Noninvasive in vivo measurement of retinal physiology with high-speed ultrahigh resolution OCT

Non-invasive in vivo functional optical imaging is emonstrated using high-speed, ultrahigh resolution optical coherence tomography (UHR-OCT). A high-speed, UHR-OCT system using spectral/Fourier domain detection was developed for functional imaging experiments in the rodent retina. Using a spectrally multiplexed superluminescent diode light source, imaging was performed with 2.8 μm resolution at a rate of 24,000 axial scans per second. OCT measurement protocols were designed to minimize noise sources that cause undesired fluctuations in the measured OCT signal. A white light stimulus was applied to the retina and the average reflectivity from each intraretinal layer was monitored over time using OCT. A white light stimulus induces a response consisting of an increase in the reflectance of the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of functional imaging using OCT in the retina. Further systematic investigation will be required to fully characterize the observed optical changes. Eventually, this may prove to be an objective method for measuring photoreceptor function in the human retina.

[1]  Donald C. Hood,et al.  PII: S0042-6989(97)00143-0 , 2003 .

[2]  S L Graham,et al.  Early magnocellular loss in glaucoma demonstrated using the pseudorandomly stimulated flash visual evoked potential. , 1999, Journal of glaucoma.

[3]  S. Boppart,et al.  Functional optical coherence tomography for detecting neural activity through scattering changes. , 2003, Optics letters.

[4]  R. Kardon,et al.  Pupil perimetry. , 1992, Current opinion in ophthalmology.

[5]  Manabu Tanifuji,et al.  Mapping cone- and rod-induced retinal responsiveness in macaque retina by optical imaging. , 2004, Investigative ophthalmology & visual science.

[6]  G. Ripandelli,et al.  Optical coherence tomography. , 1998, Seminars in ophthalmology.

[7]  S. Klein,et al.  The topography of visual evoked response properties across the visual field. , 1994, Electroencephalography and clinical neurophysiology.

[8]  A J Adams,et al.  Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy. , 1999, Investigative ophthalmology & visual science.

[9]  P A Good,et al.  The flash stimulated VEP in the diagnosis of glaucoma , 1989, Eye.

[10]  A. Fercher,et al.  Performance of fourier domain vs. time domain optical coherence tomography. , 2003, Optics express.

[11]  S E Simonsen,et al.  THE VALUE OF THE OSCILLATORY POTENTIAL IN SELECTING JUVENILE DIABETICS AT RISK OF DEVELOPING PROLIFERATIVE RETINOPATHY , 1980, Metabolic and pediatric ophthalmology.

[12]  Stuart G. Coupland,et al.  A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy , 1987, Documenta Ophthalmologica.

[13]  S L Graham,et al.  Objective VEP Perimetry in Glaucoma: Asymmetry Analysis to Identify Early Deficits , 2000, Journal of glaucoma.

[14]  Robert Ritch,et al.  Visual evoked potential assessment of the effects of glaucoma on visual subsystems , 1998, Vision Research.

[15]  Teresa C. Chen,et al.  In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography. , 2004, Optics letters.

[16]  G. Ha Usler,et al.  "Coherence radar" and "spectral radar"-new tools for dermatological diagnosis. , 1998, Journal of biomedical optics.

[17]  M Palta,et al.  Temporal aspects of the electroretinogram in diabetic retinopathy. , 1987, Archives of ophthalmology.

[18]  H. Kadono,et al.  Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo , 2003, Journal of Neuroscience Methods.

[19]  A. Fercher,et al.  In vivo human retinal imaging by Fourier domain optical coherence tomography. , 2002, Journal of biomedical optics.

[20]  S L Graham,et al.  Electrophysiology: a review of signal origins and applications to investigating glaucoma. , 1998, Australian and New Zealand journal of ophthalmology.

[21]  Kristian Klemp,et al.  The multifocal ERG in diabetic patients without retinopathy during euglycemic clamping. , 2005, Investigative ophthalmology & visual science.

[22]  M A Bearse,et al.  Mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram. , 1997, Investigative ophthalmology & visual science.

[23]  E Zrenner,et al.  Implicit time topography of multifocal electroretinograms. , 1998, Investigative ophthalmology & visual science.

[24]  A. Palmowski,et al.  The multifocal ERG in open angle glaucoma – A comparison of high and low contrast recordings in high- and low-tension open angle glaucoma , 2000, Documenta Ophthalmologica.

[25]  Chris A Johnson,et al.  Selective loss of an oscillatory component from temporal retinal multifocal ERG responses in glaucoma. , 2002, Investigative ophthalmology & visual science.

[26]  Angelika Unterhuber,et al.  Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography. , 2005, Journal of biomedical optics.

[27]  J. Fujimoto,et al.  Optical coherence tomography of the human retina. , 1995, Archives of ophthalmology.

[28]  T. Berendschot,et al.  Slow optical changes in human photoreceptors induced by light. , 2000, Investigative ophthalmology & visual science.

[29]  T Usui,et al.  Waveform changes of the first-order multifocal electroretinogram in patients with glaucoma. , 2000, Investigative ophthalmology & visual science.

[30]  G B Arden,et al.  The pattern electroretinogram , 1988, Eye.

[31]  M. Kondo,et al.  Clinical evaluation of multifocal electroretinogram. , 1995, Investigative ophthalmology & visual science.

[32]  M. Wojtkowski,et al.  Real-time in vivo imaging by high-speed spectral optical coherence tomography. , 2003, Optics letters.

[33]  P. Romano.  Association for Research in Vision and Ophthalmology. , 2000, Binocular vision & strabismus quarterly.

[34]  M A Bearse,et al.  Imaging localized retinal dysfunction with the multifocal electroretinogram. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[35]  Vaegan,et al.  The spatial distribution of ERG losses across the posterior pole of glaucomatous eyes in multifocal recordings. , 1996, Australian and New Zealand journal of ophthalmology.

[36]  Peter Mierdel,et al.  The pattern ERG in glaucoma: effect of pattern reversal time , 1992, International Ophthalmology.

[37]  R. Kardon,et al.  Automated pupil perimetry. Pupil field mapping in patients and normal subjects. , 1991, Ophthalmology.

[38]  B Brown,et al.  Multifocal ERG changes in glaucoma. , 1999, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[39]  H Iijima,et al.  Photopic electroretinogram implicit time in diabetic retinopathy. , 1994, Japanese journal of ophthalmology.

[40]  Ke Yao,et al.  Assessment of macular function by multifocal electroretinogram in diabetic macular edema before and after vitrectomy , 2004, Documenta Ophthalmologica.

[41]  Changhuei Yang,et al.  Sensitivity advantage of swept source and Fourier domain optical coherence tomography. , 2003, Optics express.

[42]  W Seiple,et al.  A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy. , 1992, Investigative ophthalmology & visual science.

[43]  S L Graham,et al.  Objective perimetry in glaucoma: recent advances with multifocal stimuli. , 1999, Survey of ophthalmology.

[44]  E Zrenner,et al.  Multifocal electroretinography in retinitis pigmentosa. , 1998, American journal of ophthalmology.

[45]  M. Tanifuji,et al.  Implementation of optical coherence tomography (OCT) in visualization of functional structures of cat visual cortex , 2002 .

[46]  M Palta,et al.  Predicting progression to severe proliferative diabetic retinopathy. , 1987, Archives of ophthalmology.

[47]  B. Bouma,et al.  Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. , 2003, Optics letters.

[48]  Donald C. Hood,et al.  Multifocal ERG and VEP responses and visual fields: comparing disease-related changes , 2004, Documenta Ophthalmologica.

[49]  A. Villringer,et al.  Non-invasive optical spectroscopy and imaging of human brain function , 1997, Trends in Neurosciences.

[50]  S Kangovi,et al.  An interocular comparison of the multifocal VEP: a possible technique for detecting local damage to the optic nerve. , 2000, Investigative ophthalmology & visual science.

[51]  J. Fujimoto,et al.  In vivo retinal imaging by optical coherence tomography. , 1993, Optics letters.

[52]  Ron Ofri,et al.  Functional damage to inner and outer retinal cells in experimental glaucoma. , 2003, Investigative ophthalmology & visual science.

[53]  R. Frostig,et al.  Optical imaging of neuronal activity. , 1988, Physiological reviews.

[54]  W Drexler,et al.  Ultrahigh resolution Fourier domain optical coherence tomography. , 2004, Optics express.

[55]  S. Graham,et al.  Multifocal topographic visual evoked potential: improving objective detection of local visual field defects. , 1998, Investigative ophthalmology & visual science.

[56]  W. Drexler,et al.  In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid. , 2005, Optics express.

[57]  R. Kardon,et al.  Comparison of pupil perimetry and visual perimetry in normal eyes: decibel sensitivity and variability. , 2001, Investigative ophthalmology & visual science.

[58]  G B Arden,et al.  The electroretinogram in diabetic retinopathy. , 1999, Survey of ophthalmology.

[59]  Young H. Kwon,et al.  Intrinsic Signal Optical Imaging of Retinal Responses to Patterned Stimuli , 2003 .

[60]  Kazuo Kawasaki,et al.  Electrical responses from diabetic retina , 1998, Progress in Retinal and Eye Research.

[61]  A. Fercher,et al.  Measurement of intraocular distances by backscattering spectral interferometry , 1995 .

[62]  Geoffrey B. Arden,et al.  The multifocal pattern electroretinogram in glaucoma , 2004, Vision Research.

[63]  S L Graham,et al.  The diagnostic significance of the multifocal pattern visual evoked potential in glaucoma. , 1999, Current opinion in ophthalmology.

[64]  S. Yun,et al.  In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve. , 2004, Optics express.

[65]  M A Bearse,et al.  Assessment of early retinal changes in diabetes using a new multifocal ERG protocol. , 2001, The British journal of ophthalmology.

[66]  J. Duker,et al.  Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. , 2004, Optics express.

[67]  Vaegan,et al.  Absence of ganglion cell subcomponents in multifocal luminance electroretinograms. , 1997, Australian and New Zealand journal of ophthalmology.

[68]  Teresa C. Chen,et al.  Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography. , 2004, Optics express.