High-resolution, in vivo retinal imaging using adaptive optics and its future role in ophthalmology

Until recently it was impossible to fully realize the optical resolution afforded by the human eye due to the inherent optical aberrations. These aberrations limit the ability to see fine structure in the retinal layers and visual perception of the outside world. A conventional spectacle or contact lens refraction only provides a static amelioration of the lowest order aberrations, namely defocus and astigmatism. In addition, all of these distortions are constantly evolving due to changes in accommodation and head/eye movements. The technique of adaptive optics not only corrects all of the static spatial modes but also measures and corrects any dynamic changes. Such systems have allowed for routine in vivo cellular imaging, the classification of individual photoreceptor cells and have enabled psychophysical testing of human visual function at the neural level. This review introduces the principle of adaptive optics and the key hardware required to implement such a scheme. The integration of adaptive optics into different imaging modalities is presented along with descriptions of current systems in use today and the experimental results obtained to date. Finally, the review concludes by discussing future technology and gives the author’s prediction of how the field will evolve over the coming years.

[1]  N. Doble,et al.  The application of MEMS technology for adaptive optics in vision science , 2004, IEEE Journal of Selected Topics in Quantum Electronics.

[2]  M. Vorontsov,et al.  The principles of adaptive optics , 1985 .

[3]  R. Nickells,et al.  Retinal Ganglion Cell Death in Glaucoma: The How, the Why, and the Maybe , 1996, Journal of glaucoma.

[4]  David R Williams,et al.  Neural compensation for the eye's optical aberrations. , 2004, Journal of vision.

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

[6]  Choun-Ki Joo,et al.  Hepatocyte growth factor induces proliferation of lens epithelial cells through activation of ERK1/2 and JNK/SAPK. , 2004, Investigative ophthalmology & visual science.

[7]  Rinaldo Cubeddu,et al.  Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium , 1990, Vision Research.

[8]  Satoshi Kawata,et al.  Enhancement of laser trapping force by spherical aberration correction using a deformable mirror , 2003 .

[9]  Roberto Ragazzoni,et al.  Extended source pyramid wave-front sensor for the human eye. , 2002, Optics express.

[10]  J. C. Dainty,et al.  Low-order adaptive optics: a possible use in underwater imaging? , 1997 .

[11]  P. Artal,et al.  Compensation of corneal aberrations by the internal optics in the human eye. , 2001, Journal of vision.

[12]  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.

[13]  Francois Lacombe,et al.  Towards wide-field retinal imaging with adaptive optics , 2004 .

[14]  G. M. Morris,et al.  Images of cone photoreceptors in the living human eye , 1996, Vision Research.

[15]  Justo Arines,et al.  Hybrid technique for high resolution imaging of the eye fundus. , 2003, Optics express.

[16]  P Artal,et al.  High-resolution retinal images obtained by deconvolution from wave-front sensing. , 2000, Optics letters.

[17]  J. Bille,et al.  An ASIC for Hartmann-Shack wavefront detection , 2002 .

[18]  David Williams,et al.  Visual performance after correcting the monochromatic and chromatic aberrations of the eye. , 2002, Journal of the Optical Society of America. A, Optics, image science, and vision.

[19]  Peter Kurczynski,et al.  Fabrication and measurement of low-stress membrane mirrors for adaptive optics. , 2004, Applied optics.

[20]  David R Williams,et al.  Adaptive optics for vision: the eye's adaptation to point spread function. , 2003, Journal of refractive surgery.

[21]  Donald J Zack,et al.  Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. , 2003, Investigative ophthalmology & visual science.

[22]  F W Fitzke,et al.  Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. , 1995, The British journal of ophthalmology.

[23]  A. Roorda,et al.  Optimal pupil size in the human eye for axial resolution. , 2003, Journal of the Optical Society of America. A, Optics, image science, and vision.

[24]  C. Gray,et al.  Natural movies evoke precise responses in cat visual cortex that are not predicted from non-uniform Poisson processes , 2004 .

[25]  Pablo Artal,et al.  Adaptive optics visual simulator. , 2002, Journal of refractive surgery.

[26]  Geunyoung Yoon,et al.  Deformable Mirror Requirements for Adaptive Correction of the Population of Normal Human Eyes , 2003 .

[27]  F. Campbell,et al.  Optical quality of the human eye , 1966, The Journal of physiology.

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

[29]  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.

[30]  Naohisa Mukohzaka,et al.  Phase Modulation Characteristics Analysis of Optically-Addressed Parallel-Aligned Nematic Liquid Crystal Phase-Only Spatial Light Modulator Combined with a Liquid Crystal Display , 1998 .

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

[32]  R. W. Rodieck The First Steps in Seeing , 1998 .

[33]  Paul D. Gamlin,et al.  Fireworks in the Primate Retina In Vitro Photodynamics Reveals Diverse LGN-Projecting Ganglion Cell Types , 2003, Neuron.

[34]  M. Horenstein,et al.  Microelectromechanical deformable mirrors , 1999 .

[35]  R. D. Ferguson,et al.  Wide-field retinal hemodynamic imaging with the tracking scanning laser ophthalmoscope. , 2004, Optics express.

[36]  J. Hardy,et al.  Adaptive Optics for Astronomical Telescopes , 1998 .

[37]  P Artal,et al.  Correction of the aberrations in the human eye with a liquid-crystal spatial light modulator: limits to performance. , 1998, Journal of the Optical Society of America. A, Optics, image science, and vision.

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

[39]  Shaya Fainman,et al.  Retinal imaging with a low-cost micromachined membrane deformable mirror. , 2002, Journal of biomedical optics.

[40]  Tomohiro Shirai,et al.  Liquid-crystal adaptive optics based on feedback interferometry for high-resolution retinal imaging. , 2002, Applied optics.

[41]  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.

[42]  Junzhong Liang,et al.  Aberrations and retinal image quality of the normal human eye. , 1997, Journal of the Optical Society of America. A, Optics, image science, and vision.

[43]  R. Weinreb,et al.  Active optical depth resolution improvement of the laser tomographic scanner. , 1989, Applied optics.

[44]  Thomas Nirmaier,et al.  Very fast wave-front measurements at the human eye with a custom CMOS-based Hartmann-Shack sensor. , 2003, Optics express.

[45]  David Williams,et al.  The arrangement of the three cone classes in the living human eye , 1999, Nature.

[46]  I Iglesias,et al.  Closed-loop adaptive optics in the human eye. , 2001, Optics letters.

[47]  David R Williams,et al.  Deconvolution of adaptive optics retinal images. , 2004, Journal of the Optical Society of America. A, Optics, image science, and vision.

[48]  P Artal,et al.  High-resolution imaging of the living human fovea: measurement of the intercenter cone distance by speckle interferometry. , 1989, Optics letters.

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

[50]  W. Hauswirth,et al.  Glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[51]  R. Shack,et al.  History and principles of Shack-Hartmann wavefront sensing. , 2001, Journal of refractive surgery.

[52]  N. G. Iroshnikov,et al.  Adaptive system for eye-fundus imaging , 2002 .

[53]  A. Roorda,et al.  Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope. , 2004, Journal of biomedical optics.

[54]  Jessica I. Wolfing,et al.  High-resolution retinal imaging of cone-rod dystrophy. , 2006, Ophthalmology.

[55]  David Le Mignant,et al.  Performance of the Keck Observatory adaptive-optics system. , 2004, Applied optics.

[56]  P Artal,et al.  Dynamics of the eye's wave aberration. , 2001, Journal of the Optical Society of America. A, Optics, image science, and vision.

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

[58]  Pablo Artal,et al.  Adaptive optics with a programmable phase modulator: applications in the human eye. , 2004, Optics express.

[59]  Christopher Dainty,et al.  High-resolution imaging of the human retina with a Fourier deconvolution technique. , 2002, Journal of the Optical Society of America. A, Optics, image science, and vision.

[60]  Pablo Artal,et al.  Adaptive optics simulation of intraocular lenses with modified spherical aberration. , 2004, Investigative ophthalmology & visual science.

[61]  Krishnakumar Venkateswaran,et al.  Non-Invasive Direct Assessment of Parafoveal Capillary Leukocyte Velocity , 2003 .

[62]  Tadataka Yamada,et al.  Biochemistry and localization of somatostatin in the retina , 1988 .

[63]  P. Sarro,et al.  High-speed wavefront sensor compatible with standard CMOS technology , 2004 .

[64]  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.

[65]  B. Boycott,et al.  Organization of the Primate Retina: Light Microscopy , 1969 .

[66]  Ravi S. Jonnal,et al.  Optical coherence tomography for an adaptive optics retina camera , 2003, International Commission for Optics.

[67]  Horace W. Babcock,et al.  THE POSSIBILITY OF COMPENSATING ASTRONOMICAL SEEING , 1953 .

[68]  David R. Williams,et al.  Microstimulation and Imaging of the Trichromatic Cone Mosaic in the Living Human Eye , 2003 .

[69]  S. Kawata,et al.  Adaptive aberration correction in a two‐photon microscope , 2000, Journal of microscopy.

[70]  J M Seddon,et al.  Drusen characteristics in patients with exudative versus non-exudative age-related macular degeneration. , 1988, Retina.

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

[72]  L. Chalupa,et al.  Organization of Visual Areas in Macaque and Human Cerebral Cortex , 2002 .

[73]  Christian Rembe,et al.  Micromirrors for Adaptive-Optics Arrays , 2001 .

[74]  Lelia Adelina Paunescu,et al.  Tracking optical coherence tomography. , 2004, Optics letters.

[75]  LARRY N. THIBOS,et al.  Use of Liquid-Crystal Adaptive-Optics to Alter the Refractive State of the Eye , 1997, Optometry and vision science : official publication of the American Academy of Optometry.

[76]  David Williams,et al.  The reflectance of single cones in the living human eye. , 2002, Investigative ophthalmology & visual science.

[77]  Geunyoung Yoon,et al.  Use of a microelectromechanical mirror for adaptive optics in the human eye. , 2002, Optics letters.

[78]  Li Guo,et al.  Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[79]  J F Bille,et al.  Preoperative simulation of outcomes using adaptive optics. , 2000, Journal of refractive surgery.

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

[81]  R. Webb Confocal optical microscopy , 1996 .

[82]  P. Sarro,et al.  Flexible mirror micromachined in silicon. , 1995, Applied optics.

[83]  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.