During his term of office, he waged a violent feud against the bishop of Alexandria, Cyril, and their struggle precipitated the death of the philosopher and scientist Hypatia.
On one occasion, Cyril sent the grammaticus Hierax to discover the content of an edict that Orestes was to promulgate on the mimes shows, which attracted great crowds.
[5] The threat of conflict with Orestes induced Nitrian monks, whom Cyril may have lived amongst for five years, to come from the desert in order to defend the Patriarch.
Prefect Orestes enjoyed the political backing of Hypatia, a philosopher whose considerable moral authority gave her extensive influence in the city of Alexandria.
Modern historians think that Orestes had cultivated his relationship with Hypatia to strengthen a bond with the pagan community of Alexandria, as he had done with the Jewish one, to better handle the difficult political life of the Egyptian capital.