February 16, 2001
Use of indocycnine green (ICG) dye in medicine began in the mid-1950¹s as part of a method for determining cardiac output and for characterizing cardiac valvular and septal defects. Two characteristics of ICG made it ideal for these applications: its sharply defined peak absorption of near-infrared light at 805 nm (the same wavelength at which the optical densities of oxygenated and reduced hemoglobin in blood are approximately equal) and its bio-compatibility. Soon thereafter, a method was developed for assessment of hepatic function, based on the fact that ICG is excreted exclusively by the liver. ICG¹s use in ophthalmology began in the early 1970s as an experimental imaging agent for examination of ocular blood flowæagain based on its strong near-infrared absorption characteristicsæbut only the largest diameter veins in the eye, behind the sensory retina, could be visualized. However, the discovery that the dye in circulating blood also has a weakæbut detectableæfluorescence emission eventually led to an efficacious method of clinical ophthalmic angiography. During the 1980s and 1990s, refinement of ICG fluorescence imaging technology and of methods for extraction of ocular hemodynamics data from such images led to development of a novel treatment for age-related macular degeneration, a major sight-destroying eye disease; currently that treatment modality is undergoing clinical trials. This presentation focuses on the ophthalmology-oriented ICG technologies, virtually all of which were developed under the auspices of the APL biomedical programs. Those technologies and their medical applications, including the very recent one in cardiology, will be discussed.
Dr. Robert W. Flower a physicist by training, has been involved principally in ophthalmic research for more than 30 years. Shortly after joining the staff of The Johns Hopkins University Applied Physics Laboratory in 1966, he was invited by Dr. Arnall Patz of Hopkins¹ Wilmer Institute to collaborate on an investigation of the effects of oxygen on the developing retinal vasculature of the premature infant eye. That collaboration led to a general interest in the role of the choroidal circulation in retinal disease etiology, which eventually became his career pursuit. In addition to providing some of the first sub-cardiac-cycle resolution descriptions of choroidal blood flow, he developed the first clinical method for routine visualization of the human choroidal circulation, indocyanine green(ICG) dye fluorescence angiography, now a standard method in use throughout much of the world. In 1982, Dr. Flower became Director of the Applied Physics Laboratory/Hopkins Medical School Collaborative Biomedical Program, a position he held for ten years, while continuing to pursue his ophthalmic research interests as time permitted. During that time he also was Associate Professor of Ophthalmology and of Biomedical Engineering at the Hopkins School of Medicine. In 1990, he received the H. J. Fitzgerald Dunning Professorship for a two-year period, during which he gradually increased his research activities, relinquishing the Biomedical Programs Directorship in 1991. In 1995 Dr. Flower left APL to resume his research activities full-time and joined the faculty of the University of Maryland Department of Ophthalmology as Associate Professor. Since then, he has continued to apply ICG angiography to characterization of choroidal blood flow patterns in normal and diseased eyes. His work has led to a new treatment for age-related macular degeneration (AMD) in eyes for which conventional laser treatment is not possible ænow the subject of an FDA-approved clinical trial; AMD is the most common cause of irreversible vision loss in people over 65 years of age and is typically bilateral. Coincidentally in 1998, he became involved in establishment of the Digital Angiography Reading Center (DARC) at the Manhattan Eye, Ear & Throat Hospital as Senior Scientist; DARC has become the largest international network for evaluation of ophthalmic images used in clinical trials.