Acting mechanism of squalamine is not clearly understood yet. All that I have read is that it acts on NaH pump of the new endothelial cell which is an exchange mean of these cells with their environment and as a consequence, it affects cell volume (shrink?), acidity, growth, mobility and may alter cellular response to growth stimuli (Vegf). Beside that, it is also a Vefg inhibitor.
As it prevent new blood vessels from growing, they don't reach the point when they start to leak. I don't know if it will acts on leaks, but I would not bet on it.
Inside the eye, blood is not cleaned by macrophage but by constant circulation of fluids inside the globe (some kind of overpressure mechanism where more fluids enter in than going out, the same way they keep rooms clean in the electronic industry). Anything that is injected in the vitreous is rapidly washed out (think of Genentech and Eyetech intravitreal administration). That is why Alcon injects a depot drug behind the eye that slowly perfuse at the retina. That is also why, when a drug is administered intravenously and can effectively cross the blood-retina barrier (Squalamine, Combretastatin), it will stay longer in the retina vessels and will not be washed out.
Unless there is some systemic side-effect not know today for the long term administration of these drug, they are more advantageous than others.
Lucentis and Macugen could not choose IV for a short half-life (or acting time) of their molecule.
Hope I have helped you
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