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Environmental disasters and conflicts between the Orthodox and Catholic congregations have influenced the evolution of the church.
Conflicts between Orthodox and Catholic locals, especially at the Feast of the Assumption, were pivotal moments in the church's history. Patriarch Cyril V of Constantinople officially expelled from the church Orthodox Christians who prayed in the church alongside Catholics in 1758 as a result of the dispute over who would lead the services on the eve and feast day. A firman issued by Sultan Mustafa III gave the Orthodox people ownership of the church. Tensions returned when the Catholics continued to utilize the church while being shielded by Western ambassadors.
The church grounds, which included two chapels and the summit of Profitis Ilias, were given to two brothers in 1614, and they established the Monastery of the Prophet Elias, which is still standing today. The church started selling off its properties in the late 19th century, with the final vineyards sold in 1902, after the episcopal seat was relocated to Fira in 1827.
In 1915, a fire badly damaged the church, destroying most of its records and clergy garments but sparing the icons. The church structure was destroyed by the 1956 earthquake. Restoration efforts continued until the 1980s, when significant work was carried out.
Three framed frescoes and 26 movable icons were taken in 1982 while repair work was underway. There is still a blank chapter in the church's history because the stolen icons have never been located.
Despite centuries of conflict, natural calamities, and change, Panagia Episkopi continues to serve as a reminder of the island's religious and cultural resilience. The community's dedication to preserving this historic monument for future generations is demonstrated by its repair.