184
literature included 81 consecutive eyes (79 patients)
with subfoveal choroidal neovascularization treated with
1.25 mg (0.05 cc) intravitreal bevacizumab, at baseline
and 1 month later if morphologic changes attributable
to the CNV persisted (subretinal fluid, pigment epi-
thelial detachment, retinal thickening). Seventy-eight
percent had prior treatment with pegaptanib, photody-
namic therapy (PDT), or both. After one IVB injection,
30 of 81 eyes had resolution of their subretinal fluid.
At 2 months, 50% demonstrated resolution of leakage.
The mean best corrected visual acuity (BCVA) improved
from 20/200 to 20/125 at week 8 (p < 0.0001)
(91)
.
Spaide et al. in a subsequent study evaluated 266 eyes,
70% of which had prior treatment for exudative AMD
(PDT or pegaptanib). At the 3-month follow-up (data
available for 141 patients) 38.3% patients improved by
2 or more Snellen lines. Mean BCVA improved from
20/184 to 20/109 at 3 months (p<0.001). Central
retinal thickness measured by OCT improved over 3
months from a mean of 340 microns to a mean of 213
microns (p<0.001)
(95)
.
A greater visual acuity effect has been reported in
naïve eyes compared to those that have received previ-
ous treatment, for example in a study of 50 eyes (48
patients) treated with bevacizumab for exudative AMD
found that naïve eyes responded more favorably than
previously treated eyes. Six of the 14 (43%) of naïve eyes
gained 3 lines or more of vision versus 17% of eyes that
had undergone prior treatment. The naïve group’s mean
visual acuity improved from 20/160 at baseline to 20/63
(p<0.001) at week 24
(96)
. Such visual acuity gains were
not reported with PDT or pegaptanib treatment and
were comparable to the results of the phase III studies
of ranibizumab.
However, those with longstanding exudative AMD have
also been shown to improve with treatment. One ret-
rospective study in 48 eyes with exudative AMD for
5 months or longer (mean 17.9 months) showed that
25% of those improved at least 3 lines with bevaci-
zumab intravitreous injection after a mean follow-up of
27 weeks
(96)
.
In another prospective case series, Bashshur et al.
injected 2.5 mg (0.1ml) of bevacizumab (twice the
dose most frequently used) into the vitreous in 17 eyes
with wet AMD patients and followed by two additional
injections at four-week intervals. Mean best-corrected
visual acuity was 20/252 at baseline and 20/76 at week
12 (P < 0.001). Mean central subfield retinal thickness
also improved between baseline and week 12 in all 17
patients. No systemic or ocular side effects were noted
(85)
.
5.3 Safety
Data on the safety of intravitreal bevacizumab are more
limited than data on ranibizumab or pegaptanib safety
because there are no large, prospective, controlled safety
studies with this treatment.
Local side-effects are similar to those found for the other
anti-VEGF agents
(98)
.
A safety retrospective study evaluating the side effects
of intravitreal bevacizumab reviewed 1265 patients for
12 months, with 92 lost to follow-up. Ocular complica-
tions included seven (0.16%) bacterial endophthalmi-
tis, seven (0.16%) tractional retinal detachments, four
(0.09%) uveitis, and a case (0.02%) of rhegmatogenous
retinal detachment and another case (0.02%) of retinal
detachment and vitreous hemorrhage
(99)
.
In electrophysiological studies no negative side-effects
were seen on the retina. In contrast, the results showed a
recovery effect on photoreceptors even at the site of the
CNV
(100)
. Most of the in vitro, ex vivo and in vivo exper-
iments excluded short-term negative effects on ocular
cells and histology
(101, 102, 103, 104, 105)
. A paper, however,
discloses mitochondrial disruption in the inner seg-
ment of photoreceptors and apoptosis after high doses
of intravitreal bevacizumab in the rabbit eye. The elec-
trophysiological investigation and light microscopy, in
contrast appeared unaltered. This suggests that potential
side-effects on the cellular level cannot be detected with
the present diagnostic tools in clinical practice
(98, 106)
.
Intravenous use of bevacizumab in patients with
colorectal cancer is associated with severe systemic side
effects including arterial thromboembolism, gastrointes-
tinal perforation, hemorrhage, hypertensive crisis and
nephrotic syndrome. Initial studies using this therapy
intravenously for ocular disease in a healthier popula-
tion did not find nearly the same risks
(107, 108)
.
The dose of intravitreal bevacizumab is much lower
(1/400
th
) of the dose used for intravenous treatment and
has not been found to result in unexpected systemic side
effects
(92)
.
There are no studies adequately undertaken to identify
rare systemic events. In a 3-month retrospective study
of bevacizumab treatment in 266 patients, 1 (0.4%)
developed a nonfatal myocardial infarction after the
third injection. Two patients (0.8%) had apparent tran-
sient ischemic attacks (diagnosis was not definitive).
There were 2 deaths, one from myocardial infarction.
Nevertheless, that patient was a smoker with a history
of emphysema. It is important to consider, however,
that this population (mean age, 80.3 years) is at risk for
