High-Resolution In Vivo Imaging of Regimes of Laser Damage to the Primate Retina

Purpose. To investigate fundamental mechanisms of regimes of laser induced damage to the retina and the morphological changes associated with the damage response. Methods. Varying grades of photothermal, photochemical, and photomechanical retinal laser damage were produced in eyes of eight cynomolgus monkeys. An adaptive optics confocal scanning laser ophthalmoscope and spectral domain optical coherence tomographer were combined to simultaneously collect complementary in vivo images of retinal laser damage during and following exposure. Baseline color fundus photography was performed to complement high-resolution imaging. Monkeys were perfused with 10% buffered formalin and eyes were enucleated for histological analysis. Results. Laser energies for visible retinal damage in this study were consistent with previously reported damage thresholds. Lesions were identified in OCT images that were not visible in direct ophthalmoscopic examination or fundus photos. Unique diagnostic characteristics, specific to each damage regime, were identified and associated with shape and localization of lesions to specific retinal layers. Previously undocumented retinal healing response to blue continuous wave laser exposure was recorded through a novel experimental methodology. Conclusion. This study revealed increased sensitivity of lesion detection and improved specificity to the laser of origin utilizing high-resolution imaging when compared to traditional ophthalmic imaging techniques in the retina.

[1]  Bernard S. Gerstman Theoretical modeling of laser-induced explosive pressure generation and vaporization in pigmented cells , 2000, Laser Damage.

[2]  T. Maiman Stimulated Optical Radiation in Ruby , 1960, Nature.

[3]  J. Zuclich,et al.  Retinal damage induced by red diode laser. , 2001, Health physics.

[4]  Dirk Theisen,et al.  Plasma formation in water by picosecond and nanosecond Nd:YAG laser pulses. I. Optical breakdown at threshold and superthreshold irradiance , 1996 .

[5]  R. Glickman,et al.  Phototoxicity to the Retina: Mechanisms of Damage , 2002, International journal of toxicology.

[6]  M. Tassignon,et al.  The effect of wavelength on glial fibrillary acidic protein immunoreactivity in laser-induced lesions in rabbit retina , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[7]  Rebecca L Vincelette,et al.  Thermal lensing in ocular media exposed to continuous-wave near-infrared radiation: the 1150-1350-nm region. , 2008, Journal of biomedical optics.

[8]  Kareem M. Ahmad,et al.  Cell density ratios in a foveal patch in macaque retina , 2003, Visual Neuroscience.

[9]  Gary D. Noojin,et al.  Trends in retinal damage thresholds from 100‐millisecond near‐infrared laser radiation exposures: A study at 1,110, 1,130, 1,150, and 1,319 nm , 2009, Lasers in surgery and medicine.

[10]  S. Schein,et al.  How Müller glial cells in macaque fovea coat and isolate the synaptic terminals of cone photoreceptors , 2002, The Journal of comparative neurology.

[11]  Paul K. Kennedy,et al.  Laser-induced retinal damage thresholds for annular retinal beam profiles , 2004, SPIE BiOS.

[12]  J. Stone,et al.  The role of müller cells in the formation of the blood-retinal barrier , 1993, Neuroscience.

[13]  C. Toth,et al.  Retinal damage and laser-induced breakdown produced by ultrashort-pulse lasers , 2006, Graefe's Archive for Clinical and Experimental Ophthalmology.

[14]  J. Marshall,et al.  A comparative histopathological study of argon and krypton laser irradiations of the human retina. , 1979, The British journal of ophthalmology.

[15]  A C Bird,et al.  Histopathology of ruby and argon laser lesions in monkey and human retina. A comparative study. , 1975, The British journal of ophthalmology.

[16]  Zuclich Ja,et al.  Retinal damage induced by red diode laser. , 2001 .

[17]  D. Henson,et al.  Barely visible 10-millisecond pascal laser photocoagulation for diabetic macular edema: observations of clinical effect and burn localization. , 2010, American journal of ophthalmology.

[18]  Ralf Brinkmann,et al.  Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells. , 2004, Journal of biomedical optics.

[19]  Daniel X Hammer,et al.  Line-scanning laser ophthalmoscope. , 2006, Journal of biomedical optics.

[20]  Jessica I. W. Morgan,et al.  Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium. , 2008, Investigative ophthalmology & visual science.

[21]  S. Seregard,et al.  Photochemical damage of the retina. , 2006, Survey of ophthalmology.

[22]  D. Palanker,et al.  LONG-TERM SAFETY, HIGH-RESOLUTION IMAGING, AND TISSUE TEMPERATURE MODELING OF SUBVISIBLE DIODE MICROPULSE PHOTOCOAGULATION FOR RETINOVASCULAR MACULAR EDEMA , 2012, Retina.

[23]  D M Snodderly,et al.  The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas. , 1984, Investigative ophthalmology & visual science.

[24]  C. Distler,et al.  Glia Cells of the Monkey Retina—II. Müller Cells , 1996, Vision Research.

[25]  J. Gerss,et al.  Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage. , 2011, Investigative ophthalmology & visual science.

[26]  W P Roach,et al.  Visible retinal lesions from ultrashort laser pulses in the primate eye. , 1995, Investigative ophthalmology & visual science.

[27]  Ralf Brinkmann,et al.  RPE damage thresholds and mechanisms for laser exposure in the microsecond-to-millisecond time regimen. , 2005, Investigative ophthalmology & visual science.

[28]  Charles P. Lin,et al.  CAVITATION AND ACOUSTIC EMISSION AROUND LASER-HEATED MICROPARTICLES , 1998 .

[29]  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.

[30]  Michael S. Foltz,et al.  Damage Thresholds for Exposure to NIR and Blue Lasers in an In Vitro RPE Cell System. , 2006, Investigative ophthalmology & visual science.

[31]  Y. Tano,et al.  Imaging of titanium:sapphire laser retinal injury by adaptive optics fundus imaging and Fourier-domain optical coherence tomography. , 2009, American journal of ophthalmology.

[32]  Cathy Frey,et al.  Investigative Ophthalmology and Visual Science , 2010 .

[33]  W. T. Ham,et al.  Ocular damage thresholds and mechanisms for ultrashort pulses of both visible and infrared laser radiation in the rhesus monkey. , 1977, Experimental eye research.

[34]  Reginald Birngruber,et al.  Optoacoustic detection of selective RPE cell damage during μs-laser irradiation , 2001, European Conference on Biomedical Optics.

[35]  J. Fujimoto,et al.  Retinal response of Macaca mulatta to picosecond laser pulses of varying energy and spot size. , 2004, Journal of biomedical optics.

[36]  C. Grimm,et al.  Müller cell response to blue light injury of the rat retina. , 2008, Investigative ophthalmology & visual science.

[37]  M. Blumenkranz,et al.  THE IMPACT OF PULSE DURATION AND BURN GRADE ON SIZE OF RETINAL PHOTOCOAGULATION LESION: Implications for Pattern Density , 2011, Retina.

[38]  David J. Lund,et al.  RETINAL INJURY THRESHOLDS FOR BLUE WAVELENGTH LASERS , 2006, Health physics.

[39]  A. Welch,et al.  Laser physics and laser-tissue interaction. , 1989, Texas Heart Institute journal.

[40]  Karl Schulmeister,et al.  Variation of laser-induced retinal injury thresholds with retinal irradiated area: 0.1-s duration, 514-nm exposures. , 2007, Journal of biomedical optics.

[41]  F. Delori,et al.  The macular pigment. II. Spatial distribution in primate retinas. , 1984, Investigative ophthalmology & visual science.

[42]  A. M. Clarke,et al.  SENSITIVITY OF THE RETINA TO RADIATION DAMAGE AS A FUNCTION OF WAVELENGTH * , 1979, Photochemistry and photobiology.

[43]  Michael L Denton,et al.  Mathematical model that describes the transition from thermal to photochemical damage in retinal pigment epithelial cell culture. , 2011, Journal of biomedical optics.