136
prove the efficacy or safety of anyone.
Direct laser photocoagulation of leaking polyps has
proven short-term safety and efficacy for extrafoveal
lesions
(35,36,37,38)
. Other authors however described poor
results
(39)
and persistence or even increasing exudation
in up to 44% of the cases
(10)
, or VA decrease of 2 or
more lines in near half of the eyes and legal blindness in
up to two third of the eyes
(28)
. Yuzawa et al.
(38)
reported
good efficacy of laser photocoagulation in near 90% of
the eyes if all the polyps and abnormal vascular network
were treated. If the treatment involved only the polyps
more than half of the eyes suffered VA decrease related
with exudation, recurrences, or foveal scars. Direct laser
photocoagulation of feeder vessels, identified in ICG,
was also reported as showing VA improvement of 2 or
more lines in 8 out of 15 eyes
(40)
. Considering the pos-
sibility of using other treatment modalities, laser photo-
coagulation should be reserved for well defined extrafo-
veal active polyps.
Transpupillary thermotherapy has shown to be useful
in PCV
(41)
. A large number of reports on photodynamic
therapy with verteporfin in subfoveal PCV has been
published
(17,20,42-46)
. Results at one year and even at two
years are apparently superior to those of PDT in pre-
dominantly classic or occult CNV. A longer follow-up
shows a trend to a progressive but not significant VA
decline at two
(46)
and 3 years follow-up
(47)
: the rate of
eyes gaining a significant amount of vision dropped from
26% in the first year to 15% in the third year, and the
rate of eyes with significant VA loss (3 or more ETDRS
lines) increased from 17% to 26%. A high rate of recur-
rence (44%) occurred during the 3-years follow-up but
it was not associated with significant VA decline
(47)
. This
high rate of recurrences may be associated with a poor
response of the vascular network to PDT
(48)
. VA decline
at 3 years may partially be explained by photoreceptors
death due to chronic or recurrent neurosensory detach-
ment, massive hemorrhages and progressive retinal PE
atrophy. The number of treatments decreases mark-
edly after the first year from an average of 2.0 to 0.4
and 0.5 in the second and third years respectively
(47)
.
Complications like subretinal haemorrhages, haemor-
rhagic PED or even massive hemorrhages have been
associated to PDT in PCV eyes
(49)
. However, all of these
complications may also occur without any treatment.
Surgical removal of polypoidal lesions and associated
hemorrhages has been reported
(10-14,50)
with and without
macular translocation. Considering the potential alter-
native treatments and the high rate of serious complica-
tion macular translocation is no longer being considered
for PCV
(51)
. The relatively large vascular lesions of PCV
patients needs to be considered if a vitrectomy is planned
in cases without associated massive hemorrhage.
Intravitreal antiangiogenic drugs, like bevacizumab
(52)
and ranibizumab
(53)
have been used for treating PCV
eyes. Ranibizumab short-term results
(53)
seem to be
promising in terms of maintenance of VA or VA
improvement, resolution of subretinal fluid and PED.
Polyps were reported to disappear in 69% of the cases,
at 3 months when using ranibizumab
(53)
but not with
bevacizumab
(52)
. Intravitreal bevacizumab appeared
also to result in stabilisation of vision and reduction of
exudative retinal detachment in PCV patients in short-
term evaluation. However, it had limited effectiveness
in causing regression of the polypoidal lesions
(52)
. Some
exudative AMD eyes refractory to ranibizumab or beva-
cizumab may be, in fact, PCV cases. Combined treat-
ments associating PDT and intravitreal ranibizumab or
bevacizumab have been reported to show good efficacy
in these refractory cases of AMD
(54)
.
The EVEREST study is the first multi-center, double-
masked, indocyanine green angiography (ICG-A)-
guided randomized controlled trial with an angio-
graphic treatment outcome designed to assess the effect
of Visudyne® (verteporfin photodynamic therapy) alone
or in combination with Lucentis® (ranibizumab) com-
pared with Lucentis® alone in patients with symptom-
atic macular polypoidal choroidal vasculopathy (PCV).
A total of 61 PCV patients of Asian ethnicity from 5
countries (Hong Kong, Taiwan, Korea, Thailand, and
Singapore) participated in the study.
The six months EVEREST study results
(55)
suggests
that in a majority of patients, Visudyne® therapy, with
or without Lucentis®, may lead to complete regres-
sion of the polyps that can cause vision loss in patients
with PCV. A complete polyp regression (primary end-
point) was achieved in 77.8% of patients who received
the Visudyne® – Lucentis® combination, in 71.4%
of Visudyne® monotherapy patients and in 28.6% of
patients in the Lucentis® monotherapy group (p=0.0018
for combination, p=0.0037 for Visudyne® vs. Lucentis®).
Best corrected visual acuity from baseline to month six
improved in average in all groups with patients in the
combination group achieving the highest gain (+10.9
letters from baseline). Lucentis® monotherapy patients
gained +9.2 letters, and Visudyne® monotherapy
patients +7.5 letters. Differences between the groups are
not statistically significant. All therapies were well tol-
erated and the safety findings were consistent with the
established safety profiles of Visudyne® and Lucentis®.
