After every boss beaten an eye will start following you and once in a while you will have to shoot it in order to calm it down.
After 3 bosses you will have 3 eyes after you and in the room between levels you will have to put the eyes in the hands. The room will open and you will enter the last level.
At the boss just stay far away and shoot. The granny will eventually die.
A full playthrough with the granny achievement at the end in the video.