Are they comfortable or uncomfortable?

Does having a large wheel on the side of your leg exert pressure on ankles or against the leg?

No the opposite is true they are more comfortable than inline skates because the leg support eliminates ankle strain (see ABC New Inventors: Episode 21, 2009).

I (the inventor) often go skating for 3 or 4 hours at a time with no discomfort. At the Shanghai bike show I had them on for over 10 hours continuously. Years ago I smashed my left knee on the ice while skating and have also twisted it a couple of times when snow skiing so it is not as strong as my right knee. However, I have never strained it while wheel-skating, even during the falls I've had. I'm not sure if I'm just fortunate or if it is because the large wheel has protected me.