The importance of vitreous in the pathogenesis of various retinal disorders has been well recognized, and currently vitreous can only be dealt with surgically. Anomalous posterior vitreous detachment (PVD), which is a condition where the vitreous liquefies without vitreoretinal dehiscence (1), can worsen diabetic retinopathy and cause retinal tears, detachment, macular pucker, macular hole, or vitreous hemorrhage (2). Vitreous hemorrhage is a major cause of vision loss. The most common cause of vitreous hemorrhage is diabetic retinopathy, which can also lead to tractional retinal detachment (3). Various enzymes have been investigated to dissolve the vitreous hemorrhage or modify the structural characteristics of the vitreous to allow diffusion of blood out of the visual axis. Enzymatic vitreolysis has several advantages over conventional surgery, including the ability to treat the hemorrhage earlier, in an office setting, and with lower costs. With pharmacologic vitreolysis, complications of surgery such as cataract, endophthalmitis, retinal hemorrhage, tear or detachment, and anesthesia-related complications can be avoided. A number of vitreolytic enzymes have been investigated, including hyaluronidase, plasmin, dispase, tissue plasminogen activator, and chondroitinase, with varying effects. Such pharmacologic therapies rely upon a good understanding of the biochemical composition and organization of the vitreous.

Ultrastructural studies have shown that the adult human vitreous contains fine, parallel fibers of collagen coursing in an anteroposterior direction (4,5). Although several agents have been investigated in animal models, only a few have been employed in humans. Autologous plasmin enzyme (APE) has been used in some patients but has never been subjected to the rigors of a controlled clinical trial. Chondroitinase and hyaluronidase have been tested in clinical trials, but the former never entered Phase II testing. Hyaluronidase (Vitrase) failed a Phase III U.S. Food and Drug Administration (FDA) trial conducted in the United States. The Vitrase clinical trial results will be discussed in more detail later in this chapter.