Age-related macular degeneration (ARMD) is the late stage of
age-related maculopathy and the most common cause of
blindness in developed countries.
The condition is characterised
by progressive, bilateral atrophic changes in the choriocapillaris,
Bruch’s membrane, and the retinal pigment epithelium.
The
incidence of blinding ARMD increases sharply with increasing
age, and it is present in about 15% of all people over the age of 85.
ARMD can be divided clinically into dry (atrophic) and wet
(exudative) forms.
Dry (atrophic, non-exudative) ARMD
This is the common form of ARMD; about 85% of all ARMD is
of this type.
It is characterised by widespread atrophic changes
in the macular area and is bilateral.
Dry ARMD usually
progresses only slowly and with great variability and may result
in severe visual impairment over five to ten years in some
patients.
Wet (exudative, neovascular) ARMD
Wet ARMD is a more aggressive disease and although only
15% of all ARMD cases are of this type, the exudative form is
responsible for 90% of all severe visual loss in ARMD.
The
clinical course of the disease is much more rapid than dry
ARMD and 75% of patients will have a marked reduction in
vision over about three years.
The chance of second eye
involvement in wet ARMD is very high.
In wet ARMD the problem stems from an abnormal growth of
new blood vessels (choroidal neovascularisation) that invade the
retina from the choroid.
These abnormal blood vessels leak fluid
and are associated with bleeding in the macular region. Risk factors for ARMD
The aetiology of ARMD is multifactorial and currently is not
fully understood.
The main risk factor for the development of
this degenerative condition seems to be increasing age.
Clinical presentation
Most patients with dry, atrophic ARMD present with a gradual
reduction in the central vision of both eyes, which affects their
ability to read, to recognise faces, and to see clearly in the
distance.
Patients may notice mild distortion of their central
vision (metamorphopsia) but characteristically retain a good
peripheral visual field.
In the wet, exudative form of ARMD, patients present more
acutely with a sudden change in their central vision (usually in
one eye initially).
They often experience marked central
distortion (“straight lines have a bend in the middle”) or
a precipitous fall in their vision.
Signs in dry ARMD
The earliest clinically detectable sign of dry ARMD is the
appearance of drusen in the macular region of both eyes.
Drusen are tiny pinpoint, discrete yellow deposits, which
correspond histopathologically to focal accumulations of
abnormal hyaline material located specifically at the interface
of Bruch’s membrane and the retinal pigment epithelium
(RPE).
Later atrophic changes occur in the macular area,
causing a diffuse pale, mottled appearance.
This appearance
corresponds histopathologically to atrophy of the RPE and
choroid, with some areas of secondary RPE hyperplasia.
In advanced geographical atrophy of the macula there is a large,
well demarcated area of atrophy and it is possible to see clearly
the underlying choroidal vessels.
Signs in wet ARMD
As in dry ARMD, there are drusen and atrophic changes at the
macula, but the distinctive signs of wet ARMD relate to the
abnormal growth of new blood vessels and leakage of serous
fluid and blood into the macula region.
Choroidal
neovascularisation appears as a small, focal, pale pink-yellow or
grey-green elevation at the macula.
There may be associated
exudation of serous fluid or blood in the subretinal or sub-RPE
space.
Investigation
Fundus fluorescein angiography (FFA), sometimes augmented
with indocyanine green angiography (ICG), is used to confirm
the presence of an area of choroidal neovascularisation at the
macula.
In both techniques, intravenous administration of
a dye allows assessment of the retinal and choroidal circulations
and highlights areas of macular pathology (particularly the
presence of abnormal, leaking blood vessels).
Fundus fluorescein angiography is a safe and commonly performed
investigation in ophthalmic practice.
However, very rarely a
patient may experience a serious episode of laryngeal oedema,
bronchospasm, or anaphylactic shock as a result of the
fluorescein injection.
On the basis of fluorescein angiography,
choroidal neovascularisation can be divided into classic
(neovascularisation fully delineated) and occult (full extent of
neovascularisation not visible).
The classic form usually
progresses faster than the occult form.
Management of ARMD
The ophthalmologist has a very important role in managing
patients with ARMD, even though very little can be done at
present to influence the natural progression of the disease in
the majority of patients. When told that they have ARMD, most
patients will immediately worry about the risk of total blindness.
Although ARMD will almost certainly cause
a progressive reduction in central visual acuity in many patients,
the rate of deterioration is extremely variable, and most
patients will continue to lead active independent lives with full
preservation of their peripheral visual fields.
The
ophthalmologist has a key role here in demonstrating to the
patient that the peripheral visual fields (to confrontation) are
full.
Together with appropriate information about ARMD and
self help groups, this reassurance is the essential component of
the consultation.
The patient can be offered visual rehabilitation (refraction
and low vision assessment) and registration as partially sighted
or blind.
Specific advice about diet and lifestyle
measures can be offered, based on recent research findings in
this field.
Much interest in recent years has focussed on the
possible role of dietary supplementation in ARMD, and recent
evidence suggests that the progression of ARMD in some
patients can be reduced by vitamin supplementation.
A balanced diet (rich in fresh fruit and green leafy vegetables) is
important and this can be supplemented by preparations
containing multivitamins, vitamin C, vitamin
A and
beta-carotene, zinc, omega 3 fatty acids (found in fish), lutein,
and xeaxanthin.
Specific management of wet ARMD
Treatments specifically for wet ARMD aim to close off blood
flow through the area of choroidal neovascularisation, to allow
resolution of the exudative changes at the macula and the
restoration of central visual function.
The first stage is to
determine whether the patient is in the subgroup of ARMD
patients for whom ablation of the choroidal neovascularisation
is effective.
Patients with severe secondary fibrotic changes in
the delicate tissues of the macula are less likely to regain visual
function through this treatment.
The pattern of choroidal
neovascularisation, determined using fundus fluorescein
angiography and indocyanine green angiography, is also very
important.
Monitoring of patients who have been treated for
wet ARMD is essential, because the choroidal
neovascularisation can recur.
Several different methods of ablation of choroidal
neovascularisation are available for treating wet ARMD.
Laser photocoagulation
The neovascularisation is occluded by direct laser
photocoagulation.
In the process of destroying the deeper
abnormal vessel leakage, the overlying retina also sustains
significant damage.
This type of treatment is often used for
extrafoveal and juxtafoveal choroidal neovascularisation that
does not lie directly beneath the fovea.
In subfoveal disease
laser photocoagulation will result in an immediate reduction in
vision.
Photodynamic therapy (PDT)
This new technique uses a light activated photosensitiser
(verteporfin), given intravenously.
An ophthalmic laser
delivery system is used to generate the specific wavelength of
light to activate the photosensitiser, which causes
photochemical damage and vessel occlusion in the selected
target area.
This makes it possible to cause vessel occlusion
without damage to the retina, which has the advantage of
preserving visual function, particularly with choroidal
neovascularisation in the subfoveal region.
PDT has become
the treatment of choice in subfoveal choroidal
neovascularisation.
External beam radiation
Precisely focused radiotherapy is used to ablate the neovascular
membrane.
This treatment is currently undergoing evaluation
in certain centres.
Agents that inhibit choroidal neovascularisation
A variety of agents that may inhibit subfoveal choroidal
neovascularisation are being investigated.
These include
novel molecules such as antibodies and aptamers (RNA-like
molecules).
The molecules neutralise growth factors such as
vascular endothelial growth factor, which stimulates new vessel
growth. Anti-angiogenic steroids are also being tested.
Submacular surgery
This is an operation involving microsurgical vitrectomy to
remove the vitreous gel, combined with a retinal incision and
then removal of the choroidal neovascularisation.
This
technique may be appropriate for selected cases.
Macular rotation or transposition surgery
This is a complex surgical technique in which the macular
region of the retina is physically moved to overlie another area
of healthy retinal pigment epithelium elsewhere in the adjacent
retina. Subsequent strabismus surgery is need to rotate the
macula back into the primary position.
This complicated
operation is still under development and carries significant risk
at present.
