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I have a bunch of PDF ebooks ... while I know that traditional PDF readers (Acrobat, Preview) can be used to read them, I wonder if there are ebook software specifically tailored for long starring at the computer screen? Like white-on-black (night reading)? Is there any?

Preferably a software that runs on MacOSX. If not, then Windows would be nice too.

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Man I am facing this exact issue! did you find a decent solution? I am also looking for a program that will maintain each book where I am up to, and so control my daily reading. case studies etc. – Shimmy Feb 23 '11 at 1:48

You can go to System Preferences => Universal Access, go to the Seeing tab, and change the Display option from Black on White to White on Black. (This reverses all the colours on the screen.) Then just read the e-book on Preview or Acrobat and the text will be white on black (as long as the text was black on white before).

The default keyboard shortcut to toggle this setting is "Control+Option+Command+8" but you can edit this shortcut via System Preferences => Keyboard and then the Keyboard Shortcuts tab.

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Typical ebook readers can do this, but they aren't made for PDF ebooks. They are for ebook formats like EPUB, etc. If you don't care about the layout of the books, just use pdftohtml to convert the books, and then use some dedicated reader software like FBReader (available for lots of platforms, but don't know if there is a version for Mac). pdftohtml will keep paragraphs and headings, but the rest will be lost, and I think that the images, if any, get misplaced in the conversion. So it works quite well for fiction, but not for technical books or textbooks.

If you're going with the "change system colours solution" which Mew2468 proposed, don't use white on black, if possible. The easiest on the eye is a very dark grey (maybe 80%) on a very light grey (about 7%). Another good combination is very dark maroon font on light beige background. If you insist on light-on-dark, flipping one of these combinations will be better than just white on black. Also, turn down your monitor brightness. Most monitors I've seen are set at 75%-100% brightness, and when you work inside with these settings, even next to a window, you go snowblind. Set it between 25%-30%, it is much better on the eyes. It looks somewhat drab the first 10 minutes, but as an avid e-book reader (ca. 3 e-books a week) I can confirm that it reduces eyestrain considerably.

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