Meyer CH (ed): Vital Dyes in Vitreoretinal Surgery. Dev Ophthalmol. Basel, Karger, 2008, vol 42, pp 5–28 To See the Invisible: The Quest of Imaging Vitreous J. Sebag VMR Institute, University of Southern California, Los Angeles, Calif., USA Abstract Purpose: Imaging vitreous has long been a quest to view what is, by design, invisible. This chapter will review important historical aspects, past and present imaging methodologies, and new technologies that are currently in development for future research and clinical applications. Methods: Classic and modern histologic techniques, dark-field slit microscopy, clinical slit lamp biomicroscopy, standard and scanning laser ophthalmoscopy (SLO), ultrasonography, optical coherence tomography (OCT), com- bined OCT-SLO, magnetic resonance and Raman spectroscopies, and dynamic light scattering method- ologies are presented. Results: The best available histologic techniques for imaging vitreous are those that avoid rapid dehydration of vitreous specimens. Dark-field slit microscopy enables in vitro imaging without dehydration or tissue fixatives. OCT enables better in vivo visualization of the vitreoretinal inter- face than SLO and ultrasonography, but does not adequately image the vitreous body. The combination of OCT with SLO has provided useful new imaging capabilities, but only at the vitreoretinal interface. Dynamic light scattering can evaluate the vitreous body by determining the average sizes of vitreous macromolecules in aging, disease, and as a means to assess the effects of pharmacologic vitreolysis. Raman spectroscopy can detect altered vitreous molecules, such as glycated collagen and other pro- teins in diabetic vitreopathy and possibly other diseases. Conclusions: A better understanding of normal vitreous physiology and structure and how these change in aging and disease is needed to develop more effective therapies and prevention. The quest to adequately image vitreous will likely only succeed through the combined use of more than one technique to provide better vitreous imaging for future research and clinical applications. Copyright © 2008 S. Karger AG, Basel Historical Perspective Clear by design (fig. 1), vitreous has fascinated men for years. Among the early theo- ries of vitreous structure that were reviewed by Duke-Elder [1] is a description that vitreous is composed of ‘loose and delicate filaments surrounded by fluid’. This is remarkably close to present-day concepts. During the 18th and 19th centuries, how- ever, there were no less than four very different theories of vitreous structure. In 1741, Demours formulated the alveolar theory, claiming that there are alveoli of fluid DOP42005.qxd 4/15/08 11:34 AM Page 5