Anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the treatment of various retinal diseases, such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). By inhibiting the protein that stimulates abnormal blood vessel growth, these treatments can preserve and improve vision. However, anti-VEGF agents are not suitable for all patients, and a thorough assessment of contraindications is essential before beginning treatment. Contraindications can be categorized as either absolute, which strictly prohibit treatment, or relative, which require careful consideration of the risks versus benefits.
Absolute Contraindications
These conditions present a direct and significant risk to the patient, making anti-VEGF therapy an unsafe option. Treatment is typically not an option until the condition is resolved.
Active Ocular or Periocular Infections
An ongoing infection in or around the eye is an absolute contraindication for an intravitreal injection. Introducing a needle into an infected area can spread pathogens into the eye, leading to a serious internal infection known as infectious endophthalmitis. This is a rare but potentially devastating complication that can cause severe pain, inflammation, and permanent vision loss. Before receiving an injection, any signs of active infection, such as conjunctivitis or significant blepharitis, must be treated and resolved.
Active Intraocular Inflammation
Patients with active inflammation inside the eye, often referred to as uveitis, should not receive an anti-VEGF injection. The injection procedure or the drug itself could exacerbate the inflammation. The inflammation should be brought under control before considering treatment. In contrast, sterile intraocular inflammation, a less severe reaction, may be more tolerable but still requires cautious management.
Hypersensitivity to the Drug
A known allergy or severe hypersensitivity to any component of the anti-VEGF agent is a critical contraindication. Hypersensitivity reactions can range from skin rashes to severe intraocular inflammation or anaphylaxis. Allergic reactions can be life-threatening and require immediate medical attention. Patients must inform their doctor of any previous reactions to medications or excipients.
Pregnancy and Breastfeeding
Anti-VEGF therapy is contraindicated for women who are pregnant or breastfeeding. The antiangiogenic effects of these drugs are considered potentially teratogenic, meaning they could harm the developing fetus by interfering with crucial vascular development. For example, VEGF is vital for placental formation. While data is limited, animal studies and some case reports have raised concerns. The FDA recommends that women of reproductive potential use effective contraception during and for a period after treatment with some agents. Given that VEGF is also present in breast milk and plays a role in infant development, it is also contraindicated in lactating mothers.
Relative Contraindications and Precautionary Measures
These conditions do not automatically prevent treatment but warrant a careful risk-benefit analysis and close monitoring.
- Recent Arterial Thromboembolic Event: There is a theoretical concern and some evidence suggesting a small, increased risk of arterial thromboembolic events (ATEs), such as stroke or myocardial infarction (MI), following intravitreal anti-VEGF injections, particularly with higher systemic exposure agents like aflibercept and bevacizumab. A recent Swedish registry study highlighted a small, increased risk of stroke/TIA within the first 60 days post-injection. In patients with a recent history of stroke or MI (e.g., within 6 months), a low-systemic-exposure agent like ranibizumab might be considered, or treatment delayed.
- Uncontrolled Hypertension: Systemic anti-VEGF therapies, typically used for cancer, are known to cause hypertension. While intravitreal use has lower systemic absorption, it can still affect systemic blood pressure, especially with agents known for higher systemic exposure. Patients with uncontrolled hypertension should have their blood pressure managed before starting treatment to mitigate the risk of serious cardiovascular events.
- High Intraocular Pressure (IOP) or Glaucoma: The injection procedure can cause a transient spike in IOP. In patients with pre-existing glaucoma or ocular hypertension, this can be particularly problematic and requires careful monitoring and management. Repeated injections are associated with a greater risk of sustained IOP elevation.
- Retinal Pigment Epithelial (RPE) Tears: In patients with large or high pigment epithelial detachments, anti-VEGF therapy can increase the risk of RPE tears. These tears can occur spontaneously but are more frequent following treatment due to the contraction of the underlying neovascular membrane. The decision to treat in such cases must weigh the risk of a tear against the potential visual benefit.
- Rhegmatogenous Retinal Detachment or Macular Holes: Treatment is generally withheld in patients with a rhegmatogenous retinal detachment or a Grade 3 or 4 macular hole until the condition is surgically corrected. The injection procedure could potentially worsen these conditions.
Comparison of Systemic Risks for Anti-VEGF Agents
The level of systemic exposure varies among different anti-VEGF agents, influencing their systemic risk profiles. This comparison is a generalized overview and individual patient factors must always be considered.
Feature | Aflibercept (Eylea) | Ranibizumab (Lucentis) | Bevacizumab (Avastin) |
---|---|---|---|
Mechanism | VEGF Trap, binds VEGF-A, VEGF-B, PlGF | Antibody fragment (Fab) of humanized Mab, binds VEGF-A | Full-length humanized Mab, binds VEGF-A |
Systemic Exposure | Higher, longer-lasting systemic VEGF suppression | Lower, minimal systemic VEGF suppression | Higher, significant systemic VEGF suppression |
Systemic Risk (ATEs) | Elevated risk, especially in high-risk patients or with recent ATEs | Lower relative risk compared to others | Elevated risk, comparable to aflibercept |
Pregnancy/Lactation | Contraindicated due to risk and systemic exposure | Contraindicated, but less systemic exposure could be considered in limited cases with counseling | Contraindicated due to risk and systemic exposure |
Contraception Required | Yes, for several months after last dose | Yes, typically for 3 months after last dose | Yes, timing can vary by agent, discuss with physician |
Procedural Risk Factors and Management
Beyond the drug itself, the injection procedure carries its own set of risks, which can be mitigated through strict aseptic technique. Common procedural complications include:
- Sterile Intraocular Inflammation: A non-infectious inflammatory reaction that can follow injection. It often resolves on its own but may mimic infectious endophthalmitis, requiring close monitoring.
- Increased Intraocular Pressure: Transient IOP spikes are common and usually resolve within hours. Sustained elevation, though less common, requires management.
- Subconjunctival and Vitreous Hemorrhage: Small hemorrhages are relatively common and typically resolve without intervention. Larger bleeds are rarer.
- Retinal Detachment/Tear: Rare, but serious complications that can be procedure-related. Attention to injection technique can help minimize this risk.
Conclusion
While anti-VEGF therapy is a powerful tool for preserving sight, its application requires careful consideration of what are the contraindications for anti-VEGF therapy. A comprehensive patient assessment should include a review of absolute contraindications, such as active infections, inflammation, hypersensitivity, pregnancy, and breastfeeding. Relative contraindications, including recent cardiovascular events and uncontrolled hypertension, also necessitate a detailed risk-benefit discussion, particularly given the varying systemic exposure risks associated with different anti-VEGF agents. By adhering to these guidelines, clinicians can maximize patient safety and optimize treatment outcomes.
Key Outbound Link
For more information on the systemic effects and safety profiles of anti-VEGF agents, including details on pharmacodynamics and pharmacokinetics, refer to the review published in Springer.