Thank you for that thought. It certainly sounds related ...

I'm actually already running FFXIV in Windowed mode, but I will take a look at the options.

I still haven't pinned down the precise repro conditions as to exactly what sort of window focus change causes it. It does seem a little random and most recently happened when switching out to Photoshop and back.

Hoping to try and identify it further, and also test with another mouse when I can get hold of one. It never happened at all before the Mac OS Catalina update.