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ANTI VEGF IN
OPHTHALMOLOGY
PRESENTER: DR. SIDDHARTH GAUTAM
DR.PAVITRA PATEL
INTRODUCTION
 VEGF means Vascular Endothelial Growth Factor,
which is responsible for growth of blood vessels.
 Besides ...
 VEGF PROPERTIES:
1. Stimulates angiogenesis
2. Potent inducer of vascular permeability
3. Pro-inflammatory
 VEGF was fi...
PROCESS OF ANGIOGENESIS
 Induction
◦ Vasodilation and increased
permeability of pre-existing
vessels
◦ Activated endothel...
ANGIOGENIC FACTORS
Angiogenic factors secreted by tumors include :
• - VEGF ( Vascular Endothelial Growth Factor )
• - FGF...
VEGF
Originally known as vascular permeability factor (VPF).
VEGF is a signal protein produced by cells that stimulate
vas...
HISTORY OF VEGF
VEGF was first identified in guinea pigs, hamsters and mice by Senger
et.al in 1983.
It was purified and c...
CLASSIFICATION OF VEGF
 Archetypal member of the VEGF family is VEGF – A.
 Other members are
1. Placental growth factor ...
FUNCTIONS
TYPE OF VEGF FUNCTIONS
VEGF – A Angiogenesis
Increases migration of endothelial cells
Increases mitosis of end...
TYPE OF VEGF FUNCTIONS
VEGF – C Lymphangiogenesis
VEGF – D Development of lymphatic vasculature
surrounding lung bronchiol...
CLINICAL SIGNIFICANCE
VEGF – A is important in diabetic
retinopathy.
The microcirculatory problems in the
retina in Diabet...
 VEGF – A plays a role in the disease pathology of
the wet form Age related macular
degeneration,which is the leading cau...
 Patients suffering from pulmonary emphysema have
decreased levels of VEGF in the pulmonary arteries.
 In kidneys, incre...
ROLE OF VEGF IN HEALTHY EYE
 High concentrations are seen in RPE.
 May be important for choriocapillary survival.
 Neur...
VEGF RECEPTORS
• VEGF initiates endothelial cell proliferation when it
binds to a member of VEGF receptor (VEGFR) family, ...
ANTI-VEGF
 The anti-VEGF agents block the VEGF molecules and
thus benefit the patients by decreasing the abnormal and
har...
HYPOXIA
VEGF Isoforms
VEGF A Proteins
Anti VEGF
VEGF receptors
Neovascularization
Retina Anterior Segment
ANTI –VEGF DRUGS
Monoclonal antibody Bevacizumab (Avastin®)
Antibody derivative Ranibizumab (Lucentis®)
Aptamer Pegaptanib...
COMMON INDICATIONS OF
ANTI-VEGF USE
WET ARMD CNVM
SEVERE
DIABETIC
RETINOPATHY
MACULAR
EDEMA
VASCULAR
OCCLUSIONS
NEOVASCULA...
OTHER INDICATIONS
POSTERIOR SEGMENT ANTERIOR SEGMENT
1. ROP 1. Iris neovascularization
2. EALES disease 2. Before Keratopl...
 USE IN ROP:
 Bevacizumab was claimed as a wonder drug for all stage
3 + ROP.
 However, results revealed that safety wa...
 USE IN EALES DISEASE:
 Recent articles have suggested intraocular bevacizumab
as a new form of treatment in neovascular...
 USE IN PTERYGIUM:
 VEGF have been detected in pterygium.There is marked
elevation of VEGF in pterygia in comparison to ...
ANTI-VEGF FOR EYE DISEASES
 BEVACIZUMAB: AVASTIN
 Recombinant humanized monoclonal antibody that
blocks angiogenesis by ...
 Not yet approved by FDA-Off label use in
Ophthalmology.
 Rosenfield et al were the first ones to describe & publish
the...
 MECHANISM OF ACTION:
Bevacizumab
(Avastin) binds
directly to VEGF
Forms protein
complex
Incapable of
further binding to
...
 USE IN EYE DISEASE:
 Successfully used to inhibit VEGF and slow the
progress of Age-related macular degeneration (AMD)
...
 Although not currently approved by the FDA for such
use, the injection of 1.25-2.5 mg of bevacizumab into
the vitreous c...
 ADMINISTRATION AND DOSAGE:
 Bevacizumab is typically given by transconjunctival
intravitreal injections into the poster...
 COMBINATION THERAPY:
 Photodynamic Therapy
 Anti PDGF
 Intravitreal Triamcinolone
 Triple Therapy
 Radiation
 BENE...
 PHARMACOKINETICS:
Absorption
 Time to reach steady state is predicted to be 100 days.
Elimination
 Estimated half-life...
 DRUG INTERACTIONS:
Irinotecan/5–
fluorouracil/leucovorin
Incidence of epistaxis and GI
hemorrhage, minor gum bleeding,
v...
 BENEFITS:
1. High efficacy
2. Longer half life upto 20 days & thus fewer injections
3. Lack of preservative
4. Higher sa...
 ADVERSE REACTIONS:
CNS:
Headache,
Dizziness,
Sensory
neuropath
y
CVS: HTN,
Thrombo-
embolsim
Dermat:
Alopecia
(32%)
GI:
...
 PEGAPTANIB: MACUGEN
 Pegylated Aptamer
 Pegaptanib sodium injection (brand name Macugen) is an
anti-angiogenic medicin...
 MECHANISM OF ACTION:
Specifically binds to
VEGF 165 ISOMER
Protein that plays a
critical role in
angiogenesis (the
forma...
 ADMINISTRATION AND DOSAGE:
 Administered in a 0.3 mg dose once every six weeks
by intravitreal injection.
 Marketed as...
 PHARMACOKINETICS:
(Not adequately studied in humans)
Absorption
 Very slow systemic absorption
 Occurs within 1 to 4 d...
 RANIBIZUMAB: LUCENTIS
 Lucentis is an monoclonal antibody fragment( Fab)
developed from the identical parent antibody a...
 MECHANISM OF ACTION:
 Much smaller than the parent molecule and has been
affinity matured to provide stronger binding t...
 ADMINISTRATION AND DOSAGE:
 Available as Injection, intravitreal 10 mg/mL
 Dose: 0.5 mg/0.05 ml once every month
 PHA...
 Reduction in Ranibizumab clearance in renal
impairment is considered clinically insignificant & dose
adjustment is not e...
 SAFETY PROFILE:
 Serious ocular adverse events in 2 year MARINA study
for ranibizumab 0.5 mg:
1. Endophthalmitis – 1.3%...
 Serious ocular adverse events in 1 year ANCHOR
study for ranibizumab 0.5 mg :
1. Endophthalmitis – 1.4 %
2. Uveitis – 0....
DIFFERENCE
BEVACIZUMAB
(AVASTIN)
RANIBIZUMAB
(LUCENTIS)
Full sized antibody Antibody fragment
148 kilodaltons 48 kilodalto...
 AFLIBERCEPT: EYLEA (NEW DRUG)
 Recombinant fusion protein consisting of VEGF-
binding portions from the extracellular d...
 INDICATIONS FOR USE:
1. Neovascular (Wet) Age-Related Macular Degeneration
(AMD)
 Recommended dose for EYLEA is 2 mg (0...
2. Macular Edema Following Central Retinal Vein
Occlusion (CRVO)
 Recommended dose for EYLEA is 2 mg (0.05 mL or 50
micro...
CONTRAINDICATIONS:
 Contraindicated in patients with infections or
active inflammations of or near the eye
 AFLIBERCEPT ...
HOW TO GIVE INTRAVITREAL
INJECTION?
 Injection volume
 An injection volume of 0.05 mL is most commonly
used.
 Maximum s...
 Needle selection
 Needle size varies according to the substance injected,
with 27-gauge needles often used for crystall...
 Injection site
 The patient should be
instructed to direct his or her
gaze away from the site of
needle entry.
 The in...
 Injection technique
 Some guidelines suggest pulling the conjunctiva over
the injection site with forceps or a sterile ...
 The needle is removed, and a sterile cotton swab is
immediately placed over the injection site to prevent
reflux.
 IOP ...
CONTRA-INDICATIONS OF
ANTI-VEGF
1. Fibrovascular proliferation threatening the macula
2. Active ocular or periocular infla...
COMPLICATIONS
Raised IOP
(13-17.6%)
Cataract
(0.07%)
Endophthal
mitis (0.1-
1%)
Risk of
ATE(4.6%)(
decrease
the
synthesis ...
PEGAPTANIB RANIBIZUMAB BEVACIZUMAB
TRADE NAME Macugen® Lucentis® Avastin®
COMPOUND Aptamer Antibody
fragment
Full humanize...
Anti vegf' s in Ophthalmology
Anti vegf' s in Ophthalmology
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Anti vegf' s in Ophthalmology

DR.SIDDHARTH GAUTAM
DR.PAVITRA PATEL

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Anti vegf' s in Ophthalmology

  1. 1. ANTI VEGF IN OPHTHALMOLOGY PRESENTER: DR. SIDDHARTH GAUTAM DR.PAVITRA PATEL
  2. 2. INTRODUCTION  VEGF means Vascular Endothelial Growth Factor, which is 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 vessels growth and by increasing leakage and thus causing retinal swelling.
  3. 3.  VEGF PROPERTIES: 1. Stimulates angiogenesis 2. Potent inducer of vascular permeability 3. Pro-inflammatory  VEGF was first identified, purified, and cloned in 1989.
  4. 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
  5. 5. ANGIOGENIC FACTORS Angiogenic factors secreted by tumors include : • - VEGF ( Vascular Endothelial Growth Factor ) • - FGF ( Fibroblast Growth Factor ) • - TGF – b ( Transforming Growth Factor – Beta ) • - PDGF ( Platelet derived Growth Factor ) Multiple tumor types over express these angiogenic factors.
  6. 6. VEGF Originally known as vascular permeability factor (VPF). VEGF is a signal protein produced by cells that stimulate vasculogenesis and angiogenesis. It is a part of system that restores the oxygen supply to tissues when blood circulation is inadequate. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus.
  7. 7. HISTORY OF VEGF VEGF was first identified in guinea pigs, hamsters and mice by Senger et.al in 1983. It was purified and cloned by Ferrara and Henzel in 1989. VEGF alternate splicing was discovered by Tischer et.al in 1991. 1996: Dr. Jeffery Isner published first clinical trials regarding VEGF Between 1996 and 1997, Christinger and Devos obtained the crystal structure of VEGF, first at 2.5A0 resolution and later at 1.9 A0 . 2004: FDA approves first antiangiogenic drug to treat colorectal cancer (Avastin)
  8. 8. CLASSIFICATION OF VEGF  Archetypal member of the VEGF family is VEGF – A.  Other members are 1. Placental growth factor (PGF), 2. VEGF – B, 3. VEGF – C, and 4. VEGF – D.  A new member of VEGF – ◦ Related family encoded by viruses (VEGF – E) ◦ In the venom of some snakes (VEGF – F ) have also been discovered.
  9. 9. FUNCTIONS TYPE OF VEGF FUNCTIONS VEGF – A Angiogenesis Increases migration of endothelial cells Increases mitosis of endothelial cells Increases matrix metalloproteinase activity Creation of blood vessel lumen Creates fenestration Chemotactic for macrophages and granulocytes Vasodilation ( Indirectly by NO release ) VEGF – B Embryonic angiogenesis (myocardial tissue to be specific )
  10. 10. TYPE OF VEGF FUNCTIONS VEGF – C Lymphangiogenesis VEGF – D Development of lymphatic vasculature surrounding lung bronchioles. Placental Growth Factor (PGF) Vasculogenesis Angiogenesis during ischemia Inflammation Wound healing and Cancer • The human isoforms are 121, 145, 165, 189, & 206. • The isoform number refers to the number of amino acids contained in the mature, secreted protein.
  11. 11. CLINICAL SIGNIFICANCE VEGF – A is important in diabetic retinopathy. The microcirculatory problems in the retina in Diabetics can cause retinal ischemia Ischemia results in the release of VEGF – A VEGF – A causes creation of new blood vessels in the retina and else where in the eye
  12. 12.  VEGF – A plays a role in the disease pathology of the wet form Age related macular degeneration,which is the leading cause of blindness for the elderly of the industrialized world.  The vascular pathology is similar to diabetic retinopathy with some differences in neovascularization.  VEGF – D levels are significantly elevated in patients with Angiosarcoma.
  13. 13.  Patients suffering from pulmonary emphysema have decreased levels of VEGF in the pulmonary arteries.  In kidneys, increased expression of VEGF – A in glomeruli directly causes the glomerular hypertrophy that is associated with proteinuria.  VEGF alternatives can be predictive of early onset pre- eclampsia.
  14. 14. 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).
  15. 15. VEGF RECEPTORS • VEGF initiates endothelial cell proliferation when it binds to a member of VEGF receptor (VEGFR) family, a group of highly homologous receptors with intracellular tyrosine kinase domain that includes : - VEGFR1(FLT1) - VEGFR2(KDR) - VEGFR3(FLT4)
  16. 16. ANTI-VEGF  The anti-VEGF agents block 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.
  17. 17. HYPOXIA VEGF Isoforms VEGF A Proteins Anti VEGF VEGF receptors Neovascularization Retina Anterior Segment
  18. 18. ANTI –VEGF DRUGS Monoclonal antibody Bevacizumab (Avastin®) Antibody derivative Ranibizumab (Lucentis®) Aptamer Pegaptanib (Macugen®) Oral small molecules (Inhibit tyrosine kinases) Lapatinib Sunitinib Sorafenib Fusion proteins VEGF Trap-eye (aflibercept) Miscellaneous siRNA-Bevasiranib, adPEDF
  19. 19. COMMON INDICATIONS OF ANTI-VEGF USE WET ARMD CNVM SEVERE DIABETIC RETINOPATHY MACULAR EDEMA VASCULAR OCCLUSIONS NEOVASCULAR GLAUCOMA VITREOUS HAEMORRHAGE
  20. 20. OTHER INDICATIONS POSTERIOR SEGMENT ANTERIOR SEGMENT 1. ROP 1. Iris neovascularization 2. EALES disease 2. Before Keratoplasty to reduce to reduce corneal neovascularization 3. Refractory post surgical CME 3. Pterygium 4. COATS disease 4. Trabeculectomy (to modulate wound healing)
  21. 21.  USE IN ROP:  Bevacizumab was claimed as a wonder drug for all stage 3 + ROP.  However, results revealed that safety was still an issue.  Choroidal rupture has been reported with injection of bevacizumab.  Adverse influence on the development of choroidal vessels.
  22. 22.  USE IN EALES DISEASE:  Recent articles have suggested intraocular bevacizumab as a new form of treatment in neovascular eales disease or as a possible adjunctive treatment to vitreoretinal surgery for the management of eales disease with tractional retinal detachment.  However, this treatment has a legacy of serious complications like secondary rhegmatogenous retinal detachment, within a week of receiving intravitreal bevacizumab.  Combination therapy of laser treatment and intraocular bevacizumab was effective in improving and stabilizing the vision.
  23. 23.  USE IN PTERYGIUM:  VEGF have been detected in pterygium.There is marked elevation of VEGF in pterygia in comparison to normal conjunctival samples.  Subconjunctival bevacizumab is used in recurrent pterygium.  Topical bevacizumab is used in the treatment of corneal neovascular vessels, higher concentration has adverse effects.  Therefore, duration of treatment may well determine the safety of topical bevacizumab.
  24. 24. ANTI-VEGF FOR EYE DISEASES  BEVACIZUMAB: AVASTIN  Recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting VEGF-A  It received its first approval in 2004, for combination use with standard chemotherapy for metastatic colon cancer  It has since been approved for use in ◦ Certain lung cancers, ◦ Renal cancers, ◦ Ovarian cancers ◦ Glioblastoma multiforme of the brain
  25. 25.  Not yet approved by FDA-Off label use in Ophthalmology.  Rosenfield et al were the first ones to describe & publish the off label use of intravitreal Bevacizumab in 2005.
  26. 26.  MECHANISM OF ACTION: Bevacizumab (Avastin) binds directly to VEGF Forms protein complex Incapable of further binding to VEGF receptor sites which would initiate vessel growth effectively reducing available VEGF
  27. 27.  USE IN EYE DISEASE:  Successfully used to inhibit VEGF and slow the progress of Age-related macular degeneration (AMD) & diabetic retinopathy  Off-label use as an intravitreal agent in the treatment of proliferative (neovascular) eye diseases  Particularly for Choroidal neovascular membrane (CNV) in AMD.
  28. 28.  Although not currently approved by the FDA for such use, the injection of 1.25-2.5 mg of bevacizumab into the vitreous cavity has been performed without significant intraocular toxicity.  Many retina specialists have noted impressive results in the setting of: 1. CNV 2. Proliferative diabetic retinopathy 3. Neovascular glaucoma 4. Diabetic macular edema 5. Retinopathy of prematurity 6. Macular edema secondary to retinal vein occlusions.
  29. 29.  ADMINISTRATION AND DOSAGE:  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.  DOSE: Typical dose is 1.25mg in 0.05ml in adults, and half that dose in babies.
  30. 30.  COMBINATION THERAPY:  Photodynamic Therapy  Anti PDGF  Intravitreal Triamcinolone  Triple Therapy  Radiation  BENEFITS:  Reduces frequency of injections  Reduces recurrence
  31. 31.  PHARMACOKINETICS: Absorption  Time to reach steady state is predicted to be 100 days. Elimination  Estimated half-life is approximately 20 days.
  32. 32.  DRUG INTERACTIONS: Irinotecan/5– fluorouracil/leucovorin Incidence of epistaxis and GI hemorrhage, minor gum bleeding, vaginal hemorrhage increases Live vaccines Coadministration of live vaccines may result in a reduced immune response Paclitaxel Decreased paclitaxel exposure when given in combination with bevacizumab Sunitinib Coadministration of Bevacizumab and sunitinib has been reported to cause unexpected severe toxicity (eg, microangiopathic hemolytic anemia)
  33. 33.  BENEFITS: 1. High efficacy 2. Longer half life upto 20 days & thus fewer injections 3. Lack of preservative 4. Higher safety dose  Retinal toxicity occurs at dosage > 3.5mg 5. Lower cost 6. Wide availability
  34. 34.  ADVERSE REACTIONS: CNS: Headache, Dizziness, Sensory neuropath y CVS: HTN, Thrombo- embolsim Dermat: Alopecia (32%) GI: Abdominal pain, vomiting, anorexia Haemat: Bleeding, leukopenia, neutropenia Genitourinar y: Proteinuria, vaginal haemorrhag e RS: URTI, epistaxis
  35. 35.  PEGAPTANIB: MACUGEN  Pegylated Aptamer  Pegaptanib sodium injection (brand name Macugen) is an anti-angiogenic medicine for the treatment of neovascular WET AMD.  Discovered by Gilead Sciences and licensed in 2000 to EyeTech Pharmaceuticals.  Approval was granted by the U.S. Food and Drug Administration (FDA) in December 2004.
  36. 36.  MECHANISM OF ACTION: Specifically binds to VEGF 165 ISOMER Protein that plays a critical role in angiogenesis (the formation of new blood vessels) Increased permeability (leakage from blood vessels) Two primary pathological processes responsible for vision loss associated with neovascular AMD.
  37. 37.  ADMINISTRATION AND DOSAGE:  Administered in a 0.3 mg dose once every six weeks by intravitreal injection.  Marketed as a pre-filled syringe.  CONTRAINDICATED in patients with ocular or periocular infections.
  38. 38.  PHARMACOKINETICS: (Not adequately studied in humans) Absorption  Very slow systemic absorption  Occurs within 1 to 4 days after 0.3 mg monocular dose. Metabolism & Excretion  By Endo & Exonucleases excreted by kidney.  DRUG INTERACTIONS: Not affected by Cytochrome P450 system.
  39. 39.  RANIBIZUMAB: LUCENTIS  Lucentis is an monoclonal antibody fragment( Fab) developed from the identical parent antibody as Avastin.  Lucentis was approved for neovascular AMD in the U.S. in 2006, and is authorized for multiple ocular conditions in Australia, Canada, and Europe.  It has a licensed indication for use in DME in Australia, Canada and Europe.
  40. 40.  MECHANISM OF ACTION:  Much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A.  Anti-angiogenic property.  Unlike the full length antibody, it penetrates the ILM and can gain access to the sub retinal space.
  41. 41.  ADMINISTRATION AND DOSAGE:  Available as Injection, intravitreal 10 mg/mL  Dose: 0.5 mg/0.05 ml once every month  PHARMACOKINETICS:  Vitreous t1/2 = 3 days (animals) 9 days (humans)  Serum concentrations upto 2000x lower than in the vitreous.
  42. 42.  Reduction in Ranibizumab clearance in renal impairment is considered clinically insignificant & dose adjustment is not expected to be needed.  DRUG INTERACTIONS: Have not been studied.
  43. 43.  SAFETY PROFILE:  Serious ocular adverse events in 2 year MARINA study for ranibizumab 0.5 mg: 1. Endophthalmitis – 1.3% 2. Uveitis – 1.3% . 3. Retinal tear – 0.4% 4. Lens damage – 0.4%
  44. 44.  Serious ocular adverse events in 1 year ANCHOR study for ranibizumab 0.5 mg : 1. Endophthalmitis – 1.4 % 2. Uveitis – 0.7%  There was no increase in systemic adverse effects such as HTN, arterial thromboembolism in either study.
  45. 45. DIFFERENCE BEVACIZUMAB (AVASTIN) RANIBIZUMAB (LUCENTIS) Full sized antibody Antibody fragment 148 kilodaltons 48 kilodaltons Half life-20 days Half life- 3 days Clearance is slow Clearance 100 folds faster Long action & less dosage 140 times higher affinity Cost’s less Costly
  46. 46.  AFLIBERCEPT: EYLEA (NEW DRUG)  Recombinant fusion protein consisting of VEGF- binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.
  47. 47.  INDICATIONS FOR USE: 1. Neovascular (Wet) Age-Related Macular Degeneration (AMD)  Recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters).  Administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
  48. 48. 2. Macular Edema Following Central Retinal Vein Occlusion (CRVO)  Recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters).  Administered by intravitreal injection once every 4 weeks.
  49. 49. CONTRAINDICATIONS:  Contraindicated in patients with infections or active inflammations of or near the eye  AFLIBERCEPT is moving through clinical trials for further intraocular and systemic indications.
  50. 50. HOW TO GIVE INTRAVITREAL INJECTION?  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 are uncommon, with two exceptions: the injection of gas for pneumatic retinopexy and the injection of multiple intravitreal agents in one session.
  51. 51.  Needle selection  Needle size varies according to the substance injected, with 27-gauge needles often used for crystalline substances such as triamcinolone acetonide and 30- gauge needles commonly used for the anti-VEGF agents ranibizumab, bevacizumab, and aflibercept.  Studies suggest that smaller, sharper needles require less force for penetration and result in less drug reflux.  Needle length between 0.5 and 0.62 inches (12.7 to 15.75 mm) is recommended, as longer needles may increase risk of retinal injury if the patient accidentally moves forward during the procedure.
  52. 52.  Injection site  The patient should be instructed to direct his or her gaze away from the site of needle entry.  The injection is placed 3 to 3.5 mm posterior to the limbus for an aphakic or pseudophakic eye, and 3.5 to 4 mm posterior to the limbus for a phakic eye.  Injection in the inferotemporal quadrant is common, although any quadrant may be used.
  53. 53.  Injection technique  Some guidelines suggest pulling the conjunctiva over the injection site with forceps or a sterile cotton swab to create a steplike entry path.  While this approach may, in theory, decrease reflux and risk of infection, a straight injection path is most commonly employed.  After the sclera is penetrated, the needle is advanced toward the center of the globe and the solution is gently injected into the midvitreous cavity.
  54. 54.  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.
  55. 55. CONTRA-INDICATIONS OF ANTI-VEGF 1. Fibrovascular proliferation threatening the macula 2. Active ocular or periocular inflammation 3. Known hypersensitivity to drugs 4. Uncontrolled hypertension 5. Cardiovascular disease 6. Pregnancy and lactation 7. Pre pubescent children
  56. 56. COMPLICATIONS Raised IOP (13-17.6%) Cataract (0.07%) Endophthal mitis (0.1- 1%) Risk of ATE(4.6%)( decrease the synthesis of matrix metalloprote inases)Rebound macular edema Immunoreac tivity(4.4- 6.3%) Retinal detatchment (0.08%) Central Retinal Artery Occlusion
  57. 57. PEGAPTANIB RANIBIZUMAB BEVACIZUMAB TRADE NAME Macugen® Lucentis® Avastin® COMPOUND Aptamer Antibody fragment Full humanized monoclonal antibody VEGF BINDING PROPERTY VEGF-A165 Selective VEGF-A all forms (1 binding site) VEGF-A all forms (2 binding site) VITREOUS t1/2 4 Days 3 Days (Rabbits) 9 Days (Humans) 5.6 Days 21 Days (Systemic) DOSE 0.3 mg in 90 ul 1/6 weeks 0.5 mg in 0.05 ml 1/month 1.25 mg in 0.05 ml 1/3 months COST Rs 47,000/syringe Rs 56,000/vial Rs 37,000/vial ADVANTAGES • Low immunogenicit y • Selective action • More prospective safety & efficacy data • Cost effective • Long acting

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