MILESTONES IN RETINA

Expert perspectives on the evolution of retina practice, procedures, technologies and instrumentation.

MILESTONE

Optical Coherence Tomography

Tavish Nanda, MD; Michelle C. Liang, MD, FASRS; Jay S. Duker, MD, FASRS

Prototype OCT machine used at the New England Eye Center in 1993. 

The history of optical coherence tomography (OCT) reads like a fossil record, with a primordial decades-long process followed by a more recent, explosive evolution in technology. The early ‘protozoal’ period started in the early to mid-1970s at Bell Laboratories (AT&T), where Drs. Duguay and Ippen built the foundation for a concept called optical reflectivity, the idea that light interference could be used to produce a non-invasive optical ‘biopsy’.[1-2] The eye, as a clear, low interference media, became a natural choice for testing this theory. In the late 1980s, a team of researchers, led by Dr. James Fujimoto at the Massachusetts Institute of Technology (MIT) and assisted by ophthalmologists Joel Schuman, M.D., David Huang, M.D. Ph.D. and Carmen Puliafito, M.D., trialed this concept by using low-coherence interferometry for the measurement of corneal thickness. Faced with limited success, however, the group decided to test its potential in retinal imaging.[3] This proved to be transformative, and in 1991, Huang et al. published the very first retinal OCT images of an ex-vivo human eye, pioneering the conversion of several individual A-scans into a single B-scan image.[4] 

Early prototype OCT images. (A) Normal macula. (B) Vitreomacular traction. (C) Full-thickness macular hole. (D) Cystoid macular edema. 

A subsequent collaboration with Eric Swanson of MIT Lincoln Laboratories led to dramatic advances in early OCT technology. The application of fiber optic and intersatellite communication technology shrunk lab-based mega-OCTs into an instrument that was only 19 inches wide and 100x faster.[1] Just two years after Huang’s seminal paper, a new prototype produced the very first images of an in-vivo human retina outside of a laboratory. The clinical utility of these images, however, remained obscure. 

Starting in 1993, with support from the National Institutes of Health, OCT imaging using a prototype device was performed on over 5000 out-patients at the New England Eye Center at Tufts Medical Center .[5-6] This led to the development of the first OCT atlas in 1996, which would serve as a framework for OCT image interpretation.[7] During the same period, Michael Hee, M.D., Ph.D. (using an early Macintosh Apple computer) developed the ability to produce quantitative data, such as peripapillary nerve fiber layer thickness.[5] Armed with some normative data, quantitative software, and an interpretive guide, OCT appeared ready for widespread adoption.  

In 1996, Zeiss - after acquiring MIT start-up Advanced Ophthalmic Diagnostics - released the first commercially available machine, aptly named OCT 1. Only around 180 units were sold in a 3-year span. The development and release of a second machine, OCT 2, in 1999 sold only 400 units. However, improvement in the final model, OCT 3 (time-domain Stratus OCT), in addition to a plethora of scientific publications by its original creators and a revamped marketing strategy by Zeiss, invigorated clinical adoption.1 With the concurrent advent of vitrectomy surgery for macular hole repair and, soon after, treatment with intravitreal corticosteroids and eventually anti-VEGF agents, the newfound need to diagnose and quantify macular disease and assess response on a microscopic scale bolstered the establishment of OCT imaging as the standard of ophthalmic care.[1]

Progression of OCT development. Normal macula demonstrated by (A) OCT 1, 2, (B) Stratus OCT 3 (time-domain), and (C) spectral-domain OCT machines. Images courtesy of Andre Witkin, MD. 

By 2006, over 6000 Stratus OCT devices had been sold.[1] From there, the investment and competition in OCT device development increased exponentially, starting with the transition to spectral-domain (SD) OCT.[8] This new technology offered an unparalleled improvement when compared to time-domain (TD) technology, allowing scanning speeds from 25,000 up to 100,000 A-scans/s vs. the prior 400 A-scans/s using time-domain detection .[9-10] Today, the “dinosaur” TD-OCT is extinct, and SD-OCT has become the dominant species, produced by a variety of competing industry titans (Zeiss, Heidelberg, Optovue, Canon, etc.). Almost fifty years after Dr. Fujimoto’s theoretical ‘light biopsy’, OCT technology continues to advance, with the more recent arrival of swept-source OCT, which can produce a whopping 500,000 A-scans/s, and OCT angiography, which uses motion contrast imaging to generate high-resolution volumetric blood flow information.[9-10] At present, OCT is the most important ancillary test in ophthalmology. The evolution of OCT technology, not just in ophthalmology, but in spaces like vascular imaging and skin cancer, is a remarkable testament to the power and impact of human ingenuity, persistence, and application.[1]

References

  1. Fujimoto J, Swanson E. The development, commercialization, and impact of optical coherence tomography. Investigative ophthalmology & visual science. 2016 Jul 1;57(9):OCT1-3.
  2. Duguay MA, Mattick AT. Ultrahigh speed photography of picosecond light pulses and echoes. Applied optics. 1971 Sep 1;10(9):2162-70.
  3. Schuman J. A Brief History of OCT. American Academy of Ophthalmology Annual Meeting 2013. 
  4. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA. Optical coherence tomography. science. 1991 Nov 22;254(5035):1178-81.
  5. Schuman JS, Hee MR, Arya AV, Pedut-Kloizman T, Puliafito CA, Fujimoto JG, Swanson EA. Optical coherence tomography: a new tool for glaucoma diagnosis. Current opinion in ophthalmology. 1995 Apr 1;6(2):89-95.
  6. Hee MR, Baumal CR, Puliafito CA, Duker JS, Reichel E, Wilkins JR, Coker JG, Schuman JS, Swanson EA, Fujimoto JG. Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology. 1996 Aug 1;103(8):1260-70
  7. Fujimoto JG, Hee MR, Huang D, Schuman JS, Puliafito CA. Optical coherence tomography of ocular diseases. Principles of Optical Coherence Tomography. 2nd ed. Thorofare, NJ: Slack, Inc. 2004:3-19
  8. Wojtkowski M, Leitgeb R, Kowalczyk A, Bajraszewski T, Fercher AF. In vivo human retinal imaging by Fourier domain optical coherence tomography. Journal of biomedical optics. 2002 Jul 1;7(3):457-63
  9. Gabriele ML, Wollstein G, Ishikawa H, Kagemann L, Xu J, Folio LS, Schuman JS. Optical coherence tomography: history, current status, and laboratory work. Investigative ophthalmology & visual science. 2011 Apr 1;52(5):2425-36.
  10. Ulmer E. The Evolution of Optical Coherence Tomography. Cambridge Technology. 


(Milestone essay published 2021)