For each letter, we can build a histogram of contexts that letter occurs in for a sufficiently large corpus. An example is the letter "o", whose occurrences in the previous sentence have the following contexts: f_r (twice), t_g, c_n, _c, c_r.
Each letter's context histograms have some similarity with each other letter's. We want different letters that have similar contexts to have widely differing appearances, because if their appearances were similar, their contexts will be of less help to the reader in disambiguating. And letters with sufficiently different contexts may be allowed to be more similar in appearance (note e.g. the archaic long "s", which despite visual ſimilarity to "f" is easily distinguished from it by the different contexts it appears in).
Another way to use language statistics would be to make the font variable-width (which may help with legibility) but make commonly-occurring letters thin.
I'm not convinced I could differentiate M N and O without context, having a known vowel to differentiate the heights you're looking at would help?
Try it yourself!
http://dotsies.org/design-your-own
Hit the "random" link a few times and you'll get an idea of the possible variations. In the Dotsies pattern, vowels are at the tops and bottoms of words. The variations can look grainy, chunky, loopy, checker-board-ish (you'll see what I mean if you try it). The version I picked is a balance that leans toward being sparse and loopy, and is one of the many variations that has an intuitive letter ordering. Here's a decent one, but with a crappy ordering.
http://dotsies.org/design-your-own/#comeyhangrxdtwqpsfubzljv...
Surprisingly, none of them jump out as significantly better than the others (the overly dense ones being exceptions).
[from another comment] > I am pretty sceptical that an "optimized" alphabet glyph would be one dot for a b c d e, two adjacent dots for f g h i, etc.
There are other mappings that looked marginally better to me, but I deemed picking one with a nice ordering was worth doing. A and E happen to be the 1st and 3rd most common letters, which works out if you want to lean toward the sparse end. Also O (the 4th), A, and E all stick to the top and bottom edges of words, so if you want your words to tend to have holes in the middle they are a good fit. Getting a decent mapping for the commonest letters seems to be key, but by all means, try the above link and post an alternative that you think is better.