In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy.

We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with non-proliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.

[1]  Tien Yin Wong,et al.  Retinal Vascular Caliber as a Biomarker for Diabetes Microvascular Complications , 2013, Diabetes Care.

[2]  Donald T. Miller,et al.  In vivo functional imaging of human cone photoreceptors. , 2007, Optics express.

[3]  Gang Huang,et al.  A Clinical Planning Module for Adaptive Optics SLO Imaging , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[4]  D. Friedman,et al.  Disparities in adult vision health in the United States. , 2012, American journal of ophthalmology.

[5]  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.

[6]  Ruikang K. Wang,et al.  In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography. , 2008, Optics express.

[7]  Toco Y P Chui,et al.  Adaptive-optics imaging of human cone photoreceptor distribution. , 2008, Journal of the Optical Society of America. A, Optics, image science, and vision.

[8]  Stephen A Burns,et al.  Wavefront-aberration sorting and correction for a dual-deformable-mirror adaptive-optics system. , 2008, Optics letters.

[9]  Stefan Scholl,et al.  Pathophysiology of Macular Edema , 2010, Ophthalmologica.

[10]  Jennifer K. Sun,et al.  Antiangiogenic therapy for ischemic retinopathies. , 2012, Cold Spring Harbor perspectives in medicine.

[11]  Toco Y P Chui,et al.  Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels. , 2011, Investigative ophthalmology & visual science.

[12]  Mette Owner-Petersen,et al.  Noninvasive imaging of human foveal capillary network using dual-conjugate adaptive optics. , 2011, Investigative ophthalmology & visual science.

[13]  Marco A Zarbin,et al.  Diabetic macular edema: pathogenesis and treatment. , 2009, Survey of ophthalmology.

[14]  Ann L. Albright,et al.  Prevalence of diabetic retinopathy in the United States, 2005-2008. , 2010, JAMA.

[15]  A. Dubra,et al.  In vivo dark-field imaging of the retinal pigment epithelium cell mosaic. , 2013, Biomedical optics express.

[16]  Phillip Bedggood,et al.  Direct visualization and characterization of erythrocyte flow in human retinal capillaries , 2012, Biomedical optics express.

[17]  Ursula Schmidt-Erfurth,et al.  Imaging of the Parafoveal Capillary Network in Diabetes , 2013, Current Diabetes Reports.

[18]  John S Werner,et al.  In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function. , 2006, Investigative ophthalmology & visual science.

[19]  M. C. Leske,et al.  The prevalence of diabetic retinopathy among adults in the United States. , 2004, Archives of ophthalmology.

[20]  Marco Lombardo,et al.  ANALYSIS OF RETINAL CAPILLARIES IN PATIENTS WITH TYPE 1 DIABETES AND NONPROLIFERATIVE DIABETIC RETINOPATHY USING ADAPTIVE OPTICS IMAGING , 2013, Retina.

[21]  Toco Y P Chui,et al.  The relationship between peripapillary crescent and axial length: Implications for differential eye growth , 2011, Vision Research.

[22]  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.

[23]  Ravi S. Jonnal,et al.  Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics , 2011, Vision Research.

[24]  David Williams,et al.  Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope , 2011, Biomedical optics express.

[25]  Ruikang K. Wang,et al.  Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds. , 2010, Optics express.

[26]  Toco Y P Chui,et al.  Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy. , 2013, Investigative ophthalmology & visual science.

[27]  Stephen A. Burns,et al.  Infrared imaging of sub-retinal structures in the human ocular fundus , 1996, Vision Research.

[28]  D. Abrahamson Recent studies on the structure and pathology of basement membranes , 1986, The Journal of pathology.

[29]  A. Garner Histopathology of diabetic retinopathy in man , 1993, Eye.

[30]  Robert J Zawadzki,et al.  Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique. , 2009, Optics express.

[31]  S. Burns,et al.  In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy. , 2008, Optics express.

[32]  Quan Dong Nguyen,et al.  Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. , 2012, Ophthalmology.

[33]  E. Rossi,et al.  The relationship between visual resolution and cone spacing in the human fovea , 2009, Nature Neuroscience.

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

[35]  Daniel X Hammer,et al.  Adaptive optics scanning laser ophthalmoscope with integrated wide-field retinal imaging and tracking. , 2010, Journal of the Optical Society of America. A, Optics, image science, and vision.

[36]  Stephen A. Burns,et al.  Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm , 2011, Biomedical optics express.

[37]  Stephen A. Burns,et al.  Foveal Avascular Zone and Its Relationship to Foveal Pit Shape , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[38]  M. Davis,et al.  Clinicopathologic correlations in diabetic retinopathy. I. Histology and fluorescein angiography of microaneurysms. , 1976, Archives of ophthalmology.

[39]  Jessica I. W. Morgan,et al.  In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic. , 2009, Investigative ophthalmology & visual science.

[40]  Toco Y P Chui,et al.  Variation of cone photoreceptor packing density with retinal eccentricity and age. , 2011, Investigative ophthalmology & visual science.

[41]  Austin Roorda,et al.  Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy. , 2011, Investigative ophthalmology & visual science.

[42]  Shuichi Makita,et al.  Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography. , 2011, Optics express.

[43]  P. Lennie,et al.  Packing arrangement of the three cone classes in primate retina , 2001, Vision Research.

[44]  J. Sparrow,et al.  The National Diabetic Retinopathy Laser Treatment Audit. I. Maculopathy , 1998, Eye.

[45]  Austin Roorda,et al.  Subclinical Capillary Changes in Non-Proliferative Diabetic Retinopathy , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[46]  Austin Roorda,et al.  Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy. , 2011, Journal of biomedical optics.

[47]  Toco Y P Chui,et al.  The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope , 2012, Biomedical optics express.

[48]  Ingrid U Scott,et al.  Diabetic macular edema: what is focal and what is diffuse? , 2008, American journal of ophthalmology.