الفهرس 
VEGF and its role in neovascular and
Heparin binding affinityOnly 14 pages are availabe for public view
 |  | from | 170 |  |  |
| | | from | 170 | | |
Abstract
Ocular neovascularization is the fundamental pathology
in the form of abnormal angiogenesis that leads to vision
loss in a wide range of ocular diseases. The most frequent
sites of ocular neovascularization are:
1- Choroidal: as in wet Age related macular degeneration
and pathologic (progressive) myopia.
2- Retinal: as in proliferative diabetic retinopathy, central
and branch retinal vein occlusion and retinopathy of
prematurity.
3- Corneal: due to ischemia, trauma, infections, keratoplasty
and interstitial keratitis.
A number of cytokines and growth factors that activate
endothelial cells were found to modulate the formation and
regression of the abnormal vessels in this process. Under
certain pathological circumstances such as hypoxia,
ischemia, inflammation, infection and trauma, the balance
between angiogenic stimulators and angiogenic inhibitors is
disturbed, leading to the formation of new vessels.
Vascular endothelial growth factor (VEGF) has been
demonstrated in multiple studies to be necessary and central
to the process of ocular neovascularization. VEGF binds to
two receptor tyrosine kinases: VEGF receptor (VEGFR)-1
and VEGFR-2. Another receptor (VEGFR-3) involved in
the regulation of the lymphatic system.
It was found that VEGF inhibition can effectively
abolish the neovascular process. Targeting VEGF includes:
1- Monoclonal antibodies directed against VEGF.
2- Targeting its receptors: VEGFR-1 and VEGFR-2. or
118
3- Small molecule tyrosine kinase inhibitors that act
intracellularly to prevent autophosphorylation and activation
of downstream growth –promoting signaling cascades.
Examples of anti-VEGF therapies
Pegaptanib sodium ( Macugen ) .
Ranibizumab ( Lucentis ) .
Bevacizumab ( Avastin ) .
VEGF trap (Regeneron).
Small Interfering RNA-Based therapies as Cand5,
Sirna-027.
Tyrosine kinase inhibitors such as vatalanib.
Bevacizumab ( Avastin ) is a recombinant full-length
humanized monoclonal IgG1 antibody that is derived from
the murine VEGF monoclonal antibody. It binds all
isoforms of VEGF-A and its biologically active cleavage
by-products. It is currently approved as an intravenous
treatment for colorectal cancer with the most significant
disadvantages of the possibility of life-threatening adverse
events as thromboembolic events, hypertension, proteinuria,
bleeding events, allergic reactions and delayed wound
healing after surgery. Furthermore, systemic VEGF
inhibition could be deleterious to the normal eye as
maintenance of the choriocapillaris in a normal eye is
believed to require VEGF.
In neovascular eye diseases, bevacizumab shows :
1-Antiangiogenic capabilities
2-Anti-exudative effects through lowering transendothelial
permeability of blood vessels
The initial trials on systemic avastin in ophthalmology
were on AMD (SANA study). Then, A lot of studies and
case reports evaluated the efficacy and safety of intravitreal
bevacizumab in treatment of AMD.
119
Bevacizumab in AMD
Intravitreal bevacizumab for AMD showed visual
improvement that can last 9 months with continued
treatment with no significant difference between various
types of subfoveal CNV lesions in AMD and the patients
who previously treated with some other form of therapy had
the same change in VA as those treated primarily with
bevacizumab. These improvements in VA were related to
decrease in CRT and fluorescin leakage from CNV in the
majority of subjects.
Also, combined therapy in AMD was associated with
improvements in BCVA and central foveal thickness
reductions with PDT and intravitreal bevacizumab. With
triamcinolone, there was significant decrease in
postinjection foveal thickness in addition to a significant
decrease in fluid volume.
Bevacizumab in pathological myopia
Visual improvement was reported in cases of CNV
secondary to pathological myopia with systemic
bevacizumab or after intravitreal injections. Also, reduction
of FA leakage, decreased SRF, retinal thickness and
intraretinal fluid by OCT were reported in such cases. It was
suggested that bevacizumab may be a good strategy for
management of CNV secondary to pathologic myopia but
further studies are needed to confirm the role of VEGF in
pathogenesis of CNV in such cases.
Bevacizumab in diabetic retinopathy
Short-term results suggest that IVB is well tolerated and
associated with a rapid regression of retinal and iris
neovascularization secondary to proliferative diabetic
retinopathy with improvement of VA after IVB and also
120
after intracameral injection of the drug in anterior chamber.
Also, there were involution of neovascular vessels with a
reduction in caliber or absence of visible perfused vessels
and marked reduction of vitreous hemorrhage and
subhyaloid hemorrhages due to PDR after IVB.
An interesting finding was reported because there was a
significant reduction in the leakage of NVD of the fellow
uninjected eye raising the concern that systemic side effects
are possible in patients undergoing treatment with
intravitreal bevacizumab.
Bevacizumab in diabetic macular edema
There was an improvement in BCVA in most cases of
DME after IVB with reduction in mean CRT by OCT that
maintained up to 6 months of follow up but a significant
higher change in BCVA and CRT reductions with
intravitreal triamcinolone rather than bevacizumab were
noted suggesting a possible higher efficacy of triamcinolone
in cases of DME.
Bevacizumab in macular edema secondary to RVO
Intravitreal bevacizumab for patients with ME secondary
to CRVO resulted in a significant decrease in ME and
improvement in VA with more favorable results within the
first 3 months after RVO compared to later injections and a
less VA improvement for BRVO patients compared to
CRVO patients