57
Development and Progression of AMD
angiography may demonstrate neovascular connections
between the choroid and retina, in the form of anasto-
moses. The presence of late ICG hot-spots may be an
important biomarker in the development of neovascu-
lar membrane. They appeared not only when a RAP
developed but in other forms of CNV as well. The hot
spots may appear not only when conversion occurs but
even before conversion suggesting that this finding may
be associated to future conversion in some subtypes of
neovascular AMD.
8.4 Fundus autofluorescence
Fundus autofluorescence (FAF) imaging is a
non-invasive method for examination and follow-up
patients with macular disease that supplies additional
information to that obtained using fundus photog-
raphy and fluorescence angiography
(36)
. It is based
on the detection of fundus autofluorescence, which
is associated primarily with the lipofuscin content
of retinal pigment epithelium
(36)
. Areas of increased
FAF may correlate to areas of hyperpigmentation,
yellowish soft drusen, or normal fundus appearance.
However some drusen are related to areas of decreased
FAF. Areas covered with reticular drusen usually
show a reticular FAF pattern with small areas of
decreased FAF surrounded by normal FAF. The areas
of hypopigmentation on fundus photographs may be
associated with decreased FAF suggestive of absence
of retinal pigment epithelium or degeneration. There
are also FAF images with no or minimal changes in
patients with funduscopically visible drusen, and vice
versa
(36)
. Smith et al
(37)
have retrospectively studied
the relationship between reticular patterns of auto-
fluorescence and choroidal neovascularization. They
showed that reticular hyperfluorescence appears to
be a marker for reticular pseudodrusen, which are
known to be frequently associated with CNV devel-
opment. Other studies have suggested a higher risk of
CNV development in eyes showing a patchy pattern
of autofluorescence
(38,39)
. In our series, among the eyes
which developed CNV in study eye during follow-up
no clear pattern of association could be established
to their predominant FAF pattern at baseline. In this
study the presence of a pattern of minimal change in
fundus autofluorescence at baseline in eyes with neo-
vascular AMD in the fellow eye appears to indicate a
lower risk of developing CNV at two years. Eyes with
fewer abnormalities in FAF pattern at baseline appear
to have a slower progression to neovascular AMD in
patients with unilateral neovascular AMD. The rela-
tively small population studied makes necessary fur-
ther studies with a more prolonged follow-up in order
to clarify the relationship between fundus autofluo-
rescence and the risk for progression to neovascular
AMD, which was not apparent in this two-year study.
Fundus autofluorescence imaging can be even more
effective in evaluating ARM progression when it is
combined with Optical Coherence Tomography, as
with Spectralis HRA+OCT (Heidelberg Engineering).
With the simultaneous recordings of high-resolution
OCT, it is possible to evaluate corresponding mor-
phological substrates like underlying microstruc-
tural changes in the retina and the retinal pigment
epithelium
(40,41).
8.5 Stratus OCT
Stratus OCT showed increased retinal thickness from
intraretinal fluid accumulation in every eye that devel-
oped CNV. This increase in fluid accumulation, how-
ever, could not be identified before conversion, in any
of the eyes. OCT findings confirm that this method
is a good indicator of the presence of active CNV
and therefore can be used reliably to monitor CNV
treatments
(42)
.
8.6 Retinal leakage analyser
The retinal leakage analyzer showed leakage of fluo-
rescein into the vitreous associated with the area of
CNV, confirming the observations of Merin et al
(43)
,
using vitreous fluorometry. Leakage location corre-
lated well with the CNV site. Furthermore, it showed,
before conversion, sites of abnormal breakdown of the
blood-retinal barrier in 13 of the 17 eyes (76%) that
converted to exudative AMD. An alteration of the
blood-retinal barrier appears, in this study, to be a par-
ticularly promising predictor of conversion from dry
to wet AMD. There were also sites of alteration of the
blood-retinal barrier in 23% of the study eyes that did
not convert during the two-year period of the study. It
is now of particular interest to follow closely the future
evolution of these eyes to see if these eyes with early
ARM and localized alterations of the blood-retinal bar-
rier demonstrated by the retinal leakage analyzer are the
first to develop CNV.
We believe that by examining the natural history of eyes
at high risk of converting from early ARM to exudative
AMD designing a different imaging methodologies of
these will help us to obtain a better understanding of what
