What are the contraindications for intravitreal bevacizumab (recombinant humanized monoclonal antibody) in patients with a history of severe allergic reactions, cardiovascular disease, or recent myocardial infarction?

Contraindications of Intravitreal Bevacizumab

The primary absolute contraindication to intravitreal bevacizumab is a history of severe allergic reaction (anaphylaxis) to bevacizumab itself or any of its components. 1

Absolute Contraindications

• Severe allergic reaction (anaphylaxis) to bevacizumab or any component of the formulation is the only established absolute contraindication 1
• Active ocular or periocular infection (endophthalmitis or active intraocular inflammation) should preclude injection until resolved, as with any intravitreal procedure 1

Relative Contraindications and High-Risk Situations Requiring Careful Consideration

Recent Cardiovascular or Cerebrovascular Events

• Recent myocardial infarction or stroke warrants withholding treatment temporarily, though no specific timeframe is definitively established 1
• Patients with history of MI or cerebrovascular infarction have significantly increased risk of MI after intravitreal bevacizumab (P = 0.005 in multivariate analysis), with events occurring 3 days to 3 weeks post-injection 2
• However, large real-world studies show no increased risk of acute MI or cerebrovascular disease compared to other anti-VEGF agents (ranibizumab, aflibercept) in routine practice 3

Ocular Ischemic Syndrome

• Ocular ischemic syndrome represents a particularly high-risk condition, with 50% (2 of 4 eyes) developing central retinal artery occlusion 3-4 days after bevacizumab injection 4
• This complication rate is dramatically higher than in other neovascular glaucoma etiologies (2% overall vs 50% in ocular ischemic syndrome) 4
• Perform thoughtful risk-benefit analysis with strict follow-up in these patients, as visual prognosis after central retinal artery occlusion is typically poor 4

Pregnancy

• Pregnancy is a relative contraindication, and treatment should be withheld during pregnancy 1
• This recommendation is based on the theoretical systemic absorption and potential effects on fetal development, though specific data are limited 1

Important Clinical Caveats

Cardiovascular Disease Context

• Despite theoretical concerns, no deaths or thromboembolic events were observed in systematic surveillance studies of 578 injections over 6 months 5
• No differences in MI, CVD, major bleeding, or all-cause hospitalization were found when comparing bevacizumab to ranibizumab or aflibercept in 87,844 patients (HR 0.96,95% CI 0.74-1.25 for MI) 3
• The presence of cardiovascular disease alone is not an absolute contraindication, but recent acute events warrant delay 1, 3

Pre-existing Retinal Pigment Epithelial Detachment

• While not a contraindication, 7% of AMD eyes with preexisting RPE detachments developed RPE tears after bevacizumab treatment 5
• This represents a known complication rather than a contraindication, requiring informed consent and monitoring 5

Common Pitfalls to Avoid

• Do not confuse relative contraindications with absolute contraindications: cardiovascular disease history requires caution but is not an absolute barrier to treatment 3, 2
• Do not overlook ocular ischemic syndrome as the underlying etiology in neovascular glaucoma cases, as this dramatically increases complication risk 4
• Do not assume all neovascular glaucoma patients have equal risk: the etiology matters significantly for safety profile 4