ANTI-VEGF Recent Advances in DR

VEGF- Vascular Endothelial Growth factor is an important growth factor for angiogenesis and is necessary for normal angiogenesis. It is secreted by hypoxic RPE cells and induces endothelial cell proliferation and retinal vascular permeability. Its levels are increased in the vitreous and retina of patients with active neovascularization. The VEGF family includes: Placental growth factor, VEGF A, B, C, D& E. VEGF effects can be blocked by Anti- VEGF antibodies, anti- VEGF Aptomer, Gene therapy and Protein Kinase-C Inhibition.

Anti VEGF Antibodies are full length humanized monoclonal Antibodies against VEGF. These include RANIBIZUMAB (LUCENTIS) AND BEVACIZUMAB (AVASTIN) Anti –VEGF Aptamers are small, stable RNA like molecules, that bind exclusively with isoform of human VEGF- PEGAPTANIB (MACUGEN) Protein Kinase C inhibitor: VEGF TRAP (R1 R2) is a fusion protein that combines ligand binding of VEGF R1,R2 to Fc portion of Ig G. Gene therapy: RNA i activates the protein that breaks down Anti sense VEGF mRNA hence prevents formation of VEGF Protein.

BEVACIZUMAB (AVASTIN) Is a full length humanized, monoclonal antibody directed against all biolaogically active forms of VEGF -A. It is a recombinant Ig G1 antibody with mol.wt 149KD, produced in chinese hamster ovary. MOA: It prevents interaction between VEGF-A and its receptors (Flt-1 and KDR) on the surface of the endothelium. Dosage: mg intra vitreally every 6 weeks. Side effects: ocular RPE tears and PED Effects on contralateral eye Systemic Risk of hypertension and thromboembolic events

RANIBIZUMAB (LUCENTIS) Is a monoclonal antibody fragment directed towards all isoforms of VEGF-A. Has a mol.wt of 48KD and is produced by E-Coli expression. It is specifically designed for ocular disease, as it has just the ‘Fab’ Fragment and hence confers less antigeniciy. Dose: mg intra vit. Every monthly. Side effects: ocular Conjunctival haemorrhage Vitreous floaters Raised IOP Intra ocular inflammation Visual disturbance (cataract) Systemic: thromboembolic episodes.

BEVACIZUMAB RANIBIZUMAB FC REGION OF AbPRESENTABSENT SYSTEMIC HALF LIFELONGERshorter MOLECULAR SIZELARGER(149KD)SMALLER(48KD) BINDING SITETWOONE DOSINGLONGER INTERVALSSHORTER INTERVALS

PEGAPTANIB SODIUM( MACUGEN) Is a selective RNA aptamer that inhibits VEGF. It is a 29 nucleotide aptamer, 40 KD polyethylene glycol moiety for prolonged tissue residence.stable in human plasma for 18 hrs Dose:0.3 mg intra vitreally every 6 weeks side effects: endophthalmitis, traumatic cataract, retinal detachment.

Indications for Anti VEGF in diabetic retinopathy Diffuse macular edema Non resolving VH Heavy amount of new vessels requiring surgery (2 weeks prior) NVG