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Right, you basically cannot block all comments from those instances. Though it does prevent notifications if they reply to you. The only way to avoid wasting your time with them is to block each and every single person that comes along, including every single new one. Which also does nothing to stop them from downvoting you. In short, unless an entire instance defederates from them and you join it - which none of the well-known instances do, and it is not entirely so trivial to spin up your own - there is nothing that an individual user can do about the situation, atm.

And sometimes I even have enjoyable conversations with people on those instances - still, those are in the extreme minority (fewer than 1/1000) and I would choose to sacrifice that to have the option to walk away entirely, if I could. Especially since I could always have an alt account elsewhere to get the best of both worlds. As they also do in turn (several have openly admitted this), to get around the instance defederations.