Question

Evolution of Anti-VEGF factors.

Hint:

The evolution of Anti-VEGF therapies, from bevacizumab to newer agents like aflibercept and faricimab, has dramatically improved the treatment options for retinal diseases, offering better efficacy and longer intervals between injections.

Answer 1

Anti-VEGF (Vascular Endothelial Growth Factor) therapies have revolutionized the treatment of various ocular diseases, particularly those involving neovascularization and vascular leakage. The evolution of Anti-VEGF therapies has progressed over time, with the introduction of newer agents improving efficacy and safety profiles.
Evolution of Anti-VEGF Factors:
1. First Generation: Bevacizumab (Avastin):
- Bevacizumab was the first systemic anti-VEGF therapy, initially developed for cancer treatment. It was later found to be effective in ocular conditions such as wet age-related macular degeneration (AM, diabetic macular edema (DME), and retinal vein occlusion (RVO).
- Bevacizumab is off-label used for ocular conditions, where it has been shown to reduce neovascularization, macular edema, and improve visual outcomes.
2. Second Generation: Ranibizumab (Lucentis):
- Ranibizumab is a monoclonal antibody fragment derived from bevacizumab but with a smaller molecular size and higher ocular bioavailability. It was developed specifically for ocular use and approved by the FDA for the treatment of wet AMD, DME, and RVO.
- Ranibizumab works by directly binding to VEGF-A, preventing its interaction with the VEGF receptor and inhibiting angiogenesis.
3. Third Generation: Aflibercept (Eyle:
- Aflibercept, also known as VEGF Trap-Eye, is a fusion protein that binds to multiple forms of VEGF-A and placental growth factor (PlGF). It has a higher affinity for VEGF and longer half-life than ranibizumab, allowing for less frequent injections (up to every 8 weeks).
- It is FDA-approved for the treatment of wet AMD, DME, RVO, and myopic choroidal neovascularization.
4. Emerging Anti-VEGF Agents:
- Brolucizumab (Beovu): A newer anti-VEGF agent that binds to VEGF-A with higher affinity and has a longer duration of action (up to 12 weeks).
- Faricimab (Vabysmo): This bispecific antibody targets both VEGF-A and Ang-2, which may improve outcomes in wet AMD and other retinal conditions by addressing both angiogenesis and vascular permeability.