After further reflection, the before-and-after of my vision strain is starting to make sense (if temporal dithering is the cause), given my finding that GPUs I tested tended to dither on DisplayPort outputs only and not on HDMI (and I assume not on DVI).
Years ago I ran dual 8-bit (purportedly) displays on a 2014 Mac Mini, which (if consistent with my iGPU MacBook Pro) would not have had dithering on the Intel iGPU outputs. I later upgraded to a Mac Pro (with various GPUs over time) and a 3-monitor setup, but my standard refresh rate monitors (same purportedly 8-bit ones) were on either HDMI or DVI, while the DP output went to a high-refresh gaming monitor (likely reducing the effects of dithering on that output).
Later, after ditching the horrible 14" M1 Pro MacBook Pro, I ran my Mac Pro with an AMD Radeon Pro WX 5100 (4x DP outputs) with DisplayPort going to all three monitors (including the standard refresh rate ones). I also tried some of my NVIDIA cards using the DisplayPort outputs. After that, I never had 100% of the comfort level I had previously.
For the last few weeks, I've been using one of my original ASUS VS239H(-P, I think) monitors with a 2012 non-retina MacBook Pro with Intel HD 4000 graphics, running a fairly clean install of the latest Ventura. So far this has been giving me no issues (so far as I can tell… there is still some unavoidable strain from other screens at work and LED lighting). I am tempted to try going back to a 2014 Mac Mini with an Intel iGPU, or just keep running one of my MacBooks with Intel iGPUs in clamshell mode.
Interestingly, I just booted into my main data drive running Monterey (which was a migration from my 14" M1 Pro MacBook Pro originally) for the first time in about a month and a half, using roughly the same hardware, and I could instantly tell there was some kind of strain there. So, either I screwed up some macOS graphics settings on the 14" M1 Pro MacBook Pro while trying to stop the strain (and those settings migrated over), or else there was something inherent in the Monterey setup on that Apple silicon machine that came over with the migrated settings. This is consistent with my observation in another thread:
macsforme When I happened to boot another disk with a clean Monterey installation on that same computer, it looked "calmer" than my main Monterey environment, making me wonder if some strain-inducing setting(s) were migrated back with my data (although plausibly, my condition could just be deteriorating).