The objectively best way to do any kind of extended reading on a computer is with a gamepad. They are designed to be ergonomic, comfortably fitting the hands in a relaxed position, and allow arms, wrists, and hands to be adjusted independently of the text's presentation. Most gamepads can be mapped in a way to allow for one handed book reading, and can also be set up in a way so that pages can be flipped in different ways (e.g. A/B , left/right, L2/R2) to further reduce hand and wrist strain.

The number of functions you really need for an ebook are very limited, but extra buttons & sticks can be utilized for things as bookmarking, chapter navigation, zoom/pan, etc. I generally read EPUB/HTML rather than PDF, so I use different buttons/directions/sticks for slowing faster or slower.

Reading a 1000 page PDF with the space bar / scroll wheel is a hell on your wrists, and I will be damned if most ebook reader machines are not a pain in the ass to read for more than 4 or 5 hours.