180
were: loss of 5 letters in VA, presence of fluid in the
macula detected by OCT; increase ≥ 100 µm in central
retinal thickness (CRT); de novo classic choroidal neo-
vascularization; de novo macular haemorrhage; or per-
sistent macular fluid detected by OCT. Despite similar
VA outcomes to those observed in the
MARINA
and
ANCHOR
studies having been observed with a smaller
number of intravitreal injections, comparisons are lim-
ited by substantial differences in study design. Although
being a small, open-label trial, this study suggests that
individual retreatment based on OCT results allows
visual gains to be maintained with a smaller number of
injections
(45,54)
.
The
SAILOR
-cohort 1 study evaluated the efficacy and
safety of 3 consecutive monthly injections followed by
quarterly monitoring visits, injections according to VA
criteria (loss of > 5 letters from the maximum previous
VA score) and OCT, if available (increase > 100 µm in
CRT from the lowest previous measurement). Additional
visits/injections would take place if required. Average
VA increased from baseline after the first 3 injections,
having subsequently decreased to an average gain of 2.3
letters for both ranibizumab doses, a better outcome
than that observed for the
PIER
study, albeit subopti-
mal compared to those observed in the
ANCHOR
and
MARINA
studies. These results indicate that quarterly
visits are not sufficient to monitor and evaluate disease
progression
(45,55)
.
The objective of the
SUSTAIN
study was to evaluate the
efficacy of 3 consecutive monthly injections followed by
monthly monitoring and treatment according to the fol-
lowing criteria: loss of > 5 letters from the maximum
previous VA score, in the first 3 months; or increase >
100 µm in CRT from the lowest previous measurement,
in the first 3 months. It was observed at month 12 that
the majority of visual gains achieved in the first 3 months
had been maintained. Although this study consisted only
of an interim analysis of 69 patients, the corresponding
results suggest that efficacy outcomes may be maintained
by a flexible regime with a smaller number of intravit-
real injections and monthly monitoring. However, some
VA loss occurred after month 3, whereas fixed monthly
injections led to additional VA gains during the mainte-
nance stage
(51,56)
.
In summary, the best VA outcomes were achieved with
the monthly regime. The poorest, albeit variable, efficacy
outcomes were observed in studies with < 5 intravitreal
injections. The
PrONTO
and
SUSTAIN
studies demon-
strated that monthly monitoring is required to maintain
efficacy benefits, when compared to the
SAILOR
-cohort
1 study, which included compulsory quarterly monitor-
ing visits, although more frequent follow-up was per-
formed in many patients.
Therefore, ranibizumab emerges as the first approved
neovascular AMD therapy (FDA approval in June 2006)
able to improve visual acuity, having thus been recom-
mended as first line therapy by many Ophthalmological
Societies (e.g., the Royal College of Ophthalmologists,
the German Ophthalmologists Association, etc.) and
NICE (National Institute for Health and Clinical
Excellence)
(57)
.
Extension study
HORIZON
was performed in order
to evaluate efficacy and safety after the first 2 years.
This study was designed as a post-marketing surveil-
lance to monitor the safety and tolerability of Lucentis®,
with a follow-up period of up to 3 years. HORIZON
enrolled 853 patients who had already completed one
of the 2-year randomized Lucentis® trials,
ANCHOR,
MARINA
or
FOCUS
(58,59)
.
While participating in the
ANCHOR, MARINA
or
FOCUS
studies, patients received monthly injec-
tions (active treatment with Lucentis® or Visudyne®, or
sham). During the
HORIZON
study, patients attended
fixed quarterly visits; however, visit frequency could be
increased by the investigator if they deemed it necessary
to see the patient more often. Lucentis® 0.5 mg injec-
tions were given on an as-needed basis, when the inves-
tigator felt that the patient would benefit from Lucentis®
treatment. The interval between injections was at least 30
days.
After 2 years (preliminary results), 69% of the 600 initial
Lucentis®-treated patients received their injections. Visual
Acuity was available for 384/600 patients. Among these
384 patients, median Snellen VA had increased by 3 lines,
from 20/100 to 20/50, during the initial 2-year trial, hav-
ing subsequently decreased by 2 lines from the
HORIZON
baseline to 20/80, at year 2 of the
HORIZON
study.
Overall, the safety profile of Lucentis® was very good and
consistent with previous pivotal clinical trials of Lucentis®.
In general, better VA and anatomical outcomes after the
first 2 years delayed the need for subsequent retreatment.
Additionally, the need for early AMD treatment was
somewhat confirmed. Some loss of previously achieved
VA gains occurred, eventually related to sub-treatment
during the extension period.
Loss of visual acuity and the need for retreatment dur-
ing the
HORIZON
study shows that the disease remains
active after the first two years of monthly injections, evi-
dencing the need for careful patient monitoring, as well as
timely retreatment.
