The new design using isolation is now ready. You can find it on the projects GitLab page. The new design is called ncn5100rh-2.
I've thrown out the opto-couplers on recommendation of @Sean McVeigh. The digital isolator is much more compact and uses the same amount of power as the logic gate opto-couplers.
Exclusively using opto-couplers (not the logic gate versions) would lower power consumption, but would greatly increase board space. I am in favour of lowering the BoM count and board space in exchange for slightly higher power consumption.
I will be looking into producing the board and assembling it in the coming month.