173
the Anchor
(16)
and
Focus
(19)
trials showed more favour-
able results in terms of visual acuity gain in the Anchor
patients, which included only treatment naïve patients,
suggesting that adding PDT to Ranibizumab may not
increase the visual acuity gain.
The SUMMIT program, which includes three random-
ized clinical trials - DENALI, EVEREST and MONT
BLANC, was designed to compare a combination
therapy with PDT and ranibizumab with ranibizumab
monotherapy. The DENALI study is a two-year, ran-
domized, double-blind multicentric study conducted
at 45 centres in the United States and five centres in
Canada. Enrolled patients with subfoveal CNV of all
angiographic subtypes were randomized to receive either
ranibizumab monotherapy, a combination of ranibi-
zumab and standard fluence PDT or a combination
of ranibizumab and reduced-fluence PDT. Results are
being awaited. MONT BLANC, a similar study con-
ducted at 50 centres throughout Europe, enrolled sub-
jects with subfoveal CNV of all angiographic subtypes,
who were randomized to receive either ranibizumab
monotherapy or ranibizumab in combination with
standard-fluence PDT. Preliminary visual acuity results
at 12 months revealed the non-inferiority of the com-
bined treatment (PDT+Ranibizumab), when compared
with Ranibizumab alone; the number of treatments and
safety evaluation were similar in both groups. These
results and those from Focus trial suggest that PDT with
standard fluence may be useful in combination with
Ranibizumab for treating predominantly classic, mini-
mally classic or occult AMD lesions. The awaited results
from the Denali study will show whether reduced flu-
ence entails any additional efficacy or safety.
Certain angiographic lesion subtypes, such as retinal
angiomatous proliferation (RAP) and polypoidal cho-
roidal vasculopathy appear to respond differently to
PDT treatment
(25,26)
when compared to predominantly
classic, minimally classic or occult lesions. It is unclear
whether they are more likely to benefit from a combina-
tion therapy.
Polypoidal choroidal vasculopathy (PCV) may be con-
sidered as a well-defined subtype of AMD with a distinct
natural history characterized by multiple recurrences
and specific response to treatment. PCV often follows a
remission-relapsing course and usually has a good visual
prognosis. However, up to half of patients may have per-
sistent bleeding and leakage, leading to vision loss.
Although no data are available from randomized con-
trolled trials of verteporfin PDT in PCV, numerous cases
demonstrated that total polyp regression or complete dis-
appearance of PCV lesions occurred in 56–95% of ≥200
eyes treated with verteporfin PDT
(25,26)
. These studies indi-
cated that many verteporfin-treated patients had stable or
improved vision (Table 4), with outcomes that compared
favourably with the natural history of PCV. Few reports
have been published on the use of intravitreal antiangio-
genic drugs, namely Bevacizumab, for the treatment of
PCV. Although a reduction in leakage was shown, this
appears to be ineffective in reducing choroidal vascular
changes. The EVEREST study (part of the SUMMIT
programme) is being performed in Asia and is designed to
evaluate whether verteporfin PDT monotherapy, or com-
bination with ranibizumab, is superior to ranibizumab
alone in symptomatic PCV. Until more evidence emerges,
PDT, alone or in combination with antiangiogenic drugs,
remains the first choice for treating PCV.
Photodynamic Therapy
