After a brain injury, I had continually evolving difficulties with eyesight. Initially, inflammation changed the shape of my eyes and caused images to be out-of-focus. A larger font was helpful.
Then, as my symptoms progressed, I began having a lot of difficulties distinguishing ads from articles. I blocked all websites that place ads within the text of articles, or that required hitting a button to "page" between screens.
Retinal tears (torn away from the back of the eye) developed in both eyes. The tears were small initially but caused a "black snowstorm" of blood cells blocking my view. A high contrast setting initially helped me see through the "snow," but as the retinal tearing progressed, and the blood settled out of my way, I needed low contrast and dim light so less light would reflect onto sections of my retina.
The lenses in both of my eyes began to become cloudy a few months after retinal reattachment surgery. In the months before I ended up having to have lenses in both eyes replaced, bright white screens were impossible for me to read because of glare, and bright text over a dark background was even worse. The best solution I found was to find the lowest contrast with the largest fonts, and I had to adjust my monitor a dim as possible, which enabled me to navigate on the computer, but I ended up copying all text from my computer to my Kindle where the room lighting controlled the glare.
Now, after the lens replacements and the retinal reattachments, I still deal with continual inflammation-related changes in focus. With all of these different challenges to my use of a computer, the most valuable "generic" setting to improve my ability to read my screen has been a variety of medium-dark backgrounds with lots of variety to enable me to distinguish different parts of the screen, with light or dark gray text (depending on the background colors). Dark black text and bright white text are both distractors, but the most important element of a helpful screen is that it not be excessively bright or dim, and the contrast should not be extreme. The right balance within this range (which requires a dark theme) provides noticeable comfort to the eyes that anyone can feel, regardless of vision difficulties.