Tips for Annihilation
It is tactics you need. You can always try to max out relics/hearts with a ring and an amulet that reduces chance of consumption.
Just focus on dodge and shoot the boss with slower waepons that hit hard in between. Most red glowy stuff is just to get into your head, it does not concern you.
Wait for sound quees to dodge and duck in phase 2 for the cross things. Be patient be sure in movment. Not much needed (movment).
Note: Also do play solo and kill the orbs. In coop the orbs wil not be linked so it is harder.
You can outlevel it, but keep in mind power level will never go down and all further instances will be higher with only having one weapon buffed up to it. Stats mean nothing since the game will get on par when you open the instance.
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