I believe the problem is that the objects (IE, orbs and arrows) have a slight stutter as they move. If your eyes are sensitive enough, then as you track the objects your eyes constantly start and stop moving very quickly, leading to strained eye muscles. The human eye is extremely sensitive, so this can very easily happen without your knowledge.

At this moment, I have determined three possible solutions players can use to solve the problem individually. The best solution would be to remove the object stutter entirely, but that may or may not be possible ( I am not a developer and do not know enough about this game to say.)

Solution 1: Decrease your screen resolution. It seems that, as the resolution decreases, so does the stutter. Playing on a windowed mode with lower resolution decreases the distance your eyes have to move and the amount of stutter they detect, and it's possible that they can stop detecting the stutter completely. Below about 600x400 resolution, however, the text for song selection becomes very difficult to read.

Solution 2: Focus on Melody rather than the orbs and arrows. Since Melody herself has very little movement along the game screen, and her animations are fairly fluid, focusing on her can significantly reduce eye strain. This option forces you to concentrate on the approaching orbs and arrows with only peripheral vision, but might be considered the best solution by many.

Solution 3: Limit your playtime. This sounds obvious and has been stated by many videogame publishers, but limiting your playtime is the best way to reduce eye strain.

I would like to point out that this is all conjecture of my own consideration, and nothing in this guide should be treated as medical fact or tested-and-proved hypothesis. This is simply what I have noticed, and what I have done to fix it.

The guide's picture is from TheSHaDoW2013's Deviantart gallery, and I claim no part in its creation or ownership.