In Reply Beebe makes an interesting point regarding the broad substrate specificity of ocriplasmin (JETREA). He points out that ocriplasmin is derived from plasmin, which cleaves proteins at the same basic amino acids. There are likely many additional substrates that are not listed in the JETREA package insert. The cleavage of these unknown substrates by ocriplasmin may contribute to the structural and functional effects on the retina outlined in our article and by Fahim et al.1