Rooney was again an unused sub as United required extra-time to beat Anderlecht 2-1 in the Europa League quarter-final second leg at Old Trafford, which suggests to club legend Keane that it could be all over for the Red Devils' all-time leading scorer.
"In terms of the bigger picture, that is the end of Wayne at United," he told ITV Sport.
"He will contribute from now until the end of the season but that is the final nail in the coffin for him.
"He must be fuming, he'll be like a mad man. If he isn't then he has lost the eye of the tiger."