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Perhaps the font you're using has too little contrast/is too light. Did you adjust the weight? What font are you using?
Another reason may be that line-spacing or margins are too narrow. Try to increase them.
It took me a little time to get my Libra look the way I wanted and felt comfortable reading (I use a custom font and have my Kobo patched so I can increase its weight - you can't adjust the weight of custom fonts out of the box), but afterwards I've never had any problems with tired eyes (and I have pretty weak eyes).
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