Ranibizumab, Aflibercept, Faricimab, Bevacizumab

Mechanism

💊 Commercial Names

Lucentis, Eylea, Vabysmo, Avastin (repackaged off-label ocular use).

🔬 Pharmacological Group

Monoclonal antibodies and recombinant fusion proteins directed against VEGF. Faricimab (bispecific anti-VEGF-A and anti-Ang-2 antibody).

🧪 Standard Formulations

Single-dose vials for intravitreal injection: ranibizumab 0.5 mg/0.05 mL, aflibercept 2.0 mg/0.05 mL, faricimab 6.0 mg/0.05 mL, bevacizumab 1.25 mg/0.05 mL.

Mechanism of Action

Vascular endothelial growth factor A (VEGF-A) is the main regulator of pathological retinal angiogenesis:

• Selective Binding and Neutralization of VEGF-A (Ranibizumab, Bevacizumab): They bind molecularly to the soluble active isoforms of VEGF-A, preventing their physical coupling to endothelial-type transmembrane tyrosine kinase receptors. VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/KDR) de la retina.
• Receptor "Trap" Mechanism (Aflibercept): It is a recombinant fusion protein consisting of the ligand binding domains of the human VEGFR-1 and VEGFR-2 receptors fused to the Fc portion of human IgG1. It acts as a very high affinity mobile decoy receptor (K_d ≈ 0.5 pM, 100 times greater than ranibizumab), trapping not only VEGF-A but also VEGF-B and Placental Growth Factor (PlGF).
• Innovative Bispecific Mechanism (Faricimab): Simultaneously locks the VEGF-A and the Angiopoietin-2 (Ang-2). By inhibiting Ang-2, the Tie-2 pathway of the microvasculature of the eye is stabilized, significantly reducing capillary leakage, peripheral retinal inflammation and the propensity for neovascularization, prolonging the treatment interval to every 16 weeks.
• Clinical Effects in the Eye: They stop the proliferation of abnormal subretinal choroidal vessels (choroidal neovascular membrane in wet AMD), promote the dissolution of intraretinal and subretinal fluid (diabetic macular edema), and stabilize the internal blood-retinal barrier.

Pharmacokinetics

Quantitative Ocular and Systemic Pharmacokinetics

Acute Infectious Endophthalmitis after Intravitreal Injection

The intravitreal injection of anti-VEGF agents physically crosses the sclera and the pars plana of the ciliary body, directly penetrating the acellular vitreous cavity, the optimal biological medium for microbial growth. The most feared complication of this invasive procedure is acute bacterial infectious endophthalmitis (caused mainly by Gram-positive bacteria of the eyelid flora, such as Staphylococcus epidermidis or Streptococcus of the viridans group). It manifests itself in the first 24-72 hours by severe and sudden visual loss, deep dull eye pain, intense conjunctival hyperemia and the presence of hypopyon (level of pus in the anterior chamber). It is an absolute emergency that requires diagnostic vitreous puncture and immediate injection of intravitreal antibiotics (Vancomycin + Ceftacidime).

Security

Contraindications

• Absolute: Active infection or suspicion of active ocular or periocular infection (suppurative blepharitis, bacterial conjunctivitis, active keratitis); active intraocular inflammation of moderate course (anterior or intermediate uveitis); hypersensitivity to the active ingredient or to the excipients of the sterile ampoule.
• Relative: Recent stroke or transient cerebral ischemia (within the previous 3-6 months - although the risk is extremely low, there is a theoretical basis for a minor increase in systemic thromboembolic events due to prolonged suppression of circulating VEGF with bevacizumab).

Adverse Effects (ADR)

• Ocular Sites: Subconjunctival hemorrhage at the needle point (very common and self-limiting); self-limited transient elevation of IOP immediately after injection (due to added intrinsic volume); transient floating myodesopsias (fatty accumulation of the drug in the vitreous); sterile uveitis or mild reactive inflammatory vitritis; tear of the retinal pigment epithelium.
• Systemic: Mild headaches, transient elevations in systolic blood pressure, and potential marginal increase in stroke in very predisposed populations.