type 2
diabetes (UKPDS 33).
Lancet 1998; 352:83753.
4. Diabetes Control and
Complications Trial
Research Group.
Progression of
retinopathy with
intensive versus
conventional treatment in
the Diabetes Control and
Complications Trial.
Ophthalmology 1995;
102:647-61.
5. Chaturvedi N, et al.
Effect of candesartan on
prevention (DIRECTPrevent 1) and
progression (DIRECTProtect 1) of retinopathy
in type 1 diabetes:
randomised, placebocontrolled trials. Lancet
2008; 372:1394-402.
6. Sjolie AK, et al. Effect of
candesartan on
progression and
regression of retinopathy
in type 2 diabetes
(DIRECT-Protect 2): a
randomised placebocontrolled trial. Lancet
2008; 372:1385-93.
7. Keech A, et al. Effect of
fenofibrate on the need
for laser treatment for
diabetic retinopathy
(FIELD study): a
randomised controlled
trial. Lancet 2007;
370:1687-97.
8. Gillies MC, et al.
Intravitreal triamcinolone
for refractory diabetic
macular edema: two-year
results of a doublemasked, placebocontrolled, randomized
clinical trial.
Ophthalmology 2006;
113:1533-38.
9. Nguyen QD, et al. Twoyear outcomes of the
Ranibizumab for Edema
of the mAcula in
Diabetes (READ-2) study.
READ-2 Study Group.
Ophthalmology 2010;
117:2146-51.
10. Michaelides M, et al. A
prospective randomized
trial of intravitreal
bevacizumab or laser
therapy in the
management of diabetic
macular edema (BOLT
study) 12-month data:
report 2.
Ophthalmology 2010;
117:1078-86.
cont’d page 34
AD_ 0 3 4 _ _ _ APR2 2 _ 1 1 . p d f
Pa ge
3 4
1 4 / 4 / 1 1 ,
1 0 : 4 5
AM
HOW TO TREAT Retinal conditions — Part 1
GP’s contribution
Case study
DR LIZ MARLES
Redfern, NSW
AMY, 18, has type 1 diabetes, first diagnosed at age
11. Her parents are divorced
and she has lived at different times with her mother,
father and grandparents.
Both her parents have substance-abuse issues and consequently she often misses
appointments and has had
to be ‘the adult’ in the
family.
For the past five years
Amy has had poor glucose
control, despite a variety of
insulin regimens initiated by
the Children’s Hospital, who
suspect that she frequently
misses doses. Her HbA1c has
ranged from 11.9% to
15.2% over this time, but is
at its best now at 10.6%.
Similarly her cholesterol
control has been suboptimal,
with total cholesterol ranging
from
7.4mmol/L
to
5.9mmol/L over the past two
years. At her last visit to the
Children’s Hospital before
turning 18, Amy’s blood pressure was noted to be
140/95mmHg.
Amy has been having her
eyes checked annually by an
optometrist for the past three
years and at this stage no
retinopathy has been reported.
Her mother was told by the
doctors at the hospital that if
Amy didn’t improve her glucose control she would probably become blind in her 20s.
Questions for the author
Is this a likely outcome? Can
improved glucose control at
this point avert retinopathy
and blindness?
How to Treat Quiz
Good glucose control has
been shown again and again
to reduce the risk and progression of diabetic retinopathy.
Optimising glucose control
(and blood pressure control)
is especially important in such
a young person.
As Amy currently does not
have any retinopathy, if she
were to become engaged in
managing her diabetes, is there
any risk in rapidly reducing
her blood glucose levels?
No one knows the answer
to this specific question, that
is, whether rapid improvement in glucose control in a
diabetic patient with no existing retinopathy has any negative impact on (future) diabetic eye disease. Sudden
tightening of blood glucose
control can lead to initial
worsening of existing diabetic
retinopathy. Therefore it is
recommended that HbA 1c
levels be reduced gradually.
Close observation by an
ophthalmologist would be
very important in this patient,
and in any diabetic patient
with retinopathy in whom
poor glycaemic control is
being normalised (eg, by
adding insulin in type 2 diabetes).
How is diabetic retinopathy
affecting the macula treated?
The gold standard treatment of diabetic macular
oedema is gentle macular grid
or focal laser. Some forms of
diabetic macular oedema,
however, respond poorly to
laser therapy, such as diffuse
centre-involving oedema. In
this case intravitreal injections
with an anti-VEGF agent or
corticosteroid can be considered, but these are currently
considered off-label treatments in Australia.
Is it likely that intravitreal
steroid injection will replace
laser in the treatment of nonproliferative diabetic retinopathy?
No. Non-proliferative diabetic retinopathy without diabetic macular oedema is not
considered sight threatening
and is generally not treated.
These patients need close
follow-up, however.
How successful is laser treatment in halting the progression of diabetic retinopathy?
Appropriate laser has been
shown to more than halve the
risk of severe visual loss
(defined as vision less than
6/240) in eyes with proliferative diabetic retinopathy and
moderate vision loss (defined
as a loss of approximately
three lines) in eyes with clinically significant diabetic macular oedema at 2-3 years.
INSTRUCTIONS
Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes
by post or fax.
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.
Retinal conditions — Part 1
— 22 April 2011
1. Which TWO statements are correct?
a) Non-surgical treatments for retinal disorders
include laser and intravitreal injections
b) The macula is responsible for fine vision,
such as reading, and recognising colours
and faces
c) The retina has a single blood supply via the
choroidal blood vessels
d) The vitreous is normally attached to the
entire retinal surface
2. Which TWO statements are correct?
a) Floaters are usually due to age-related
vitreous degeneration and/or posterior
detachment of the vitreous
b) A degenerating vitreous may pull away from
the retina, causing a retinal tear
c) A scotoma is usually due to abnormalities of
the peripheral retina
d) Distortion of central vision
(metamorphopsia) is usually due to
haemorrhage into the vitreous
3. Which TWO statements are correct?
a) Flashes always signify retinal detachment
b) Important causes of sudden loss of vision in
one eye include retinal detachment, retinal
vein or artery occlusion, and optic neuritis
c) In an elderly patient with visual symptoms
and headache, temporal arteritis needs to
be excluded urgently
d) Amaurosis fugax is usually due to retinal
artery thrombosis
ONLINE ONLY
www.australiandoctor.com.au/cpd/ for immediate feedback
4. Which THREE visual symptoms require
urgent review by an ophthalmologist?
a) Distortion of central vision
b) Sudden onset of flashes and floaters
c) Gradual onset of blurred vision correctable
using pinhole visual acuity testing
d) Sudden scotoma
5. Which TWO statements are correct?
a) Hypertension, smoking, hyperglycaemia
and hypercholesterolaemia are risk factors
for retinal vein or retinal artery occlusion
b) Prior ocular surgery or trauma or shortsightedness are risk factors for retinal tears
and detachment
c) Measuring visual acuity using a Snellen
chart is an inaccurate assessment in those
with visual symptoms
d) If the cause of reduced vision is due to
retinal pathology, a pinhole will improve
visual acuity
6. Which TWO statements are correct?
a) An Amsler grid is a useful screening tool
for peripheral retinal pathology
b) If there is a problem with the left optic
nerve, the left pupil will constrict
more when light is shone directly into the
left eye than when light is shone directly
into the right
c) Fundus fluorescein angiography is used to
assess retinal and choroidal vascular
disease
d) Optical coherence tomography is a noninvasive investigation that provides highresolution transpupillary imaging of retinal
structures
7. Which THREE statements are correct?
a) B-scan ultrasonography can be used to
assess retinal detachment when cataract
and/or vitreous haemorrhage prevent direct
visualisation
b) Important modifiable risk factors for
diabetic retinopathy include poor
glycaemic control and hypertension
c) In Australians with diabetes, about 20%
have diabetic retinopathy, and 5% have
retinopathy that threatens vision
d) In patients with type 2 diabetes and good
glycaemic and blood pressure control,
fenofibrate reduces the incidence of sightthreatening retinopathy
8. Which TWO statements are correct?
a) In diabetic macular oedema there is
decreased permeability of retinal vessels
b) In non-proliferative diabetic retinopathy,
capillary occlusion causes retinal
ischaemia, which appears as ‘cotton wool
spots’ and retinal haemorrhages
c) In proliferative retinopathy, increasing
retinal ischaemia stimulates new blood
vessel formation
d) Retinal neovascularisation usually
threatens sight by growing over the macula
and directly preventing light from
penetrating to the deeper layers of the
retina
9. Which TWO statements are correct?
a) Screening for diabetic retinopathy should
occur at diagnosis and 1-2 yearly thereafter
b) Screening for diabetic retinopathy consists
of visual acuity testing and fundus
fluorescein angiography
c) Sudden improvement in glycaemic control
results in rapid improvement in existing
diabetic retinopathy
d) Anaemia and renal disease may worsen
diabetic retinopathy
10. Which TWO statements are correct?
a) Laser for macular oedema reliably prevents
progressive loss of vision in all affected
eyes, and significantly improves visual
acuity in most patients
b) Laser pan-retinal photocoagulation for
proliferative diabetic retinopathy ablates the
ischaemic peripheral retina, thereby
reducing the vascular endothelial growth
factor (VEGF) drive for new vessel
formation
c) Intravitreal injection of steroid or
anti-VEGF agents may be more effective
than laser for the treatment of macular
oedema
d) Laser photocoagulation for proliferative
diabetic retinopathy usually improves vision
CPD QUIZ UPDATE
The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can
complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or
fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
HOW TO TREAT Editor: Dr Giovanna Zingarelli
Co-ordinator: Julian McAllan
Quiz: Dr Giovanna Zingarelli
NEXT WEEK How to Treat Retinal conditions concludes next week with a look at retinal dystrophies, inflammatory and infectious retinal conditions, retinal vessel occlusion and emboli, central serous
retinopathy, hypertensive retinopathy, retinal arterial macroaneurysm and vitreoretinal surgery.
34
| Australian Doctor | 22 April 2011
www.australiandoctor.com.au