As a focal dilatation of a retinal arteriole, macroaneurysms typically occur in female hypertensive patients [3]. Observation is appropriate in asymptomatic patients. However, patients may present with an acute deterioration in vision secondary to macular oedema or vitreous haemorrhage [3]. Intravitreal bevacizumab has been shown to improve macroaneurysm-associated macular oedema [4].
Bevacizumab, commonly referred to by its trade name Avastin, is often prescribed off-license in the United Kingdom for macular oedema or neovascularisation, in patients who do not meet funding criteria for aflibercept or ranibizumab. Although anti-VEGF drugs are detectable in the systemic circulation following intravitreal injection, systemic side effects are rare [1, 5]. Intravitreal anti-VEGF therapy has been linked to non-ocular haemorrhage, arterial thromboembolic events and systemic infections [1]. The systemic safety profiles of bevacizumab, ranibizumab and aflibercept, the three most commonly prescribed anti-VEGF agents, are not considered to be significantly different [1].
In a twelve-month case series of 1,173 patients receiving intravitreal bevacizumab, systemic adverse events were reported in 1.5% of patients. These included acute elevations in blood pressure (0.59%), cerebrovascular accidents (0.5%), myocardial infarctions (0.4%) and death (0.4%) [6].
Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A) [3]. Other monoclonal antibody therapies are associated with systemic inflammation; this is the result of a hypersensitivity drug reaction and referred to as serum sickness [2]. In these type III hypersensitivity reactions, antibodies develop in response to an antigen, forming antigen-antibody or immune complexes [2]. If the mononuclear phagocyte system is saturated by the immune complex load, excess complexes can form and deposit throughout the body, triggering an inflammatory response and activating the complement system. In this case, although the mechanism of systemic inflammation is likely the result of a bevacizumab hypersensitivity reaction, the patient did not meet criteria for a diagnosis of serum sickness.
Following a change in anti-VEGF therapy from bevacizumab to aflibercept, the patient has not experienced any further inflammatory episodes. Aflibercept is a recombinant fusion protein that acts as a decoy receptor for VEGF-A and VEGF-B, as well as binding to placental growth factor [3]. Its different molecular composition to bevacizumab may explain why the patient has not developed an immune response to this drug.
Though rare, this case serves as a reminder that patients can develop serious and potentially life-threatening systemic adverse effects from intravitreal anti-VEGF treatment. Ophthalmologists should enquire about systemic side effects in patients undergoing anti-VEGF injections. In this way, adverse effects may be recognised sooner and a change or cessation of therapy considered.