In Reply We thank Beebe for reminding us that the precise mechanism by which ocriplasmin causes a variety of panretinal structural and functional abnormalities is unknown and that plasmin enzyme has broad substrate specificity that extends far beyond laminin and fibronectin. Given the emerging evidence for retinal damage seen in some patients, the enzymatic activity and specificity of ocriplasmin warrant further study and more thorough characterization. We agree with him that it is not surprising that an enzyme capable of digesting a large diversity of proteins found in the eye could produce widespread damage to intraocular tissues such as the retina and lens zonules. We also share his concern about other possible long-term complications.