Anti-VEGF agents and their

clinical applications
Dr Jay Daxini
Ruby eye
hospital
 INTRODUCTION
• VEGF-Vascular Endothelial Growth Factor

• Originally known as vascular permeability factor (VPF), is a

signal protein produced by cells that stimulates the formation
of blood vessels

• They are important signalling proteins involved in

both vasculogenesis and angiogenesis
 TYPES(5 major subtypes)
• VEGF-A, B, C, D and PIGF

• VEGF-A:
– Original VEGF
– Prominent role in angiogenesis and vascular permeability,
often with respect to tumor proliferation
– Also affects other angiogenic processes such as wound
healing, ovulation, menstruation and pregnancy
 ROLE OF VEGF IN HEALTHY EYE

• High concentrations are seen in RPE

• May be important for choriocapillary survival
• Neuroprotective role
• Two major prevalent isoforms in retina are VEGF121(120) &
VEGF165(164)
COMMON INDICATIONS OF
ANTI-VEGF
• WET AMD(Age Related Macular Degeneration)
• CNVM (Choroidal Neovascular Membrane)
• SEVERE DIABETIC RETINOPATHY
• VASCULAR OCCLUSIONS
• MACULAR EDEMA
 OTHER INDICATIONS
POSTERIOR SEGMENT ANTERIOR SEGMENT

1. ROP 1. Iris Neovascularization

2. EALES disease 2. Before keratoplasty to reduce

corneal neovascularization

3. Refractory post surgical CME 3. Pterygium

4. COATS disease 4. Neovascular Glaucoma

 RANIBIZUMAB: LUCENTIS
• Monoclonal antibody
fragment (Fab)
developed from the
identical antibody as
Avastin
MECHANISM OF ACTION
• Much smaller than parent molecule and has been affinity
matured to provide stronger binding to VEGF-A
• Anti-angiogenic property
• Unlike full length antibody, it penetrates the ILM and can
gain access to the subretinal space

ADMINISTRATION AND DOSAGE

• Available as injection, intravitreal 10mg/ml
• Dose: 0.5mg/0.05ml once every month
 HOW TO GIVE INTRAVITREAL
INJECTIONS?
• INJECTION VOLUME
• An injection volume of 0.05 mL is most commonly
used
 Maximum safe volume to inject without preinjection
paracentesis is believed to be 0.1 ml to 0.2 ml
 Larger injection volumes given in 2 conditions: the
injection of a gas for pneumatic retinopexy and injection
of multiple intravitreal agents in one session
 INJECTION SITE
 The patient must be instructed to direct his her gaze away
from the site of needle entry

 The injection is placed 3-3.5 mm posterior to the limbus for

aphakic or pseudophakic eye, and 3.5 to 4 mm posterior to the
limbus for a phakic eye

 Injection in the inferotemporal/superotemporal quadrant is

common, although any quadrant may be used
 CONTRAINDICATIONS OF ANTI-
VEGF
• 1. Fibrovascular proliferation threatening the macula
• 2. Known hypersensitivity to drugs
• 3. Active ocular or periocular inflammation
• 4. Uncontrolled hypertension
• 5. Cardiovascular disease
• 6. Pregnancy and lactation
 PEGAPTANIB RANIBIZUMA BEVACIZUMA Aflibercept
B B
TRADE
NAME
Macugen
IN SUMMARY
Lucentis Avastin Eyelea

COMPOUND Aptamer Antibody Full Fusion Protein

fragment humanized
monoclonal
antibody
VEGF VEGF-A165 VEGF-A all VEGF-A all VEGF-A & B
BINDING Selective forms (1 forms (2 PIGF
PROPERTY binding site) binding site)
VITREOUS 4 days 3 days 21 days
t1/2 (rabbits)
9 days
(humans)
DOSE 0.3mg in 90μl 0.5 mg in 1.25mg in 2mg in 0.05ml
0.05ml 0.05ml
COST Rs.47314/ Rs. Rs. Rs. 40,000/vial
syringe 26400/vial(10 32,800/vial(4m single use
mg/ml) g/100ml)

ADVANTAGE •Low •More • Cost effective • Low

S immunogenicity prospective •Long lasting immunogenicity
THANK YOU