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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 3 — Mar. 1, 2014
  • pp: 961–974

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

Stephen A. Burns, Ann E. Elsner, Toco Y. Chui, Dean A. VanNasdale, Jr., Christopher A. Clark, Thomas J Gast, Victor E. Malinovsky, and Anh-Danh T. Phan  »View Author Affiliations

Biomedical Optics Express, Vol. 5, Issue 3, pp. 961-974 (2014)

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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.

© 2014 Optical Society of America

OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4460) Medical optics and biotechnology : Ophthalmic optics and devices
(170.4470) Medical optics and biotechnology : Ophthalmology

ToC Category:
Ophthalmology Applications

Original Manuscript: January 15, 2014
Revised Manuscript: January 15, 2014
Manuscript Accepted: February 21, 2014
Published: February 27, 2014

Stephen A. Burns, Ann E. Elsner, Toco Y. Chui, Dean A. VanNasdale, Christopher A. Clark, Thomas J Gast, Victor E. Malinovsky, and Anh-Danh T. Phan, "In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy," Biomed. Opt. Express 5, 961-974 (2014)

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  1. J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A14(11), 2884–2892 (1997). [CrossRef] [PubMed]
  2. A. Roorda, A. B. Metha, P. Lennie, and D. R. Williams, “Packing arrangement of the three cone classes in primate retina,” Vision Res.41(10-11), 1291–1306 (2001). [CrossRef] [PubMed]
  3. J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: An alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004). [CrossRef] [PubMed]
  4. S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006). [CrossRef] [PubMed]
  5. R. S. Jonnal, J. Rha, Y. Zhang, B. Cense, W. H. Gao, and D. T. Miller, “In vivo functional imaging of human cone photoreceptors,” Opt. Express15(24), 16141–16160 (2007). [CrossRef]
  6. T. Y. P. Chui, H. X. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A25(12), 3021–3029 (2008). [CrossRef] [PubMed]
  7. E. A. Rossi and A. Roorda, “The relationship between visual resolution and cone spacing in the human fovea,” Nat. Neurosci.13(2), 156–157 (2010). [CrossRef] [PubMed]
  8. A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011). [CrossRef] [PubMed]
  9. H. Song, T. Y. Chui, Z. Zhong, A. E. Elsner, and S. A. Burns, “Variation of cone photoreceptor packing density with retinal eccentricity and age,” Invest. Ophthalmol. Vis. Sci.52(10), 7376–7384 (2011). [CrossRef] [PubMed]
  10. A. Roorda, Y. H. Zhang, and J. L. Duncan, “High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease,” Invest. Ophthalmol. Vis. Sci.48(5), 2297–2303 (2007). [CrossRef] [PubMed]
  11. J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008). [CrossRef] [PubMed]
  12. D. Scoles, Y. N. Sulai, and A. Dubra, “In vivo dark-field imaging of the retinal pigment epithelium cell mosaic,” Biomed. Opt. Express4(9), 1710–1723 (2013). [CrossRef] [PubMed]
  13. T. Y. P. Chui, Z. Y. Zhong, and S. A. Burns, “The relationship between peripapillary crescent and axial length: Implications for differential eye growth,” Vision Res.51(19), 2132–2138 (2011). [CrossRef] [PubMed]
  14. O. P. Kocaoglu, B. Cense, R. S. Jonnal, Q. Wang, S. Y. Lee, W. H. Gao, and D. T. Miller, “Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics,” Vision Res.51(16), 1835–1844 (2011). [CrossRef] [PubMed]
  15. G. Huang, X. Qi, T. Y. Chui, Z. Zhong, and S. A. Burns, “A clinical planning module for adaptive optics SLO imaging,” Optometry and Vision Science: Official Publication of the American Academy of Optometry.89, 593–601 (2012).
  16. Z. Y. Zhong, B. L. Petrig, X. F. Qi, and S. A. Burns, “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy,” Opt. Express16(17), 12746–12756 (2008). [CrossRef] [PubMed]
  17. Z. Y. Zhong, H. X. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive Measurements and Analysis of Blood Velocity Profiles in Human Retinal Vessels,” Invest. Ophthalmol. Vis. Sci.52(7), 4151–4157 (2011). [CrossRef] [PubMed]
  18. T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express3(10), 2537–2549 (2012). [CrossRef] [PubMed]
  19. P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express3(12), 3264–3277 (2012). [CrossRef] [PubMed]
  20. Z. Popovic, P. Knutsson, J. Thaung, M. Owner-Petersen, and J. Sjöstrand, “Noninvasive Imaging of Human Foveal Capillary Network Using Dual-Conjugate Adaptive Optics,” Invest. Ophthalmol. Vis. Sci.52(5), 2649–2655 (2011). [CrossRef] [PubMed]
  21. T. Y. P. Chui, Z. Y. Zhong, H. X. Song, and S. A. Burns, “Foveal Avascular Zone and Its Relationship to Foveal Pit Shape,” Optom. Vis. Sci.89(5), 602–610 (2012). [CrossRef] [PubMed]
  22. J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the Retinal Parafoveal Capillary Network in Type 2 Diabetes before the Onset of Diabetic Retinopathy,” Invest. Ophthalmol. Vis. Sci.52(12), 9257–9266 (2011). [CrossRef] [PubMed]
  23. J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt.16(3), 036002 (2011). [CrossRef] [PubMed]
  24. Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. H. Gao, and D. T. Miller, “Imaging Retinal Capillaries Using Ultrahigh-Resolution Optical Coherence Tomography and Adaptive Optics,” Invest. Ophthalmol. Vis. Sci.52(9), 6292–6299 (2011). [CrossRef] [PubMed]
  25. J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical Capillary Changes in Non-Proliferative Diabetic Retinopathy,” Optom. Vis. Sci.89(5), E692–E703 (2012). [CrossRef] [PubMed]
  26. G. G. Deák and U. Schmidt-Erfurth, “Imaging of the Parafoveal Capillary Network in Diabetes,” Curr. Diab. Rep.13(4), 469–475 (2013). [CrossRef] [PubMed]
  27. M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina33(8), 1630–1639 (2013). [CrossRef] [PubMed]
  28. T. Y. Chui, T. J. Gast, and S. A. Burns, “Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.54(10), 7115–7124 (2013). [CrossRef] [PubMed]
  29. J. H. Kempen, B. J. O’Colmain, M. C. Leske, S. M. Haffner, R. Klein, S. E. Moss, H. R. Taylor, R. F. Hamman, S. K. West, J. J. Wang, N. G. Congdon, D. S. Friedman, and Eye Diseases Prevalence Research Group, “The prevalence of diabetic retinopathy among adults in the United States,” Arch. Ophthalmol.122(4), 552–563 (2004). [CrossRef] [PubMed]
  30. N. R. Burrows, I. A. Hora, Y. F. Li, and J. B. Saaddine, “Self-Reported Visual Impairment Among Persons With Diagnosed Diabetes-United States, 1997-2010 (Reprinted from MMWR, vol 60, pg 1549-1553, 2011),” JAMA307, 25–27 (2012).
  31. X. Z. Zhang, J. B. Saaddine, C. F. Chou, M. F. Cotch, Y. J. Cheng, L. S. Geiss, E. W. Gregg, A. L. Albright, B. E. K. Klein, and R. Klein, “Prevalence of Diabetic Retinopathy in the United States, 2005-2008,” JAMA304(6), 649–656 (2010). [CrossRef] [PubMed]
  32. A. Zambelli-Weiner, J. E. Crews, and D. S. Friedman, “Disparities in Adult Vision Health in the United States,” Am. J. Ophthalmol.154(6Suppl), S23–S30 (2012). [CrossRef] [PubMed]
  33. M. K. Ikram, C. Y. Cheung, M. Lorenzi, R. Klein, T. L. Z. Jones, T. Y. Wong, N. J. W. Retinal, and NIH/JDRF Workshop on Retinal Biomarker for Diabetes Group, “Retinal Vascular Caliber as a Biomarker for Diabetes Microvascular Complications,” Diabetes Care36(3), 750–759 (2013). [CrossRef] [PubMed]
  34. T. J. Wolfensberger and Z. J. Gregor, “Macular Edema - Rationale for Therapy,” in Macular Edema: A Practical Approach, G. Coscas, J. CunhaVaz, A. Loewenstein, and G. Soubrane, eds. (2010), pp. 49–58.
  35. G. de Venecia, M. Davis, and R. Engerman, “Clinicopathologic correlations in diabetic retinopathy. I. Histology and fluorescein angiography of microaneurysms,” Arch. Ophthalmol.94(10), 1766–1773 (1976). [CrossRef] [PubMed]
  36. S. Scholl, J. Kirchhof, and A. J. Augustin, “Pathophysiology of Macular Edema,” Ophthalmologica224(Suppl 1), 8–15 (2010). [CrossRef] [PubMed]
  37. A. Garner, “Histopathology of diabetic retinopathy in man,” Eye (Lond.)7(2), 250–253 (1993). [CrossRef] [PubMed]
  38. N. Bhagat, R. A. Grigorian, A. Tutela, and M. A. Zarbin, “Diabetic Macular Edema: Pathogenesis and Treatment,” Surv. Ophthalmol.54(1), 1–32 (2009). [CrossRef] [PubMed]
  39. D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med.366(13), 1227–1239 (2012). [CrossRef] [PubMed]
  40. D. R. S. R. Group and The Diabetic Retinopathy Study Research Group, “Preliminary report on effects of photocoagulation therapy,” Am. J. Ophthalmol.81(4), 383–396 (1976). [PubMed]
  41. A. E. Elsner, S. A. Burns, J. J. Weiter, and F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res.36(1), 191–205 (1996). [CrossRef] [PubMed]
  42. T. Y. P. Chui, T. J. Gast, and S. A. Burns, “Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.54(10), 7115–7124 (2013). [CrossRef] [PubMed]
  43. R. D. Ferguson, Z. Y. Zhong, D. X. Hammer, M. Mujat, A. H. Patel, C. Deng, W. Y. Zou, and S. A. Burns, “Adaptive optics scanning laser ophthalmoscope with integrated wide-field retinal imaging and tracking,” J. Opt. Soc. Am. A27, 265–277 (2010).
  44. W. Zou, X. Qi, and S. A. Burns, “Wavefront-aberration sorting and correction for a dual-deformable-mirror adaptive-optics system,” Opt. Lett.33(22), 2602–2604 (2008). [CrossRef] [PubMed]
  45. W. Y. Zou, X. F. Qi, and S. A. Burns, “Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm,” Biomed. Opt. Express2(7), 1986–2004 (2011). [CrossRef] [PubMed]
  46. A. E. Elsner, Q. Zhou, F. Beck, P. E. Tornambe, S. A. Burns, J. J. Weiter, and A. W. Dreher, “Detecting AMD with Multiply Scattered Light Tomography,” Int. Ophthalmol.23(4/6), 245–250 (2001). [CrossRef] [PubMed]
  47. D. R. Abrahamson, “Recent Studies On The Structure And Pathology Of Basement Membranes,” J. Pathol.149(4), 257–278 (1986). [CrossRef] [PubMed]
  48. Q. D. Nguyen, D. M. Brown, D. M. Marcus, D. S. Boyer, S. Patel, L. Feiner, A. Gibson, J. Sy, A. C. Rundle, J. J. Hopkins, R. G. Rubio, J. S. Ehrlich, and RISE and RIDE Research Group, “Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE,” Ophthalmology119(4), 789–801 (2012). [CrossRef] [PubMed]
  49. M. Al-Latayfeh, P. S. Silva, J. K. Sun, and L. P. Aiello, “Antiangiogenic Therapy for Ischemic Retinopathies,” Cold Spring Harbor Perspectives in Medicine 2 (2012).
  50. L. An, J. Qin, and R. K. Wang, “Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds,” Opt. Express18(8), 8220–8228 (2010). [CrossRef] [PubMed]
  51. J. Fingler, R. J. Zawadzki, J. S. Werner, D. Schwartz, and S. E. Fraser, “Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique,” Opt. Express17(24), 22190–22200 (2009). [CrossRef] [PubMed]
  52. L. An and R. K. Wang, “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express16(15), 11438–11452 (2008). [CrossRef] [PubMed]
  53. S. Makita, F. Jaillon, M. Yamanari, M. Miura, and Y. Yasuno, “Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography,” Opt. Express19(2), 1271–1283 (2011). [CrossRef] [PubMed]
  54. C. C. Bailey, J. M. Sparrow, R. H. B. Grey, and H. Cheng, “The National Diabetic Retinopathy Laser Treatment Audit. I. Maculopathy,” Eye (Lond.)12(1), 69–76 (1998). [CrossRef] [PubMed]
  55. Early Treatment Diabetic Retinopathy Study Research Group, “Grading Diabetic Retinopathy from Stereoscopic Color Fundus Photographs--An Extension of the Modified Airlie House Classification. ETDRS Report Number 10,” Ophthalmology98(5Suppl), 786–806 (1991). [CrossRef] [PubMed]
  56. D. J. Browning, M. M. Altaweel, N. M. Bressler, S. B. Bressler, I. U. Scott, and Diabetic Retinopathy Clinical Research Network, “Diabetic Macular Edema: What Is Focal and What Is Diffuse?” Am. J. Ophthalmol.146(5), 649–655 (2008). [CrossRef] [PubMed]

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