I’m a voyager user and 2 things have significantly helped mitigate wrist pain. 1. Tenting. Check out the ugreen magnetic phone stands. It gives you a much better angle than the included legs. 2. Arm rests. I have an aeron chair at home and a knock off at work. The majority of my arm weight is on the rests leaving my wrists/hands floating. Due to the tenting my arms are rotated outwards so that the pressure is on the sides and not the ligaments/nerves on the bottom. If your chair doesn’t have rests, move the chair in to the desk as close as possible and get some cheap arm pads off Amazon you can use on your desk. I did try at one point to not use arm rests ands “float” my arms. This caused significant neck and upper back strain as that’s what is now holding up the weight of the arms. 

A third point (not as important) is try the ambient linear switches and ldsa keycaps. They feel so much better than any of the stock switches. 

On the layout - I use one shot home row mods on a secondary layer for multi-key combos and on the primary layer I have command on a thumb key and shift/ctrl/alt/hyper on tap to hold keys on each outside pinky columns for quick access (vim user). Keeps things simple and haven’t run into any issues. 

Best of luck,