Michael McKillop and Jason Smyth will be unable to defend their respective T37 800m and T13 200m Paralympic titles following the removal of both disciplines from the schedule for Rio 2016.
The T37 800m title McKillop won in London, and in Beijing in 2008, has been removed from the programme, leaving him with just the T37 1,500m title to defend, while Smyth is left with just the T13 100m after the 200m was axed.
McKillop wrote on Twitter: "Unfortunately I will not have the opportunity to retain my 800m title in Rio. I am deeply disappointed with this outcome."
The announcement of the athletics events for Rio - 177 events, seven more than London 2012 and a 22% increase in the number of events for women - was two years in the making after widespread consultation.
The aim of IPC Athletics was for a better spectrum of events to be offered within the programme (short, middle distance and long distance running events, jumps and throwing events) and some events were casualties of the restructuring.
The long-term intention of the IPC is for single-class events, but in some instances events will be combined in Rio.
Earlier this month, the IPC announced that Rio 2016 will see around 4,350 athletes compete in 526 medal events across 22 sports.