55
Development and Progression of AMD
ability to induce complement activation. Several stud-
ies performed by Seddon and colleagues
(21,22)
showed an
association between CRP levels and AMD and elevated
CRP levels may serve as a marker for AMD progres-
sion. However, Hogg and colleagues found no signifi-
cant association between CRP plasma levels and AMD
or AMD progression in both case–control and prospective
studies
(23)
.
5. Interleukin-6
IL-6 is a marker for systemic inflammation, such as acute
pancreatitis, chronic arthritis and geriatric syndromes.
Seddon and colleagues found a correlation between the
level of IL-6 and chances of AMD progression
(22)
. This
study shows that elevated IL-6 levels may serve as a marker
for progression of AMD. However, Klein and colleagues
found no significant association between IL-6 plasma levels
and AMD or AMD progression
(24)
.
6. Fibrinogen
Fibrinogen is an established biomarker of acute and
chronic inflammation
(25,26)
. Lip and colleagues found ele-
vated levels of plasma fibrinogen in AMD cases compared
with controls
(25)
. A case–control analysis from the large
Blue Mountains Eye Study in Australia detected signifi-
cantly elevated plasma fibrinogen levels in AMD patients
compared with controls (p < 0.05)
(27)
. In another study
using patients recruited from the Muenster Aging and
Retina Study population in Münster (Germany), no asso-
ciation between plasma fibrinogen levels and AMD was
showed
(28)
.
7. Vascular endothelial
growth factor
There is strong evidence suggesting that VEGF is a good
candidate AMD biomarker. VEGF is also elevated in
RPE cells of AMD patients and in the AMD patient post-
mortem eyes
(25)
. This evidence points to a role for elevated
VEGF levels in AMD. A study by Lip found increased
plasma VEGF levels in 78 AMD patients compared with
25 age-matched controls (p = 0.0196)
(25)
with no signifi-
cant difference found between dry and wet AMD cases in
a comparison of plasma VEGF values
(25)
.
Tsai and colleagues found increased plasma VEGF lev-
els in 77 AMD patients compared with 42 controls
(p < 0.001)
(30)
and significantly higher plasma VEGF levels
in wet AMD patients compared with dry AMD patients
(p < 0.05)
(30)
. These results suggest that high VEGF levels
may play a role in predisposing individuals to neovascular
AMD. Additional studies must be undertaken to establish
its role as a biomarker for this disease.
8. Functional multimodal imaging of
the macula
Multimodal imaging of the macula provides improved
visualization of the macular alterations seen in early
ARM.
• Color Fundus Imaging
• Fluorescein Angiography
• Indocianine Green Angiography
• Fundus Autofluorescence
• Optical Coherence Tomography
• Retinal Leakage Analyzer
8.1 Color fundus imaging
Grading of stereoscopic color photographs collected dur-
ing 5 years of follow-up in more than 3000 AREDS par-
ticipants were used to develop a detailed grading scale
(29)
.
A simplified scale was developed based on the presence
or absence of 2 features characteristic of AMD that were
easily identified clinically (drusen size and pigment
abnormalities) and highly associated with the develop-
ment of advanced AMD, especially when the status of
both eyes was considered.
Color fundus imaging and AREDS photographic grad-
ing helps us to make an AMD severity scale that would
provide clinically useful risk categories for the develop-
ment of advanced AMD in persons with earlier stages of
AMD. Defining risk factors and counting them provides
a convenient way to define risk categories. These catego-
ries may be useful in discussing with patients their risk of
progression to vision-threatening AMD and in develop-
ing inclusion criteria for clinical studies of AMD. The
simplest scheme counts the presence of at least 1 large
drusen (diameter greater than or equal to that of a large
vein at the disc margin) and the presence of any pigment
abnormality as 1 risk factor each and sums their pres-
ence across both eyes when both are free of advanced
AMD. One risk factor is assigned to patients who have
no large drusen in either eye but intermediate-sized dru-
sen (diameter ≥ one half that of a large drusen) in both
eyes (Table 1).
The 5-year risk of advanced AMDusing this scale increases
