O-OH sorry for the double post but this just came into mind as well… What if its not that she cant open her eyes, shes just ashamed of the color?
Maybe Monoe bullied her about them (her squinting eyes) and Monoko defended her but stopped once she got beat up (her disfiguration with the stoplight effect)
Maybe Masuda was someone (teacher or not, sensei is just a fan name after all…) who defended her as well and ignored the bullying (his calm spaceship where the two are alone) but it really does hurt him deep down, even if he doesnt want to admit it (the way he backs up when you pull out the knife)
His eyes going in different directions could symbolize how he was made an outcast and bullied alongside Mado and her own red eyes (I say red because of the eyeball world, red eyes torn from their sockets are everywhere)
The way Mado falls asleep in his spaceship could symbolize how she was finally becoming comfortable and close with him, and the way it crashes when she falls asleep all the way could mean the bullying became too much just when they really started to get closer. His panicked bloops, the fast beeping of the ship and the way he frantically looks around could be symbolization of a mental breakdown. When the ship crashes, his slower bloops could symbolize how upset he was in the aftermath and how Mado realized he was seriously hurt by all the bullying. The way they landed on mars could mean how he was mentally suffocating by all this
Perhaps he began to ignore Mado afterwards (the way you can only access mars san when youre small) and the stairs down to mars san could symbolize Masudas mental decline
The way the crying mars sans eyes change color when you stab him could symbolize how Masuda stopped being her friend after the breakdown. The way the stab wounds linger could mean the mental wounds on Masuda could not be reversed and Mado-chan feels guilty
… SO THEREFORE SHE DOESNT WANT TO OPEN HER EYES the end