Regarding USB, you could try a separate Sonnet USB3 PCIe card dedicated for the UFX+ with FL1100 chip.
Works very reliable even with lowest ASIO buffersizes (32 samples @single- and 64 samples @double- speed), see my blog article about a "synthetic" Cubase project with 400 tracks and ~800 VST to check performance and computer settings (thats what my PC is able to deliver):
https://www.tonstudio-forum.de/blog/Ent … cks-de-en/

Another advantage of USB3 over TB: cable length, 3m instead of approx 2m with TB.

I use Lindy premium USB3 cables: https://www.lindy.de/3m-USB-3-2-Typ-A-a … ;ci=800504

Here a link to the Sonnet card. The driver is included in Win10 and uses MSI (message signalled interrupts) which are working more efficient, with google you can get more information about it: https://www.sonnettech.com/product/lega … 3pcie.html

Then you could also try some performance tunings in Windows that lower DPC latency, this link leads you to a collection of postings that can give you some ideas what to look for:
https://forum.rme-audio.de/viewtopic.ph … 04#p187204

When I arm channels in Nuendo, the corresponding RME Total Mix hardware input channels and hardware outputs do not reflect the fader and pan values in Nuendo - they do nothing.  So ASIO Direct Monitoring is no longer working.  This worked really well for months and suddenly stopped.  ADM with Nuendo works if I switch to the USB connection, but Thunderbolt otherwise seems to perform better.