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Procedures
The
examination begins with the intravenous injection through an arm vein
of sodium fluorescein diluted 10-20%: the dose varies from 3-5 cc for
traditional fluoroangiography to 1-2.5 cc in the case of laser scanning.
When
excited at a wavelength of 465-490 nm, this substance emits fluorescent
light of beyond 520-530 nm.
Its
characteristic low molecular weight allows its free diffusion outside
the choriocapillaris, but the adhesive junctions between the endothelial
cells of the retinal capillaries do not allow the free circulation of
fluorescein in the retina unless the permeability of the retinal vessels
is altered.
There
are currently two types of fluoroangiograms: the traditional type (also
called videoangiograms), which allow the immediate digitalisation of
individual images; and the laser scanning type (SLO Rodenstock – Waco
Pro Laser and Heidelberg HRA), the light source of which is a monochromatic
laser beam moved by two rotating mirrors in such a way as to illuminate
30-40oof the ocular fundus, which makes it possible to record a higher-resolution
dynamic angiogram.
Indications
FA
is not indicated for all AMD patients or at every visit. In the majority
of cases, an angiographic examination is required because of the possibility
of finding neovascular lesions in any patient (usually those aged more
than 65 years with soft drusen) complaining of “metamorphopsia”***,
central or paracentral scotoma****, or any acute variation in vision.
Any one of these symptoms should suggest the need to look for clinical
signs of neovascular membranes (NVM), but not all NVM patients are symptomatic.
Preferably
performed using contact or indirect (78 D) lenses, an ophthalmoscopic
examination revealing exudative or hemorrhagic neuroepithelial detachment
should give rise to a suspicion of NVM; in such cases, FA can confirm
the diagnosis, show whether treatment is indicated and offer a guide
as to the type of therapy itself.
FA
is not generally indicated for patients with atrophic AMD but, if they
complain of a recent change in central vision, it is reasonable to use
it in order to verify a possible extension of the atrophic area or exclude
the development of a more aggressive neovascular form.
Angiography
is also useful in patients who have undergone laser treatment in order
to check that the lesion has been fully treated and that there is no
recurrence.
To
this end, the MPS suggested using FA 1, 2, 3, 6, 9 and 12 months after
laser treatment.
Angiographic
appearance of age-related macular degeneration
Non-neovascular
form
This
accounts for the majority of AMD patients, who are affected by drusen
in the ocular fundus and alterations involving the retinal pigment epithelium
(RPE).
Drusen
are nodular deposits that can be distinguished on the basis of their
ophthalmoscopic, fluoroangiographic and histopathological characteristics.
They
can be divided into small (<64 µm in diameter) “hard” drusen, which
are normally hydrophilic and therefore hyperfluorescent during the early
stages of angiography, and disappear during the late stages; or larger
(>64 µm) “soft” drusen with poorly demarcated margins, which are normally
hydrophobic and initially hypofluorescent, becoming fluorescent during
the late stages (Fig.1 and Fig.2 ).
RPE
alterations are another characteristic of the non-neovascular forms,
and may appear as hyperpigmented dots.
They
are histopathologically characterised by hypertrophy or hyperplasia
and the migration of RPE cells to the spaces between the external layers
of the neurosensory retina; during fluoroangiography, they appear as
hypofluorescent areas, without the normal background fluorescence but
with the formation of linear or reticular patterns (Fig. 3). Chorioretinal
atrophy represents the normal evolution of non-neovascular disease and
can be divided into geographic and non-geographic forms on the basis
of its severity.
It
appears as an atrophic area of the pigmented epithelium with indistinct
borders that subsequently evolves into a clearly demarcated area (geographic
atrophy) (Fig.4). The two forms can be histopathologically distinguished
on the basis of the differences in the degree of atrophy of the pigmented
epithelium, choriocapillaris and photoreceptors.
They
are fluoroangiographically characterised by areas of early hyperfluorescence
that remain stable during the course of the examination, but vary according
to the severity of the atrophy. When they are small, they are known
as “window defects”. In the case of more advanced forms of geographic
atrophy involving the choriocapillaris, it is possible to visualise
the layer of the great choroidal vessels.
The
late phases are characterised by the fluorescence of the atrophic area
due to the impregnation of the deep and scleral choroidal tissues.
Neovascular
form
This
occurs when neovascular extensions grow from the choriocapillaris, cross
the layers of Bruch’s membrane, and are distributed below the RPE basal
membrane; they may subsequently also involve subretinal spaces.
The
presence on MNV can be clinically suspected in the case of an uneven
elevation of the RPE or when the neurosensory retina becomes grey-greenish
in colour; other clinical signs include bleeding or the presence of
sub- or intra-retinal fluid.
Although
all of these signs demonstrate the presence of MNV in a patient with
AMD, fluoroangiography is indispensable for a correct differential diagnosis
because similar signs can be found in the case of macroaneurysms and
choroiditis.
FA
plays an important role in determining the extension and type of neovascularisation
and allows more precise decisions concerning therapy and prognosis.
Choroidal
neovascularisations may continue to grow and rapidly increase in size
in a very short period of time; it is therefore necessary to use FA
in order to discover the size and precise location of the borders of
the lesion within one week of laser treatment.
Neovascular
lesions can be fluoroangiographically classified as having an “occult”
or “classic” (manifest) appearance, and an “extrafoveal”, juxtafoveal”
or “subfoveal” location (Fig. 5) depending on their distance from the
foveal region.
Classic
choroidal neovascular membranes
Classic
neovascular lesions are fluoroangiographically characterised by an early
hyperfluorescence that appears even before the complete filling of the
retinal vessels.
It
is sometimes possible to see the filling take place in the form of a
carriage wheel.
The
lesion is clearly demarcated.
During
the course of the examination, the size of the fluorescent area increases
because of the high degree of permeability of the new vessels, but the
borders of the lesion become blurred during the late phases.
The
involvement of the foveal region may cause the formation of a cystoid
macular edema (Fig. 6).
Occult
choroidal neovascular membranes
As
suggested by the MPS, “occult” lesions can be fluoroangiographically
divided into fibrovascular pigmented epithelium detachments (PED) (Fig.
7) and lesions showing late leakage of undetermined source (Fig. 8).
From
a histopathological point of view, they are all fibrovascular lesions.
Fibrovascular PEDs are characterised by an uneven raising of the RPE
with irregular borders.
The
level of fluorescence slightly increases in these lesions and appears
unevenly after about 30-60 seconds; the hyperfluorescence increases
for up to 90-120 seconds, but never reaches the levels of classic lesions.
The
lesions showing late leakage of undetermined source are characterised
by a poorly demarcated hyperfluorescence that accumulates at the level
of the RPE during the late phases.
They
are more easily seen 2-5 minutes after the injection and lead to the
accumulation of the marker in the neurosensory retina. Neovascular lesions
can often have both a classic and occult component (Fig. 9).
New
fluoroangiographic terminology introduced with the advent of photodynamic
therapy The results of the first studies of photodynamic therapy with
verteporfin (TAP) have made it possible to evaluate the lesions that
best respond to the new treatment by introducing a new angiographic
differentiation of “predominantly classic” and “minimally classic” lesions.
The “predominantly classic” lesions are characterised by the presence
of a classic component covering more than 50% of the whole lesion (Fig.
10), whereas the “minimally classic” lesions have a classic component
covering less than 50% (Fig. 11).
Giovanni
Staurenghi
Professore
Associato, Università di Brescia
*
Macular Photocoagulation Study (MPS): randomised, controlled clinical
trial to evaluate the efficacy of laser treatment in the neovascular
forms of age-related macular degeneration
**
TAP: the first RCT to evaluate efficacy and safety of photodinamic therapy
for neovascular AMD.
***
Metamorphopsia: distorted vision due to the imperfect alignment of photoreceptors.
****
Scotoma: blind spot or area of reduced vision (traduzione dell'autore)
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