CATT: Into the eye of a tiger

The anti-vascular endothelial growth factor (anti-VEGF) treatment of exudative age-related macular degeneration (AMD) provides an outstanding example of how the fruits of basic science research have been harvested to reduce blindness. After the initial discovery of VEGF,1 speculation that inhibiting the action of this protein alone might halt pathologic angiogenesis led to the development of neutralising anti-VEGF antibodies for use in understanding animal models of neovascularisation and as an adjunctive treatment for cancer.2 The next rational step was to design an ocular drug that was active against the VEGF epitope but was also otherwise inert to avoid interactionwith the immune system. The former was developed as bevacizumab and the latter as ranubizumab. It was then that clinicians returned a favour to basic scientists who discovered VEGF and its pathways, in two big surprises. First, it was amazing that blocking the action of a single protein induced such a dramatic inhibition, and regression, of choroidal neovascularisation, which depends on a complex cascade of inter and intra-molecular factors, proven in the ANCHOR and MARINA trials.3 4 Second, after understanding that systemic bevacizumab reduced blindness from exudative AMD, the courageous, off-label use of bevacizumab as an intravitreal treat-ment not only worked, but was not accompanied by the dire forecasts thatmost scientists would assume might accompany the use of a potent, full length antibody