VEGF: it's role in the eye and beyond

In February 2007 a workshop sponsored and hosted by Pfizer Ophthalmics was held in London to discuss the current perspectives on age-related macular degeneration (AMD), and in particular the existing and potential future role that anti-VEGF therapies have to play in this extremely debilitating condition.

The role of VEGF in the body

In addition, VEGF is increasingly being proven to be associated with cardiovascular wellbeing, as expounded by Professor Frank Ruschitzka, a cardiologist and nephrologist from University Hospital Zurich, Switzerland. When VEGF is removed from the body, nitric oxide levels diminish; endothelial function relies on nitric oxide. Professor Ruschitzka emphasized this point by saying that if one was going to have angina or a heart attack, they would want a lot of VEGF in their system. It is vital therefore that any thought of inhibiting VEGF in the body to aid AMD should take the wider implications of doing so into consideration.

Inhibiting VEGF: a double-edged sword

Both Professor Ruschitzka and Dr Shima stressed that inhibiting VEGF to treat AMD is a "double-edged sword". Whilst it is undoubtedly an underlying indicator and cause of neovascular AMD, the important role it plays in other functions throughout the body means that targeting VEGF is a fine and precise balancing act.

However, VEGF is a collection of proteins; as a result, there is the potential to specifically target "bad" VEGF whilst leaving enough "good" VEGF in the body for all the beneficial reasons noted above.

Based on his personal experience, Professor Giovanni Staurenghi of the University of Milan in Italy went on to argue that pan-VEGF therapies, which inhibit all isoforms of VEGF in the body, should be used primarily to preserve sight in the short-term, but used with caution in the long-term. Although potentially very good for short-term use in patients with high levels of oedema (blood vessel leakage), he argued that the theoretical safety risk might outweigh the benefit in the long-term.

Indeed, it has been acknowledged by the FDA that "there is a theoretical risk of arterial thromboembolic events following intravitreal use of inhibitors of VEGF".²

A targeted approach

Professor Staurenghi suggested that, in the chronic phase of neovascular AMD, when there is little or no oedema and visual acuity is stabilizing, it may be useful to employ selective VEGF inhibition to safely maintain visual function and to spare the other physiological processes which rely on VEGF in the body.