I find it bothers my eyes more to have a dark background in all circumstances except when there is no other light source than the reading device.
In reality, I find the best route is to use the brightest white background and the blackest black text, find the font size I prefer to read, lower the backlight as far as I can stand, then, after all that, increase the font size by one because I am always picking a font size that is just too small. In fact, I would guess that the font size is the most meaningful setting in terms of eye strain for many people.
To understand why, you need to understand how modern devices render fonts that look so smooth. Fonts, like any other vector graphics, are rendered using shapes that when displayed raw will have jagged edges and look poorly on most display devices. To combat this we use a technology called antialiasing. It's a big fancy word for bluring the edges of letters. When you antialias a font that is small, however, the antialiasing blur becomes noticeable and will actually subconsciously trigger your eyes to attempt refocusing constantly. This leads to eye strain. So finding a comfortable font size then upping it one seems to do the trick for me, to help get over that "hazy hump" for smaller screens with smaller fonts.
Incidentally this is exactly the reason many systems have a lower threshold for font sizes where antialiasing will not occur. It seems that this has not been implemented in most handheld devices that do antialiasing.
So, turn down the light, turn up the font size, and even consider trying a different type of font. If you are using a Serif font, use a Sans Serif font (in other words, if your letters have the little decorative flourishes coming off of them, it's a serif font.)
Also, if your experience with LCD-caused eyestrain is based on computer screens, you simply cannot use that experience to predict what a handheld device will do. You will naturally move the handheld device closer or further away from your face to help find the most comfortable reading situation, which is something you can't practically do so easily with even a laptop. It's simply not the same.
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