What happens to my immune system when I get anti-VEGF injections for AMD?
Anti-VEGF injections are the standard treatment for neovascular (wet) age-related macular degeneration (AMD). They work by blocking a protein called vascular endothelial growth factor (VEGF) that drives abnormal blood vessel growth and leakage in the eye 168. While these injections are effective at preserving vision, research shows they can also affect your immune system. Studies have found that anti-VEGF therapy may activate certain immune pathways in the eye, including signals related to T-cells and inflammation 5. This immune activation might contribute to incomplete responses or long-term changes in the retina, such as fibrosis (scarring) 7.
What the research says
A 2024 proteomic study analyzed vitreous fluid from patients with neovascular AMD who were receiving anti-VEGF therapy. It found 107 proteins that were expressed differently compared to controls, including key regulators of immune signaling. Specifically, pathways related to T-cell activation, interleukin signaling, and leukocyte-mediated cytotoxicity were significantly activated 5. This suggests that even though anti-VEGF injections block VEGF, other immune pathways remain active or become more active.
Long-term use of anti-VEGF therapy is associated with the development of subretinal fibrosis (scarring under the retina) in 40-50% of eyes after 5 years 7. Fibrosis is a major cause of irreversible vision loss and is linked to chronic inflammation and immune cell activity. The immune activation seen in the proteomic study may help explain why some patients develop fibrosis despite treatment.
Clinical trials of anti-VEGF drugs, including biosimilars, have monitored for anti-drug antibodies (immune responses against the drug itself). A systematic review and meta-analysis found no significant difference in anti-drug antibody development between biosimilars and reference aflibercept 3. This indicates that while the immune system may be activated locally in the eye, systemic immune reactions to the drug are uncommon.
Other research has explored combining anti-VEGF therapy with radiotherapy. A systematic review found that adding radiotherapy increased the risk of vision loss compared to anti-VEGF alone 4. This highlights that additional treatments can alter the immune and inflammatory environment, potentially worsening outcomes.
What to ask your doctor
- What are the signs that my immune system might be overreacting to anti-VEGF injections?
- Could the immune activation in my eye affect my long-term vision or increase the risk of scarring?
- Are there any tests to monitor immune-related changes in my retina during treatment?
- If I develop anti-drug antibodies, would switching to a different anti-VEGF drug be an option?
- How does my overall health or other medications influence the immune response to these injections?
This question is drawn from common patient questions about Allergy & Immunology and answered using cited medical research. We do not provide individualized advice.