Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina.

Cellular in vivo visualization of the three dimensional architecture of individual human foveal cone photoreceptors is demonstrated by combining ultrahigh resolution optical coherence tomography and a novel adaptive optics modality. Isotropic resolution in the order of 2-3 microm, estimated from comparison with histology, is accomplished by employing an ultrabroad bandwidth Titanium:sapphire laser with 140 nm bandwidth and previous correction of chromatic and monochromatic ocular aberrations. The latter, referred to as pancorrection, is enabled by the simultaneous use of a specially designed lens and an electromagnetically driven deformable mirror with unprecedented stroke for correcting chromatic and monochromatic aberrations, respectively. The increase in imaging resolution allows for resolving structural details of distal elements of individual foveal cones: inner segment zones--myoids and ellipsoids--are differentiated from outer segments protruding into pigment epithelial processes in the retina. The presented technique has the potential to unveil photoreceptor development and pathogenesis as well as improved therapy monitoring of numerous retinal diseases.

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

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

[3]  R. H. Steinberg Research update: report from a workshop on cell biology of retinal detachment. , 1986, Experimental eye research.

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

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

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

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

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

[9]  Don H. Anderson,et al.  Disc morphogenesis in vertebrate photoreceptors , 1980, Vision Research.

[10]  W. Krebs,et al.  Primate Retina and Choroid: Atlas of Fine Structure in Man and Monkey , 1991 .

[11]  Donald T. Miller,et al.  Measuring retinal contributions to the optical Stiles-Crawford effect with optical coherence tomography. , 2008, Optics express.

[12]  Junzhong Liang,et al.  Objective measurement of wave aberrations of the human eye with the use of a Hartmann-Shack wave-front sensor. , 1994, Journal of the Optical Society of America. A, Optics, image science, and vision.

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

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

[15]  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.

[16]  D. Anderson,et al.  Disc shedding and autophagy in the cone-dominant ground squirrel retina. , 1986, Experimental eye research.

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

[18]  N. Roberts The optics of vertebrate photoreceptors: Anisotropy and form birefringence , 2006, Vision Research.

[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]  H. Taylor,et al.  World blindness: a 21st century perspective , 2001, The British journal of ophthalmology.

[21]  David Williams,et al.  Optical fiber properties of individual human cones. , 2002, Journal of vision.

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

[23]  P Artal,et al.  Analysis of the performance of the Hartmann-Shack sensor in the human eye. , 2000, Journal of the Optical Society of America. A, Optics, image science, and vision.

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

[25]  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.

[26]  J. J. Plantner,et al.  Increase in interphotoreceptor matrix gelatinase A (MMP-2) associated with age-related macular degeneration. , 1998, Experimental eye research.

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

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

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

[30]  D. Borwein,et al.  The ultrastructure of monkey foveal photoreceptors, with special reference to the structure, shape, size, and spacing of the foveal cones. , 1980, The American journal of anatomy.

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

[32]  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.

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

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

[35]  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.

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

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

[38]  Pablo Artal,et al.  Membrane deformable mirror for adaptive optics: performance limits in visual optics. , 2003, Optics express.

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

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

[41]  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.

[42]  A. Hendrickson,et al.  Distribution of cones in human and monkey retina: individual variability and radial asymmetry. , 1987, Science.

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