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Still evolving, OCT technology has revolutionized diagnostics
In the first installment of a series of articles commemorating OSN’s 25-year anniversary, researchers reflect on how optical coherence tomography has transformed the way ophthalmic surgeons diagnose and care for their patients.
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Since the early 1990s, optical coherence tomography has revolutionized the way retinal and glaucoma surgeons approach diagnostics in their practices, and it continues to show promise for additional applications.
When the technology for optical coherence tomography (OCT) was first developed in 1991, surgeons were impressed by the precise imaging created by this modality but questioned if it would become clinically indispensable. Now, many cannot imagine their practices without it.
“At first I was doubtful that this would only be a research tool, but after imaging some of my patients with various macular diseases, the utility of the machine became obvious,” said Jay S. Duker, MD, an OSN Retina/Vitreous Section Member. “One of the reasons OCT has caught on so quickly is that it doesn’t take a retinal specialist many patients imaged with OCT before they realize how useful the machine is.”
OCT works by measuring the echoed time delays of a reflected light beam. When the beam is scanned, it generates a cross-sectional image.
Since its introduction to the commercial market in 1996, OCT has become a common tool in thousands of retina and glaucoma practices, but it took a lot of work and time to convince the community that the technology was not only useful but vital to the treatment of many patients.
“Throughout the 1990s, we started to develop more treatments for macular edema, and it became apparent very quickly that to be able to quantify retinal thickening was very important,” Dr. Duker said.
Several companies have now harnessed OCT technology to develop imaging instruments, but the first to the market was Carl Zeiss Meditec, with what is now called the Stratus OCT.
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Images: Li Y, Huang D |
The birth of OCT
OCT technology was conceived in the Department of Electrical Engineering and Computer Science at Massachusetts Institute of Technology.
James G. Fujimoto, PhD, professor of electrical engineering and computer science, and his students had collaborated with Carmen A. Puliafito, MD, MBA, OSN Retina/Vitreous Section Editor, who was then at the Massachusetts Eye and Ear Infirmary.
“The [initial] collaboration was investigating the applications of femtosecond lasers for surgery,” Dr. Fujimoto told OSN. “At that time, we were also interested in using femtosecond light pulses to measure distances in the eye.”
In the late 1980s, this technology was being investigated for the measurement of anterior structures.
Joel S. Schuman, MD, an OSN Glaucoma Section Member, was a glaucoma fellow at Massachusetts Eye and Ear at the time and was working on another project in Dr. Puliafito’s laser laboratory in 1989.
“I became aware of the technology and realized that it could have an application for measuring retinal thickness,” Dr. Schuman said.
In 1991, David Huang, MD, PhD, who was a student under Dr. Fujimoto in the Harvard/MIT Health Sciences and Technology program, was working on this project, and he had the idea of generalizing axial scans to transverse images.
“I thought this is much more useful as an imaging modality than just a ranging or thickness measurement,” Dr. Huang said. “So we got a bunch of data and plotted it out [on a false color scale] to get the image, and it looked amazing.”
The team demonstrated the first OCT images, which were done in the retina ex vivo, and the data were reported in Science in 1991. Dr. Huang was the first author of the paper, which is widely regarded as the first demonstration of OCT.
Clinical applications
Eric Swanson, the leader of the Optical Communications Group at MIT Lincoln Laboratories at the time, got involved by creating a system that was a lot faster and more clinically ergonomic than the original system Dr. Huang developed in the lab.
In 1993, Mr. Swanson designed the first clinical prototype ophthalmic OCT that was built in an engineering laboratory.
The prototype was used at the New England Eye Center to image close to 10,000 patients over the years, Dr. Fujimoto said.
The technology was ultimately sold to Humphrey Instruments, which was later acquired by Zeiss, Dr. Huang explained.
The clinical studies that were performed at the New England Eye Center set the stage for many clinical applications of the technology, Dr. Fujimoto said. At that time, Michael Hee, MD, PhD, joined the research efforts.
“Dr. Hee developed many of the protocols that are now clinical standards. At that time we recognized that you could use OCT to acquire circumpapillary scans for glaucoma assessment or map retinal thickness for macular edema,” Dr. Fujimoto said.
“At the same time, we realized that in order to have an impact on clinical care, ultimately it was necessary to transfer the technology to industry,” he said.
Transferring to industry
Recognizing that the technology was still in an early stage, Mr. Swanson, Dr. Puliafito, Dr. Schuman, Dr. Huang and Dr. Fujimoto created a start-up company in 1994 known as Advanced Ophthalmic Diagnostics to transfer the technology to industry.
“At that time, we spoke to several major ophthalmic companies. Zeiss recognized the potential and became very interested in the technology. They acquired our start-up company, and that led to the first introduction of the OCT instrument,” Dr. Fujimoto said.
Clinical studies were developed between 1994 and 1995, and the first commercial instrument from Zeiss became available in 1996, Dr. Fujimoto said. Within the last year, several companies in the market have adopted the technology and designed similar machines for ophthalmic applications.
Optovue, Heidelberg Engineering, Topcon, Bioptigen, Optopol and Ophthalmic Technologies Inc. are some of the other companies that have developed or are currently developing spectral domain imaging instruments, according to Dr. Schuman.
Late last year, Heidelberg received FDA approval for its combined spectral domain OCT and laser angiographar, the Spectralis. In January, Bioptigen, a spinoff company from Duke University’s biomedical engineering department, received FDA clearance to market its own spectral domain OCT system.
“It was not clear what the clinical indications of the technology would be at the beginning. We saw that it was possible to visualize the retina and to see structure and pathology with resolutions that were not available previously, but in order to have an impact on clinical care, it is necessary for a technology to have a diagnostic function or to be used to make therapeutic decisions, and none of that was clear at the beginning,” Dr. Fujimoto said. “I think one of the challenges was that OCT-provided data was unlike anything seen previously.”
Evolving technology
The adoption of the technology went relatively slowly, Dr. Fujimoto said.
“It wasn’t until 2002 or 2003 that we started to see larger-scale acceptance, and that is a period of 10 years,” Dr. Fujimoto said. “The process of technology development and transfer is not simple, and it is fraught with many difficulties in terms of actually understanding where a new technology can be used, engineering systems that can be used in the clinic and clearing regulatory hurdles.”
The second generation of the Zeiss instrument was introduced in 2000, and the third generation instrument, the Stratus OCT, introduced in 2002, has been the most popular OCT system with the largest market penetration, Dr. Fujimoto said.
“The Stratus was significant because it had a higher imaging speed and therefore allowed higher pixel densities and better image quality,” Dr. Fujimoto said. “At the same time, there was extensive clinical information available because many clinicians and researchers had been working with OCT and had published numerous studies.”
All of those factors, combined with the initiation of insurance reimbursement for the diagnostic procedure, are what really started to drive the technology in the market, Dr. Fujimoto said.
“In 2002, we began to see this technology accepted more as a clinical standard in ophthalmology. Many retinal specialists and glaucoma specialists have this technology, and we also started to see adoption by many comprehensive ophthalmologists,” he said.
The use of OCT is now considered a standard of care for retinal specialists, and glaucoma specialists use the technology to objectively assess the retinal nerve fiber layer and optic nerve head.
Anterior imaging
“I worked with Zeiss for a few years with developing anterior segment OCT with a longer wavelength of 1.3 µm, and that resulted in the Visante system, the current standard in anterior segment OCT,” said Dr. Huang, who is now the director of Doheny Laser Vision Center at Doheny Eye Institute. “For the next step, I am working on an even faster anterior segment OCT system with Fourier domain technology. It is actually fast enough to capture corneal shape, and I think it will be able to eventually replace corneal topography as the standard diagnostic technology in corneal and refractive surgery.”
When the posterior segment OCT technology hit the market, anterior segment surgeons realized they could image the cornea also, said OSN Refractive Surgery Section Editor Daniel S. Durrie, MD.
The Visante received approval in 2005 and has been available on the market for about a year.
“Now that we have the first device and there are others coming, we are in the situation the retinal surgeons were in initially, which is finding the best uses of this technology,” he said.
Refractive surgeons are beginning to look at the LASIK flaps in detail, corneal thickness, flap architecture, corneal transplants, cataract incisions and sizing phakic IOLs.
“It is really an excellent tool, and we can be very consistent. I think we have just scratched the surface of its uses. Here in the first year of availability, there have been some major breakthroughs in anterior segment surgery that would not have been possible without the ability for us to see in detail the cornea,” Dr. Durrie said.
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Glaucoma progression
OCT plays a major role in diagnosing and monitoring glaucoma, Dr. Schuman said.
“It is an essential part of the diagnostic technology we have for evaluating patient care,” Dr. Schuman said. “It plays a major role in decision making regarding glaucoma, retinal disease, cataract and now also anterior segment diseases, corneal disease and angle conformation.”
OCT technology is now being used to not only detect whether glaucoma is present but, more importantly, how it is progressing, Dr. Schuman said.
“Another interesting facet is that with these new high-speed high-resolution OCT devices, we are seeing the entry into the market of a variety of manufacturers, so we are going from a situation where we had a single manufacturer, Carl Zeiss Meditec, to one where there are at least seven manufacturers,” Dr. Schuman said.
Higher speed imaging
In the past year, there have been significant advances in detection techniques, Dr. Fujimoto said. Spectral-domain detection technology, otherwise known as Fourier-domain detection technology, now makes it possible to detect all echoes of light from different delays simultaneously and greatly improves imaging speed.
“The result of this is it is possible to acquire larger numbers of images in the same amount of time that was previously possible and also to acquire data that can be used for 3-D data sets,” Dr. Fujimoto said. “I think this is going to have a powerful impact, both in terms of fundamental research where we can better understand the pathogenesis of retinal disease, but also in clinical medicine because it will enable much more sensitive diagnosis as well as monitoring of disease progression and response to therapy.”
Dr. Huang has received several National Institutes of Health grants, including the Advanced Imaging for Glaucoma grant, which uses Fourier domain OCT to map the macula and the optic nerve for glaucoma diagnosis.
“I think this is very promising because one thing we have found is that mapping the ganglion cells over a wide area in the macula is actually even better for glaucoma diagnosis in terms of sensitivity and specificity than the standard measurement of nerve fiber layers around the optic nerve that are seen with OCT,” Dr. Huang said.
OCT technology is also being studied to measure the nerve fiber birefringence for glaucoma diagnosis, as well as for mapping the cornea.
According to Dr. Huang, “An emerging technology that could quickly find many clinical applications is Doppler OCT measurement of retinal blood flow. This is one additional functionality or contrast that does not add much to the cost of OCT but could have applications in retinal vascular diseases and glaucoma.”
“The capabilities of the 3-D OCT imaging are still not well clinically developed because these advances are so new, and there are still many clinical studies that need to be done to understand how this will impact improving diagnosis or monitoring of care,” Dr. Fujimoto said.
Future of OCT
“The future is that OCT is going to get even faster,” Dr. Huang said. “The resolution will continue to get better, and the instruments will get even more economical. I think more and more people will be using this everyday.”
Dr. Fujimoto said, “If we look just at the last year, there have been significant improvements in technology and also broadening of the marketplace. I think it is a very exciting time because we will start to see the results of many new clinical studies in the next couple of years.”
“I think that we will see comprehensive ophthalmologists use this technology more and more, and eventually, with improvements in price, we will even start to see adoption by optometrists in the future,” he said.
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“OCT has tremendous clinical utility in both the diagnosis and management of a very wide range of disease states that affect the macula.” 
“For posterior segment retinal disorders, OCT has largely replaced fluorescein angiography … and is advancing the evaluation of the optic nerve and retinal nerve fiber layer in glaucoma. 
“OCT easily gives us retinal detail we never had before. The technology is also superior for following glaucoma and great for the anterior segment. It is very simple to use and is only getting better.” 
“OCT provides a non-invasive way to image the retina, recognize vitreous detachments, further characterize retinal edema, quantitate retinal thickness and allow for an objective method of clinical change. It is of value to specialists in retina and neuro-ophthalmology, as well as to generalists.” 
“OCT is exceptional for looking at the retinal profile and quantitating/following macular disease.” For more information:
- Jay S. Duker, MD, can be reached at New England Eye Center, 750 Washington St., Box 450, Boston, MA 02111-1533; 617-636-4604; fax: 617-636-4866; e-mail: jduker@tufts-nemc.org. Dr. Duker does not have a direct financial interest in any products mentioned. He is a paid consultant for Carl Zeiss and RTVue.
- Daniel S. Durrie, MD, can be reached at Durrie Vision, 5520 College Blvd., Suite 200, Overland Park, KS 66211; 913-491-3737; fax: 913-491-9650; e-mail: ddurrie@durrievision.com. Dr. Durrie does not have a direct financial interest in any products mentioned.
- James G. Fujimoto, PhD, can be reached at Massachusetts Institute of Technology, Room 36-361, 77 Massachusetts Ave., Cambridge, MA 02139; 617-253-8528; fax: 617-253-9611; e-mail: jgfuji@mit.edu. Dr. Fujimoto receives royalties for intellectual property licensed by MIT to Carl Zeiss Meditec.
- David Huang, MD, PhD, can be reached at 1450 San Pablo St., Doheny Eye Institute 5702, Los Angeles, CA 90033; 323-442-6710; fax: 323-442-6517; e-mail: dhuang@usc.edu. Dr. Huang is a consultant to Optovue Inc. and has received stock options and travel reimbursement. He also receives patent royalty from OCT technology licensed to Carl Zeiss Meditec and has received research funding from both Optovue and Zeiss.
- Joel S. Schuman, MD, can be reached at Eye & Ear Institute, Suite 816, 203 Lothrop St., Pittsburgh, PA 15213; 412-647-2205; fax: 412-647-5119; e-mail: schumanjs@upmc.edu. Dr. Schuman receives research support and honoraria from Carl Zeiss Meditec, Heidelberg Engineering and Optovue. He also receives royalties for intellectual property licensed by MIT to Carl Zeiss Meditec.
- Bioptigen can be reached at 104 T.W. Alexander Drive, Park Research Center, Building 2, Research Triangle Park, NC 27709; 919-314-5500; fax: 919-314-5501; Web site: www.bioptigen.com. Carl Zeiss Meditec can be reached at 5160 Hacienda Drive, Dublin, CA 94568; 925-557-4100; fax: 925-557-4101; Web site: www.zeiss.com. Heidelberg Engineering can be reached at 1499 Poinsettia Ave., Suite 160, Vista, CA 92081; 760-598-3770; fax: 760-598-3060; Web site: www.heidelbergengineering.com. Ophthalmic Technologies Inc. can be reached at 37 Kodiak Crescent, Unit 16, Toronto, Ontario M3J 3E5; Canada; 416-631-9123; fax: 416-631-6932; Web site: www.oti-canada.com. Optopol can be reached at 42-400 Zawiercie, Poland; 48-32-67-09-173; fax: 48-32-67-09-173; Web site: www.optopol.com. Optovue can be reached at 41752 Christy St., Fremont, CA 94538; 510-623-8868, fax: 510-623-8668; Web site: www.optovue.com. Topcon America Corporation can be reached at 37 West Century Road, Paramus, NJ 07652; 800-223-1130; fax: 201-387-2710; Web site: www.topcon.com.
- Daniele Cruz is an OSN Staff Writer who covers all aspects of ophthalmology, focusing on optics, refraction and contact lenses.