To determine if sequential treatment with
Bevacizumab (
Avastin), a monoclonal,
VEGF antibody that blocks angiogenesis;
Saratin, a 12 kD
polypeptide with anti-inflammatory and anti-thrombotic properties; and
Ilomastat, a
matrix metalloproteinase (
MMP) inhibitor, prolongs
bleb life following
glaucoma filtration surgery (GFS) in a rabbit model. Thirty-two New Zealand White rabbits (eight rabbits per group) underwent GFS in the left eye. Group 1 received a perioperative injection of both
Saratin and
Bevacizumab, and later, subconjuctival
injections of
Ilomastat on days 8 and 15. Group 2 received only
Saratin perioperatively, and also received
Ilomastat injections on days 8 and 15. Group 3, the negative control, received a single perioperative injection of Balanced
Saline Solution (BSS) along with post-operative BSS
injections on days 8 and 15. Group 4, the positive control, received topical treatment with
Mitomycin-C (MMC) at the time of surgery with no further treatment.
Blebs were evaluated by an observer masked to treatment every third day. Histology was obtained on two eyes in each group on post-op day twelve as well as all eyes following
bleb failure. Eyes in group 1 had a mean
bleb survival time of 29 ± 2.7 days, whereas those in group 2 that received the experimental treatment without
Bevacizumab had a mean survival time of 25.5 ± 2.7 days. An ANOVA test showed that the
Saratin/
Ilomastat/
Bevacizumab group demonstrated a significant prolongation of
bleb survival compared to the BSS control-mean survival time of 19.7 ±2.7 days-(p = 0.0252) and was not significantly different from the MMC positive control group (p = 0.4238)-mean survival time of 32.5 ± 3.3. From tissue histology at day 12, the four different groups showed marked differences in the cellularity and
capsule fibrosis. The MMC eyes showed minimal cellularity, were avascular and had minimal fibrous tissue. BSS group showed high cellularity, moderate to high
fibrosis, and thicker and more defined capsules than either of the treatment groups and the positive control. Both the
Saratin/
Ilomastat/
Bevacizumab and
Saratin/
Ilomastat only eyes showed moderate cellularity with minimal
fibrosis, with less cellularity and
fibrosis present in the triple treatment group. Sequential
therapy with multiple agents, including
Bevacizumab, prolonged
bleb function following GFS in the rabbit model and were significantly better than the negative BSS control. The experimental group did not show the same surface tissue histological thinning and side effects associated with MMC treatment.