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This is a pretty long topic. In short, the Byzantine empire continually lost ground to new invaders -- barbarians from the northwest and a rising Muslim superstate in the East that would dominate the Middle East and North Africa. It was essentially fighting on all fronts and that eroded its power, slowly draining its wealth as its trade routes were strangled. It's capital was even sacked by fellow Christians during the Fourth Crusade when they couldn't afford the boats to take them to the Holy Land.
The Ottoman Empire, which came to dominate the Middle East and North Africa, eventually crushed what was left because by then, the Byzantine "empire" was little more than a few islands and the city of Constantinople.