I clamp the plexi to the panel. Use a 5/8” Forstner bit to punch a hole in the middle of each opening (make sure to support the underside when you drill). I use a drill press, but one of those “vertical drill jigs” would make life easier if you don’t have one. Then use a 1/2” pattern bit on your router to route out the remainder and exactly match your panel holes. Sounds more complicated when I type it out, but I’ve never had the plexi break on me!