Dr.

Maharshi Maitra
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VEGF
y Vascular Endothelial Growth Factor. y It is an angiogenic factor responsible for growth of new

blood vessels (neovascularization). y VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, placental growth factor. y VEGF is responsible for many retinal diseases by causing new vessels growth and by increasing leakage and causing retinal swelling. y At least six human VEGF-A isoforms of 121, 145, 165, 183, 189 and 206 amino acids are known to exist.
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y Bevacizumab (Avastin) : Bevacizumab is a full-length recombinant humanized monoclonal antibody. Aptamers are nucleic acid ligands. which was the first anti-VEGF agent to be approved for use in neovascular AMD. which bind different targets such as proteins with high specificity and affinity. It binds to and inhibits all isoforms of VEGF-A. 3 .Anti VEGF Agents y Pegaptinib (Macugen) : It is an oligonucleotide aptamer.

humanized antibody antigen-binding fragment (Fab) that binds and neutralizes all known active forms of VEGF-A.y Ranibizumab (Lucentis) : Ranibizumab is a recombinant. 4 .

This leads to stabilization of vision and even improvement of vision in many cases.Mechanism of Action y The anti-VEGF agents block the VEGF molecules and decreases the abnormal and harmful new blood vessels formation and decreases the leakage and swelling of the retina. 5 .

8° C and not frozen.25 mcg/0. y Pegaptanib is administered in a 0. It may be repeated once every six weeks.05 mL (0.05 cc. y Ranibizumab should be refrigerated at 2° .5mg) is given by intravitreal injection. 6 . y The intravitreal dosage of Bevacizumab is 1.3 mg dose by intravitreal injection.Dosage y Ranibizumab is available in a 10mg/mL single use vial and 0.

Indications y ARMD (Age-related macular degeneration) y CNVM (Choroidal neovascular membrane) y Severe Diabetic Retinopathy y Macular Oedema y Vascular blocks (CRAO. CRVO) y Neovascular Glaucoma y Vitreous Haemorrhage 7 .

y ARMD (Age-related macular degeneration) 8 .

y Choroidal/Sub-Retinal Neo-Vascular Membrane (CNVM/SRNVM) 9 .

y Severe Diabetic Macular Edema 10 .

y Macular edema due to Vascular Block of the retina 11 .

.Fundus and high-resolution OCT images of a patient with BRVO (a) before and (b) 2 months after treatment with ranibizumab showing resolution of bleedings and macular 12 edema.

y Vitreous hemorrhage due to diabetic retinopathy or vascular block 13 .

y The injection is most commonly given inferotemporally because of ease of access. 14 .5.Technique of Intravitreal Injections y Anaesthesia : Subconjunctival 2% lidocaine at the injection site or with topical xylocaine jelly.to 4mm posterior to the limbus through pars plana. y Lids and periocular area should be prepped with 5% povidone/iodine with a drop in the cul de sac. 3.

and also 2 days prior to the procedure. patients should use topical antibiotics for at least 3 days.y Visualization of the fundus via indirect ophthalmoscopy should then be performed to ensure that no complications have occurred. y Following the procedure. 15 .

15 ± 0. 16 .Complications y y y y y y y y Foreign body sensation Tearing(watering) Pain Redness Injection-related complications such as Infectious endophthalmitis Retinal detachment Traumatic cataract may occur with a frequency of about 0.05% after intravitreal injections.

and the Fc region of human IgG which binds all VEGFA isoforms. y It has higher affinity in comparison to other antiVEGFs. 17 .VEGF Trap y The VEGF Trap-Eye (Regeneron) is a recombinant fusion protein of portions of VEGF receptors 1 and 2. including bevacizumab and ranibizumab.

which have been shown to contribute to excessive vascular permeability.y VEGF Trap-Eye has a longer half-life in the eye after intraocular injection and it binds other members of the VEGF family including placental growth factors 1 and 2. y This higher affinity may allow lower doses to be and to maintain a longer duration of action. 18 .

19 . y Rapamycin is a macrocyclic antibiotic produced by the bacterium Streptomyces hygroscopicus. The antiangiogenic properties of rapamycin are associated with a decrease in VEGF production and a reduction in the response of vascular endothelial cells to stimulation by VEGF.Newer Agents y RNA interfering molecules : Bevasiranib is a specific siRNA designed to decrease the level and activity of VEGF mRNA.

20 .y Angiostatic steroids (Cortesenes) like anecortave acetate. y Tyrosine kinase inhibitors are also being tried as the VEGFRs are receptors of the tyrosine kinase receptor family.

controlled study. single-masked. 21 . randomized. multicenter.Studies y The FOCUS Study assessed the efficacy and adverse- events profile of a combined treatment with ranibizumab and verteporfin PDT in patients with predominantly classic CNV secondary to AMD during a 2-year.

y The VISION Study showed that patients receiving pegaptanib lost vision in a smaller rate than those treated with conventional care. 22 .y The PIER Study evaluated the efficacy and safety of ranibizumab administered monthly for 3 months and then quarterly in patients with CNV secondary to AMD.

MARI A St y y In the MARINA (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD) Study. 716 patients with either minimally classic or occult (with no classic lesions) CNV secondary to AMD were randomly assigned to receive 24 monthly intravitreal injections of ranibizumab (either 0. 23 .5 mg) or sham injections.3 or 0.

presumed endophthalmitis was identified in 5 patients (1. y The study showed that the intravitreal administration of ranibizumab during 2 years did prevent vision loss and improved mean VA and had low rates of serious adverse events.3%) given ranibizumab. During 24 months. 24 .y The benefit in VA was maintained at 24 months.0%) and serious uveitis in 6 patients (1.

ANCHOR Study y The ANCHOR Study (published 2009) demonstrated that ranibizumab was superior to PDT with respect to VA and morphologic efficacy outcomes and that intravitreal treatment of predominantly classic CNV in AMD with ranibizumab had a low rate of serious ocular adverse events. 25 . y Ranibizumab provided greater clinical benefit than verteporfin PDT in patients with AMD with newonset. predominantly classic CNV.

uncontrolled. y The study design was a 2-year prospective. 26 . variable-dosing regimen with intravitreal ranibizumab treatment based on OCT findings.PrONTO Study y The long-term efficacy of a variable-dosing regimen with ranibizumab was assessed in the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular Age-Related Macular Degeneration Treated with Intraocular Ranibizumab (PrONTO) Study. in which patients were followed for 2 years.

patients with AMD involving the central fovea and a central retinal thickness of 300 m or more as measured by OCT received 3 consecutive monthly intravitreal injections of ranibizumab (0. VA improved by 15 letters or more in 43% of patients.y In this open-label.5 mg). uncontrolled clinical study. These VA and OCT outcomes were achieved with an average of 9. mean VA improved by 11. 27 . prospective. y At month 24.9 injections over 24 months. single-center.1 letters and the OCT-CRT decreased by 212 m.

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