EpistemisRanibizumab, Aflibercept, Faricimab, Bevacizumab
Anti-VEGF biological agents specifically block proangiogenic and vascular permeability cytokines in the retina, stopping neovascularization in devastating macular pathologies.
Mechanism
💊 Commercial NamesLucentis, Eylea, Vabysmo, Avastin (uso off-label ocular re-envasado).
🔬 Pharmacological GroupAnticuerpos monoclonales y proteínas de fusión recombinantes dirigidos contra VEGF. Faricimab (anticuerpo biespecífico anti-VEGF-A y anti-Ang-2).
🧪 Standard PresentationsViales monodosis para inyección intravítrea: 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
El factor de crecimiento endotelial vascular de tipo A (VEGF-A) es el regulador principal de la angiogénesis patológica retinal:
- Unión Selectiva y Neutralización del VEGF-A (Ranibizumab, Bevacizumab): Se unen de forma molecular a las isoformas activas solubles del VEGF-A, impidiendo su acoplamiento físico a los receptores transmembrana de tirosina quinasa endoteliales de tipo VEGFR-1 (Flt-1) y VEGFR-2 (Flk-1/KDR) de la retina.
- Mecanismo de "Trampa" de Receptores (Aflibercept): Es una proteína de fusión recombinante constituida por los dominios de unión a ligando de los receptores humanos VEGFR-1 y VEGFR-2 fusionados a la porción Fc de la IgG1 humana. Actúa como un receptor señuelo móvil de altísima afinidad (Kd ≈ 0.5 pM, 100 veces superior a ranibizumab), atrapando no solo al VEGF-A, sino también al VEGF-B y al Factor de Crecimiento Placentario (PlGF).
- Mecanismo Biespecífico Innovador (Faricimab): Bloquea simultáneamente el VEGF-A and the Angiopoyetina-2 (Ang-2). Al inhibir la Ang-2, se estabiliza la vía Tie-2 de la microvasculatura del ojo, reduciendo de forma significativa la filtración capilar dural, la inflamación retiniana periférica y la propensión a la neovascularización, prolongando el intervalo de tratamiento a cada 16 semanas.
- Efectos Clínicos Oculares: Detienen la proliferación de vasos coroideos anormales subretinianos (membrana neovascular coroidea en la DMAE húmeda), promueven la disolución del fluido intrarretiniano y subretiniano (edema macular diabético) y estabilizan la barrera hematorretiniana interna.
Pharmacokinetics
Quantitative Ocular and Systemic Pharmacokinetics
| Parameter | Ranibizumab (0.5 mg) | Aflibercept (2.0 mg) | Bevacizumab (1.25 mg) |
|---|---|---|---|
| Molecular Structure | Recombinant human IgG1 antibody Fab fragment (48 kDa, unglycosylated). | Heavy homodimeric fusion protein (115 kDa, glycosylated). | Full-length human IgG1 monoclonal antibody (149 kDa, glycosylated). |
| Intravitreal Half-Life (t1/2) | t1/2 in human vitreous ≈ 9.0 days. | t1/2 in human vitreous ≈ 11.0 days. | t1/2 in human vitreous ≈ 10.0 days. |
| Clearance and Purification | Passive elimination from the vitreous cavity to the anterior chamber by flow of aqueous humor, subsequently penetrating the systemic blood circulation. | ||
| Systemic Half-Life (t1/2) | Ultra-rapid transient course in plasma (≈ 2 hours). | Mean plasma elimination (≈ 5 - 6 days). | Very long plasma half-life (≈ 18 - 20 days). |
| Effect on Systemic VEGF | No or transient reducing effect on circulating free VEGF. | Moderate reduction in free plasmatic systemic VEGF. | Persistent dural reduction in systemic free VEGF for months. |
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.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Ophthalmology
- Cluster
- Retinal Angiogenesis Modulators