Anti-VEGF agents and

their clinical applications

Dr. Sriniwas Atal

MD. Resident
Ophthalmology
Overview
• Introduction

• Available Anti-Vascular Endothelial Growth Factor Agent

• Use of Anti-Vascular Endothelial Growth Factor Agents

in Clinical Practice

• Treatment Modalities

• Intravitreal Delivery
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 (the de novo formation of the
embryonic circulatory system) and angiogenesis (the
growth of blood vessels from pre-existing vasculature)
HISTORY
• “Factor X”1948- Michaelson postulated a soluble and
diffusible growth factor “Factor X” responsible for retinal
vascular growth in development and disease
• 1970- Judan Folkman proposed angiogenesis essential for
tumor formation
• 1983- Vascular endothelial growth factor (VEGF), first
identified in guinea pigs, hamsters and mice by Senger
• 1989- Purified and cloned by Ferrara and Henzel
• 1994 -The American Journal of Pathology article suggests a
role for VEGF in ocular neovascularization
• 2004- Pegaptinib therapy gets FDA approval
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
Other VEGFs

VEGF-B Embryonic Angiogenesis (skeletal muscle,

myocardium, brown fat)

VEGF-C Lymphangiogenesis without accompanying

angiogenesis

VEGF- D Tumor lymphangiogenesis and lymphatic metastasis

as well as angiogenesis

Placental Growth Factor (PIGF) • Placenta but is also expressed in the heart and
lungs
• It’s loss impairs angiogenesis in ischemia, wound
healing, inflammation, and cancer

VEGF-E Encoded by the Orf virus genome 31

VEGF-F Viper snake venom, 32 which may have therapeutic

implications down the road
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)

• Br J Ophthalmol, 2006 Dec (Vascular endothelial growth factor biology: clinical

implications for ocular treatments.)
ANTI-VEGF DRUGS
MONCOLONAL BEVACIZUMAB (AVASTIN)
ANTIBODY

ANTIBODY DERIVATIVE RANIBIZUMAB (LUCENTIS)

APTAMER PEGAPTANIB (MACUGEN)

FUSION PROTEIN VEGF Trap-eye (AFLIBERCEPT)

MISCELLANEOUS siRNA-BEVASIRANIB
adPEDF
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

 Pegaptanib(MACUGEN)
PEGAPTANIB (MACUGEN)

First Anti Angiogenic Agent

28 Base RNA Aptamer Selectively binds

extra cellular VEGF-A 165

NON-IMMUNOGENIC NATURE DOES NOT AFFECT

NORMAL VASCULAR GROWTH
DOSAGE AND ADMINISTRATION

• FDA approved for the treatment of neovascular (wet)

Age-related macular degeneration(AMD)
• Administered in a 0.3 mg dose once every six weeks by
intravitreal injection
• Marketed as a pre-filled syringe
• Plasma t ½ is about 10 days
• Usage stopped as it doesn’t inhibit VEGF completely,
thus lower efficacy
 AIM: To evaluate the safety
Study : Two concurrent, of up to 2 years of
prospective, multicentre Pegaptanib sodium therapy
double-masked , in the treatment of
randomised, Sham neovascular age-related
controlled studies macular degeneration (NV-
AMD).

VISION
Subjects with all
angiographic lesion Those initially assigned to
compositions of NV- pegaptanib were re-randomized
(1:1 )to continue or discontinue
AMD to receive
therapy for 48 more
intravitreous Pegaptanib weeks; sham-treated patients were
sodium (0.3, 1 and 3 re-randomized (1:1:1:1:1) to
mg) or sham injections continue sham, discontinue, or
every 6 weeks for 54 receive one of
the Pegaptanib doses
weeks
In year 1, serious injection-related
In year 1, serious injection-related
complications included endophthalmitis (12 events,
complications included endophthalmitis (12 events,
0.16%/injection), retinal detachment (RD) (6 events [4
0.16%/injection), retinal detachment (RD) (6 events [4
rhegmatogenous, 2 exudative], 0.08%/injection), and
rhegmatogenous, 2 exudative], 0.08%/injection), and
traumatic cataract (5 events, 0.07%/injection)
traumatic cataract (5 events, 0.07%/injection)

Conclusion: The 2-year safety profile of Pegaptanib

Conclusion: The 2-year safety profile of Pegaptanib
sodium is favorable in patients with exudative AMD
sodium is favorable in patients with exudative AMD

Br J Ophthalmol.2008 Dec.
Singerman LJ, Masonson H, Patel M, Adamis AP, Buggage R, Cunningham E, Goldbaum M, Katz
B, Guyer D
• Despite its early advantage, the emergence of additional anti-
VEGF agents with wider isoform antagonism has limited the
use of Pegaptanib
• More recent clinical trials focus on Pegaptanib as a
supplemental therapy, such as preoperative injection to
improve surgical outcomes of patients with proliferative
diabetic retinopathy
 BEVACIZUMAB: AVASTIN
• Full length humanized murine
monoclonal antibody directed
against human VEGF-A

• FDA approved in 2004 for i.v

treatment of colorectal cancer
Bevacizumab
• Approved for use in:
-certain lung cancer
-renal cancers
-ovarian cancers
-glioblastoma multiforme of the brain

• No FDA approval for intravitreal injections: off label use

Injection of 1.25-2.5mg of bevacizumab into vitreous
cavity has been performed without significant intraocular
toxicity
DOSAGE AND ADMINISTRATION
• In ophthalmology, Bevacizumab is typically given by
transconjunctival intravitreal injections into the posterior
segment

• Intravitreal injections for retinal pathologies are typically

administered at 4-6 week intervals, although this varies
widely based on disease and response

• The typical dose is 1.25mg in 0.05ml in adults and half

that dose in babies
• Estimated half-life is approximately 20 days
BENEFITS
1. Low cost
2. High efficacy
3. Longer half life upto 20 days & thus fewer injections
4. Lack of preservative
5. Higher safety dose: retinal toxicity at dosage >3.5mg
6. Wide availability
Adverse Ocular Events
• Infectious endophthalmitis remains one of the most
devastating complications of intravitreal injections

• In multicenter clinical trial the incidence is 0.019 to 1.6%

• Intraocular inflammation 1.4–2.9%

• Accidental injury to Lens capsule

Eye (Lond). 2013 Jul;

Adverse events and complications associated with intravitreal injection of anti-VEGF
agents: a review of literature
K Ghasemi Falavarjani1,* and Q D Nguyen2
• Rhegmatogenous retinal detachment (RRD) is low (0 to
0.67%)

• Subconjunctival hemorrhage has been reported to occur

in nearly 10% of injections, with higher frequency in
patients who were receiving aspirin

• Increase in IOP

Eye (Lond). 2013 Jul;

Adverse events and complications associated with intravitreal
injection of anti-VEGF agents: a review of literature
K Ghasemi Falavarjani1,* and Q D Nguyen2
ADVERSE SYSTEMIC REACTIONS
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
BEVACIZUMAB (AVASTIN) RANIBIZUMAB (LUCENTIS)
Full sized antibody Antibody fragment
149 kilo daltons 48 kilo daltons
Half life 20 days Half life 3 days
Clearance is slow Clearance is 100 folds faster
Long action & less dosage 140 times higher affinity
Costs less Costly
 AIM:
AIM: To
To determine
determine the
the efficacy
efficacy and
and
safety of ranibizumab
ranibizumab in in the
the
treatment
treatment of minimally-classic and
STUDY TYPE:The MARINA trial trial was
was aa occult neovascular
neovascular age-related
age-related
phase III multi-centre,
multi-centre, randomised,
randomised, macular
macular degeneration
degeneration.. The primary
primary
double-blind,
double-blind, sham-controlled trial endpoint was the
the proportion ofof
patients
patients losing
losing fewer than 15 letters
letters
from baseline acuity atat 12 months
months

MARINA
716
716 patients
patients (VA
(VA 6/12
6/12 to
to 6/96)
6/96) were
were
randomised
randomised to to receive
receive monthly
monthly Minimally
Minimally Classic/Occult
Classic/Occult CNV
CNV Trial
Trial of
of
intravitreal injections of ranibizumab the
of ranibizumab the Anti-VEGF
Anti-VEGF Antibody
Antibody Ranibizumab
Ranibizumab
(either
(either 0.3mg
0.3mg or
or 0.5mg)
0.5mg) or sham in the
or sham the Treatment
Treatment ofof Neovascular AMD
injections
injections for
for 24
24 months
months [MARINA]2006
[MARINA]2006
 Patients gaining more than 15
Patients losing fewer than 15 letters at 12 months: 25% and
letters at 12 months: 95% 34% treated groups (0.3mg and
treatment groups v/s 62% in the 0.5mg respectively) v/s 5%
sham group (p<0.0001) controls

RESULTS

Adverse events: endophthalmitis

Average change in visual acuity: (<1%), uveitis (<1%), serious non-
7 letters gained in the treated ocular events were not
groups vs 10 letters lost in the significantly different in treated
controls groups v/s control
AFLIBERCEPT: EYLEA (NEW DRUG)
• Recombinant fusion
protein consisting of
VEGF binding
portions from the
extracellular domains
of human VEGF
receptors 1 and 2, they
are fused to the Fc
portion of the human
IgG1 immunoglobulin
Intravitreal Aflibercept Injection Binds a
Single VEGF Dimer “Like a Trap”
Aflibercept1,2 Bevacizumab1,2 Ranibizumab1,2

Affinity
maturation
2

r
a
n
i
1:1 Bevacizumab can “daisy-chain” or b
“paper-doll” with VEGF leading to i
Stoichiometric
large, multimeric conglomerates2,3 z
binding
u
m
a
b
molecules can bind
1. Dixon JA et al. Expert Opin Investig Drugs. 2009;18(10):1573-1580. 2. Stewart MW. CML – Ophthalmology. 2012;22(4):105-113. 3. Zhang A each VEGF
et al. Pharm dimer
Res. 2012;29(1):236-250. 19
 INDICATIONS FOR USE
1. Neovascular (wet) Age Related Macular
Degeneration (AMD)

• Recommended dose is 2 mg (0.05 ml)

• Administered by intravitreal injection every 4 weeks for
the first 12 weeks, followed by once every 8 weeks
2. Macular edema following CRVO

• Recommended dose 2mg (0.05mL )

• Administered by intravitreal injection once every 4 weeks

CONTRAINDICATIONS
• Contraindicated in patients with infections or active
inflammations of or near eye
• AFLIBERCEPT is moving through clinical trials for
further intraocular and systemic indications
 BROLUCIZUMAB: BEOVU
(Recent)
• Humanized, single-
chain variable
fragment (scFv) that
inhibits VEGF-A

• Composed of the
monoclonal antibody’s
variable light and
heavy chain domains
tethered by a flexible
linker, a small protein
fragment of
approximately 26 kDa
• INDICATIONS FOR USE
1. Neovascular (wet) Age Related Macular
Degeneration (AMD)
Recommended dose 6mg (0.05mL )

Administered by intravitreal injection

every 3 months

Approved on 8th October 2019 by FDA

 HAWK and HARRIER studies were double-masked,
active-controlled trials, with a combined enrollment of
1,817 patients. All patients had untreated active
choroidal neo­vascularization caused by age-related
macular degeneration (AMD) in the study eye

• Participants were assigned randomly to receive

intravitreal brolucizumab (3 mg or 6 mg) or aflibercept (2
mg). After three monthly injections (loading dosage),
brolucizumab-treated eyes received an injection every 12
weeks (q12w), which was adjusted to every eight weeks
(q8w) if disease activity persisted. Aflibercept-treated
eyes received q8w dosing
 At week 16, before any variations in treatment exposure, disease
activity was more common with aflibercept than with brolucizumab 6
mg (HAWK: 34.5% vs. 24.0%, p = .001; HARRIER: 32.2% vs. 22.7% p = .
002). Reductions in central subfield thickness from baseline to week
48 were greater with brolu­cizumab 6 mg than with aflibercept in
HAWK (LS mean, –172.8 μm vs. –143.7 μm; p = .001) and in HARRIER
(LS mean, –193.8 μm vs. –143.9 μm; p < .001). Anatomic retinal fluid
outcomes favored brolucizumab. Overall, adverse event rates were
similar for the study drugs.

• In two similarly designed phase 3 trials (HAWK and

HARRIER), Dugel et al. compared the efficacy and
safety of brolucizumab and aflibercept for treatment of
neovascular age-related macular degeneration. The
findings of both studies indicate that broluci­zumab is
noninferior to aflibercept in terms of visual function at
week 48. Anatomic outcomes were better with
brolucizumab, and overall safety was comparable for the
two treatments
 The authors noted that the forth­coming 96-week data
will provide further insight into the efficacy and safety
of brolucizumab (q12w and q8w) relative to aflibercept
(q8w)

• AAO JOURNAL 10.1016/j.ophtha.2019.04.017

• Pravin U. Dugel, MD,1 Adrian Koh, MD, FRCS,2 Yuichiro Ogura, MD,3 Glenn J. Jaffe,
MD,4 Ursula Schmidt-Erfurth, MD,5 David M. Brown, MD,6 Andre V. Gomes, MD,
PhD,7 James Warburton, MBBS,8 Andreas Weichselberger, PhD,8 Frank G. Holz, MD,9
on behalf of the HAWK and HARRIER Study Investigators
Aflibercept, bevacizumab, or ranibizumab
for diabetic macular edema
Study:Multicenter, AIM: The relative efficacy and safety
Study:Multicenter,
randomized clinical of intravitreous aflibercept,
randomized clinical
trial at 89 clinical sites bevacizumab, and ranibizumab in the
trial at 89 clinical sites
in the United States treatment of diabetic macular edema
in the United States

Method: randomly assigned 660 adults (mean age, 61±10 years) with
Method:
diabetic randomly assigned
macular edema 660 adults
involving (mean age,
the macular 61±10
center years) with
to receive
diabetic macular
intravitreous edemaatinvolving
aflibercept a dose ofthe
2.0macular
mg (224center to receive
participants),
intravitreous
bevacizumab aflibercept
at a dose at a(218
of 1.25 mg doseparticipants),
of 2.0 mg (224 participants),at a
or ranibizumab
bevacizumab at a dosedose of
of 1.25 mg(218
0.3 mg (218participants)
participants), or ranibizumab at a
dose of 0.3 mg (218 participants)

• N Engl J Med 2015

DOI: 10.1056.Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman
AR, Ayala AR Jampol LM Aiello LP, Antoszyk AN, Arnold-Bush B,Baker CW,Bressler
NM Browning DJ
 CONCLUSIONS:
Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in
eyes with center-involved diabetic macular edema, but the relative effect
depended on baseline visual acuity. When the initial visual-acuity loss was
mild, there were no apparent differences, on average, among study groups.
At worse levels of initial visual acuity, aflibercept was more effective at
improving vision.

• N Engl J Med 2015

DOI: 10.1056.Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman
AR, Ayala AR Jampol LM Aiello LP, Antoszyk AN, Arnold-Bush B,Baker CW,Bressler
NM Browning DJ
 EVEREST STUDY: Efficacy and Safety of Verteporfin Photodynamic Therapy in
Combination with Ranibizumab or Alone Versus Ranibizumab Monotherapy in
Patients with Symptomatic Macular Polypoidal Choroidal Vasculopathy

Purpose: To assess the effects of

Study: Phase IV, multicenter, verteporfin photodynamic therapy
randomized, (PDT) combined
active controlled, double- with ranibizumab or alone
masked, exploratory versus ranibizumab monotherapy
in patients with symptomatic
macular polypoidal choroidal
61 Asian patients were EVEREST vasculopathy
EVEREST
randomized to verteporfin STUDY
PDT (standard STUDY
fluence), ranibizumab 0.5
mg, or the combination. multicenter, double-
Patients were administered masked,
with verteporfin primarily indocyanine
PDT/placebo and initiated
with three consecutive green angiography–
monthly ranibizumab/sham guided trial
injections starting Day 1,
and re-treated (Months 3–5)
• Koh, Adrian MD, FRCS; Lee, Won Ki MD, PhD; Chen, Lee-Jen MD; Chen, Shih-Jen MD, PhD,The journal of Retina and
vitreous disease: September 2012
 At Month 6, verteporfin
combined with ranibizumab or mean change ± standard deviation
alone was superior in best-corrected visual acuity
to ranibizumab monotherapy in (letters) was 10.9 ± 10.9
achieving complete polyp (verteporfin PDT + ranibizumab),
regression (77.8% and 71.4% 7.5 ± 10.6 (verteporfin PDT), and
vs. 28.6%; P < 0.01); 9.2 ± 12.4 (ranibizumab)

EVEREST
STUDY
Verteporfin PDT combined
with ranibizumab 0.5 mg or alone
The primary endpoint was the
was superior to ranibizumab
proportion of patients
monotherapy in achieving
with indocyanine green
complete regression of polyps in
angiography–assessed
this 6-month study in patients
complete regression of polyps
with symptomatic
at Month 6
macular polypoidal choroidal
vasculopathy
Studies Evaluating Anti- VEGF therapy for retinal vein occlusion
Studies
CRUISE ; Central Retinal Vein Randomized Study comparing
occlusion Study Ranibizumab 0.5mg to sham injection
over a month
Results showed improvement in BCVA
and Central Subfield Retinal Thickness

BRAVO ; Branch Vein Occlusion Similar to CRUISE study with laser

Study (Local and Grid) involved
HORIZON Extension Study of CRUISE and
BRAVO showed improvement in
BRVO but not in CRVO
COPERNICUS Randomized Study comparing
Aflibercept to sham injections in
CRVO showed improvement
VIBRANT Comparison between the efficacy of
Aflibercept injections and Laser
Treatment in CME and BRVO showed
improvement
Treatment Modalities
• Continuous Treatment

• PRN Treatment

• Treat and Extend

Continuous Treatment 

Treating every month or two is effective, but it is not ideal

• It may be overtreating some patients

• Additionally, it can be costly and inconvenient for
patients, especially if they are treated monthly
Retina. 2015 Aug, Freund KB1, Korobelnik JF, Devenyi
R, Framme C, Galic J, Herbert E, Hoerauf H, Lanzetta
P, Michels S, Mitchell P, Monés J, Regillo C, Tadayoni
R, Talks J, Wolf S
Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of
Prematurity (BEAT-ROP)

• Bevacizumab causes long-term reduction in systemic

VEGF levels in adults compared to ranibizumab and,
therefore, may be more damaging to the preterm infant.
However, in preterms, ranibizumab also reduced serum
VEGF
• Ranibizumab penetrates more deeply into the eye, and
there is a concern this might affect the choroidal
circulation, which provides oxygen to the developing
retina and is believed important in the pathophysiology of
ROP
• Mintz-Hittner HA1, Kennedy KA, Chuang AZ
N Engl J Med.2011
 • Bevacizumab is contemplated in cases in which corneal,
lenticular, or vitreous opacities preclude treatment with
laser, it should only be used for stage 3+ ROP in zone I
and not for zone II ROP

Mintz-Hittner HA1, Kennedy KA, Chuang AZ

N Engl J Med.2011
Neovascular Glaucoma
RETINAL HYPOXIA

VEGF Conc. > 890 pg/ml of Aqueous

Iris and Angle Neovascularization

Intravitreal injection of Anti VEGF

VEGF Conc. < 550 pg/ml of Aqueous

NEOVASCULARIZATION REGRESSES
Anti-VEGF treatment is the key strategy for
neovascular glaucoma management in the short
term
Totally 50 patients (51 eyes) with NVG
AIM :To present a comprehensive were included. Of these, 43 patients (44
approach for the management of eyes) completed the treatment process.
patients with neovascular Patients were divided into central
glaucoma (NVG) aiming to retinal vein occlusion (CRVO) and
preserve visual function and proliferative diabetic retinopathy
complement pan-retinal (PDR) groups according to their
photocoagulation (PRP) by anti- original diagnosis. Intraocular pressure
vascular endothelial growth factor (IOP), visual function, and the status of
(anti-VEGF) treatment and anti- iris and angle neovascularization were
glaucoma surgery. recorded before and after treatment

Patients were followed up for 6–30 months

Prospective, (mean 12.2 months). The IOP of all 44
patients was effectively controlled and was
interventional significantly less after treatment (16.68 ± 4.69
case series mmHg) than before treatment (42.59 ± 9. 44
mmHg, P < 0.05)
 There was no significant difference in IOP between
the PDR and CRVO groups at the end of follow-up
(P = 0.8657), but the visual acuity in the PDR group
was much better than that in the CRVO group (P =
0.0079)

There was no significant difference in IOP between

the PDR and CRVO groups at the end of follow-up
(P = 0.8657), but the visual acuity in the PDR group
was much better than that in the CRVO group (P =
0.0079). C
Yaoyao Sun,Yong Liang,Peng Zhou,Huijuan Wu,Xianru Hou,Zeqin Ren,Xiaoxin Li and
BMC Ophthalmology Published: 30 August 2016
This prospective, interventional study establishes a therapy
strategy for NVG as follows
• First, the core purpose of all treatments is to lower IOP
and preserve the patient’s visual function
• Second, anti-VEGF treatment can regress
neovascularization at the iris and anterior chamber angle,
which allows optimal conditions for intraocular surgery
• Third, using anti-glaucoma surgery with or without
phacoemulsification or vitrectomy contributes to
creating the conditions necessary for the completion of
PRP
Pterygium
SUBCONJUNCTIVAL Anti VEGF IN PTERYGIUM
• PRIMARY PTERYGIUM :
Subconjunctival Bevacizumab (Avastin) 1.25mg/0.05ml
causes regression of vascularity, symptoms (irritation, redness)
up to 7 weeks post injection only
Teng CC, et al. Cornea. 2009 May; 28(4):468-70

TOPICAL Anti VEGF IN PTERYGIUM

• RECURRENT PTERYGIUM :
Topical Bevacizumab (Avastin) 25mg/ml QID dosing for 3
weeks, in a case of recurrent impending pterygium prevented
recurrence up 6 months follow up
Wu PC, et al. Cornea.2009 Jan;28(1):103-4
Effect of Avastin on the migration and invasion of
pterygium fibroblasts
Eye Sci2014.Liu W, Sha X, Wen Y, Zhao W, Luo W, Hua Z.

Abstract
PURPOSE:
To evaluate the effect of Avastin on human pterygium fibroblast
migration and invasiveness.
METHODS:
VEGF secretion was compared between human pterygium fibroblasts and conjunctival
fibroblasts by measuring VEGF-A by ELISA. The influence of Avastin on HPF migration and
invasiveness was observed by wound scratch and Transwell migration assays. The expression of
p-ERK1/2 and p-FAK was analyzed by western blotting.
RESULTS:(1)VEGF was secreted in higher amounts by human pterygium fibroblasts than by
conjunctival fibroblasts. (2) Avastin treatment decreased HPF migration and invasion. (3)
Avastin significantly decreased the expression of p-ERK1/2 and p-FAK in human pterygium
fibroblasts.
• CONCLUSION: Avastin can inhibit migration and invasion of
Human Pterygium Fibroblasts by decreasing the expression of
p-ERK1/2 and p-FAK
Corneal Neovascularization
Avastin has been used as a combination therapy to prevent corneal
neovascularization along with PDT and Argon Laser therapy

Avastin has also been tried for corneal stromal vascularization in

DALK
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 RANIBIZUMAB BEVACIZUMAB Aflibercept

IN SUMMARY
TRADE NAME Macugen Lucentis Avastin Eyelea

COMPOUND Aptamer Antibody Full humanized Fusion Protein

fragment monoclonal
antibody

VEGF BINDING VEGF-A165 VEGF-A all VEGF-A all VEGF-A & B

PROPERTY Selective forms (1 binding forms (2 binding PIGF
site) site)
VITREOUS t1/2 4 days 3 days (rabbits) 21 days
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/syringe Rs. Rs. Rs. 40,000/vial single
26400/vial(10m 32,800/vial(4mg use
g/ml) /100ml)

ADVANTAGES •Low •More • Cost effective • Low immunogenicity

immunogenicity prospective •Long lasting
 REFERENCES
JOURNALS

1. Br J Ophthalmol, 2006 Dec (Vascular endothelial

growth factor biology: clinical implications for
ocular treatments.)
2. Br J Ophthalmol.2008 Dec.
3. Eye (Lond) 2013 Jul
4. Epub 2015 Feb 18.
5. The journal of Retina and vitreous
disease: September 2012 -
6. BMC Ophthalmology Published: 30 August 2016
7. Teng CC, et al. Cornea. 2009 May; 28(4):468-70
8. Eye Sci2014
THANK YOU…