For the invention of optical coherence tomography, a technology that revolutionized ophthalmology—allowing rapid detection of diseases of the retina that impair vision
The 2023 Lasker~DeBakey Clinical Medical Research Award honors James G. Fujimoto (Massachusetts Institute of Technology), David Huang (Casey Eye Institute, Oregon Health & Science University), and Eric A. Swanson (Massachusetts Institute of Technology) for the invention of optical coherence tomography (OCT). This technology uses light beams to visualize microscopic structures within tissues of the body such as the retina. The ability to painlessly generate high-resolution cross-sectional images of the eye’s internal architecture in real time and without physical contact was unprecedented, and OCT revolutionized ophthalmology by allowing doctors to rapidly detect and then treat diseases of the retina that impair vision, thereby saving the eyesight of millions. OCT’s medical use is now expanding, especially because engineers have incorporated it into probes that can enter the circulatory system and they have integrated it into surgical microscopes and other instruments.
The Clinical Lasker Award has long recognized breakthroughs in technology that revolutionized medicine. We honored the inventors of cardiac catheterization, CAT scans, and MRI. This year’s Clinical Award is squarely in that tradition. We honor James Fujimoto, David Huang and Eric Swanson for their invention of ocular coherence tomography, or OCT—a technology that uses light to peer beneath the surface of an object.
In OCT a thin beam of light darts across a surface. The light penetrates beneath the surface and is reflected back to a detector. Objects beneath the surface reflect the light differently so that it returns to the detector with a time delay measured in femtoseconds. A computer converts the time delay into an image that is a cross section of the object. Multiple passes of the light create a series of cross sections. The serial sections can be assembled into a three-dimensional picture. It’s an optical biopsy and it’s better than a surgical biopsy. A surgical biopsy samples only a part of the tissue. OCT shows the whole structure.
Our three honorees built the first OCT machine in 1990 at the Massachusetts Institute of Technology. James Fujimoto is a physicist and optics expert who led the effort. David Huang was an MD/PhD student at Harvard who was pursuing his thesis in Fujimoto’s laboratory. Eric Swanson was an expert in instrumentation working on optics in another laboratory. The three inventors were collaborating with a group of Boston eye doctors. They were trying to visualize the cell layers in the cornea at the front of the eye. It should have been an easy target but they were having problems. So they got the bold idea that their instrument might reveal structures in the retina. The retina is at the back of the eye and was a more complex target. One night they obtained an eye from a calf that was slaughtered. To their amazement, their instrument revealed structures beneath the surface of the bovine retina. OCT was born.
Next, they obtained an eye from a human cadaver. The human retina is only a half millimeter thick. It contains layers of cells including photoreceptors that detect light, pigment cells that nourish the photoreceptors, and neurons that carry visual information to the brain. The retina also contains tiny blood vessels. The OCT machine showed all of these structures. The inventors also obtained a coronary artery from a woman who died of a heart attack. Their OCT machine revealed the deposits of cholesterol and fibrous tissue that had taken this woman’s life. The inventors and their clinical collaborators published their findings in Science in 1991. That paper has been cited 17,000 times.
The initial OCT instrument was slow and not too precise. It was not suitable for clinical use. So the inventors designed a faster and more precise instrument and in 1993 they published the first OCT visualization of the retina of a living human.
To develop their invention, Fujimoto and Swanson helped start a company that they sold to the German optics company Zeiss. Zeiss engineers created precision OCT instruments that can visualize structures as small as one thousandth of a millimeter.
OCT had its major impact on diseases of the retina. From the patient’s standpoint, the procedure is quick and painless. The patient stares into a lens and focuses on a target. The patient sees a thin line of red light that makes many passes across the field of vision. The whole process takes less than a minute. There is no discomfort, and the pupil does not even have to be dilated.
OCT improved the treatment of all retinal diseases including diabetic retinopathy and glaucoma. Its greatest impact has been on age related macular degeneration or AMD which afflicts one in 8 Americans over age 60. The macula is a tiny spot in the middle of the retina where the high acuity photoreceptors are located. This is where we perceive faces, watch television or read newspapers. In AMD the macula degenerates. The photoreceptors are lost and we can no longer recognize our grandchildren. In the wet variety of AMD, the tiny blood vessels in the macula become leaky. Fluid oozes out of the vessel and this causes swelling that distorts the macula. Total blindness occurs.
Fortunately, we have treatments for wet AMD. The 2010 Clinical Lasker Award was presented to Napoleone Ferrara of Genentech for his discovery that macular swelling is caused by a protein called VEGF that causes blood vessels to leak. Ferrara and his colleagues developed Lucentis, a monoclonal antibody that blocks VEGF. When injected into the eye Lucentis stops the fluid leak. The fluid is resorbed, the swelling resolves and vision improves. Another VEGF blocker called Eylea was developed by Regeneron.
VEGF blockers have a problem. Their actions are temporary. After several weeks the fluid recurs and the patient requires another injection. When the VEGF blockers were developed there was no way to tell when the fluid recurred. So the companies recommended that the eye injections be repeated every month. Soon doctors realized that they could use OCT to detect the fluid recurrence, and this would spare unnecessary injections. Currently, patients receive an initial series of 3 monthly injections. After this, they use OCT to examine the eye every month. They give the injections only when the fluid begins to recur. Many patients can go 3 or 4 months between injections. This regimen spares the patient from painful needle sticks in the eye. It also cuts costs. One estimate indicated that by 2015 OCT had saved $9 billion in drug costs.
I will conclude by addressing the most notable aspect of the OCT invention. It illustrates the awesome power of collaboration between physicians, scientists, and engineers. The physicians identified the need. The scientists provided the theory. The engineers built the machine, and the physicians figured out how to use it. The collaboration was energized by a 26 year-old medical student working on a PhD degree. Today clinical/scientific collaboration is threatened. Here are 3 reasons: 1) The public distrusts science. 2) Medical schools are consumed with the economics of patient care. And 3) Companies that invent drugs and devices are vilified as rapacious exploiters of the poor.
Fortunately, we have institutions like the Lasker Foundation that honor science. We also have people like you in this audience who invest their time to learn about discovery. You are our hope for the future. So let’s conclude with a round of applause for our honorees, for the Lasker Foundation, and for you, the enlightened audience.