Revealing fine microstructural morphology in the living human retina using Optical Coherence Tomography with pancorrection

Ultra-high speed optical coherence tomography employing an ultra-broadband light source has been combined with adaptive optics utilizing a single high stroke deformable mirror and chromatic aberration compensation. The reduction of motion artefacts, geometric and chromatic aberrations (pancorrection) permits to achieve an isotropic resolution of 2-3 μm in the human eye. The performance of this non-invasive imaging modality enables to resolve cellular structures including cone photoreceptors, nerve fibre bundles and collagenous plates of the lamina cribrosa, and retinal pigment epithelial (RPE) cells in the human retina in vivo with superior detail. Alterations of cellular morphology due to cone degeneration in a colour-blind subject are investigated in ultra-high resolution with selective depth sectioning for the first time.

[1]  B. Singer,et al.  Improvement in retinal image quality with dynamic correction of the eye's aberrations. , 2001, Optics express.

[2]  Wolfgang Drexler,et al.  State-of-the-art retinal optical coherence tomography , 2008, Progress in Retinal and Eye Research.

[3]  Norberto López-Gil,et al.  Ocular wave-front aberration statistics in a normal young population , 2002, Vision Research.

[4]  J. Fujimoto,et al.  Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. , 2003, Archives of ophthalmology.

[5]  Wolfgang Drexler,et al.  Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography. , 2005, Optics express.

[6]  P. Artal,et al.  Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser. , 2005, Optics express.

[7]  C. Dainty,et al.  Adaptive optics enhanced simultaneous en-face optical coherence tomography and scanning laser ophthalmoscopy. , 2006, Optics express.

[8]  Bernard P. Gee,et al.  In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells. , 2006, Optics express.

[9]  R W Flower,et al.  The mechanism of optic nerve damage in experimental acute intraocular pressure elevation. , 1980, Investigative ophthalmology & visual science.

[10]  Elizabeth Sanocki,et al.  Defective colour vision associated with a missense mutation in the human green visual pigment gene , 1992, Nature Genetics.

[11]  J. Winderickx,et al.  Genotype-phenotype relationships in human red/green color-vision defects: molecular and psychophysical studies. , 1992, American journal of human genetics.

[12]  Robert J Zawadzki,et al.  Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[13]  David Williams,et al.  Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Lindsay T Sharpe,et al.  The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes. , 2002, Human molecular genetics.

[15]  J. Duker,et al.  Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. , 2004, Ophthalmology.

[16]  J. Nathans,et al.  Molecular genetics of inherited variation in human color vision. , 1986, Science.

[17]  A. Roorda,et al.  High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease. , 2007, Investigative ophthalmology & visual science.

[18]  Jay Neitz,et al.  Variety of genotypes in males diagnosed as dichromatic on a conventional clinical anomaloscope , 2004, Visual Neuroscience.

[19]  Steven M. Jones,et al.  Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. , 2005, Optics express.

[20]  A C S VAN HEEL.  Correcting the spherical and chromatic aberrations of the eye. , 1946, Journal of the Optical Society of America.

[21]  Donald T. Miller,et al.  Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina. , 2005, Optics express.

[22]  Ravi S. Jonnal,et al.  Coherence gating and adaptive optics in the eye , 2003, SPIE BiOS.

[23]  P. Artal,et al.  Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator , 2005, Vision Research.

[24]  Steven M. Jones,et al.  High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography. , 2006, Optics express.

[25]  A. Fercher,et al.  Submicrometer axial resolution optical coherence tomography. , 2002, Optics letters.

[26]  Iwona Gorczynska,et al.  Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head. , 2008, Investigative ophthalmology & visual science.

[27]  C. O'brien,et al.  Three dimensional analysis of the lamina cribrosa in glaucoma , 2004, British Journal of Ophthalmology.

[28]  A. Hendrickson,et al.  Human photoreceptor topography , 1990, The Journal of comparative neurology.

[29]  Ian Munro,et al.  Benefit of higher closed-loop bandwidths in ocular adaptive optics. , 2003, Optics express.

[30]  Angelika Unterhuber,et al.  Adaptive optics with a magnetic deformable mirror: applications in the human eye. , 2006, Optics express.

[31]  J. Fujimoto,et al.  Ultrahigh-resolution ophthalmic optical coherence tomography , 2001, Nature Medicine.

[32]  A. Bradley,et al.  Statistical variation of aberration structure and image quality in a normal population of healthy eyes. , 2002, Journal of the Optical Society of America. A, Optics, image science, and vision.

[33]  Robert K. Tyson.  Principles of Adaptive Optics , 1991 .

[34]  W Drexler,et al.  Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography. , 2003, Optics letters.

[35]  T. Hebert,et al.  Adaptive optics scanning laser ophthalmoscopy. , 2002, Optics express.

[36]  A. Harman,et al.  Development and aging of cell topography in the human retinal pigment epithelium. , 1997, Investigative ophthalmology & visual science.

[37]  P. Artal,et al.  Chromatic aberration correction of the human eye for retinal imaging in the near infrared. , 2006, Optics express.

[38]  D R Williams,et al.  Supernormal vision and high-resolution retinal imaging through adaptive optics. , 1997, Journal of the Optical Society of America. A, Optics, image science, and vision.

[39]  R. D. Ferguson,et al.  Compact multimodal adaptive-optics spectral-domain optical coherence tomography instrument for retinal imaging. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[40]  David R Williams,et al.  Calculated impact of higher-order monochromatic aberrations on retinal image quality in a population of human eyes. , 2002, Journal of the Optical Society of America. A, Optics, image science, and vision.

[41]  C. Curcio,et al.  Photoreceptor inner segments in monkey and human retina: Mitochondrial density, optics, and regional variation , 2002, Visual Neuroscience.

[42]  R. Zawadzki,et al.  Simultaneous imaging of human cone mosaic with adaptive optics enhanced scanning laser ophthalmoscopy and high-speed transversal scanning optical coherence tomography. , 2008, Optics letters.

[43]  David H Sliney,et al.  Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[44]  Austin Roorda,et al.  Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[45]  Jay Neitz,et al.  The importance of deleterious mutations of M pigment genes as a cause of color vision defects , 2001 .

[46]  C. Zucker,et al.  Retinal pigment epithelial cell distribution in central retina of rhesus monkeys. , 2002, Investigative ophthalmology & visual science.

[47]  Angelika Unterhuber,et al.  Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina. , 2008, Optics express.

[48]  K. Trinkaus,et al.  Alterations in the morphology of lamina cribrosa pores in glaucomatous eyes , 2004, British Journal of Ophthalmology.

[49]  J. Fujimoto,et al.  In vivo ultrahigh-resolution optical coherence tomography. , 1999, Optics letters.

[50]  Robert J Zawadzki,et al.  Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction. , 2008, Optics express.

[51]  W. Drexler.  Ultrahigh-resolution optical coherence tomography. , 2004, Journal of biomedical optics.

[52]  Olaf Strauss,et al.  The retinal pigment epithelium in visual function. , 2005, Physiological reviews.

[53]  P. Artal,et al.  Adaptive-optics ultrahigh-resolution optical coherence tomography. , 2004, Optics letters.

[54]  H. Gao,et al.  Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. , 1992, Investigative ophthalmology & visual science.

[55]  Y. Nishida,et al.  An A−71C substitution in a green gene at the second position in the red/green visual-pigment gene array is associated with deutan color-vision deficiency , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Maureen Neitz,et al.  Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

[57]  Wolfgang Drexler,et al.  Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular pathology. , 2005, Ophthalmology.

[58]  D. Williams,et al.  Monochromatic aberrations of the human eye in a large population. , 2001, Journal of the Optical Society of America. A, Optics, image science, and vision.