The use of anti vegf in corneal neovascularization
1. THE USE OF ANTI VEGF IN
CORNEAL NEOVASCULARIZATION
INFECTION AND IMMUNOLOGY SUB DIVISION
DEPARTEMENT OPHTHALMOLOGY
MEDICAL FACULTY OF ANDALAS UNIVERSITY
2019
RIKHA ERINA
3. Affect visual
prognosis and
quality of life
Common
causes :
• Infection
• Inflammation
• Trauma
• Degeneration
It can lead to
tissue :
• Scarring
• Oedema
• Lipid deposition
• Persistent
inflammation
3
4. Corneal
Neovascularization
One study reported
the estimated incidence
rate of 1.4 million
people per year
12% of whom suffered
subsequent loss of
vision
20% of corneal
specimens taken from
corneal transplant
procedures have shown
evidence of corneal
neovascularization
4
8. DEFINITION
The formation of
new blood vessels
in previously
avascular
VASCULOGENESIS
8
NEOVASCULARIZATION
ANGIOGENESIS
￮ The formation of new blood
vessels from bone marrow-
derived angioblasts,
￮ Embryogenesis
￮ The formation of new blood
vessels from pre-existing
vasculature.
￮ menstrual changes to the
endometrium
￮ Tumor metastasis,
￮ ocular neovascular
disorders including CNV
9. CORNEAL
NEOVASCULARIZATION
￮ The formation of new blood vessels in
to conea
￮ Up regulation of pro angiogenic
cytokines
￮ Response to inflammatory, infection,
hypoxic condition, deficiency of limbal
stem cell
9
DEFINITION
11. Epidemiology
285 Million
visual
impairment
39 Million
Blind
Corneal
disease
common
cause of
blindness in
some
developing
countries
CNV
potensial
sequele
1,4 million
case of CNV
in USA
11
WHO
15. Inflammation & infection
Chemical burn,
infection,
immune
response
Macrophages
Pro Angiogenic
fc
Recruitment
macrophages
Immune
amplification
cascade
Pro Angiogenic
fc and
proteolytic
enzyme
15
17. Inflammation, Hypoxia, LSCD-induced CNV
Release of
angiogenic
growth factors
• causing vasodilation of limbic
vessels
• Recruitment of leukocytes to release
pro-angiogenic mediators
• The vascular ECM is degraded
(MMP)
• Endothelial cells loosen their cell–cell
adhesions
• Proliferate and migrate ECs
• Forming new vessels.
Bind and activate
endothelial cell
Receptors
As these vessels mature,
supporting cells (pericytes)
are recruited, and finally the
arteriovenous loops are
closed
17
PATHOGENESIS
18. VEGF
SUB FAMILY GROWTH
FACTOR
HAS A MAJOR ROLE IN
THE VASCULOGENESIS
AND ANGIOGENESIS
INCREASE CAPILLARY
PERMEABILITY
18
1979 BY HAROLD
DVORAK
FIRST IDENTIFY AS
VASCULAR
PERMEABILITY FACTOR
1989 BY NAPOLEONE
FERRARA VEGF
21. 21
VEGF A IS CRUCIAL
FACTOR FOR
FORMATION AND
MATURATION IN
EMBRYONIC AND
ADULT TISSUE
BIND WITH ITS
RECEPTOR
VEGFR-1 AND VEGFR-2
ACTIVATED
ANGIOGENIC CASCADE
24. TYPES OF ANTI VEGF
RANIBIZUMAB
￮ Humanized
antibody
fragmen
￮ Molecular
weight 48 kD
￮ All isoform
VEGF
￮ Half life 2.2
day
systemic, 9
day ocular
VEGF Trap
(AFLIBERCEPT)
￮ A fusion
protein that
bind with all
isoform
VEGF
￮ Molecular
weigh 115 kD
￮ Act as traps
of VEGF
receptors
BEVACIZUMAB
￮ Humanized
monoclonal
antibody
￮ Molecular
weigh 149 kD
￮ Off label
￮ Half life
systemic 20-
21 day,
ocular 8 day
24
26. Topical
administration
Poor penetration in to
the intact epithelium of
cornea
Well penetration in to
vascularization of
cornea
Need
repeated
administration
reach
sufficient
concentration
to cornea
MOZANO ET AL
• Topical bevacizumab
4MG/ML, 2X/DAY, 1
WEEK
• Decrease of area
neovascularization
26
27. Adverse effect
King et al
Bevacizumab
1,25% topical
2xday, 3
month
￮ 6 from 10 eye
￮ Epitheliopathy
Thinning of cornea
￮ In the second month
27
28. Subconyungtival administration
￮ Difuse to
stromal of
cornea
￮ Persist
several day
after
injection
￮ Bevacizumab
injection has a
maximum effect
around the cornea
￮ while the opposite
peripheral side of the
cornea can get
inadequate
concentration.
28
Garten
￮ Divided in 2 doses
￮ Injected at 6 & 12
o’clock
￮ 1 mm, posterior
limbus
29. Doses :
￮ 2.5 mg / 0.1
ml
￮ 1.25 mg /
0.05 ml
￮ The
injection
must be
repeated
to get the
optimal
effect.
Bahar et al
￮ No reaction at the
first anti-VEGF
injection, but the
reaction only
appeared after
repeated
injections.
29
Subconyungtival administration
30. Intrastromal
administration
Belghmaidi,
et al
25 eyes with
deep corneal
neovessel
￮ Bevacizumab
intrastromal
0,25mg/0,01 ml
￮ Complete regression
neovessel in 14 eyes,
￮ parsial regression in 6 eyes,
￮ reduce opacity of cornea in
5 eyes
30
intrastromal injection of
bevacizumab is effective as
adjunctive therapy including mature
neovessels
34. DESTAFENO
￮ A, The patient’s cornea is shown prior to topical
bevacizumab treatment, displaying extensive
neovascular vessels, most evident inferiorly.
￮ B, Reduction in vascularization resulted after 25
days of topical therapy. 34
A B
38. Nn. A, 13 y
Post corneal rupture
￮ Before topical bevacizumab
38
￮ After topical bevacizumab 5%,
4x/day, 2 weeks
3 w
39. conclusion
Corneal neovascularization is characterized by new invasive blood vessels
into the cornea from pre-existing blood vessel structures, this is caused by an
imbalance between pro angiogenic and anti angiogenic factors.
Corneal neovascularization caused by three mechanism such as hypoxia,
infection and inflammation as well as the limbus barrier function.
VEGF is considered a key mediator of the process of angiogenesis in corneal
neovascularization.
39
40. 4. VEGF can be expressed in 3 layers of corneal, epithelial,
stromal, and endothelial cells, most strongly expressed in
endothelial cells of limbic vascular pericornea and macrophages.
5. Several clinical trials prove that the administration of anti-
VEGF in cases of corneal neovascularization has an efficacy and
is efficient in reducing corneal neovascularization, either by
topical, subconyunctival, or intrastromal administration.
6. Long-term use of anti-VEGF can have side effects on the
cornea, depending on the route of administration of the drug.
7. Provision of anti-VEGF in corneal neovascularization only as
additional therapy.
40
45. 45
Cheng
dkk
• Short-term topical bevacizumab
treatment reduce the extent of
stable CNV as measured by the
area and caliber of vessels.
• Treatment effects persisted after
treatment discontinuation.
• Eyes with smaller areas of stable
CNV at baseline demonstrated
greater responses to topical
bevacizumab treatment than eyes
with larger areas of
neovascularization invasion,
Bevacizumab 1 %
topical
3 weeks
75. Fig. 1. Slit lamp photographs
demonstrating CNV.
Necrotic corneal ulcer and
persistent epithelial defect with
surrounding ring infiltrate and
CNV secondary to
acanthamoeba (1 A,)
Stromal CNV from acute stromal
rejection of a deep anterior
lamellar keratoplasty (1 B).
Regressing deep CNV with mild
surrounding haze and lipid
secondary to HSV immune
stromal keratitis (1C).
Deep frond of CNV with
accompanying lipid deposition
from long-term rigid gas
permeable contact lens abuse
(1D).
75
76. ￮ Slit lamp photographs of
CNV secondary to limbal
stem cell deficiency
￮ from various etiologies
are depicted:
￮ Stevens Johnson
Syndrome (2 A),
￮ Alkaline chemical
injury (2 B),
￮ Mucous membrane
pemphigoid (2C),
￮ Long-term soft contact
lens abuse (2D).
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