In some aspects, methods of detecting complement activation in vivo, e.g., in an eye, are provided. In some aspects, methods of detecting high risk drusen are provided. In some aspects, presence of one or more high risk drusen in an eye indicates increased likelihood of developing AMD, GA, or advanced AMD or increased likelihood of rapid progression of AMD. In some embodiments, methods comprise detecting drusen containing or in close proximity to complement activation. In some embodiments methods comprise detecting one or more drusen having inflamed endothelium underlying or in close proximity thereto. In some embodiments methods comprise detecting eye-derived extracellular microvesicles, e.g., exosomes, in a body fluid. In some embodiments methods comprise detecting Th17 cells or a Th17 biomarker in a body fluid. In some embodiments the Th17 biomarker is a cytokine. Methods may be applied individually or in any combination. In some embodiments any of the methods further comprises treating a subject at risk of developing AMD, GA, or advanced AMD or at increased likelihood of rapid progression of AMD with a complement inhibitor. In some aspects, agents useful for performing one or more of the methods are described.
