There are probably waaay more than three, but I can give you three major milestones and their approximate dates.
1.) Battle of Manzikert (~1071) The Empire lost that battle, and with it, large portions of Anatolia, roughly modern Turkey, which had been a prime recruiting area for the Byzantine army.
2.) Sack of Constantinople (~1204) The Fourth Crusade was short on funds, so the Venetians agreed to provide transport if the crusaders would intervene on their behalf in a dynastic struggle. Constantinople never really recovered, and Venice became the leading commercial empire of the Mediterranean.
3.) Battle of Adrianople (~1365) At this point, Constantinople started to become surrounded, by being cut off from the Balkans. In the next few decades, the Ottomansadvanced to the Danube, and past it in some places. In the process, many of the Balkan leaders agreed to become Ottoman vassals.
By that point, Constantinople was like a fruit ready to by plucked…
Source: charliea384fa on yahoo answers

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