Yes. Optimized mode requires exact sampling rate of console dot clock output, otherwise you will get exactly those types of fuzzy or trembling columns.
Iirc, the default samplerate for 320×240 optimized is 426, but MD is more like 427 or 428. Adjust that and you should see an improvement.
(obviously, if it’s a 256 horizontal game, you need to use the 256×240 mode instead, I believe FirebrandX made a list at some point which may be googleable.
Additionally, optimized modes usually requires some adjustment to sample phase, which is under Sampling Options.
http://junkerhq.net/xrgb/index.php?title=Optimal_timings