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⇱ Ultrahigh-resolution ophthalmic optical coherence tomography | Nature Medicine


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An Erratum to this article was published on 01 May 2001

Here we present new technology for optical coherence tomography (OCT) that enables ultrahigh-resolution, non-invasive in vivo ophthalmologic imaging of retinal and corneal morphology with an axial resolution of 2–3 μm. This resolution represents a significant advance in performance over the 10–15-μm resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution for in vivo ophthalmologic imaging achieved to date. This resolution enables in vivo visualization of intraretinal and intracorneal architectural morphology that had previously only been possible with histopathology. We demonstrate image processing and segmentation techniques for automatic identification and quantification of retinal morphology. Ultrahigh-resolution OCT promises to enhance early diagnosis and objective measurement for tracking progression of ocular diseases, as well as monitoring the efficacy of therapy.

Current clinical practice emphasizes the development of techniques to diagnose disease in its early stages, when treatment is most effective and irreversible damage can be prevented or delayed. In ophthalmology, the precise visualization of pathology is especially critical for the diagnosis and staging of ocular diseases. Therefore, new imaging techniques have been developed to augment conventional fundoscopy and slit-lamp biomicroscopy. Ultrasonography is routinely used in ophthalmology, but requires physical contact with the eye and has axial resolutions of approximately 200 μm (ref. 1). High-frequency ultrasound enables approximately 20 μm axial resolutions, but due to limited penetration, only anterior eye structures can be imaged2. Confocal microscopy has been used to image the cornea with sub-micrometer transverse resolution3. Scanning laser ophthalmoscopy enables en face fundus imaging with micron-scale transverse and approximately 300-μm axial resolution4,5. None of these techniques, however, permits high-resolution, cross-sectional imaging of the retina in vivo.

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Figure 1: Conventional (top) and ultrahigh-resolution (bottom) in vivo OCT images along the papillomacular axis.
Figure 2: Comparison of an in vivo ultrahigh-resolution OCT image (top) of the normal human macula to a histologic micrograph of the normal macula (bottom) taken from an ophthalmic textbook26.
Figure 3: Quantification of intraretinal structures.
Figure 4: In vivo ultrahigh-resolution corneal OCT image of a normal human subject.
Figure 5: Ultrahigh-resolution ophthalmologic OCT system using a titanium:sapphire laser light source.

References

  1. Bamber, J.C. & Tristam, M. Diagnostic Ultrasound. in The Physics of Medical Imaging. (ed. Webb, S.) 319–388 (Adam Hilger, Bristol and Philadelphia, 1988).

    Google Scholar 

  2. Pavlin, C.J., McWhae, J.A., McGowan, H.D. & Foster, F.S. Ultrasound biomicroscopy of anterior segment tumors. Ophthalmology 99, 1220–1228 (1992).

    Article  CAS  Google Scholar 

  3. Masters, B.R. & Thaer, A.A. Real-time scanning slit confocal microscopy of the in vivo human cornea. Appl. Opt. 33, 695–701 (1994).

    Article  CAS  Google Scholar 

  4. Webb, R.H., Hughes, G.W. & Pomerantzeff, O. Flying spot TV ophthalmoscope. Appl. Opt. 19, 2991–2997 (1980).

    Article  CAS  Google Scholar 

  5. Bille, J.F., Dreher, A.W. & Zinser, G. Scanning laser tomography of the living human eye. in Noninvasive Diagnostic Techniques in Ophthalmology. (ed. Master, B.R.) 528–547 (Springer Verlag, New York, 1990).

    Chapter  Google Scholar 

  6. Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).

    Article  CAS  Google Scholar 

  7. Puliafito, C.A., Hee, M.R., Schuman, J.S. & Fujimoto, J.G. in Optical Coherence Tomography of Ocular Disease. (Slack, Thorofare, New Jersey, 1995).

    Google Scholar 

  8. Youngquist, R.C., Carr, S. & Davies, D.E.N. Optical coherence domain reflectometry: A new optical evaluation technique. Opt. Lett. 12, 158–160 (1987).

    Article  CAS  Google Scholar 

  9. Takada, K., Yokohama, I., Chida, K. & Noda, J. New measurement system for fault location in optic waveguide devices based on an interferometric technique. App. Opt. 26, 1603–1606 (1987).

    Article  CAS  Google Scholar 

  10. Fercher, A.F., Hitzenberger, C.K., Drexler, W., Kamp, G. & Sattmann, H. In vivo optical coherence tomography. Am. J. Ophthalmol. 116, 113–114 (1993).

    Article  CAS  Google Scholar 

  11. Swanson, E.A. et al. In vivo retinal imaging by optical coherence tomography. Opt. Lett. 18, 1864–1866 (1993).

    Article  CAS  Google Scholar 

  12. Fujimoto, J.G. et al. Optical biopsy and imaging using optical coherence tomography. Nature Med. 1, 970–972 (1995).

    Article  CAS  Google Scholar 

  13. Boppart, S.A. et al. In vivo cellular optical coherence tomography imaging. Nature Med. 4, 861–865 (1998).

    Article  CAS  Google Scholar 

  14. Tearney, G.J. et al. In vivo endoscopic optical biopsy with optical coherence tomography. Science 276, 2037–2039 (1997).

    Article  CAS  Google Scholar 

  15. Fujimoto, J.G., Pitris, C., Boppart, S. & Brezinski, M. Optical coherence tomography, an emerging technology for biomedical imaging and optical biopsy. Neoplasia 2, 9–25 (2000).

    Article  CAS  Google Scholar 

  16. Hee, M.R. et al. Optical coherence tomography of the human retina. Arch. Ophthalmol. 113, 325–332 (1995).

    Article  CAS  Google Scholar 

  17. Hee, M.R. et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology 105, 360–370 (1998).

    Article  CAS  Google Scholar 

  18. Hee, M.R. et al. Optical coherence tomography of macular holes. Ophthalmology 102, 748–756 (1995).

    Article  CAS  Google Scholar 

  19. Hee, M.R. et al. Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology 103, 1260–1270 (1996).

    Article  CAS  Google Scholar 

  20. Schuman, J.S. et al. Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch. Ophthalmol. 113, 586–596 (1995).

    Article  CAS  Google Scholar 

  21. Schuman, J.S. et al. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 103, 1889–1898 (1996).

    Article  CAS  Google Scholar 

  22. Bowd, C., Weinreb, R.N., Williams, J.M. & Zangwill, L.M. The retinal nerve fiber layer thickness in ocular hypertensive, normal and glaucomatous eyes with optical coherence tomography. Arch. Ophthalmol. 118, 22–26 (2000).

    Article  CAS  Google Scholar 

  23. Drexler, W. et al. In vivo ultrahigh resolution optical coherence tomography. Opt. Lett. 24, 1221–1223 (1999).

    Article  CAS  Google Scholar 

  24. Morgner, U. et al. Spectroscopic optical coherence tomography. Opt. Lett. 25, 111–113 (2000).

    Article  CAS  Google Scholar 

  25. Morgner, U. et al. Sub-two-cycle pulses from a Kerr-lens mode-locked Ti:sapphire laser. Opt. Lett. 24, 411–413 (1999).

    Article  CAS  Google Scholar 

  26. Gass, J.D.M. Normal macula. in Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. vol. 1, 1–49 (Mosby, St. Louis, Missouri, 1997).

    Google Scholar 

  27. Hogan, H., Alvarado, J.A. & Wedell, J.E. Histology of the Human Eye: An Atlas and Textbook. 393–522 (W.B. Saunders, Philadelphia, 1971).

    Google Scholar 

  28. Zeimer, R., Asrani. S., Zou. S., Quigley. H. & Jampel, H. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping. Ophthalmology 105, 224–231 (1998).

    Article  CAS  Google Scholar 

  29. Krebs, W. & Krebs, I. in Primate Retina and Choroid—Atlas of Fine Structure in Man and Monkey. 4–8 (Springer, New York, 1991).

    Book  Google Scholar 

  30. Spalton, D.J., Hitchings, R.A. & Hunter, P.A. Anatomy of the retina. in Atlas of Clinical Ophthalmology 2nd edn., 13.3–13.9 (Mosby, St. Louis, Missouri, 1994).

    Google Scholar 

  31. Oyster, C.W. in The Human Eye — Structure and Function. (ed. Oyster, C.W.) 660–661 (Sinauer Associates, Sunderland, Massachusetts, 1999).

    Google Scholar 

  32. Ramrattan, R.S. et al. Morphometric analysis of Bruch's membrane, the choriocappillaris, and the choroid in aging. Invest. Ophthalmol. Vis. Sci. 35, 2857–2864 (1994).

    CAS  Google Scholar 

  33. Rohen, J.W. Morphologie und embryologie des sehorgans. in Augenheilkunde in Klinik und Praxis (ed. Francois, J. & Hollwich, F.) 1.17–1.19 (Georg Thieme, Stuttgart, 1977).

    Google Scholar 

  34. Marshall, J. & Heckenlively, J.R. Pathologic findings and putative mechanisms in retinitis pigmentosa. in Retinitis Pigmentosa. (ed. Heckenlively, J.R.) 37–67 (J.B. Lippincott, Philadelphia, 1988).

    Google Scholar 

  35. Toth, C.A. et al. A comparision of retinal morphology viewed by optical coherence tomography and light microscopy. Arch. Ophthalmol. 115, 1425–1428 (1997).

    Article  CAS  Google Scholar 

  36. Huang, Y. et al. Relation of optical coherence tomography to microanatomy in normal and rd chickens. Invest. Ophthalmol. Vis. Sci. 39, 2405–2416 (1998).

    CAS  Google Scholar 

  37. Chauhan, D.S. & Marshall, J. The interpretation of optical coherence tomography images of the retina. Invest. Ophthalmol. Vis. Sci. 40, 2332–2341 (1999).

    CAS  PubMed  Google Scholar 

  38. Knighton, R.W. & Huang, X.R. Optical coherence tomography of retinal nerve fiber layer (e-letter). Invest. Ophthalmol. Vis. Sci. 41 (2000).

  39. Howland, H.C. & Howland, B. A subjective method for the measurement of monochromatic aberrations of the eye. J. Opt. Soc. Am. 67, 1508–1518 (1977).

    Article  CAS  Google Scholar 

  40. Thrane, L., Yura, H.T. & Andersen, P.E. Analysis of optical coherence tomography systems based on the extended Huygens-Fresnel principle. J. Opt. Soc. Am. A. Opt. Image Sci. Vis. 17, 484–490 (2000).

    Article  CAS  Google Scholar 

  41. Safe Use of Lasers, ANSI Z 136.1. (American National Standards Institute, New York, 1993).

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Acknowledgements

We thank S. Bursell, A. Claremont, E. Ippen, C. Pitris, K. Saunders, E. Swanson, J. MacNutt, V.M. Miller, J. Prien, S. Hel and C. Bang. Supported in part by the NIH contract RO1-EY11289-13 and EY11006-04, the Air Force Office of Scientific Research contract F49620-98-1-0139, the Joint Services Electronics Program contract DAAH04-95-1-0038 and the Medical Free Electron Laser Program N00014-97-1-1066. W.D. was supported by the Max Kade Foundation and the Österreichische Akademie der Wissenschaften. U.M. and F.X.K. were supported by the Deutsche Forschungsgemeinschaft. R.K.G. was supported from the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Wolfgang Drexler, Uwe Morgner, Ravi K. Ghanta, Franz X. Kärtner & James G. Fujimoto

  2. New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts, USA

    Joel S. Schuman

Authors
  1. Wolfgang Drexler
  2. Uwe Morgner
  3. Ravi K. Ghanta
  4. Franz X. Kärtner
  5. Joel S. Schuman
  6. James G. Fujimoto

Corresponding author

Correspondence to James G. Fujimoto.

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Drexler, W., Morgner, U., Ghanta, R. et al. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat Med 7, 502–507 (2001). https://doi.org/10.1038/86589

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