Anti-VEGF Agents

VEGF & Its Blockers - The Growth Stoppers

• VEGF (Vascular Endothelial Growth Factor): Key protein promoting angiogenesis (new vessel growth) & ↑ vascular permeability.
  • VEGF-A: Primary isoform in ocular neovascular diseases.
  • Receptors: VEGFR-1, VEGFR-2 (main signaling for angiogenesis).
• Pathological Role: Hypoxia (e.g., diabetic retinopathy, CRVO) ↑VEGF → neovascularization (CNV, NVD, NVE) & macular edema.
• Anti-VEGF Agents: Monoclonal antibodies or fragments that bind VEGF, preventing its action, thus "stopping growth."

⭐ Upregulation of VEGF is a critical factor in the switch from dry to wet Age-related Macular Degeneration (AMD).

The Anti-VEGF Crew - Meet the Agents

• Ranibizumab (Lucentis): Fab fragment; Targets VEGF-A; Dose: 0.5 mg.
• Bevacizumab (Avastin): Full mAb; Targets VEGF-A; Dose: 1.25 mg (off-label); Cost-effective.
• Aflibercept (Eylea): Fusion protein (VEGF Trap); Targets VEGF-A, VEGF-B, PlGF; Dose: 2 mg.
• Brolucizumab (Pagenax/Beovu): scFv; Targets VEGF-A; Dose: 6 mg; Smallest, ⚠️ IO inflammation risk.
• Faricimab (Vabysmo): Bispecific Ab; Targets VEGF-A & Ang-2; Dose: 6 mg; Dual action.

⭐ Aflibercept, a "VEGF trap," binds VEGF-A, VEGF-B, and PlGF, offering broader blockade than other early generation agents like ranibizumab or bevacizumab.

Eye Spy a Problem? - Indications Unveiled

Anti-VEGF agents target pathological angiogenesis and vascular leakage. Key indications:

• Wet AMD (nAMD): Primary therapy for choroidal neovascularization.
• Diabetic Macular Edema (DME): First-line for center-involving DME.
• Retinal Vein Occlusion (RVO): Reduces macular edema in CRVO & BRVO.
• Myopic Choroidal Neovascularization (mCNV): Effective for subfoveal/juxtafoveal lesions.
• Neovascular Glaucoma (NVG): Adjunctive to regress iris/angle neovessels pre-PRP.
• Proliferative Diabetic Retinopathy (PDR): Adjunct to PRP, or with vitreous hemorrhage.
• Retinopathy of Prematurity (ROP): For aggressive posterior ROP (Zone I, posterior Zone II).

⭐ For Wet AMD, early and consistent anti-VEGF treatment is crucial for preserving vision.

The Jab & The Plan - Dosing & Delivery

• Route: Intravitreal injection (IVT) - "The Jab".

• Technique: Strict asepsis, topical anesthesia, povidone-iodine. Post-injection IOP check, patient education on warning signs.

• Common Doses:

  • Ranibizumab: 0.5 mg
  • Bevacizumab (off-label): 1.25 mg
  • Aflibercept: 2 mg
  • Brolucizumab: 6 mg ⚠️ (risk of IOI/vasculitis)
  • Faricimab: 6 mg

• Dosing Strategies ("The Plan"): Goal: Maximize vision, minimize injections.

  

⭐ The "Treat-and-Extend" (T&E) regimen aims to reduce treatment burden while maintaining efficacy.

Uh Oh! Side Effects - Risks & Red Flags

• Ocular (Local):
  • Endophthalmitis (⚠️ vision-threatening infection!)
  • Intraocular inflammation (uveitis)
  • ↑IOP (transient or sustained)
  • Retinal detachment, vitreous/conjunctival hemorrhage
  • Cataract (progression/new)
• Systemic (Rare but Serious):
  • Arterial Thromboembolic Events (ATE): Stroke, MI
  • Hypertension, proteinuria
  • Impaired wound healing
• Contraindications/Cautions:
  • Active ocular/periocular infection
  • Pregnancy (teratogenic)
  • Recent CVA/MI (high risk)

⭐ Risk of endophthalmitis post-injection is approximately 0.05% per injection; strict aseptic technique is crucial.

High‑Yield Points - ⚡ Biggest Takeaways

• Anti-VEGF agents (Ranibizumab, Bevacizumab, Aflibercept) inhibit angiogenesis by binding VEGF-A.
• Key indications: wet AMD, Diabetic Macular Edema (DME), Retinal Vein Occlusion (RVO).
• Administered via intravitreal injection; Bevacizumab is a common off-label choice.
• Aflibercept also binds PlGF and VEGF-B, acting as a trap receptor.
• Ranibizumab is a monoclonal antibody fragment (Fab) with shorter systemic half-life.
• Major risks: endophthalmitis, sterile inflammation/uveitis, ↑IOP, rare thromboembolic events.