This document discusses anti-VEGF drugs, which block VEGF to inhibit abnormal blood vessel growth in retinal diseases. VEGF stimulates angiogenesis and vascular permeability. Anti-VEGF drugs like bevacizumab, ranibizumab, and pegaptanib work by binding to VEGF and preventing its interaction with receptors. They are administered via intravitreal injections and used to treat wet AMD, diabetic retinopathy, and other retinal conditions involving neovascularization or edema.

1. ANTI VEGF's
Dr.Sahitya

2. Introduction
• VEGF's are responsible for growth of blood
vessels.
• Besides having a role in normal vascular growth,
VEGF is also responsible for many retinal
diseases by causing new vessel growth and by
increasing leakage and thus causing retinal
swelling.

3. • VEGF PROPERTIES:
1. stimulates angiogenesis
2. Potent inducer of vascular permeability
3. Pro-inflammatory

4. PROCESS OF
ANGIOGENESIS
• Induction
• Vasodilation and increased permeability of pre-existing vessels
• Activated endothelial cells release proteases to degrade matrix
• Endothelial cells proliferate and migrate
• Proliferating cells adhere to one another
• Resolution
• Differentiation and maturation of blood vessels

6. Classification of VEGF
• Archetypal member of VEGF family is VEGF-A
• Other members are
1. Placental growth factor
2. VEGF-B
3. VEGF-C and
4. VEGF-D

7. Clinical significance
Vegf-A is important in diabetic retinopathy
• The microcirculatory problems in the retina in
diabetics can cause retinal ischemia
• Ischemia results in release of vegf-A
• Vegf-A causes creation of new blood vessels in the
retina and elsewhere in the eye
Vegf-A also plays a role in the disease pathology of wet
form of age related macular degeneration, which is the
leading cause of blindness for elderly

8. VEGF RECEPTORS
• Vegf initiates endothelial cell proliferation when it
binds to a member of vegf receptor family, a
group of highly homologous receptors with
intracellular tyrosine kinase domain that includes:
• VEGFR1
• VEGFR2
• VEGFR3

9. ANTI - VEGF
• The anti- vegf agents blocks the vegf
molecules and thus benefit the patients by
decreasing the abnormal and harmful new blood
vessels formation and by decreasing the leakage
and swelling of the retina .
• This leads to stabilization of vision and even
improvement in vision in many cases

10. ANTI - VEGF DRUGS
1. Monoclonal antibody - Bevacizumab (Avastin)
2. Antibody derivative - ranibizumab (Lucentis)
3. Aptamer - Pegaptanib (Macugen)
4. Oral small molecules - Lapatinib ,Sunitinib,
Sorafenib
5. Fusion proteins - VEGF Trap-eye (aflibercept)
6. Miscellaneous - siRNA-Bevasiranib

11. COMMON INDICATIONS
OF ANTI- VEGF USE
• Wet ARMD
• CNVM
• Severe Diabetic Retinopathy
• Macular Edema
• Vascular Occlusions
• Neovascular Glaucoma
• Vitreous Haemorrhage

12. OTHER INDICATIONS
• POSTERIOR SEGMENT
1. ROP
2. EALES disease
3. Refractory post surgical CME
4. COATS disease

13. • ANTERIOR SEGMENT
1. Iris neovascularization
2. Before keratoplasty to reduce corneal
neovascularization
3. Pterygium
4. Trabeculectomy ( to modulate wound healing)

14. BEVACIZUMAB:AVASTI
N
• Blocks angiogenesis by inhibiting VEGF-A
• MECHANISM OF ACTION
• Bevacizumab binds directly to VEGF
• Forms protein complex
• Incapable of further binding to VEGF receptor sites which
would initiate vessel growth effectively reducing available
VEGF

15. • It showed impressive results in the setting of
1. CNV
2. Proliferative diabetic retinopathy
3. Neovascluar glaucoma
4. Diabetic macular edema
5. Retinopathy of prematurity
6. Macular edema secondary to retinal vein occlusion

16. ADMINISTRATION AND
DOSAGE
• Bevacizumab is typically given by
transconjunctival intravitreal injections into the
posterior segment.
• They are typically administered at 4-6 weeks
intervals although this varies widely based on
disease and response.
• Typical dose is 1.25mg in adults and half of that
in children.

17. PEGAPTANIB:
MACUGEN
• MECHANISM OF ACTION:
Specifically binds to VEGF 165
ISOMER which plays a critical role in angiogenesis
and increased permeability
• ADMINISTRATION AND DOSAGE
0.3mg dose once every six weeks by
intravitreal injection

18. RANIBIZUMAB:
LUCENTS
• MECHANISM OF ACTION:
• It has strong affinity to VEGF-A and thus
prevents binding of VEGF to receptors.
Available as intravitreal injections ,
Dosage: 0.5mg/0.05ml once every month

19. METHOD OF GIVING
INTRAVITREAL INJECTION
• An injection volume of 0.05ml is given most commonly.
• The patient should be instructed to direct his or her
gaze away from the site of needle entry.
• The needle is placed 3 to 3.5mm posterior to the
limbus for an aphakic or pseudophakic eye, and 3.5 to
4.5mm posterior to the limbus for a phakic eye
• Injection in the inferotemporal quadrant is common,
although any quadrant is used.

20. INJECTION
TECHNIQUE
• By pulling the conjunctiva over the injection site with
forceps or a sterile cotton swab to create a step like
entry
• This approach may decrease reflux and risk of
infection, a straight path is most commonly employed
• After the sclera is penetrated, the needle is
advanced towards the centre of the globe and the
solution is gently injected into the midvitreous cavity.

21. • The needle is removed, and a sterile cotton swab
is immediately placed over the injection site to
prevent reflux.
• IOP and CRA perfusion is assessed.
• Topical antibiotic is administered for one week.

22. CONTRA-INDICATIONS OF
ANTI-VEGF
1. Fibrovascular proliferation threatening the macula
2. Active ocular inflammatiom
3. Uncontrolled hypertension
4. Cardiovascular disease
5. Pregnancy and lactation
6. Pre pubescent children

23. COMPLICATIONS
1. Raised IOP
2. Endophthalmitis
3. Catarct
4. Immunoreactivity
5. Rebound macualr edema
6. Retinal detachment
7. Central retinal artery occlusion